Journals on Biomedical Science | BJSTR

Love Addiction: “I Can’t be with You, I Can’t be without You.” Psychological Aspects and Clinicals Intervention

Introduction

Love as an Addiction

Romantic love is a universal phenomenon that every individual seeks during his life, for the purposes of reproduction and survival. Love inevitably influences the quality of life of each subject, as it can bring joy and happiness, but also pain and suffering. It has been the object of interest of artists, singers, poets and philosophers, who described it as a deep and intense feeling, capable of causing both euphoria and despair. In this regard, Ovid wrote: “I cannot live without you or with you”; in Plato’s Symposium, Aristophanes argued that, in the beginning, man was a perfect and complete being, a creature with four arms, four legs and one head with two faces; there was, therefore, no distinction between man and woman. To reduce the superiority of men, Zeus, envious of their perfection, decided to divide them in two, condemning them to the continuous search for their half, to recover the lost perfection and feel complete again. From this, it emerges the common conviction of having to find one’s own soul mate, “the other half of the apple” that can fill its own void, a conviction that influences people’s behavior and how they conceive love. The English term “addiction” comes from the Latin “addictus” which means “ enslave “. The expression is also used for the use and abuse of chemicals. In recent years, the scientific community has also treated behavioral addictions that are obsessively repeated, these addictions however, are socially accepted and refer to “new addiction” and dependent love, can take on the connotation of slavery.

The boundary between love and emotional dependence is thin, in the early stages of a relationship is physiological the need to want to spend more time with your partner, the addiction to the loved one and his idealization, are part of the physiological process, in a healthy relationship, these aspects gradually fade with time, leading to seeing and accepting the partner in its uniqueness, despite differences; while, in emotional dependence, idealization persists excessively and one-way, The desire of the other becomes a compulsive and necessary need to function, and you continue to remain in a relationship despite the negative consequences. In the literature, there is no unanimous agreement on the relationship between love and addiction; in this regard, Earp and colleagues [1] have proposed two perspectives: the narrow view and the broad view. The narrow view considers love as an affective dependence, only in some conditions, in reference to the phases of falling in love and the most extreme and pathological behaviors. Advocates of this view consider aspects such as: sexual compulsions, pedophilia, toxic or abusive relationships, abnormal attachment and lack of tolerance of the negative outcomes of life and relationships [2,3]. According to neuroscientists and psychiatrists, the prevailing model of substance dependence assumes that drugs generate addiction, as they gradually trigger abnormal and non-natural functioning patterns [4], therefore, addictive behaviors are the result of brain processes not present in the brain of unrelated subjects.

Volkow and colleagues [5] have shown how the intake of substances activates neurotransmitters in the brain to create reward signals, learning patterns occur in the brain cellular adaptation that would not occur if there were no intake of substances. The addict who continuously searches for drugs acts a typical drug addict behavior. Other researchers have, instead, found behavioral and neurological similarities between, for example, those who take food uncontrollably and those who use substances. The narrow view of affective dependence, therefore, argues that one can be dependent on love, but only in the presence of abnormal brain processes, analogous to those that form when taking illicit drugs. The lover suffers from addiction if he engages in sexual behavior or abnormal attachment, probably related to abnormal brain processes, therefore his search for love:

1) Interferes with his ability to carry out daily life activities.
2) Prevents healthy relationships.
3) It has negative consequences for themselves or for others. The broad view considers love an addiction, i.e. being in love is equivalent to being addicted, with similar chemical and behavioral processes [6,7]. Proponents of this view place emphasis on the similarities of experience between addicts and those involved in a phase of falling in love. Such analogies are found as stated by Fisher and colleagues [6] in “mood swings, desire, obsession, compulsion, distortion of reality, emotional dependence, personality changes, risk taking and loss of self-control”.

Burkett and Young [7] hypothesize that there is “a deep and systemic concordance between the brain regions and the neurochemicals involved in both addiction and social attachment”. Love produces a gratification, similar to that obtained from drugs, food, gambling, or sex [4,8,9]. Addictions are appetites that each individual possesses and such appetites if they are not satisfied for a long time, manifest themselves in a more intense way. Therefore, each individual is dependent on something, food, sex or love; what differs is the intensity with which it manifests itself [1].

Affective Dependence

Affective addiction [love addiction], a term introduced for the first time by Peele and Brodsky [10] in Love and addiction, is a widespread problem, especially in women. Affective dependence is a new addiction that refers to a series of dysfunctional behaviors, in which the object of dependence is not a substance, but a socially accepted behavior or activity; however, it has not yet been included in any nosographic system, therefore, there are no recognised diagnostic criteria for diagnosis, nor a precise definition. Despite this, several scholars, including Reynaud and collaborators [3] have proposed a number of criteria similar to those for substance dependence. They define emotional dependence as “A maladaptive or problematic love relationship pattern leading to clinically significant impairment or distress, as manifested by three [or more] of the following [the first five of which occur at any time in the same 12-month period]” [3]:

1. Presence of withdrawal syndrome in the absence of a loved one, characterized by significant suffering and compulsive need of the other.
2. A considerable amount of time invested in the relationship [or with thought].
3. Reduction of important social, professional, or recreational activities.
4. Persistent desire or unsuccessful efforts to reduce or control the relationship.
5. Continuation of the report despite the existence of problems created by the report.
6. Presence of attachment difficulties, as demonstrated by at least one of the following:
a) Repeated love relationships exalted without any lasting period of attachment.
b) Repeated painful love relationships characterized by an insecure attachment.

The “women who love too much” [Robin Norwood] tend to enter relationships with distant people, cold, unable to enter into intimacy, with the belief that with their love they can change them; a vicious circle is thus established that confirms the belief that we are not worthy of being loved, increasing their suffering. In addition, the attitude of the other is justified, attributing it to traumatic or painful situations experienced during childhood. The relationship, despite causing pain, is not interrupted, as it has become the center of their life: the desire to spend as much time as possible with the loved one increases, when this does not happen you think obsessively about the relationship; his absence is experienced as intolerable; you lose interest in everything that was important before; friends, family, work/ study take second place. The partner is idealized, and it is thought that without him his existence has no meaning. Their goal is to take care of the partner, putting them completely aside, until they cancel themselves. One’s well-being depends on one’s partner and they tend to entrust responsibility for one’s own happiness to the other.

Psychobiology of Affective Dependence

Studies have shown that all forms of dependence are based on a common substrate, the mesolimbic reward system. It consists of a network of brain structures which are activated in response to pleasant stimuli, rewarding and that interact with each other for the regulation of motivated behavior, for associative learning and for the attribution of salience. This system consists of some main areas:

1. The ventral tegmental area [VTA] is a group of neurons located at the base of the midbrain. Dopaminergic cells of the Mess corticolimbic system originate in VTA, which play a crucial role in the reward system.
2. The nucleus accumbent is a brain region located in the basal forebrain, and also plays a fundamental role in the reward system. It is involved in motivated behavior, the regulation of pleasure and gratification associated with specific stimuli and, therefore, in learning by reinforcement.
3. The prefrontal cortex, is localized in the anterior portion of the frontal lobe of the brain, precedes the primary motor cortex and the premotor cortex. It is a cortex involved in several higher cognitive functions, such as planning, motivation, cognitive control, regulation of social and emotional behavior; specifically, the frontal orbiting cortex is involved in decision-making processes. In relation to addictions, it has been observed that the activity of the prefrontal cortex increases during abstinence, thus demonstrating that it has a role in the reiteration of addictive behaviors [11]. Furthermore, by being implicated in executive control over decision-making processes, Goldstein and Volkow [12] suggest that an alteration in the way it works may result in the loss of impulse behavior control, Decisions are therefore taken based on an immediate reward; at the expense of the negative consequences of one’s conduct.

4. The limbic system, responsible for motivation and reward, regulates emotions and stores emotionally significant events. It is formed by two structures, amygdala, and field, important for emotions and memory. In particular, the amygdala is in the anterior portion of the medial temporal lobe of the brain and plays a crucial role in the processing and regulation of emotions especially negative ones [such as fear, sadness, anxiety] it is also involved in the formation and storage of memories related to emotional experiences, associating emotions with events. The hippocampus is localized in the medial portion of the temporal lobe and is implicated in learning and memory processes, especially in the encoding of memories and emotional valences related to such memories [13].

At the neurobiological level, studies of biochemistry, functional neuroimaging and genetics highlight a close relationship between behavioral addictions and substance dependence [14], as, for example, food, gambling, Affective dependence are activities that activate the circuits responsible for gratification, like those caused by the use of drugs [15]. Goodman [16] hypothesized that behavioral addictions are the basis of a common “additive process” resulting from the alteration of three functional systems: “motivation-gratification”, “regulation of affections” and “behavioral inhibition”. the negative consequences of their conduct.The alteration of the motivation-gratification system causes unpleasant sensations in the subject, this causes the conducts capable of activating the gratification system to acquire greater reinforcement [16]. The alteration of the regulation of affections leads the individual to avoid painful emotions, experienced as intolerable and which he is unable to control [16]. The alteration of the mechanisms of behavioral inhibition, finally, determines in the individual the need to perform a behavior able to activate the gratification system, without thinking about the negative consequences that it determines in the long term [16].

Pathological Addictions: Maccanisms

In recent years, the idea is spreading that the term addiction can also refer to the recurrence of behaviors, which we feel the need to implement compulsively. The characteristic of these behaviors is that they are socially accepted, which are part of their daily life; in this case, we speak, therefore, of behavioral dependence or new addiction defined as “a group of heterogeneous disorders […] that imply an involvement in a repetitive and persistent habit, aimed at changing the state of consciousness of the individual, and that in the long term involve a significant impairment of the sphere of work, affective-relational and social of the subject” [15]. These include pathological gambling, compulsive shopping, addictions to work, study, technology, sex, exercise, food, and relationships. However, the scientific community recognizes only pathological gambling, including it in the DSM-V among the “disorders related to substances and addiction disorders” [APA, 2013]. The English terms “dependence” and “addiction” are both translated, in Italian, with a single term “dependence”; however, these English terms refer to two different phenomena: the first indicates the physical dependence on the substance that the body needs to function; the second indicates, instead, psychological dependence on a pleasant stimulus. A subdivision of addictions that is based on social regulators is due to Francisco Alonso-Fernández [17], who distinguishes “social or legal addictions” that include legal drugs [such as alcohol, drugs, tobacco, etc.] and socially accepted activities [such as eating, working, shopping, playing], “antisocial or illegal addictions” that include drug addiction and illegal activities [such as cocaine, heroin, cannabis, non-consensual sex] [17].

From a symptomatologic point of view, there are many similarities between behavioral and substance use addictions:

• The individual is unable to control his or her behavior by acting compulsively, which gives him or her pleasure.
• Shows craving, defined as “an attraction, of varying intensity, towards certain psychotropic substances of abuse[…] at high levels of intensity, intense and serious psychophysical alterations appear that lead the subject to think only about the substances from which he is attracted and the means by which to obtain them” [18];
• Can develop abstinence in case of absence of the object of dependence and tolerance that is, the rewarding effects are no longer due to the repeated use of the same dose of the substance or the compulsive implementation of an activity and consequently, the individual is forced to increase the dose or activity to achieve the initial effect.
• The individual persists in behavior despite the negative consequences it entails.

In addition to symptomatology, drug and behavioral addictions have similar neurobiological mechanisms. Several studies have shown that when the subject acts a behavior that causes pleasure and gratification, this system is activated, resulting in a strengthening of the behavior itself, as it is encoded in memory as positive. It is a physiological system that is usually activated by adaptive behaviors, necessary for survival, such as eating, drinking etc.; however, the alteration of this circuit is also at the base even addictive behavior [18]. A malfunction of the brain mechanisms involved in gratification and motivation involving the meso-cortico-limbic circuits, seems to be the basis of both substance and behavioral addictions. The regulation of these mechanisms is made possible by the interaction of different neurotransmitter systems; in particular, in addiction a crucial role is played by the dopaminergic system, which regulates the motivation that guides the search for rewarding stimulus [20]. Dopamine produces different effects on motivated behaviors depending on how it reacts to two different motivational stimuli: appetitive stimuli, which push the individual to get a reward, and consumer stimuli, that keep the subject’s proximity to the reward. Both stimuli activate the dopaminergic neurons of the neocortical pathway; whereas, the dopaminergic neurons of the mesolimbic pathway, considered the pleasure pathway, are activated only by consumer stimuli [19].

In addition to the dopaminergic system, other systems involved in addiction mechanisms are:

• The serotonergic system, the alteration of which appears to be related to impulsive behavior, typical of addiction [15]. The authors of this theory believe that the basis of the phenomenon of craving and relapses is the process of incentive sensitization [15,20,21]. In addition, such process simple modifications of the synaptic plasticity in the nucleus accumbent and in the cortex of neurotransmitter systems such as serotonin, glutamate, noradrenaline, and GABA [15]. Some authors [15,20,21] believe that similar alterations of the circuits involved in the incentive salience are also the basis of dysfunctional behaviors typical of new addiction; Therefore, stimuli and contexts related to compulsive behavior could assume abnormal incentive-motivational properties. However, to date, there are insufficient experimental tests to support this hypothesis.

Etiopathogenesis of Affective Dependence

It has been seen how neurobiological aspects favor the onset and maintenance of affective dependence. However, it cannot be explained solely in biological terms since affective dependence is a complex and multifactorial phenomenon. For an exhaustive understanding of it, therefore, one must also consider psychological factors [such as attachment, emotional dysregulation] and sociocultural factors [such as media influence and cultural expectations], all factors that interact with each other in the determination of this type of dependence.

Psychological Factors: Attachment

John Bowlby developed the theory of attachment [22] which emphasizes the importance of the mother-child relationship and how these early relationships can influence the child’s social and emotional development. Bowlby criticizes the prevailing theories of the time, according to which the child would seek the proximity of the reference figure only to satisfy the need for nourishment. He believes that the child has an innate tendency to establish strong emotional ties with the attachment figure and seeks its proximity to gain protection and security. He calls attachment behavior “any form of behavior that leads a person to achieve or maintain closeness with another individual”, usually the mother. It is activated by distance from the reference figure and is inhibited by its proximity. Bowlby’s theory has found important confirmation in Mary Ainsworth [23], who invented the strange Situation, a standardized observational procedure that allows to evaluate the attachment of the child from twelve months of age. It is an experimental situation consisting of 8 micro episodes, lasting about three minutes each, in which the behavior of the child is observed in the presence of the mother, when it is separated from her and at the time of reunification (Figure 1). Other scholars have added other styles of attachment, notably:

• At Main and Solomon [24,25] we owe the introduction of the disorganized/disoriented attachment observed in children with mothers who did not process a trauma or mourning during their childhood [26];
• Crittenden has introduced avoidant/ambivalent attachment that seems to correspond to a defensive strategy against abusive mothers [26].

Figure 1

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Several studies have examined the relationship between attachment styles and obsessive love, Hazan and Shaver [27] were the first to broaden the theory of attachment to adult romantic relationships, suggesting that the anxious-attachment style could be a risk factor for the development of obsessive love. Feeney and Noller [28] conducted a study involving a sample of 374 university students [162 males and 212 females] aged 17-58 and almost all single. A series of questionnaires were administered that evaluated the attachment style and the love style and the results showed that the anxious-ambivalent attachment group reported high levels of dependence, the desire to be involved in romantic relationships, although these were characterized by less stability. They also highlighted a greater propensity for obsessive concern, idealization of the partner to rely on, and emotional dependence. Otherwise, subjects with safe and avoidant attachment were characterized by greater self-confidence and others, stable and positive relationships, the latter by the tendency to avoid intimacy, little or no intense relationships. This study seems to confirm that the style of attachment affects adult romantic relationships and that the anxious-ambivalent attachment style may be the basis for the development of love addiction. The study of Ahmadi, et. al. [29] aimed to investigate the relationship between obsessive love and attachment styles. It was conducted on a sample of 290 students [117 females and 173 males]. They were given the Passionate Love Scale [PLS] and the Adult Attachment Inventory. The results showed a significant relationship between anxious-ambivalent attachment style and obsessive love. The child, with such a style of attachment, manifests separation anxiety because of a reference figure who tends to have an inconsistent attitude. As a result, as adults these individuals show a constant concern for their relationships and fear separation, rejection and betrayal by the partner, becoming dependent on them.

This study also confirms that the anxious-ambivalent attachment style can determine the development of obsessive love. A more recent study aimed at investigating the relationship between attachment styles and obsessive love style is that of Honari and Saremi [30]. The sample consisted of 306 students, who were given the following questionnaires: Adult Attachment Style [AAQ] and Love Attitude Style [LAS]. From such a study emerged a significant association between the obsessive love style and the anxious-ambivalent attachment style; while the same could not be said about the relationship between safe and insecure-avoiding attachment styles and obsessive love. This study also concludes that the anxious-ambivalent attachment style can predict obsessive love style. In this regard, the authors stress that evaluating attachment styles is important as it allows prediction of people’s love styles. Borgioni [31] also associated affective dependence with anxious-ambivalent attachment. Subjects with this style of attachment had a caregiver present intermittently and often assumed the role of “adult child”, as they were the ones to take care of the parents. In adult romantic relationships these subjects tend to unconsciously recreate the same dynamics that were created with the parent. Research in the literature seems to confirm that anxious-ambivalent attachment is at the origin of affective dependence, also given the overlap of their typical characteristics. For example, concern, vigilance, rumination are factors that are observed in romantic love [32,33] and obsession [American Psychiatric Association, 2000], but are also linked to anxious attachment. It should be noted, however, that some research indicates that attachment is not stable over time and may be influenced by further relationships. For example, Belsky, et al. [34] indicate that, after three months from the initial administration of the attachment assessment questionnaires, about fifty percent of people have a different attachment style. However, the research has shown that the first experiences with the caregiver have quite important effects on the development of affective dependence.

Adult Attachment and Self-Esteem

According to Bowlby’s theory, the first relationships with the reference figures are internalized by the child and constitute the internal operating models [MOI]. The latter are mental representations of self and attachment figure that are formed during childhood, but remain over time, as they influence future interpersonal relationships, orient the subject’s worldview, behavior, and his beliefs and expectations [27]. In accordance with this concept of Bowlby, Bartholomew, and Horowitz [35] developed an “adult attachment model”. From the combination of two dimensions, the “model of self” and the “model of the other”, or the positive or negative perception that each has of oneself and the other, they have identified four different styles of adult attachment: The secure attachment style manifests itself in subjects who have a positive perception of both themselves, as they feel lovable, and others, as they expect people to be available. In addition, they are comfortable with intimacy and autonomy, and possess adequate emotional regulation strategies; The insecure, concerned attachment style is observed in subjects who, having a negative view of themselves, feel inadequate, while others are assessed positively. Such individuals need support, love, and seek the approval of others; The insecure attachment style of the buffer manifests itself in subjects who have a positive image of themselves and a negative view of others, who are considered unreliable. In addition, these subjects tend to avoid intimate relationships; Fearful insecure attachment style is typical of subjects who have a negative view of both them and others. Such individuals desire contacts and intimacy, however, given the lack of trust in others and the fear of being rejected, they avoid intimate relationships. Individuals with concerned attachment and those with fearful attachment, therefore, tend to manifest greater dependence on others.

In this regard, Gori, et. al [36] conducted research with the aim of analyzing variables that may be associated with affective dependence, with particular attention to adult attachment patterns and self-esteem. The research involved a sample of 300 individuals engaged in a love relationship. Subjects were given the following questionnaires: Love Addiction Inventory – Short form [LAI – SF], Relationship Questionnaire [RQ] and Rosenberg self-esteem Scale [RSES]. The results of such research showed, first, a significant relationship only between affective dependence and concerned and fearful adult attachment; Secondly, it emerged that self-esteem plays a mediating role in the relationship between adult attachment patterns and emotional dependence. Individuals who present these attachment styles have a negative view of themselves [37], as a result they show low levels of self-esteem, factors that can lead to dysfunctional relationships characterized by excessive dependence on the partner [38]. In the literature there are studies that examined the relationship between self-esteem and attachment, the results, showed that there is an association between insecure attachment and low self-esteem levels [39,40]; it is also shown that low levels of self-esteem can lead to the onset of interpersonal dependence [38]. However, the authors of this research believe it is necessary to emphasize that it may be the affective dependence itself that influences the self-esteem of the subject, thus determining a vicious circle.

Trauma, Dissociation and Emotional Dysregulation

Several studies have shown that pathological addictions are closely related to both childhood trauma and to emotional dissociation and dysregulation [41,42]. Exposure to childhood relational trauma, such as experiences of emotional deprivation, physical, sexual and/ or psychological abuse, can lead to conditions such as dissociation and emotional dysregulation. Dissociation is defined as a “disintegration of normally integrated functions of consciousness, memory, identity, or perception of the environment” [43]. It is a defense mechanism that isolates from his consciousness a painful experience and the emotions connected to it; It has, therefore, the aim of protecting the ego from pain through the alteration of the state of consciousness, inhibiting information experienced as intolerable and creating a more positive reality in which to take refuge [44]. Dissociation is not a dysfunctional aspect; however, a pathological recourse to this type of mechanism can lead to an impoverishment of the personality of the subject, a compromise of the sense of continuity of one’s identity, detachment from reality, causing a deficit in mentalization and self-regulation of emotions [42]. The child, in his first years of life, does not have the ability to independently regulate their emotional states; Therefore, it is necessary the intervention of the caregiver to help him manage his emotions and at the same time allow him to learn the ability to manage them independently [45]. The “good enough” caregiver Winnicott [46] will be able to provide adequate responses to the emotional states of the child and this will allow him to develop a “theory of mind” [47] becoming aware of his own emotions and those of others; This happens, therefore, in the case of a secure attachment with the parent. The child thus gradually learns and develops the ability to regulate his emotions independently [45].

Otherwise, if the child has experienced an emotionally neglectful caregiver, who is not able to regulate his emotions, he will not develop the ability to mentalize and regulate his emotions [45]. Rather, he will find himself in a state of emotional dysregulation, that is, he will not be able to regulate his emotions on his own and will have difficulty tolerating negative emotional states. As a result, the subject will most likely have to resort to an external regulator that allows him to return to a state of rest. Such a regulator can be identified in a substance or dependent behavior, the use of which represents a dysfunctional strategy of emotional self-regulation; this can lead to the onset of a pathological dependence, where the object of dependence would represent an external regulator of one’s emotional states [44]. In the literature there are several studies by Caretti and collaborators that highlight the significant correlation between dissociation and emotional dysregulation, resulting from relational trauma, and the different forms of pathological dependence. About love addiction, Stavola, et al. [46] conducted research to assess the predisposing factors of this type of addiction. They hypothesized that the dissociation and emotional dysregulation that occur as a result of a childhood relational trauma and insecure attachment style are the basis of emotional dependence. The results confirmed what the authors had assumed, as a significant association emerged between trauma, attachment, dissociation, and emotional dysregulation, confirming them as predisposing factors to love addiction. child has experienced an emotionally neglectful caregiver, who is not able to regulate his emotions, he will not develop the ability to mentalize and regulate his emotions [45]. Sociocultural factors in addition to neurobiological aspects and psychological factors, there are also sociocultural factors underlying affective dependence. The mass media seem to have a significant influence on the development of affective addiction [47]: movies, TV series, songs, novels often tend to represent love in a pathological way [48,49].

Vannini and Myers [50] conducted a study to analyze the lyrics of albums belonging to the musical genre “teen pop”, a genre of music that is aimed primarily at a teenage audience. The main theme of these songs is romantic love, which is described as an intense desire, “an overwhelming and painful experience”. Described lovers tend to have obsessive thoughts and feelings and idealize their partner. Often the lyrics of these songs convey the idea that you cannot live without the other person, now indispensable. These kinds of songs can have a significant impact on young teens, who use the meaning of lyrics to build their identity, to understand how relationships work. These texts convey a kind of pathological love, which is represented as ideal love, can affect the way young adolescents conceive love and what they expect from relationships. Even movies often transmit dysfunctional relational dynamics, and this can lead teenagers to search for those same dynamics, considered right. In addition, affective dependence seems to prevail in women, for example, Miller [50] claims that 99% of affective dependent subjects are female. According to Sussman [47] gender would affect the ways in which emotional dependence manifests itself. In this a key role is played by culture, which seems to strengthen affective dependence: the gender stereotype sees women as too sensitive, naive, weak, passive, not very rational, dependent, dedicated to the care of others, putting aside herself, submissive to the will of others; while, man tends to be seen as more rational, stronger and independent. Such stereotypes can influence the behaviour of women, who, to conform to cultural expectations, risk entering into dysfunctional, potentially dangerous relationships.

Anxious and Depressive Symptoms

Affective dependence can significantly affect the psychological and physical well-being of the person. For the affective dependent subjects, the relationship with the partner becomes of fundamental importance; consequently, everything that does not concern the relationship passes into the background: they lose interest in activities that they loved to practice previously, are unable to concentrate on work and study, friendships and family relationships are neglected. All this can lead to social isolation. Moreover, the fear of losing a partner, of being abandoned or rejected, can make the affective employee experience strong anxious and depressive states. Excessive worry and anxiety can lead to the development of a real generalized anxiety disorder that is characterized by the presence of “physical symptoms [muscle tension, restlessness, easy fatigue], neurovegetative [tachycardia, dyspnea, tremors, dizziness] and psychological [difficulty concentrating, irritability]” [19]. The affective employee may also develop a “major depressive disorder” [16] whose main symptoms are: depressed mood, loss of interest or pleasure in previous activities, impaired weight and appetite, loss of energy and fatigue, insomnia or hypersomnia, feelings of guilt and self-assessment, difficulty in contracting and suicidal thoughts [16]. Fisher and colleagues [51] point out that romantic rejection can compromise the subject’s psychological health, inducing clinical depression and in the most extreme cases can lead to suicide. It can also impair physical health, as an increase in blood pressure and a lowering of the immune system may occur, due to severe stress [52]. Even more serious consequences occur when the partner, to whom you are emotionally dependent, decides to end the relationship or when you remain in a dysfunctional relationship, despite being dangerous to your life.

Intimate Partner Violence

Affective addicts tend to enter relationships with abusive, abusive, violent, manipulative and detached persons [3]. A peculiar feature of affective dependence is that, despite suffering, the dependent subject cannot end the relationship and causes the behavior of the partner to be attributed to the traumas of his childhood [53]. The “women who love too much” have the dysfunctional belief that it is only by sacrificing and dedicating themselves totally to the other, cancelling sexless, that they can help the partner. This belief only feeds the permanence in the relationship; permanence that can prove lethal for one’s life. They do not manage to separate from their partner, as it would be too painful for them and prefer, rather, to cling to the illusion and hope that the partner changes, a wait that turns out to be useless as this will never happen. The risk that the affective addicted may face is that of entering abusive relationships, becoming a victim of domestic violence, which in English is called intimate partner violence. The UN defines IPV as “the behavior of an intimate partner or ex-partner that causes physical, sexual or psychological harm, including physical aggression, sexual coercion, psychological abuse or controlling behavior” [UN, 1993]. In addition, it is very important to understand the dynamic between the affective addicted and the abusive and violent partner, because it becomes even more difficult for her to end the relationship. In this regard, Lenore Walker [54] has developed a model of “cycle of violence” that defines “the progressive and ruinous vortex in which the woman is swallowed by the continuous, systematic, and therefore cyclical violence, by the particular party, the author believes that there are three phases of domestic violence: “phase of construction of tension”, “explosion or violence phase” and “reconciliation/ honeymoon phase” [55].

The first phase of construction of tension [“tension building phase”] is characterized by the progressive increase of tension in the relationship, due to frequent conflicts and verbal violence against the victim. The latter perceives that the partner is always nervous and irritated; therefore, to avoid further conflicts, the victim will tend to take a pandering attitude, trying to appease the partner. In the second phase of explosion or violence [“explosion phase”] there occurs the loss of control by the aggressor that results in real violence. This may include physical, psychological and/or sexual abuse of the victim. In the third phase of reconciliation/honeymoon [“honeymoon phase”] the aggressor, can show repentance, seeming, kind, makes romantic gestures, apologizes and promises that it will not happen anymore, that will change, manipulating thus the victim, who will sincerely believe his aggressor, and will continue to hope that the relationship will improve and that he can really change [56]. However, unfortunately, this will never materialize in fact, following the “honeymoon” phase, the cycle starts again from the first phase. This pattern of behavior can help to strengthen the dependency of the victim, who will feel responsible and take the blame for the situation, believing that she deserves it, further undermining the already low self-esteem. Moreover, as the dysfunctional relationship continues, these phases will occur more frequently, more intensely and more rapidly, to the point that psychological, physical, economic, and sexual violence leads to feminicide. November 25 is the international day against violence against women, “wounded, massacred, humiliated women who carry in their body and soul the bruises of what was thought to be love” “When being in love means suffering, we are loving too much. [..] When we justify her moods, her bad temper, her indifference, or consider them the consequences of an unhappy childhood and try to become her therapist, we love her too much. […] When our relationship with him jeopardizes our emotional well-being, and perhaps even our health and safety, we are loving too much” [54]. The criminal analysis service reports that from 1 January to 3 September 2023 there were 225 murders, of which 77 are female victims, 61 killed in the family/ affective; 38 of these died because of the partner or former partner (Ministry of the Interior, 2023).

Individual Therapies

According to some authors, among individual therapies, cognitive behavioral therapy and psychodynamic treatment could be beneficial in the treatment of affective dependence [55]. Some authors have suggested that cognitive behavioral therapy (CBT) may have a potential benefit in treating affective dependence. Automatic thoughts and cognitive distortions (such as generalization, catastrophization) could play a decisive role in maintaining affective dependence [55]. Cognitive behavioral therapy could be effective in addressing these distortions, through cognitive restructuring: fundamental is, therefore, to make the patient aware of his patterns of negative thoughts and adopt appropriate strategies to modify them. However, again, there are no studies on the use of CBT in the treatment of affective dependence [55].

Drug Treatment

Although there is no scientific evidence in the literature to prove the efficacy of a drug treatment of affective dependence, Sanches, and John [55] suggest that the phenomenological characteristics and neurobiological mechanisms involved in this condition, suggest that the use of drugs may be beneficial for the treatment of affective dependence. However, the bioethical implications must be considered; in particular, Earp and colleagues [57] have highlighted some situations in which it would be justified to use drug treatment for affective dependence. According to these authors, it can be considered to treat love using drugs only when this causes pain and suffering to the patient, as in the case of domestic violence, or when psychological treatments are not sufficient [56]. Sanches and John [55] hypothesize that affective dependence can be treated using drugs such as antidepressants, mood stabilizers, antipsychotics, and exogenous neuropeptides. Since obsessive-compulsive disorder (OCD) and some cases of affective dependence have similar phenomenological characteristics, the authors hypothesize that antidepressants, specifically selective serotonin reuptake inhibitors [SSRIs] may also play a role in the management of affective dependence, given the effectiveness of SSRIs in the treatment of DOC [55]. SSRIs may be useful in reducing obsessive thoughts, typical of both phenomena [56] In addition, affective dependence and impulsiveness are strongly correlated, which suggests that mood stabilizers may play a role in managing this condition [55]. Further drugs that could be useful in the treatment of affective dependence are antipsychotics, due to their function as dopamine antagonists. Antipsychotics could modulate the dopaminergic activity that is activated during falling in love [55]. As for exogenous neuropeptides, studies have shown that vasopressin and oxytocin are involved in the attachment system. Finally, it could be hypothesized that drugs used to treat addictions may be beneficial for the treatment of love addiction, given the similarity between the two conditions: for example, naltrexonee buprenorphine [55]. The authors stress the importance of further studies to investigate whether these drugs can benefit the treatment of affective dependence [55].

Group Therapy

Group therapy is considered by many authors as the treatment of choice for affective dependence [55]. Yalom [56] identified several factors that appear to be therapeutic within a group, such as: “the infusion of hope, universality, information, altruism, corrective recapitulation of the family primary group, the development of socialization techniques, imitative behavior, interpersonal learning, group cohesion, catharsis and existential factors” [56]. Within a group, therefore, a climate of trust will be created that will allow patients to tell each other without shame. This will allow members of the group to find emotional support, to feel understood and less alone, as they all share the same issue. In addition, listening to the story of others can stimulate important reflections in the patient who faces that same pain. However, there are no studies showing the effectiveness of these selfhelp groups [55].

Conclusion

During this review, we have deepened the affective dependence and we have seen that it is a complex phenomenon that involves several factors and significantly influences the psychological well-being of the people involved. The findings from this work emphasize the importance of the quality of primary relationships, as it was seen as an anxious attachment-ambivalent, having experienced relational traumas in childhood are actors predisposed to affective dependence. Studies have shown that at the base of love addiction there are neurobiological mechanisms analogous to those that occur in substance dependence. It also emerged that society and culture play a crucial role in maintaining this condition, suggesting the importance of primarily cultural change. Subjects with affective dependence tend to enter into abusive relationships, with the risk of becoming victims of domestic violence, and this makes us reflect on the importance of paying more attention and gaining greater awareness of this issue. “The general objective that every woman must achieve is the conquest of independence and emotional autonomy, without suffering the bullying of those who want to prevail by inducing feelings of guilt. And do not call it love, love is another thing, because to love is to give oneself in a perspective of reciprocity and sharing”[57].

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Lactic Acid, Magnesium, Metformin and Lactic Acidosis

Introduction

About Lactic Acid Production and Metabolism

Lactic acidosis is a medical condition characterized by a buildup of lactate [La] (especially l-lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body’s oxidative metabolism [1]. Wikipedia gave 36 causal agents for lactic acidosis, including metformin, but without magnesium deficiency [1]. PubMed Search [2] [“lactic acid” metformin magnesium] gave only one result, which was not associated with body magnesium status.

It is generally known that the production of lactic acid (often named by its anion “lactate” [3]) increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia [4]. Nowadays is known that lactate also serves as a major circulating carbohydrate fuel and enables the uncoupling of carbohydrate- driven mitochondrial energy generation from glycolysis [4]. Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues [4]. During fermentation, the NADH is used to reduce pyruvate to lactate, which is then excreted [4]. This process results in a net yield of two ATP and two lactate molecules per glucose, without consuming any oxygen [4]. In respiration, the NADH electrons and pyruvate generated by glycolysis are shuttled into the mitochondria, where they are consumed and subsequently produce copious usable energy (approximately 25 ATP molecules per glucose) [4].

Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (Krebs (TCA) cycle) while the remainder is used for gluconeogenesis (Cori cycle) [5]. Healthy mitochondria function well, even at low O2 levels such that dysoxia is rare and low O2 is likely to be a minor factor in the increasing concentrations of lactate [6]. Catecholamines promote glycogen breakdown to lactate [6]. In the (old) crossroad from pyruvate to a) lactate or b) ATP via TCA cycle the b) route can be hindered e.g. by mitochondrial diseases [6], low mitochondrial density [6] or thiamine deficiency [7], so promoting lactate production.

Observations on magnesium

Magnesium has an important role in ATP synthesis [8]. (ATP: Adenosine triphosphate, a nucleotide that provides energy to drive and support many processes in living cells, such as muscle contraction [9]). Magnesium deficiency (defined by S-Mg & lt; 0.8 mmol/) was detected by 23 % of critically ill patients, this proportion was (1.6 – 2.0- fold) higher by patients with increased S-lactate content, diabetics and alcoholics [10].

Study on Serum Metformin, Lactate, Blood pH and Mortality In a study on databases of cases by metformin overdose with documented mortality data and values of serum lowest (“nadir”) pH, highest (“peak”) lactate level, and metformin concentrations, with outlines of their treatments [11]. The databases searched included MEDLINE from 1950 to June 2007, EMBASE from 1974 to June 2007, CINAHL from 1982 to June 2007, and TOXNET from 1965 to June 2007; these ranges encompassed the maximal time range limits of each database.

Number of cases fulfilling inclusion criteria was 22, five of them died. The represented data are from Table 1 in [11], partially analyzed by the author with IBM SPSS Statistics, version 29 and MS Excel. Ranges, (means & SD) of the parameters: metformin (Met): 0.3 – 188 (67.2 & 58.1) μg/ml; peak lactate: 1.4 – 47 (17.0 & 14.1) mmol/L; (nadir) pH: 6.59 – 7.49 (7.1 &0.3). Mortality got values: 1 for death, 0 for survivors. Four of non-survivors had got renal transplantation therapy. None of the intentional overdose patients whose serum nadir pH was over 6.9, maximum lactate concentration less than 25 mmol/L, or maximum metformin concentration less than 50 μg/mL died. Regression of death by [Met, lactate and pH] represents 61 % of the total variation of death (p < 0.001). Beta coefficients of this regression equation were: [-0.0035;+0.162;-0.626 – respectively]. Beta coefficient of Met was weak, but negative. According to one pilot study the average plasma Met (prescribed 500 – 3 000 mg Met/d) concentrations was 1846 ng/mL (≦LoQ-5560 ng/mL) and independent of the prescribed daily dose [12]. By three cases in [11] plasma Met was below (5.6 μg/ml) 5600 ng/ml.

The same data [11] were selected by the highest values of Met including all (5) non-survivors. The number of cases was 12. The ranges by parameters were: Met 50.9 – 188 μg/ml, lactate 4.2-47, nadir pH 6.59 – 7.49. Regression of death by different factors: Met predicted death by 1 % (p 0.762, i.e, non-significantly), (nadir) pH by 56.4 % (p = 0.005) and lactate by 53.6 % (p = 0.007). Regression of Death by [Met, lactate and pH] explained deaths by 59.1% (p = 0.056, trend like association). Beta coefficients: Met -0.162; Lactate +0.244; Nadir pH -0.571, i.e. association of death was, as expected, negative with pH and positive with lactate and (N.B.) negative with Met. Strength of associations evaluated by single absolute Beta coefficient values divided by their sum was: Met 16.6, Lactate 25.0 and Nadir pH 58.5 %. Strongest detrimental association was with pH and protective association with Met. These results are accordant with that Met therapy improves the altered levels of magnesium and GSH in diabetic rats [13].

Experiments by Magnesium and Metformin on lactate and pH

Lactate increase of sportsmen can be prophylactically inhibited by Mg [14]. Dietary experiment has shown that serum lactic acid content can be increased by low-magnesium diet, without muscle exhaustion, increasingly, after 40-60 days ad 6.3 (vs. control 4.6) mmol/L (and base excess reduced below -4 mmol/l [15]). Even by Escherichia coli Mg-deficiency has increased production of lactate and decreased respiration [16]. In the magnesium experiment of Nuoranne et al. [15] Serum Mg: Ca ratio and duration of low-Mg diet [time (T, d)] explained blood pH by equation, pH: 6.98 – 0.0017*T+ 1.25*(Mg:Ca) (P.time ≦ 0.001, P.(Mg:Ca) ≦ 0.01). “The equation represents 62.0% of the total variation of blood pH.” A thirteen weeks experiment by rats showed that the no observable adverse effect level (NOAEL) of metformin was 200 mg/kg/day [17], i.e. 14 000 mg for a human weighting 70 kg, which responds 5 x the human maximal daily dose, 3g [18]. Minimal metabolic acidosis and lactate increase was observed with metformin level 600 mg/kg/day.

Temperature

When “energy aimed for ATP formation is disturbed, the excessive energy is changed to warmth ” [19]. In the feeding experiment of Nuoranne, et al. [15] regression of body temperature (BT, C⁰) by time (T, d, days) and serum lactate (mmol/L) gave equation: BT = 38.49 – 0.00064*T + 0.017 *lactate content (P.time non-sig, *P.lact ≦ 0.05) [15]. Nuoranne wrote that he had become accustomed to regard elevated skin temperature and sweating as signs of Mg deficiency [19]. The temperature of a sow can be increased ad 41-42 centigrade. The only acute treatment by 100 ml 20 % MgSO4 subcutaneously has been sufficient (veterinary surgeons are accustomed with high doses of magnesium). The result was to be seen even within one hour, after that treatment continued by usual oral Mg supplementation (Nuoranne 1977) [19]. Even by grass tetany temperature can increase ad 41-42 centigrade [19]. Symptoms like Delirium tremens (alcohol withdrawal syndrome) can be achieved if S-Mg declines to about 0.5 mmol/L [20]. Delirium tremens [21], (associated with Mg deficiency, e.g. [10]) “include shaking, shivering, irregular heart rate, and sweating. People may also hallucinate. Occasionally, a very high body temperature or seizures may result in death [21].” Metformin, which accumulates and increase lactate production in intestine, anyhow reduces blood lipopolysaccharides and its initiated low-grade inflammation [22]. Mg works like an on-demand antioxidant, but this ability is decreased in Mg-deficiency [23], which can increase ROS (Reactive Oxygen Species), IL-6 and TNF-α production [24] and temperature (fever).

Discussion

The understanding of the role of lactate has been increased remarkably during the last 50 years [4,5,6]. The role of magnesium in lactate formation is known, but because Mg is mainly intracellular cation and its extracellular measurement data (in serum less than 1 %) are unsatisfactory. We have need of easily available method for determination of body or muscle Mg status, [25-27]. Heart muscle damages were detected by all pigs with the lowest dietary Mg level [19], {why Nuoranne considered that Mg can have a role in the etiology of human heart diseases, too [19] as Professor Pentti Halonen taught in the 1970’s: “heart infarct is myocardial necrosis, which has two etiological factors: one is the deficiency of oxygen, the other someone (unknown) metabolic factor” [28]. Possibly the metabolic factor is lactic acid as a consequence of the weakness in ATP production [23]. In situations, where lactate concentration is 6 mmol/L at rest, as in [15], the benefits of lactate [29] have been lost. The dietary Mg experiment produced severe lactic acidosis (lactate content was 6 mmol/L) [15], c.f. a given reference for severe lactic acidosis is serum lactate concentrations of > 4 mmol/L [10]. Significance of association between body temperature (BT, C⁰) and serum lactate (mmol/L) could have been higher, if time had been removed from the regression [15]. Met can increase intestinal lactate production in epithelial cells and microbiome [22], which is possibly beneficial [30].

Conclusion

Managed lactate seems to be a beneficial power and health product, but unmanaged increased lactate predicts mortality risk. Deficiency of magnesium, associated with reduced ATP production and unmanaging of inflammation, is enriched with the diseases associated with lactic acidosis, as diabetes, which is associated with metformin medication. The role of metformin seems to be a bystander, in situations, where its help is not sufficient. Even in such situations relative Met content can associated with decreased mortality risk. Solution to Mg deficiency needs methodological (and statistical) measures.

Acknowledgement

I am grateful to Professor Osmo Hänninen and veterinary surgeon Seppo Haaranen for several discussions.

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The Urban Environment and Non-Communicable Diseases (NCDs)

Introduction

Non-communicable diseases are the leading cause of death and disability around the world. They are a category of illnesses primarily not caused by an acute infection but have long-term health implications and frequently necessitate long-term therapy and care (WHO [1], CDC [2]). Cancer, cardiovascular disease, diabetes, and chronic lung ailments are part of NCDs. NCDs originate from a mix of genetic, physiological, environmental, and behavioural variables (WHO [1], CDC [2]). According to the CDC and WHO, NCDs kill 41 million people a year, accounting for more than seven out of every ten deaths worldwide. Every year, 17 million individuals die from a non-communicable disease before the age of 70. In total, 86% of these premature fatalities occur in low- and middle-income nations, with 77% occurring exclusively in these countries (WHO [1], CDC [2]).

The NCD epidemic has been exacerbated by changing social, economic, and structural factors such as increased urbanization and the spread of unhealthy lifestyles CDC [2]. Urbanization, which is the increase in the proportion of people living in towns and cities, is a worldwide trend. Urban communities across the globe including Africa are growing rapidly. Urbanization may be seen as a double‐edged sword, that is, while its beneficial economic effects are widely acknowledged, it is commonly alleged to produce adverse side effects for NCD‐related health outcomes (Zhang [3]). The urban environment has been found to significantly impact non-communicable diseases.

This is because, the way cities are built, their density, how easy it is to get around, their building design, and overall layout have been found to have a significant impact on how much people exercise, what they eat, air quality, blood pressure, and even obesity rates. In other words, the design of cities has made it harder for people to stay healthy and avoid NCDs (Fazeli Dehkordi [4]). Research has indicated that the prevalence of non-communicable diseases (NCDs) is likely to rise in suburban and urban areas, concomitant with an increased intake of prepackaged foods and cooking ingredients (Mahawan [5]). In a study, it was reported that an increase in the death rate from coronary heart disease has been connected to the cultural shift brought about by urbanization (Tyroler & Cassel [6]). Additionally, it has been discovered that urbanization raises average body mass index and cholesterol levels especially in low- and middle-income nations and this has been linked to certain urban behavioural patterns, including altered eating habits and inactivity (Gunapala, et al. [7,8]). By 2050, two-thirds of the world’s population is predicted to reside in urban regions, up from the current 50% of people who live in cities (National Geographic Society [9]). The provision of services for people living in metropolitan areas is already a challenge for local governments. Every industry is under pressure, including the health system. The people’s health demands cannot be met by the lack of adequate medical personnel and modern facilities in the cities.

Inadequate waste management and high pollution rates has resulted in poor air and water quality, which negatively impact public health by causing respiratory disorders, cardiovascular problems, and other health complications. Countries with lower living standards are seen to be more affected by urbanization’s effects on public health than those with higher living standards. The primary determinants of disease are mainly economic and social; therefore its remedies must also be economic and social. To address NCD prevention and control, effective evidence-based multi-sectoral policies must be implemented, with an emphasis on the primary risk factors (Juma, et al. [10]). NCD policies must be integrated into urban planning. This includes designing and developing parks and recreational facilities such as pedestrian and cycling tracks. Zoning walkways where motorized vehicles are not permitted should also be established, and incentives for non-motorized vehicle use should be provided. Fiscal strategies and regulatory measures to prevent unhealthy eating environments in African metropolitan centers are required to limit the ever-increasing food marketing by food businesses (Juma, et al. [10]). It is also important to create awareness and sensitize people on the effects urbanization has on health and how it could predispose them to NCDs (Olowoyo, et al. [11]). This will foster a culture of responsibility towards personal and community health and empower individuals to make informed decisions about their well-being, enabling them to adopt healthier lifestyles and preventive measures [12].

Conclusion

The rise of non-communicable diseases in urban areas presents a pressing public health challenge that demands urgent action. As urbanization continues unabated, cities must prioritize interventions aimed at preventing and controlling NCDs. This necessitates a holistic approach that integrates health considerations into urban planning processes, promoting environments that support healthy lifestyles. From designing walkable neighbourhoods to regulating food marketing, policymakers have a crucial role to play in shaping urban environments conducive to health. Moreover, efforts to raise awareness and educate the public about the impact of urbanization on health are essential for fostering community engagement and promoting behaviour change. By addressing the root causes of NCDs through economic and social interventions, societies can work towards creating healthier and more equitable urban environments for all.

Conflict of Interest

There is no form of conflict of interest to declare.

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Effect of Diluting Epoxy Resin with Vegetable Oils on Mechanical and Adhesive Properties of Epoxypolymer Biocomposites

Introduction

Epoxy filling has been very relevant for 60 years, and the number of profilate scientific collectives and its publications in the world is regularly growing. But it is not only filling that can adjust the properties of polyepoxides. For example, the resin can be diluted with a solvent or other liquids. This can make the final product cheaper if the diluent is cheap or available. In Ukraine, such a diluent may well be vegetable oils, namely sunflower oils, since they are produced and exported. The price of a liter of new oil is almost 10 times lower than the price of epoxy resin or hardener, and if you take used oil (for example, from food establishments that are obliged to dispose of it) or rancid oil (which is available in any warehouse in a large city) – then we can be paid extra for this according state or municipal utilization programs. So, if you prove that the properties of such diluted plastics will not be significantly worse than undiluted epoxy polymers, it will already be a success. Scientists in the world are constantly working with epoxy-oil systems [1-6]. Epoxy polymers with the addition of vegetable oils make it possible to obtain cheaper polymer materials and to dispose of used vegetable oils. They also make it possible to obtain plasticized and otherwise modified composites, which is why they are of constant scientific interest [1-6].

Methods and Reagents

For the experiment, we take Epoxy520 epoxy resin (Czech production) and PEPA hardener (Czech production). Such a resin is also sold in stores, but it is obviously already diluted, because the resins from store kits (such as “EDP Glue” and “Tiger”) are much less viscous than the one I used in the laboratory. Oil samples were collected in a syringe, from where it was quantitatively dosed into the resin and there it was subjected to intensive manual mixing. We mixed the resin with oil in different proportions to understand the maximum amount of vegetable oil (TM Golden Bouquet) that could be added without losing the properties of the epoxy resin. So, in total, we got 8 types of samples- 0% (unfilled sample), 5%,10%, 20% and 33.5% of rafined (R) or un (non-)refined (NR) sunflower oil. For each sample, 10 g of epoxy resin, 1.5 g of hardener, and 0.57, 1.15, 2.8, 5.75 g of oil were used, for 5, 10, 20, and 33.5%, respectively. That will allow me to monitor the gradual increase in the effect of the diluent (which is oil) on the resin composition.

First, the oil was mixed with epoxy resin in all the necessary proportions, later, after adding a hardener, the resulting mixture was poured into the following forms: cylinders with an area of 5 cm2, which were glued together with an epoxy mixture, cubes with a side of 1 cm, flat hexagons, cylinders with with a surface area of 0.42 cm2 and a height of 1.2 to 1.5 cm, glued, using a mixture, of steel and fiberglass plates with an area of 2 cm2, .The following were used for the experiments: electronic electronic caliper, scales, LuisShopper measuring press, ID-1 tearing machine, UMM press. A microhardness test was conducted by indentation of an ultra-hard needle. Adhesion at separation was measured on the glued with epoxy mixture, using the UMM machine (Figure 1). Carrying out measurements on the UMM machine). Shore microhardness was determined using a type D durometer used for hard plastics. Microscopy was performed on a ULAB optical laboratory microscope.

Figure 1

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Visual Appearance and Consistency of Compositions and Composites

The introduction of oil into epoxies should lead to the formation of an emulsion, and at the level of polymerization processes, oil can have a significant effect. To evaluate the effect of oils on the composition, we choose a series of 5, 10, 20 and 33.5 wt% oils (Figure 2) (Table 1). In all cases, only highly concentrated ones with refined-oil are not completely hardened in their entirety. And the same 20P (20 wt% – a very heavy ball of oil in epoxy) and especially 33P (33.5 wt% – samples was hardened in ½ of form volume), where the oil was touched and rose above the hardened polymer. Also, such a quantity of oil no longer produces a homogeneous emulsion with epoxy resin; it disintegrates either immediately or during the curing process. However, the unrefined oil does not allow disintegration at 33 wt% – on the surface of the hardened sample there is no meniscus with the oil, and only single drops and pores with inclusions of the oil. Note that mixtures with machine oil (automotive synthetic oil) produce oil-like ointments that do not harden after mixing with amine hardener.

Figure 2

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Table 1: Visual characteristics of compositions (15+-5 оС)..

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Microscopy of Composition and Modeling of Possible Interactions

All unhardened mixtures were analyzed under a microscope. Can see that the introduction of unrefined oil causes the appearance of a few more streaks and (singing) droplets of oil. However, in general, the offensive type of oil will give approximately a new influx, changing the homogeneity of the system. The fragments provide visual information based on the dispersion of the oil into resins (either cloudy, dissolved in hardened composites, etc.), it is possible to create song modeling. Figure 3 can notice approximately a change in the structure of polyepoxide after dilution with olive oil. Pure epoxy resin produces a polymer that contains beads and water vapor (which is a product of the hardening reaction). In addition, there are still microcracks, fragments of epoxy resin (according to the literature [2,6-9]) and shrinkage, which can lead to their curing (under optimal curing conditions, there are few of them). The introduction of refined oil let the emerging oils of different sizes turn on, as well as a meniscus with pure (not included in polymer) oil, which will appear on the upper surface of sample (Figure 3). Such structure of the composite must will be weaker than pure epoxypolymer, and it may reduce all basic indicators (strength, durability, homogeneity). The fragments of unrefined oil have integrated entirely into the structure of the composite, so, here can reproduce the other scheme (Figure 3, left). Here there will also be inclusions of oil (both pure and mixed with water and air), but they will be only in the structure of the composite itself, and there will be no “salting” of pure oil on sample surface (Figure 3, right). Also, with such a scheme, you can experience a slight decrease in all basic indicators due to a higher percentage of dilution with oils of both types (especially refined).

Figure 3

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Experimental Results

Adhesion

Apriority, adhesion to steel is theoretically likely to decrease after dilution, since the oleic inclusions are likely to weaken interfacial contact. The weakening must be greater the greater the percentage of dilution, so that in large quantities (20-35 wt%) the oil may act as an anti-adhesive. To be sure, we also know that a significant amount of the oil is emulsified into the surrounding fraction during the process of hardening the composition (Figures 1 & 3). However, the experiment revealed another, – stronger (more than predicted) influx of plant species. Dilution with olive oil gives a somewhat weaker effect, but not such a great one, and not for all percentages of dilution. As can be seen from Table 2, at a very high (maximal possible) concentration of 33.5 wt% of unrefined oil, the solution is more likely to be a pure polymer, and some parameters may increase!What is most noteworthy is the fact that there is an even significant increase in adhesion. Olive particles can grow no less than 1.5-2, but even more (as can be seen from the displays of 10НР, 20Р, 33НР and 33Р). It is possible that the oil will quickly integrate into the adhesive, which is more springy

Table 2: Indicators of adhesive strength of epoxy-oil composites.

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And if you keep such a sample for several years, its value can increase even more.But the most interesting was the fact of a very significant increase in tearing adhesion (Table 2). Oil samples can increase it not only by 1.5-2 and more (this can be seen from the indicators of samples 10НР, 20Р, 33НР and 33Р). So far, it is difficult to find a scientific explanation for this, and for future, it is important to find him. Perhaps the oil is somehow embedded in the adhesive film, making it, for example, more elastic. Compressive strength. This is one of the main characteristics of polymers. Its change show – how strong is destructive effect of oil inclusions in the epoxy-oil composite. For research, unheated samples and samples after 270 oC were taken. Tests of 3-6 samples from one series were performed, after which the average value was entered into the table. Before the tests, the samples were subjected to normal processing (necessary for complete hardening) It can be seen (Table 3) that with normal heat treatment, the unfilled sample gives a value close to 700 kgf/cm2. All oil samples, indeed, give much lower indicators – (400-450), and (!) the concentration and quality of the oil does not really affect it. This can be explained by the influence of oil inclusions, as it was already described in the scheme of Figure 3.

Table 3: The strength of elastic resistance F to compression (kgf/ cm2) of samples. The index shows the strength of the final complete destruction (after the loss of elasticity and the beginning of plastic deformation). * – estimated

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Figure 4

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It is important that we do not have a collapse in strength, but only a decrease in ≈1,5 times. After hard heating, all the samples are carbonized (Figure 4). But unfilled sample keeps the compression strength F at the original untreated level (Table 3). Oil samples change F in different ways. For 5P (5 wt% of refined), the indicator increases even to the level of unfilled (without warming it was much lower, … kgf/cm2). Also, the 20P sample (with 20 wt% refined oil) shows a significant increase after special heating, while the 20HP practically does not change the indicator. Such interesting effects can be called “thermostrengthening” of epoxy plastics. Regarding it, there are publications on epoxy-iron , epoxy-carbide and epoxy-gypsum compositions [7-9]. But epoxy-oil composites theoretically do not have solid microparticles, heat-resistant inclusions and other that can give such strengthening. This strange fact can be explained by the fact that weak and fast-burning inclusions disappear at 275 oC, and the polymer network has not yet destroyed, and therefore we have amplification. Obviously, this can only happen at certain optimal dilution concentrations. Indeed, at 33%, and especially at 10% dilution with both oils, heating leads to a decrease in strength.

It is interesting that after standing in a strong HNO3 solution, the influence of oils becomes positive at all taken concentrations. An unfilled sample after such exposure loses its strength more than one and a half times (from 670 to 430 kgf/cm2), as well as 20 HP and some others. However, some oil samples sometimes increased it or slightly lost it. Thus, 5P reduced F from 670 to 610 kgf, and 33HP increased it by 1.5 times(from 420 to 610 kgf). Thus, there are optimal concentrations of oil, at which we have a significant increase in resistance to a strongly acidic oxidizing environment.

Microhardness

Unfilled epoxy compositions without heating give a result of 70- 85 units (Table 4). This, for comparison, is equal to the strength of the plastic used in the manufacture of industrial protective helmets. According to my expectations, the oil should have significantly reduced this indicator due to its density, but to my surprise this did not happen. За the average value of the three measurements made for each composite, it can be observed that the oil, both refined and unrefined, gave results that are within these limits, this means that the oil has no effect on the microhardness of epoxy compositions in such proportions According Table 4, the oil has stronger effect on the microhardness of epoxy compositions, that increases to 10-15%.

Table 4: Microhardness of unheated composites.

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Conclusion

1. This work is relevant in wide industrial sectors, due to the reduction in the price of the final solidified biocompatible material. This is confirmed by a number of modern publications in the scientific literature.

2. The compositions “epoxy resin – vegetable oil” can be obtained in a fairly wide range of concentrations, up to 35% by weight of oil. Further filling carries the risk of phase separation in the mixture, and this is more likely for refined than for unrefined. It was also noticed that at medium and high contents (20-33%) unrefined oil gives visually more solid composites (yellow in color), while refined oil forms an oil layer separated from the composition on surface of the samples. Optical microscopy shows that the introduction of oil leads to the appearance of large drops-inclusions of oil in the epoxy-oil emulsion.

3. Also, it was established that all oil-diluted samples (after normal treatment at 70-80°C) show a noticeable (in ≈1.5 times) decrease in compressive strength. This decrease depends little on the concentration and refinement of the tested oil. This can be explained by the softening effect of oil inclusions. However, after severe heat treatment (275 oC) unfilled loses his strength, but some oil samples (with 5-10% refined oil) can significantly increase compressive strength, or do not change it (with 20% unrefined). Even more clearly, this effect of strengthening after aggressive influences is manifested after exposure to a strong solution of nitric acid, where the unfilled sample loses its strength by 1.5 times, and some oil samples do not lose strength much (with 5% and 33% raf. and with 10% unrefined) or significantly increase it (from 33.5% unrefined). These effects may indicate an important stabilizing role of oil inclusions during extreme actions.

4. Based on all the obtained data, the author’s model scheme of the formation of the epoxy-oil mixture is presented, as well as the possible placement of inclusions and inhomogeneities in it. It partially explains the effects of the different action of refined and unrefined oil in the composition with epoxy resin.

5. The obtained results allow us to talk about the high prospects of creating such compositions to reduce the price of epoxy materials, improve their biocompatibility, resistance to aggressive influences, and increase some important strength indicators.

6. According the obtained data, the author’s model scheme of the formation of the epoxy-oil mixture (and possible placement of inclusions and inhomogeneities in it) is presented. It partially explains the effects of the different action of refined and unrefined oil in the composition with epoxy resin.

7. The obtained results allow us to talk about the high prospects of creating such biocompositions – for reduce the price of epoxy materials, improve their biocompatibility, resistance to aggressive influences, and increase some important strength indicators.

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Structural Fiber Mesh Reinforcement of a Polymeric Heart Valve: Improving Valve Durability and Leaflet Closure Effectiveness

Introduction

Valvular heart disease is an illness caused by damage to human heart valves. A human heart has four valves: the aortic, mitral (bicuspid), tricuspid, and pulmonary valves. These valves facilitate the controlled flow of blood through the heart. Thus, damage to the valves, caused by calcification, endocarditis, rheumatic disease, and congenital heart valve disease, have devastating effects on health. To treat valvular heart disease, patients must undergo valve replacement surgery, where a prosthetic heart valve is used to replace the diseased heart valve. There are two main prosthetic heart valves used today: mechanical and bioprosthetic. Mechanical heart valves are mostly made of stainless steel or titanium with leaflets of pyrolytic carbon with graphite coating [1-5]. While very resilient, mechanical heart valve replacements create high amounts of shear stress upon the blood, causing excessive coagulation, which requires patients to undergo a lifetime of therapeutic anticoagulation to reduce thrombus formation and stroke [6-8]. Meanwhile, bioprosthetic heart valves are made of bovine and porcine pericardium sewn to frames. These alternatives maintain the shape of native heart valves and are largely hem compatible, significantly lowering the risk of thrombosis and the need for anticoagulants in patients. However, bioprosthetic valves deteriorate over time because of the body’s immunological response which causes calcific degeneration upon the valve. Eventually, the patient must undergo another replacement valve within 15 years, making bioprosthetic valves non-viable for younger patients [9].

Moreover, bioprosthetic valves cannot be mass-produced, and animal pericardium is not a readily available resource, making it challenging to produce bioprosthetic valves at its demanded rate. As both mechanical heart valves and bioprosthetic valves have significant drawbacks, alternative valve replacements have gained significant interest. The principal among them are polymeric valve prostheses, which are capable of combining the mechanical durability of mechanical heart valves and the hemocompatibility of bioprosthetic valves [10-12]. Yet, polymeric valves continue to present concerns which make only a select few viable. Particularly, thrombotic complications can be provoked by changes in the hemodynamics along the valve. Indeed, the rigidity in leaflet materials and certain valve designs create high shear stresses upon the blood, leading to hemolysis, platelet activation, and ultimately thrombosis. However, modern polymeric valves have developed a tricuspid design that minimizes shear stress and damage to red blood cells, reducing thrombosis [13-15]. The properties of the polymer itself have a significant effect on thrombus formation as well. Interactions between the blood and the polymer often led to the absorption of proteins upon the surface of the leaflets due to a variety of chemical properties of each polymer. A number of these proteins (Fibrin, clotting factors) in turn stimulate platelet activation and coagulation, which commonly lead to thrombosis [16-19]. Thus, it is important that the polymers chosen have desirable chemical properties to reduce the risk of thrombosis.

Calcification, additionally, may also induce failure in unsuitable polymeric heart valves, as calcium deposits restrict leaflet mobility and lead to regurgitation and valve failure [20-22]. Some rigorous long-term in vivo tests showed that the issues such as inflammation along the valve, polymers accelerating the mineralization process, and the accumulation of blood proteins and phospholipids can accelerate the calcification process and cause even earlier valve failure. Particularly, polyurethane (PU)-based valves and expanded polytetrafluoroethylene (ePTFE) valves demonstrated issues with calcification due to calcium deposits building up in the porous structure or in cracks in the polymer to reduce flexibility [20-22]. Another main factor for polymeric valve failure is the degradation of the polymeric leaflets due to both mechanical and physiological factors. Polymers used for heart valve leaflets must possess sufficient tensile strength, flexibility, and fatigue resistance, enough to survive constant pressures of up to 1 MPa experienced by the leaflets [23,24]. To withstand these pressures, native heart valves are capable of withstanding pressures of approximately 2 MPa, which is further supported by the regenerative ability of native valves [25,26]. However, replacement valves are thought to need a significantly larger tensile strength due to their inability to recover. For example, bioprosthetic valves have tensile strengths of over 10 MPa. As a result, a large number of polymers (polyetheretherketone, etc.) are immediately unsuitable by themselves due to their inferior elasticity and strength, despite their biocompatibility.

Of similar importance, the leaflets of polymeric valves must also have sufficient fatigue and creep resistances to withstand the cumulative effect of countless loading-unloading cycles and resist deformation. Then, polymers like polyethylene are less viable alone due to their weak intermolecular bonds causing deformation over time [25,27,28]. Additionally, the physiological processes of the human body can degrade the polymer due to interactions with water, ions, proteins, and lipids in the body. These different molecules in turn lead to changes in mechanical properties in the leaflets (plasticization among others), leading to eventual failure [25,29]. Particularly, hydrolysis and oxidation create biodegradation in many polymers [30, 31]. To satisfy these various requirements for polymeric heart valve replacements, in this paper, we present a novel approach fiber-reinforced polymeric heart valve replacement, which utilizes additional structure to provide greater support. Polydimethylsiloxane (PDMS) has been observed to reduce calcification in heart valves [32]. PDMS is a polymer with well-proven, high hemocompatibility, biostability, and good elasticity, which is used today in a variety of biomedical applications ranging from aneurysm grafts to coating implantable devices and is the most frequently utilized polymer in implantation devices. Due to these qualities, using PDMS in polymeric heart valves is expected to reduce thrombus formation and calcification on the polymer’s surface, highly desirable attributes for heart valves.

Despite its superior biocompatibility, PDMS is largely regarded as a suboptimal material for polymeric heart valve leaflets due to its unfavorable mechanical qualities for a heart valve. However, PDMS has a tensile strength between 2.2 and 6.7 MPa [33], which presents concerns regarding the valve’s ability to withstand the pressure of blood flow over extended periods of time. Additionally, although PDMS is considered to have relatively decent fatigue resistance, it presented significant structural degradation under long term testing in heart valve leaflets [33]. To overcome this problem, PDMS grafting on the surface of polyurethane leaflets was recently tested, where the increased hydrophobicity of the PDMS was seen mitigating the calcification process significantly. On the other hand, imperfections in the grafting process made the graft degrade over time, leading to the same concerns with physical degradation seen in normal polyurethane valves [34]. To circumvent issues concerning grafting, this study obtains inspiration from the optimal structure of the native heart valve. In native valve leaflets, there are three primary layers: the fibrosa, spongiosa, and ventricularis layer, as shown in Figure 1a. The outermost fibrosa layer is composed of collagen fibers, which provides structural strength to the leaflet under higher stress, taking the load off the weaker spongiosa and ventricularis [35-37]. Beneath it, the spongiosa layer consists of polysaccharide compounds so that it maintains flexibility and provides additional support under lower load.

Figure 1

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The innermost ventricularis layer consists of endothelial cells and provides the valve with its hemodynamic properties, preventing clot formation and reducing shear stress. Figure 1b shows a perspective view of the aortic heart valve leaflets mimicking the natural fiber structure. Imitating the optimal design of native valves – fiber embedded flexible matrix – can eliminate the issues with grafting PDMS. This study investigates fiber reinforced PDMS leaflets as an alternative to grafting solutions. First, we describe the fabrication process of the fiber reinforced PDMS leaflets. Then, PDMS leaflets reinforced with various fiber meshes were fabricated, and their mechanical performances were tested in vitro.

Materials and Methods

Leaflet Design

The given polymeric heart valve leaflets consist of three layers: the fiber mesh layer in between the PDMS matrix layers. The fiber mesh layer has an evenly spaced grid of nylon fiber of a specified thickness embedded within the PDMS matrix. The density of the grid is determined by the thickness of the fiber – thinner fibers have denser grids. In this study, fiber meshes of three different thicknesses were manufactured to demonstrate the customizability of the fiber mesh: 100, 350, and 600 micrometers. The heart valve proposed herein is imitating a triscupid valve, and the fiber reinforced polymeric leaflets are designed to have an elliptical semilunar shape. The semicircular edge of the leaflets were sewed onto the top part of the valve to create stability and easy attachment.

Forming the Fiber-Reinforced PDMS

Figure 2 shows the fabrication process of the fiber reinforced polymeric leaflets. Two 4-inch by 4-inch glass plates and four spacers are prepared as mold for the leaflets. Both glass plates are covered with aluminum foil to make the removal process easier and ensure that both pieces of glass have no remaining debris. The thickness of the composite leaflet is controlled with four spacers that are placed between the two glass plates (Figure 2a).

To create the PDMS matrix, the Dow Corning Sylgard 184 silicone elastomer kit including both a silicone elastomer base and a curing agent is utilized. The ratio of the silicone base to curing agent is 10:1, and the elastomer is carefully mixed for 10 minutes. Before curing, the liquid PDMS is placed into an air vacuum to remove air pockets generated during mixing and to create uniform silicone leaflets. The prepared fiber mesh is put in a container, then a sufficient amount of the liquid PDMS is poured in the container to fully wet the fiber mesh. The wet fiber mesh is placed into the air vacuum to remove air pockets between fibers. The liquid PDMS is also poured on both glass plates to form the top and bottom matrix layers.

When the air pockets were removed, the PDMS covered fiber mesh is sandwiched between 2 glass plates as shown in Figure 2b. Then, the glass plates are clipped together (Figure 2c) so that the gap between the glass plates has the thickness of the spacer. The fiber reinforced PDMS in liquid phase is cured into a solid by heating at 135℃ for 30 minutes (Figure 2d). After the PDMS liquid has formed into a soft silicone, the fiber mesh film is left to cool to room temperature before prying away the foil and glass plate to create the elastomer (Figures 2e & 2f). In this final step of removing the glass plates and foils, caution should be taken to retain the elastomer’s form prior to manipulating the shape and structure. These leaflets are shown in Figures 3a & 3b, respectively.

Figure 2

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Fabricating a Polymeric Valve

Using a size guide, the fiber reinforced PDMS film is cut into the shape of semicircles (Figure 3c). To make a frame for the leaflet, 8 inches of stainless-steel wire, with a diameter of 1.0 mm, is cut, straightened, and folded in a way in which the wire is parallel with itself, but one half is slightly longer than the other. The cut fiber mesh film is placed between the steel wire so that the folded portion is tightly hooked perpendicular to the arcuate edge of the semicircle. Then the wire is gently manipulated to follow the arcuate edge all the way around, leaving. 1.0 mm of space between the wire and the arcuate edge on both sides of the fiber mesh film (Figure 3d). Then a 2- inch piece of thin stainless-steel wire (0.3 mm diameter) is utilized to stitch the steel wire frame to the silicone leaflet. Similar to the thicker steel wire frame, the 0.3 mm wire is folded to where one half is a centimeter longer than the other. Then, following the guide of the thicker steel wire, the 0.3 mm thin wire is punctured through the fiber mesh film ensuring that the 2 different halves of the wire are on opposite sides of the thick wire frame. Once the 0.3 mm wire has been pulled secured, the two thin wires are twisted using pliers. The twists should be tight and about 2.0 mm long, any excess is then cut. Continue this cycle of stitching with the 0.3 mm wire 4 more times for a total of 5 stitches evenly dispersed throughout the arcuate edge of the silicone leaflet. As a final step, the thicker 1.0 mm wire, acting as the frame of the leaflet, is cut to line up with the end of the flat edge perpendicular to the arcuate edge, and the slightly longer half on the parallel side of the silicone leaflet is bent using pliers to enclose the frame-like structure.

Figure 3

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This process is repeated to create a total of three uniform leaflets all with the same wire structure, and finally the three leaflets are arranged in a form resembling a native heart valve, stitched to secure proper commissure points, placed on a short stent, and glued onto the arcuate edge of the leaflets, beginning slightly below each commissure point (Figure 4). Alternatively, the fiber reinforced PDMS leaflets may also forgo the use of stainless wire for stability altogether and, instead, use a slightly taller stent. In this configuration, after the artificial leaflets with PDMS and fiber mesh are created, the leaflets’ arcuate edge is immediately glued to the altered stent to simplify the manufacturing process (Figure 5). The commissure points are formed at the corners of each leaflet as in the other manufacturing process; however, the leaflets will be glued together instead of sewn together with wire. Additionally, the leaflets may also be sewn to the stent instead. The stent is made of acrylonitrile butadiene styrene (ABS) and fabricated using a 3-D printer.

Figure 4

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Figure 5

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Experimental Set-Up

The hemodynamic performance of the fiber-reinforced polymeric heart valve created using the fabrication method was tested in vitro to verify its performance in a pulse duplicator. Figure 6 shows the conceptual view of our custom-designed pulse duplicator. For testing, two heart valves with 100-micrometer thick fiber-reinforced leaflets glued directly onto the stent without a metal wire structure (Figure 5) were placed onto the pulse duplicator simulating a mitral valve and an aortic valve. The pulse duplicator was then set to imitate the hemodynamic conditions of the native heart valve with a forward pressure of 100 mmHg across the valves, created by the pump. The fluid flow resistors maintain an average flow rate of approximately 5 liters per minute.

Figure 6

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Results

In the in vitro pulse duplicator test simulating blood flow in hearts, the fiber reinforced PDMS valves demonstrated promising hemodynamic behavior. Both valves demonstrated sufficient leaflet functionality: the valves opened and closed properly without any issue and responded quickly to changes in pressure caused by the pump. The valves appeared to be stable and entirely functional over repeated cycles with full opening and closing each cycle, indicating that the insertion of a fiber mesh layer does not significantly hinder the flow rate or cause regurgitation. Furthermore, the possible viability for long-term use is indicated. The valve leaflets did not undergo plastic deformation and maintained their physical properties after the tests, which demonstrate that the suggested fiber reinforced PDMS leaflets are capable of withstanding the mechanical conditions of the heart. Among the leaflets reinforced with three different fiber thicknesses, the leaflet reinforced with 100- micrometer thick nylon-mesh showed the best functionality during the opening and closing cycles as shown in Figure 7. Therefore, the leaflet reinforced with 100-micrometer thick nylon-mesh can be used for heart valve replacements without concerns regarding effective orifice area and regurgitation and with hopes of long-term structural integrity.

Figure 7

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Discussion

A sufficiently high strength is one of the essential requirements of successful polymeric heart valve to maintain the functionality of the leaflet under high-pressure conditions. As aforementioned in Figure 1b, in native heart valves, the high strength is accomplished by circumferential collagen fibers in the leaflet. In the polymeric heart valve proposed herein, the fiber mesh placed within the PDMS matrix plays the role of the circumferential fibers of the native heart valve. The strength of nylon is 85 MPa while that of PDMS is 3-5 MPa, and the insufficient strength of PDMS can be complemented by the nylon reinforcement. The composite strength can be adjusted by changing the density of fibers in the cross section. The fibers reinforcement can prevent the surrounding PDMS matrix from excessive strain, and correspondingly, the normally weak PDMS leaflet’s fatigue resistance increases and, structural damage of the PDMS matrix is prevented. Thus, by adding this additional layer of support to the leaflet, the mechanical properties of the PDMS layer are favorably altered to allow for use in heart valve leaflets. On the other hand, a successful heart valve leaflet should have the ability to stretch under relatively low strain conditions within the heart. Within native valves, the low Young’s modulus (0.3–1 MPa) and high ductility (strain of 150%) of the elastin in the ventriculitis layer provides high flexibility, allowing the valve to open and close easily in normal condition [38]. In terms of flexibility and ductility, PDMS is a perfect material mimicking the behavior of natural heart valve leaflets because PDMS has similar Young’s modulus (0.36–0.87 MPa) [33] and ductility (~140%) [39].

Although the Young’s modulus of nylon fiber is very high (0.5-3 GPa), the effect of the fiber mesh on the flexibility can be eliminated by aligning the fiber mesh in diagonal direction to the circumferential direction (the direction of maximum strain) of leaflets. The collagen fibers in natural heart valve leaflets also have diagonal alignment as shown in Figure 1b. Under low-pressure conditions, the flexibility of leaflets is a critical factor for the functionality of heart valves [40]. The fiber reinforced PDMS leaflets are highly customizable due to the fabrication method. The mechanical behavior and the life of the proposed leaflets can be engineered by adjusting the type, grid density, thickness, and direction of the fibers. These possible modifications also ensure the ability to further optimize the current design in future iterations. The thickness of the PDMS matrix is also customizable, allowing for fine- tuning of the valve’s mechanical behavior. Furthermore, the simple customizability of each leaflet allows for a variety of possibilities in optimizing the leaflets’ mechanical integrity and hemodynamic interactions by changing the mechanical properties of each leaflet. To provide additional structural stability to the leaflets, the fabrication process of the proposed valve utilizes a metal support wire along the arcuate edge of the leaflets. This added structure is expected to significantly improve the structural integrity of the leaflet along the edge attached to the stent by glue. More significantly, the stiffer support wire allows for much simpler attachment between the leaflet and valve stent, as the arcuate edge is stiffer and easier to maneuver, reducing the risk of manufacturing errors.

This wire- framed fabrication allows the fiber-reinforced polymeric heart valve to be clampable on a catheter and can be used for Transcatheter Aortic Valve Replacement (TAVR) [41,42]. Although TAVR is one of leading medical procedures in this field, this article is focused on the fabrication of the fiber-reinforced polymeric leaflets assuming regular heart valve replacements. However, it should be noted that the fiber-reinforced polymeric heart valve has potential for being optimized for TAVR through future work. An additional benefit of using PDMS for heart valve leaflets is the hydrophobicity of PDMS. The hydrophobic leaflet surface decreases the shear stress caused by the blood flow through the heart valve and eventually reduces the thrombogenicity of the valve. This then removes the necessity for the prescription of anticoagulants for patients. Moreover, the superior biocompatibility of PDMS, which only causes minimal inflammation for a short period after insertion, significantly reduces the amount of calcification occurring on the leaflets by reducing the body’s immune response to the foreign polymer, and eventually increases the valve’s longevity and structural integrity compared to other biomechanical valves. Also, the increased fatigue resistance, achieved by the fiber-reinforcement, reduces long term structural valve degradation, and increases the life of the valve.

Conclusion

An artificial heart valve made of fiber reinforced PDMS leaflets that has advantages over conventional mechanical and bioprosthetic valves is suggested, and its fabrication process is proposed. The hemodynamic performance of the fabricated composite valves with fiber reinforced PDMS leaflets were successfully validated through short-term in vitro tests under cyclic flow generated by a pulse duplicator. PDMS has excellent hemocompatibility and biocompatibility but is not a favorable polymer for heart valve leaflets because of its weak strength. However, the shortcoming of PDMS can be eliminated by embedding the fiber mesh reinforcement layer that is inspired by the collagen fibers of natural heart valves. The suggested leaflet fabrication process is simple and has potential to be customized through selection of fiber, grid density, and fiber alignment. Thus, customizability of the valve leaflets allows for the optimization of the given design and thus shows great promise. The mechanical durability of the fiber reinforced PDMS valve is expected to be superior due to the reduced stress in PDMS matrix. For further investigations, interactions between the valve and blood, particularly regarding calcification and thrombus formation, are suggested as a follow-up test with a long-term experimental setup. While the PDMS matrix is expected to reduce calcification, it needs to be confirmed whether certain protein interactions along its surface may induce undesirable calcification.

Furthermore, the effects of various modification factors such as fiber type, direction, mesh density, leaflet thickness, and wireframe on the mechanical behavior need to be investigated for the optimization and TAVR application of the fiber reinforced PDMS. In conclusion, the optimistic results of the in vitro pilot tests for the proposed design shows that the proposed fiber-reinforced PDMS valve is promising in the context of finding a biocompatible, durable, and cost- efficient alternative to the current mechanical and bioprosthetic valves and opens many exciting avenues for further research.

Acknowledgements

This work was conducted with the support of the University of Texas Rio Grande Valley.

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Drug use Evaluation on Magnesium Sulfate use in Obstetrics Wards: the Case of Ras Desta Damtew Memorial Hospital 2023 GC

Introduction

Background

Hypertension is a common medical problem that complicates pregnancy. It may be, manifested as chronic hypertension, chronic hypertension with super imposed preeclampsia, Pregnancy induced hypertension, preeclampsia or eclampsia. Hypertensive disorders in pregnancy can be manifested by increased blood pressure(BP) greater than or equal to 140/90 mmHg during pregnancy. Measured four hours apart and after 20 week of gestational age. The presence of the other clinical symptoms and signs of hypertension in pregnancy depends on the severity of the disease. Pre-eclampsia (PE)is part of pregnancy induced hypertension(PIH) which is defined as a BP > 140/90mmHg in the presence of significant proteinuria of greater than 300 mg per 24 hours urine Specimen or, less accurately, more than 1+ protein (equivalent to Approximately 100mg/dl) on dipstick in at least two randomly collected Urine specimen at least 6 hours apart after the 20th week of gestation or up to 6 weeks postpartum. Preeclampsia with severity features (Sever Preeclampsia) is the presence of Diastolic BP > 110 mmHg and the systolic BP ≥160mmHg measured twice at least six hours apart or a single measurement of >120mmHg, Hyperbilirubinemia, Hemolytic anemia, Thrombocytopenia (Less than 100,000/μL), Elevated Liver Enzymes (HELLP syndrome), Disseminated Intravascular Coagulation (DIC), Headache, visual disturbance and right upper abdominal pain, Oliguria ( less than 400ml in 24hours or 30ml/hour), Cardiac decompensation, pulmonary edema, cyanosis, Exaggerated Deep Tendon Reflexes (DTR).

Eclampsia is the occurrence of convulsions in woman who meets the diagnostic criteria for pre-eclampsia. Any convulsion occurring during pregnancy is eclampsia unless Proven otherwise. Anti-convulsants such as Magnesium Sulphate (MgSO4), as well as antihypertensive medication, are rarely required for patients on conservative management (mild preeclampsia). Delivery is the definitive treatment for mother with sever preeclampsia. The primary objective is to prevent convulsion, intracranial bleeding and other vital organ damage. MgSO4 is one of the main interventions used to decrease the morbidity and mortality from preeclampsia/eclampsia. In 2011, MgSO4 has been strongly suggested by the World Health Organization (WHO) to be the drug of choice for both treatment and prevention of eclampsia. Ethiopian Food and Drug Authority also recommends this; loading dose of 4gm as 20% solution IV over 10-15 minutes followed by 10gm as 50% IM injection divided on two sides of the buttock, followed by maintenance dose of 5gm every 4 hours as 50% concentration over 2minutes, 2gm IV as 50% solution over 2minutes if convulsion recurs. And, reduce the maintenance dose by half if there are signs of renal impairment during labor and for the first 24 hours postpartum. Adverse Drug Effects associated with the use of MgSO4 can be Respiratory Paralysis, pulmonary edema, depressed tendon reflexes, hypotension and hypocalcaemia. Therefore, renal function, BP, respiratory rate(RR), and DTR should be monitored when MgSO4 is administered parenterally. Hypersensitivity, myocardial damage, diabetic coma, hypermagnesemia, hypercalcemia, and administration during 2 hours preceding delivery for mothers with toxemia of pregnancy. In patients with renal impairment it has to be ensured that renal excretory capacity is not exceeded by halving the recommended dose.

Significance of the Study

The findings from this study could fill the gap in the obstetric use of MgSO4 in the management of PE/E. This would identify problems in MgSO4 use and suggest for further studies by researchers and healthcare facilities.

Methodology

Study Area and Study Period

The study was conducted in Obstetrics wards of Ras Desta Damtew Memorial Hospital (RDDMH) from october 1 2022 to september 30,2023 G.C. The hospital was established in 1924 E.C. RDDMH is located in Addis Ababa, Ethiopia. It has Medical, Surgical, Obstetrics and Gynecology, and Pediatrics services. In addition, there are ENT, Dental, Ophthalmology, ART, TB treatment and follow up services.

Study Design

A retrospective cross-sectional study design was used.

Study Population

All patients who received MgSO4 for the management of PE/E. Sampling Technique and Sample Size Determination Purposive sampling technique was used and 240 patient charts were collected, organized and sorted based on their MRN and according to WHO recommended sample size (75-100) for performing hospital DUE,100 charts were selected by systematic random sampling technique. From the 100 charts, 13 were excluded because there was no documentation of MgSO4.

Data Collection Procedures

Before commencing to data collection permission was received from the hospital Drug and Therapeutic Committee (DTC). Data was collected by two DUE trained personnel. The tool was adopted from Ethiopian National Medicine Use Study Guideline, 2021. And customized to our study objective. Data was directly filled on to MS-Excel data base.

Data Processing and Analysis

Data cleaning was performed after which it was imported to IBM SPSS Statistics Version 21.

Limitation of the Study

The limitation of the study was that it did not address the frequency of MgSO4 administration and control of seizure frequency. And it did not address the consumption of MgSO4 vials.

Results

As shown in Figure 1, From 87 patient chart reviewed the minimum age of mothers was 17 and the maximum age was 40 years with median age of 27 years. And 26.5% of the mothers were within the range of 15-24 years of age, the majority of mothers were within the range of 25-34 years of age (61%) and the remaining 12.5% of mothers were within the range of 35-40 years of age. From the total charts reviewed only 16.1% of the charts had a documentation of the mothers’ weight. When the pregnancies are classified based on gestational age; 13.8% were less than 28 weeks, 42.5% were in the range of 28- 37 weeks of gestation, 37.9% were in the range of 37-42 weeks, and there were no pregnancies above 42 weeks of gestation. And 5.7% of the pregnancies were of unknown gestational age by date or estimation. 41.4% of the mothers in this study were primigravida while the rest 58.6% were multigravida. From the total charts reviewed 5.7% of the mothers had previous history of pre-eclampsia/eclampsia and 1.1% had concomitant disease which was Gestational Diabetes. The diagnosis of mothers in the study period were categorized in as mild pre-eclampsia, sever pre-eclampsia and eclampsia which were 9.2%, 83.9% and 6.9% respectively. There was no mother who developed eclampsia after admission. 80(92%) of the mothers had an indication. (5.7%) mothers were assessed to have pulmonary edema and all of them were given Furosemide injection. As shown in figure 2 below, 21 (24.1%) of the mothers were Nifedipine co-administered with MgSO4 from which none of them had developed a drug-drug interaction (Figures 3 & 4).

Figure 1

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Figure 2

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Figure 3

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Figure 4

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This was assessed by BP monitoring of the patients obtained from the pre-eclampsia/eclampsia monitoring chart. There were 4(4.6%) patient with renal impairment were being administered MgSO4. There was no record of adverse drug reaction/toxicity developed due to MgSO4. It was found that 49.4% of mothers had a documented dose of MgSO4 as per STG. From the total 87 mothers 81(93.1%) of them were given MgSO4 with the STG recommended duration (24-48hrs). Urine output and DTR were monitored for 82(94.3%) and 37(42.5%) patients respectively. While Respiratory rate was monitored for all mothers. 85(97.7%) of the mothers were improved while 2(2.3%) got worsened and referred to a tertiary hospital.The assessment of Prescriber’s information showed that prescribers full name and qualification were written in 86(98.9) and 85(97.7%) respectively. While signature and date of prescribing were recorded in all of the charts.

Discussion

Being pregnant at age 35 or more is one of the highest risks of developing PE/E. A study done at Omdurman Maternity Hospital at Sudan showed the 25–34 years of age was the largest age group of women with preeclampsia/eclampsia. Our study result also showed that mothers between age 25-34 were the largest group of women with PE/E which is 60.7% (Alsiddig Y, et al. [1]). Body weight is strongly correlated with progressively increased PE risk, ranging from 4.3% from women with body mass index(BMI) below 20 kg/m2 to 13.3% in those with a BMI over 35 kg/m2 (Knight et.al, 2010). In our study the weight of mother was recorded only for 16.1%. This shows that there is a gap in the identification of risk factors for Preeclampsia by healthcare providers during ANC [2]. The study finding revealed that only 5 of the mothers had previous history of PE/E which can be the risk factor for developing recurrent PE/E and on which magnesium sulphate can be administered as a preventive therapy and all of those mothers were given MgSO4. From the findings of the study it can be concluded that most of the mothers were diagnosed with severe PE (83.9), while only some of them were diagnosed with mild PE and E (9.2% and 6.9% respectively). From the total mothers 80 (92%) were found to have appropriate indication for MgSO4. This finding is below our set threshold which was 95%. So 7 mothers took MgSO4 without indication, this includes those who were given MgSO4 for mild PE which is not recommended and also it can be due to patients who were given MgSO4 who did not fulfil the criteria for preventive therapy of PE/E [3].

Only 49.4% of the mothers took appropriate dose of MgSO4 as recommended by the STG which is much deviated from the set threshold 95%. This does not mean that those mothers did not take the recommended dose because this study did not assess that, but on the patient charts physicians did not record the recommended dose correctly on the order sheet. They just order it ‘as per protocol’ which is not correct. Even if the dosing protocol is found in the obstetric wards of the hospital, it is mandatory to write the loading and maintenance of MgSO4. This was a great obstacle which made it difficult for us to know the exact quantity of MgSO4 the patient took. Only 4(4.6%) of the mothers had renal impairment while 83 (95.4%) of them did not have renal impairment. This result is above the set criteria for contraindication of MgSO4 administration which was 95%. MgSO4 contraindication in pregnant mother not an absolute contraindication.

There needs to be dose reduction by half. It was written on the order sheet as ‘reduce the recommended dose by half’ but we did not find the exact dose administered on the medication sheet. The drug-drug interaction between MgSO4 and Nifedipine is moderate (not significant). When Nifedipine is given with MgSO4 has a synergistic physiologic effect which is hypotension which needs close monitoring of BP. The result of the study showed that 21 (24.1%) of the mothers were Nifedipine co-administered with MgSO4 [4]. They were assessed for reduced BP, from which none of them developed a drug-drug interaction. so the result is 100% which is greater than the set threshold which was 90%.

The outcome of treatment showed that 85 (97.7%) of the mothers were discharged improved. While only 2(2.3%) mothers got worsened and refereed to tertiary hospital. This finding is above the set threshold which was 95%. This result shows that MgSO4 is an effective choice of medication for the control of seizures in PE/E. Urine output and DTR were monitored for 82(94.3%) and 37(42.5%) patients respectively. While Respiratory rate was monitored for all mothers. On this study we found that a significant drawback exists in the monitoring of patients taking MgSO4. Mothers monitored for all the three parameters were 36(41.4%) which is below the set 100% threshold. The assessment of Prescriber’s information showed that prescribers full name and qualification were written in 86(98.9%) and 85(97.7%) respectively. While signature and date of prescribing were recorded in all of the charts [5]. Orders with all the four parameters recorded were 96.5% which is below the set 100% threshold.

Conclusion and Recommendation

• The study findings revealed that documentation of mother’s weight was poor; where weight(BMI) increment is a significant risk factor for PE/E. there for we strongly recommend the measurement of pre pregnancy or first ANC weight (BMI) [6].
• Indications for MgSO4 administration was found appropriate for most of the mothers, but there were mothers found taking MgSO4 against STG recommendations. However, it is ultimately the decision of the attending healthcare providers to start MgSO4.
• The dose of MgSO4 was not recorded correctly on order sheets, so we recommend physicians to write the full recommended loading and maintenance dose and also we recommend nurses to record each administered doses of MgSO4 including the route.
• Overall the correct dose of MgSO4 is not recorded obstetric order sheets [7].
• It is recommended that the duration of MgSO4 to be 24-48 hours as per STG. We found some gaps only on some mothers who were given MgSO4 below and above this duration, so it may be due to documentation gap, mothers response to treatment or duration of seizures. We strongly recommend for a complete documentation of MgSO4 duration of administration.
• Since there is a gap in monitoring of patients and recording on PE/E follow up chart. We strongly recommend the maternity ward staff to monitor and record Urine output, DTR and RR [8]. • Prescribers name, qualification, signature and date of prescription must be written on all orders.
• We found that charts in the gynecology/obstetrics ward are disorganized which made it difficult for us to find the exact data we wanted. But now since electronic medical recording is started it may fill this gap [9].

Acknowledgement

We would like to thank our hospital DTC, Research and Training Department for the technical assistance and decisions passed on ethical procedures. We thank the Obstetrics and Gynecology Department, and Medical Record Room for their great cooperation in providing assistance and retrieval of patient charts. Our deepest gratitude also goes to Federal Ministry of Health of Ethiopia and World Health Organization for organizing the orientation and providing of the tools, technical assistance in data analysis and preparation of the final document.

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Journals on Medical Microbiology |BJSTR

Boerhavia Diffusa Linn: Unravelling the Medicinal Tapestry from Ayurvedic Traditions to Modern Science

Introduction

The Nyctaginaceae family of medicinal plants, Boerhavia diffusa Linn., is well-known in Indian traditional medicine for its therapeutic qualities. It is also acknowledged in other areas of the world and in certain countries of South America. In the context of Indian traditional medicine, it goes by several names such as Punarnava, Shothaghni, Kathillaka, Varshabhu, Raktapushpa and Varshaketu [1]. Within the context of Indian Ayurveda, Boerhavia diffusa is designated as a “rasayana” herb, believed to possess diverse qualities including anti-aging effects, enhancement of life and memory power, and disease prevention. These attributes suggest that the herb fortifies the body’s resilience against external threats, essentially offering hepatoprotection and immunomodulation [2]. In specific areas, the entire plant serves as a vegetable. For instance, in regions like Assam and West Bengal in India, local communities cook the leaves as a culinary delicacy [3]. Different types of the Boerhaavia genus can be located across tropical, subtropical, and temperate regions worldwide, spanning Australia, Asia, the United States, and Africa. Within the Indian subcontinent, B. diffusa is prevalent in warmer regions of the country, reaching altitudes of up to 2000 m in the Himalayan region [4]. Six of the forty species in this genus—B. diffusa, B. erecta, B. rependa, and B. rubicunda— can be identified in the Indian subcontinent. In particular, B. diffusa has been the subject of a great deal of research because of its chemical makeup and medicinal qualities.

The roots of B. diffusa are the source of a distinct group of isoflavonoids known as rotenoids, along with flavonoids, xanthones, purine nucleosides, lignans, and steroids. Numerous studies and trials have confirmed its diverse activities, including immunomodulation, anticancer effects, antidiabetic properties, antioxidants, and anti- inflammatory attributes. During diverse studies conducted on the B. diffusa plant, preliminary examinations have detected the existence of β-sitosterol [5], and alkaloids [6]. The root of this plant has been traditionally used by several tribes to alleviate liver disorders. Specifically in South Garhwal, the tribal community has applied the roots for the treatment of various diseases such as liver enlargment [7]. Moreover, tribes have been using the plant’s roots of ‘Punarnava’ (Boerhavia diffusa) to treat jaundice in the eastern parts of Rajasthan and Gujarat state [8,9]. Besides, B. diffusa roots are recommended in some parts of Madhya Pradesh to treat kidney and liver problems [10]. This review offers a condensed overview of the bioactive components and documented pharmacological effects, presenting an ethnopharmacological evaluation of the said plant.

Geographical Distribution

The Boerhavia genus, consisting of 40 species, is distributed across tropical, subtropical, and temperate zones worldwide. Boerhavia diffusa, or B. diffusa, is a plant that was originally native to Brazil and India but is now found in tropical, subtropical, and temperate countries with elevations of up to 1200 metres above sea level. It is found in many places, such as Mexico, Asia, Africa, the Indian and Pacific oceans, Egypt, and Sudan [11,12]. In India, six out of the 40 species within this genus can be found, namely B. diffusa, Boerhavia chinensis, Boerhavia erecta, Boerhavia repanda, and Boerhavia rubicunda. B. diffusa, specifically, is indigenous to India and flourishes in wastelands and fields after the rainy season. Furthermore, there is a limited cultivation of this plant in West Bengal [13].

Traditional Uses

As noted earlier, B. diffusa holds significant importance as a primary herbal ingredient in a variety of Ayurvedic medicinal formulations. Its incorporation in different preparations is effective in managing conditions like inflammation, jaundice, asthma, nephrological disorders, anaemia, and gynaecological issues. Table 1 categorizes several traditional formulations where B. diffusa plays a central role as a key component [14].

Table 1: Traditional formulations containing B. diffusa act as a major ingredient.

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Phytochemistry

Several studies on Boerhavia diffusa species have revealed a variety of important phytochemicals across different regions, taking into account ethnopharmacological applications and advancements in technologies like mass spectroscopy, liquid chromatography-mass spectroscopy (LC-MS), Electrospray ionisation mass spectrometry (ESI-MS) etc. These investigations have unveiled significant phytochemicals in various parts of Boerhavia species, as detailed in Table 2. The conventional method for isolating compounds typically includes extraction, partitioning in different solvents, and bioactivity- guided fractionation using silica gel chromatography [15-21].

Table 2: List of chemical compounds isolated from Boerhavia diffusa.

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Pharmacological Activities in Boerhavia diffusa Linn

The plant Boerhavia diffusa has become significantly important in the field of phytochemistry due to its diverse pharmacological and biological activities. Various parts of B. diffusa are used in different parts of India to cure a variety of ailments. The whole plant, aerial parts, leaves, or root of B. diffusa are used in Ayurvedic herbal medicine for treating a range of medical conditions. Various pharmacological studies have shown that the plant roots of B. diffusa possess a broad spectrum of properties, including anti-inflammatory, diuretic, anticonvulsant, antifibrinolytic, antibacterial, anthelmintic, antileprotic, antiasthmatic and antistress activities (Figure 1). Table 3 compiles the available information on Boerhavia diffusa species from recent data published in the last 5-6 years [22-26].

Table 3: Various pharmacological activities and parts used of Boerhavia diffusa.

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Figure 1

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Antioxidant Activity

Due to its high content of tannins, phenols, and flavonoids, B. diffusa has been the subject of numerous studies examining its antioxidant potential [27-29]. The ethanolic extract of B. diffusa demonstrated the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals [28]. A fractionation guided by electron spin resonance of the methanolic extract led to the identification of boeravinone D, boeravinone G, and boeravinone H, all exhibiting significant radical-scavenging activity, with boeravinone G displaying superior antioxidant properties when compared to the other two compounds [30]. This investigation also revealed the involvement of MAP kinase and NF-kB pathways in the antioxidant effects of boeravinone G, suggesting its potential utility in injuries mediated by reactive oxygen species (ROS) [30]. In the realm of African traditional medicine, the preference for the redder stems of B. erecta prompted a study on the antioxidant potential of the redder stem bark, establishing that betacyanin’s possess greater antioxidant activity than the phenolic compounds present in the stem [31]. Similarly, the antioxidant potential of B. procumbens was attributed to its concentration of polyphenols, as demonstrated by various antioxidant assays [32]. Furthermore, B. diffusa was identified as having the capability to protect tissues from hydroxyl radical- induced DNA damage [33].

Antidiabetic Activity

B. diffusa and ethanolic extracts demonstrate notable antihyperglycemic effects in rats with alloxan-induced and streptozotocin- induced hyperglycaemia. Additionally, they show potential for improving diabetes-related conditions, as evidenced by changes in parameters such as body weight, serum cholesterol, and triglyceride levels. In recent research, the impact of streptozotocin treatment on the pancreas of diabetic control rats, along with cell regeneration facilitated by glibenclamide, was examined. Additionally, comparable regenerative effects were demonstrated through the methanolic extracts of B. diffusa [34]. An investigation was carried out on the effects of a daily oral administration of an aqueous solution containing B. diffusa L. leaf extract on the levels of hepatic enzymes and blood glucose in both normal and alloxan-induced diabetic rats over a period of four weeks. When B. diffusa L. was administered to both normal and diabetic rats, the results showed a notable decrease in blood glucose levels and a considerable increase in plasma insulin levels [35]. In rats with streptozotocin-induced noninsulin-dependent diabetic mellitus (NIDDM), the chloroform extracts from B. diffusa leaves demonstrated dose-dependent reductions in blood glucose levels. This effect was comparable to the impact of glibenclamide. These results imply that the extract’s capacity to decrease blood glucose may be linked to the regeneration of pancreatic beta cells or actions extending beyond the pancreas [36].

Anticancer Activity

The B. diffusa root and leaf extract’s in vitro cytotoxic effects show a dose-dependent response. Both the root and the leaf’s crude ethanolic extract caused 30% and 40% of the cells to die, respectively [37]. An investigation was conducted into the effect of a root extract in 95% ethanol on the growth of human peripheral blood mononuclear cells (PBMC) activated by T cell mitogen PHA and PPD antigen. The extract showed that it inhibited the proliferation of PBMCs in a human mixed lymphocyte culture as well as that induced by these stimulators. Moreover, the extract demonstrated inhibitory actions on multiple cell lines, emphasising its efficacy in experimental settings against lymphoma and leukemic cells [38]. The 95% ethanolic extract of B. diffusa root was subjected to bioassay-guided fractionation, resulting in a 30% observed cell death in the HeLa cell line. Subsequent purification through column chromatography led to the isolation of a more potent fraction. [39]. In in vivo experiments, the extract demonstrated inhibitions of 87% and 95% against metastasis both prophylactically and overall. Additionally, the survival rate of the experimental model increased by 157%. When the extract was given as a preventative intervention, serum markers linked to metastasis were reduced by 85% [40]. Furthermore, Punarnava was isolated by the author from the extract, exhibiting its capacity to trigger cytotoxicity mediated by complement and antibodies, in addition to augmenting the function of natural killer cells [41]. Numerous investigations, both in vitro and in vivo, show that a variety of plant extracts sourced from distinct plant sections may include chemicals with anticancer potential. Punarnava, an alkaloid isolated from the roots was identified and reported to possess antimetastatic properties [42].

Anti-Inflammatory Activity

The alcoholic extract of B. diffusa, which is insoluble in water, demonstrates anti- inflammatory effects in rats. Leaf and floral extracts have significant anti-inflammatory properties [43]. BD leaf extracts were tested for toxicity and for their analgesic-anti- inflammatory qualities in both juice and lyophilized decoction form. The lyophilized decoction and juice both showed about 50% reduction in abdominal writhing in mice when compared to dipyrone sodium. When compared to morphine, the juice treatment increased the mice’s latency in the hot plate test. Another noteworthy finding was the reversal of the juice’s effects following pretreatment with naloxone, except in the case of the decoction. As a result, the author suggested that the antinociceptive mechanism of the juice may be related to opioids [44]. found that BD roots contained 𝛽-sitosterol, which significantly induced swelling in mice [45]. It is commonly known that BD has anti-inflammatory qualities and is also called sothaghni, a term that denotes its ability to reduce inflammation. Most of the ayurvedic formulations mentioned in Table 1 serve purposes related to inflammation. Numerous accounts highlight the utilization of leaves, whether in their whole form, incorporated into an oral preparation, or applied topically, particularly in instances of scorpion and snake bites or for wound healing.

Antiviral Activity

Promising protective activities against potato virus X infection in both hypersensitive and systemic hosts have been observed for compounds isolated from B. diffusa L. root, Cuscuta reflexa Roxb. stem, and Euphorbia hirta L. leaves. It was found that these extracts had a systemic inhibitory effect that was actinomycin D-responsive [46]. Notable control results were obtained with the mungbean yellow mosaic illness caused by the mungbean yellow mosaic virus, which was efficiently handled by the aqueous root extract of B. diffusa. Six application sprays of B. diffusa root extract proved to be particularly efficacious, significantly delaying the onset of symptoms, mitigating symptom intensity, and reducing disease occurrence by 80-90%. In addition, enhancements in pod formation and grain output were encouraged by this treatment, along with increases in plant height, root nodulation, and primary and secondary branches [47].

Hepatoprotective Activity

Chloroform and ethyl acetate extracts were made using Bacillus cereus, an endophyte that is present in B. diffusa roots. These extracts’ hepatoprotective effects were studied in rats, with an emphasis on assessing how well they scavenged free radicals. The extract of ethyl acetate demonstrated a significant IC50 value, prompting its selection for subsequent in vivo studies [48]. The administration of endophytic bacteria extracts resulted in a normalization of the heightened levels of the aforementioned biochemicals. The findings consistently indicate that extracts derived from the endophytic bacteria of B. diffusa demonstrate antioxidant and hepatoprotective properties, ultimately leading to the conclusion. Tuberculosis presents a significant health challenge, and the primary treatment involves rifampicin therapy. While rifampicin effectively addresses tuberculosis, it is associated with liver damage. Methanolic extracts from B. diffusa leaves were investigated in the search for a natural cure. Rats were given rifampicin to induce hepatotoxicity, which resulted in a significant rise in aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase levels. In comparison to the control group, there was a concurrent decrease in serum protein levels. Studies offer proof that extracts from B. diffusa possess the ability to alleviate liver issues, attributed to the presence of flavonoids in the plant, known for their antihepatotoxic properties [49].

Anti-Arthritic Activity

Numerous research use arthritic rats to test the antiarthritic effects of extracts made from B. diffusa roots, including petroleum ether, methanol, chloroform, and water extracts. Arthritis impacted hematological factors by elevating total white blood cell counts, raising erythrocyte sedimentation rates, and diminishing red blood cell count and hemoglobin levels. Rats given extracts from B. diffusa had smaller paws and heavier bodies as a result. The recovery of red blood cells and haemoglobin, as well as the normalisation of the total white blood cell count and erythrocyte sedimentation rate, were among the several haematological indicators that were brought back to baseline [50].

Antibacterial Activity

With regard to the possible presence of phytochemicals, B. diffusa leaves have strong antibacterial qualities against both gram-positive and gram-negative bacteria. All gram- negative bacteria as well as gram-positive bacteria like S. aureus, S. faecalis, and M. luteus are inhibited by the ethanol extract. All gram-positive bacteria are inhibited by the methanol extract, with the exception of M. luteus and gram-negative bacteria. B. diffusa leaf extracts work well against E. Coli, S. aureus, and P. aeruginosa in both aqueous and ethanolic forms at various concentrations, indicating the presence of active compounds with broad antibacterial capabilities. Overall, extracts from B. diffusa demonstrate significant antibacterial effects against a range of bacteria [51,52].

Anticonvulsant Activity

In the context of Nigerian traditional medicine, B. diffusa has a historical connection to the treatment of epilepsy. As a result, studies have been undertaken to investigate its effectiveness in managing convulsions. The crude methanolic extract of B. diffusa, specifically its liriodendron-rich component, demonstrated a dose-dependent protective effect against PTZ- induced convulsions. The observed ability to prevent convulsions was attributed to the calcium channel antagonistic properties of the liriodendron-rich fraction [53].

Adaptogenic/Immunomodulatory Activity

The study assessed the antistress and adaptogenic effects of ethanol extracts from B. diffusa roots in albino mice using swim endurance and cold restraint stress tests. The extracts demonstrated enhanced stress tolerance and immunomodulatory activity, as demonstrated by enhanced carbon clearance, which suggests reticuloendothelial system activation. Furthermore, mice’s reaction to sheep red blood cells (SRBC) was elevated in terms of delayed-type hypersensitivity (DTH), indicating a stimulatory effect on lymphocytes and accessory cell types involved in cell-mediated immunity [54].

Toxicological Studies

Nausea has been linked to the ingestion of higher doses of Punarnava, according to research. The primary emphasis of the pharmaceutical industry is directed toward creating and advancing innovative and indigenous plant-based drugs by exploring leads from traditional medicinal systems. Toxicological studies on B. diffusa have verified the lack of teratogenic and mutagenic effects, with the consumption of larger doses being associated with vomiting [54].

Conclusion

In recent years, the pharmaceutical industry has significantly directed its efforts toward designing and developing novel plant-based drugs through the exploration of leads from traditional medicine systems. The ethno-botanical and traditional applications of natural compounds, particularly those of plant origin, have garnered considerable attention due to their proven efficacy and perceived safety for human consumption. The review above suggests that the utilization of B. diffusa is deeply rooted in tradition and has been prevalent worldwide across various clinical and pathological conditions. While the scientific basis for many of its pharmacological properties has been established, ongoing research is still underway. Consequently, further comprehensive studies are encouraged to explore the potential of this plant.

Acknowledgements

Authors would like to acknowledge the management of Mahatma Gandhi University for providing us an opportunity to access the e-library facilities and valuable literature resources of the Central Library.

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Journal on medical genetics |BJSTR

Evaluating the Effects of Deficit Irrigation and Mulch Type on Yield and Water Productivity of Tomato in Fogera, Ethiopia

Introduction

The escalating global population and the escalating challenges posed by climate change necessitate an increase in food production to ensure food security worldwide (Page, et al. [1,2]). Smallholder agriculture serves as the primary income source for rural communities in Sub- Saharan African (SSA) countries such as Ethiopia. However, these smallholder agricultural systems heavily rely on rainfed production, making them vulnerable to the adverse effects of rainfall variability and drought, leading to food insecurity and low agricultural productivity (Assefa, et al. [3]). The inadequacy of traditional farming techniques exacerbates the challenges faced by small-scale farmers, resulting in insufficient food production to meet the demands of the growing population (Tadesse, et al. [4-8]). Therefore, enhancing agricultural productivity is crucial to address food security issues and sustain the livelihoods of Ethiopian communities (Tewabe, et al. [9]). To address the growing food demands, it is imperative to transition from rainfed production to irrigation-supported agriculture (Belay, et al. [8]). Irrigation plays a pivotal role in mitigating the impact of rainfall variability and irregularity on agricultural productivity (Mekonen, et al. [10]).

Small-scale irrigation initiatives are crucial for poverty reduction, food security, and enhancing rural livelihoods in Ethiopia (Assefa, et al. [3,11-13]). However, the scarcity of available water resources poses a significant challenge to irrigated agriculture in many regions, including Ethiopia (Belay, et al. [8]). Climate change further exacerbates water scarcity issues, leading to droughts, moisture stress, and inadequate water management practices that strain water resources and hinder crop productivity (Tewabe, et al. [9]). Insufficient water availability for irrigation results in low crop yields, conflicts over water allocation, and challenges in sustaining agricultural productivity (Dirirsa, et al. [14]). Currently irrigated agriculture take place under water scarcity and insufficient water supply for irrigation due to these the crop productivity are low are (Kifle, et al. [15]). Enhancing Water Productivity (WP) and water savings are a major challenge for sustainable crop production in irrigated agricultural (Mubarak, et al. [16]). In the context of Ethiopia, traditional irrigation systems dominate crop production, resulting in low water and crop productivity levels (Hordofa, et al. [17]). Poor irrigation water management practices further compromise the sustainability of crop production, leading to crop failures, water disputes, and reduced household incomes. To address these challenges, innovative water-saving technologies and efficient irrigation strategies are essential for enhancing water productivity and ensuring sustainable crop production (Al-ghobari, et al. [18-21]).

Therefore, deficit irrigation and conservation agriculture practices emerge as critical strategies to optimize water use efficiency and enhance crop productivity in water-limited regions. Deficit Irrigation (DI) represents a water-saving strategy that aims to maximize net returns by reducing irrigation water without compromising crop yields (Capra and Consoli, 2015). By implementing water-saving techniques like DI, water productivity can be improved, leading to enhanced overall yields (Asmamaw, et al. [21-23]). Conservation agriculture practices, such as mulching, have proven effective in boosting water and crop productivity while reducing production costs (Erkossa, et al. [24,25]). Mulching, in particular, plays a crucial role in improving water and crop productivity under deficit irrigation conditions (Rop, et al. [26]). Evaluating various water-saving techniques, including deficit irrigation and mulching, is essential for enhancing water productivity and crop yields in water-limited environments (Khan, et al. [27]). Tomatoes are a vital crop in Ethiopia, contributing significantly to the country’s agricultural sector and economy. In the Fogera region specifically, tomato production plays a crucial role in providing livelihoods for farmers and meeting the local demand for fresh produce. However, tomato cultivation in Fogera faces various challenges, with water scarcity being a major concern. The erratic rainfall patterns and limited access to irrigation water pose significant obstacles to sustainable tomato farming in the region.

In light of these challenges, the adoption of efficient water management practices is essential to enhance tomato yield and water productivity in Fogera. Deficit irrigation, which involves supplying water to crops below their full water requirements, can help optimize water use efficiency and mitigate the impact of water scarcity on tomato production. Similarly, the use of mulching, such as plastic or organic materials, can aid in conserving soil moisture, suppressing weed growth, and regulating soil temperature, thereby improving crop yields in water-limited environments. This study aims to fill the gap in knowledge regarding the optimal water management strategies for tomato production in this region, considering factors such as water scarcity, climate variability, and sustainable agricultural practices. Therefor This research aims to address the research gap in understanding how deficit irrigation and mulching impact tomato yield and water productivity in the specific context of Fogera, Ethiopia. By investigating the effects of these practices on tomato crops, the study seeks to provide valuable insights into sustainable water management strategies for farmers in the region, and to contribute to the development of tailored recommendations and interventions to support tomato farmers in Fogera in achieving higher yields and improved water productivity and promoting sustainable agricultural practices.

Materials and Methods

Study Area Description

The field experiment was conducted at the Fogera National Rice Research and Training Center (FNRRTC) experimental site. It is located at 11º19ʹ N and 37º03ʹ E at an altitude of 1815 m.a.s.l during the 2020/21 irrigation season. Fogera is found in the South Gonder Zone of the Amhara regional state (Figure 1). Which is found at a distance of 657 km from Addis Ababa and 57km from Bahir Dar. It is predominantly classified as woinadega agro-ecology (ILRI, et al. [28]). The climatic data of the experimental site, which is situated in the middle of Fogera Plain, show that the mean annual minimum, maximum and mean temperatures of the area are 14.0ºC, 27.7ºC, and 20.8ºC, respectively. Rainfall in the area is uni-modal, usually occurring from June to October, and its mean annual rainfall is 1216.3mm and ranges from 1103 to 1336mm (Aleminew, et al. [29]). The land in Fogera shows that 44.2% is arable and another 20% is irrigated, 22.9% is used for pasture, 1.8% has shrubland, 3.7% is covered with water, and the remaining 7.4% is considered degraded or other (System, et al. [30]). The dominant soil type in the Fogera is black clay soil (ferric vertisols), while the mid and high-altitude areas are predominantly orthic Luvisols.

Figure 1

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Experimental Design and Layout

Two main factors were considered: the first factor was mulch types and the second factor was deficit irrigation level based on crop water requirement (ETc) and each factor had three levels. Three levels of deficit irrigation are; 100%ETc, 75%ETc, and 50%ETc while three mulch types: No Mulch (NM), Rice Straw Mulch (RSM), and White Plastic Mulch (WPM) were evaluated. The non- deficit and non-mulch treatments were used as controls. The application of rice straw mulch at the rate of 6tha−1, while 25micron thickness was used for white plastic mulch. A factorial combination of three levels of deficit irrigation and three mulch types was evaluated in a Randomized Complete Block Design (RCBD) with three replications and treatments were randomly assigned (by chance) to the experimental block. The field experiment has a total of nice treatment combinations and 27 plots. The plot size was 4.2m × 4m=16.8m2 area. To minimize the influence of the lateral flow of water into the plots, the block distance should be sufficient. Then, the distance between blocks and plots was 3m and 2m receptively. In this experiment, the furrow irrigation method was used (Figure 2).

Figure 2

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Agronomic Practices of the Experimental

Tomato Roma VF variety seeds were used as seed material. The nursery bed was prepared and the seed was sown on 01 December 2020 for tomato. Watering, weeding, fertilizer, chemical spray, and other agronomic activities were applied in the nursery. The seedling was transplanted to experimental plots on 01 January 2021 tomato. Furrow spacing and plant space were done according to the agronomic recommendation of the area. This was done with the spacing between rows being1m for tomato while the plant spacing being 30cm transplanted was done. Each plot has four single planting rows for tomatoes, each row accommodating about 14 plants for tomato. Each experimental plot was fertilized with one application of NPSB during transplanting only and a split application of urea at transplant and 30 days after transplanting as top dressing with the agronomic recommendation rate NPSB and urea for tomato. Chemical spray was applied to prevent the experiment from disease and pests. Each experimental plot was equally treated with fertilizer rate, chemicals, and weed. For all treatments without treatment variation, one common irrigation was applied at a depth of 25.5 mm for tomatoes based on irrigation scheduling to ensure good seedlings establishment. All treatments were weeded only once before mulch was applied. Fifteen days after transplanting, treatments were started because seedings were start root development and was well performed. All treatments were irrigated on the same day because the only difference was the depth of water based on deficit levels. The harvesting time of tomato five harvesting times were done and tomato yield was weighed from each plot during harvest and converted to t/ha.

Soil Sampling and Analysis

Soil samples were collected before crops were planted. Five soil depths were sampled from the top to the respective root depth (0-20, 20-40, 40-60,60-90, and 90-120cm) using a soil auger at three locations at the representative site of the experiment. Composite samples were made by mixing five sub-samples from the same treatment and depth. About 1 kg of soil was used for determining the soil physical and chemical properties such as soil textural class, Field Capacity (FC) and Permanent Wilting Point (PWP), soil pH, and EC analysis at the Amhara Design and Supervisory Works Enterprise. Whereas the soil bulk density was determined from undisturbed soil samples using a cylinder, drop-hammer core sampler with size 5 cm in diameter and 5 cm in height was driven into the soil with a hammer. The core sampler was driven to 20 cm depth for the upper 0–20 cm soil layer and to 40 cm depth for the next 20 cm layer. The cylinder containing an undisturbed soil core was removed and trimmed. The weight of the soil core was determined after drying it in an oven at 105°C for 24 hours. The bulk density was determined by the mass of the soil per volume (Terzaghi, et al. [31]).

Soil samples were air-dried, sieved by a 2 mm sieve, and analyzed using standard laboratory procedures. The major soil properties included pH (H2O), electrical conductivity, exchangeable Na, K, Ca, Mg, CEC and Exchangeable Na %(ESP) was determined using ammonium acetate. The soil textural class analysis of clay, silt, and sand was determined using hydrometer method. The pH meter was standardized with 4.0 and 9.2 pH buffer solutions and accordingly, the pH of the sampled soil was measured. For soil electrical conductivity determination, an extract was obtained from the saturated soil paste with the help of a vacuum pump. Then with the help of the digital electrical conductivity meter, ECe was measured. The pH and EC of water were also measured for irrigation water quality. Field capacity and permanent wilting points were determined in the laboratory using pressure- plate apparatus by applying 1/3 bars pressure to a saturated soil sample for field capacity and applying 15bars pressure to determine the permanent wilting point. The soil moisture was determined gravimetrically.

Determination of Crop Water Requirement

Monthly ETo was computed using CROPWAT model version 8.0 with the Penman-Monteith method based on the 28-year long-term climate data (Tmax. Tmin, RH, Sh, and U) collected from the West Amhara National Metrology Agency in Bahir Dar for onions and tomatoes during the growing season (Table 1). Crop water use (ETc) was determined by multiplying ETo by the crop coefficient (ETo*Kc) (Allen, et al. 32). The crop coefficient was used for the growth stages of the onion and tomato crop for the experimental years explained in Table 2. Irrigation water to be applied to the tomato was determined based on allowable constant soil moisture depletion fraction (p = 0.4) of the Total Available Soil Water (TAW), where TAW was determined from the permanent wilting point, field capacity, root depth, and bulk density variables. The depth of water applied during each irrigation event was the net irrigation requirement estimated by the Penman-Monteith method using the long-term climate data. Considering conveyance and other losses for a surface furrow irrigation system, an application efficiency of 60% was assumed (Chandrasekaran, et al. [33]). Successive irrigation depth was applied based on the readily allowable water for the root depth on that day. The different amount of water was applied with different irrigation scheduling. Because the amount of water applied of the crop depends on the crop growth stage and the monthly weather conditions. The daily crop evapotranspiration was deducted from the net irrigation depth for the control treatment (100% ETc) until the cumulative subtraction from the net irrigation depth applied approached zero. Further irrigation was applied when the cumulative ETC approach to net irrigation depth was applied to control treatment and applied to stress treatments based on their proportion to non-stressed treatment.

Table 1: Treatment combinations.

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Table 2: Agronomic management of tomatoes throughout the growing period.

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The effective root depth for mid- season and the late season was taken as a constant 1.1m for tomato. During the experiment there was no rainfall, all the water required by crops has to be supplied by irrigation, due to this, the net irrigation requirement and the readily available water were equal. The gross irrigation was calculated based on application efficiency and readily available water (FRENKEN, et al. [34]). Once the amount of water that needs to be given during one irrigation application was estimated and applied, then the next determine the irrigation interval by dividing the net irrigation depth (mm) to daily crop water requirement (mm/day). The predetermined amount of irrigation water for each plot was measured using a 3-inch standard Parshall flume. The required amount of irrigation water was applied to each experimental plot based on the deficit level of the treatment. The volume of water applied for all treatments was determined from the plot area and depth of irrigation requirement. The time required to irrigate each plot was measured from the ratio of the volume of applied water to the discharge-head relation of the 3-inch Parshall flume. The time required to deliver the desired depth of water into each furrow was calculated using the below equation 2.1 the help stopwatch (Geremew, et al. [35]).

where A = (irrigated area) in m2 d = irrigation depth in cm T = (time) in min. q = (Parshall flume discharge) in l/s.

Agronomic Data Collection

Marketable Yield: The experimental data on the fruit yield of tomato in each experimental plot was harvested and weighing the yield obtained after picking the tomato fruit. Marketable yield (kg/ha) was measured for healthy and non-diseased, non- rotten, tomato fruit recorded from the sampled plant. Marketable bulb yield was expressed as kg per plot. Finally, the yield obtained from the sample area was converted to per hectare using equation 2.2 (Demisie, [36]).

Water productivity was determined based on the ratio of yield of tomato (yield per hectare) to the amount of water used from the establishment to harvest expressed as kg of yield per m3 of water. It was calculated based on the formula using equation 2.3.

Where: WP -Water productivity (kg/m3) Ya-Actual yield (kg/ha) ETa -Seasonal applied amount of water (m3 /ha)

Crop yield response factor (Ky) was determined from the experimental data. The yield response factor (Ky) was one of the important parameters that indicate whether moisture stress due to deficit irrigation was advantageous or not in terms of enhancing water productivity. The yield response factor relates relative yield reduction to the corresponding relative deficit in Evapotranspiration (ETc). It was an indication of the response of yield to water use reduction. The yield response factor was determined based on the ratio of relative yield decrease to relative evapotranspiration deficit expressed in decimals, using the equation 2.4 (Smith, et al. [37])

Where: Ya = actual harvested yield in kg/ha, Ym = maximum harvested yield in kg/ha, ky = yield response factor, ETa = actual evapotranspiration in mm/growing period and ETm = maximum evapotranspiration in mm/growing period.

Statistical Analyses

The collected data were statistically analyzed using a statistical software in the procedure of a general linear for the variance analysis model. Analyses of variance (ANOVA) were used for yield and water productivity of tomatoes. All data collected were managed and compared with Least Square of Differences (LSD) and when the effect of the treatments was found significant, mean comparisons were tested using the Tukey test at 5% probability. Results of growth, yields, and yield component parameters were analyzed using statistix computer package version10.

Results and Discussion

Soil and Water Analysis

The soil texture laboratory analysis results showed that the average proportion of sand, silt, and clay percentages were 18.6, 17.6, and 63.8, respectively. Thus, according to the USDA soil textural classification, the soil textural class of the experimental site was heavy clay soil. The result of soil Bulk Density (BD) in the experimental field has a slight variation with its depth. The BD of the experimental site varied from 1.22 g/cm3 in the upper soil (0-20 cm) to 1.33 g/cm3 in the lower soil layer (90-120 cm). The average bulk density of the experimental site was 1.28 g/cm3 (Table 3). The BD of 1.2 g/cc may be expected for clay soil but it can vary from around 1.0-1.4 g/cc (Hazelton [38]). The soil moisture content on the weight base at FC showed varying variation within depths of 0-20, 20-40,40-60,60-90 and 90-120 cm were 35.1, 35.6, 37.5,37.8 and 38.6 %, respectively (Table 3). Whereas the soil moisture content on weight base at PWP also showed a vary within depths of 0-20, 20-40,40-60,60-90 and 90-120 cm were 21.5, 22.3, 23.6,24.8 and 25.7%, respectively. The average moisture content on weight base at FC (1/3 bar) and PWP (15 bar) were 36.92% and 23.58%, respectively. The Total Available Water (TAW) which was the amount of water that a crop can extract from its root zone was directly related to variations in FC and PWP. Based on the laboratory results of ADSW the experimental TAW also showed a variation within depths of 0-20, 20-40,40-60,60-90 and 90-120 cm were 33.2, 33.0, 36.4,49.9 and 51.9mm, respectively. The volumetric TAW of the experimental site was 170mm/m. The analysis of applied irrigation water showed that a pH value of 7.28 and ECw value of 0.24 dS/m was obtained (Table 4).

Table 3: Long-term (from 1990 to 2017) means climate data.

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Table 4: Tomato parameters used for crop water estimation.

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Note: Allen, et al., (1998).

Crop Water Requirement Of Tomato

The total irrigation water applied to tomato crops were 438.5 mm for non-stressed treatment (100%ETc) respectively (Table 5). The result was in agreement with (Doorenbos and Kassam (1986)) who reported that the seasonal crop water requirement of tomato ranges from 400-600 respectively using furrow irrigation. All treatments were irrigated on the same day because the only difference was the depth of water on deficit levels.

Table 5: Tomato parameters used for crop water estimation.

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The Effects of Deficit Irrigation on Yield and Water Productivity of Tomato

The Effects of Deficit Irrigation on Yield Components of Tomato: Deficit irrigation had no significant effect on the fruit diameter and fruit length of tomatoes (p < 0.05). Fruit diameter and fruit length were not significantly affected by deficit level. Even with a minimal amount of water, we can get reasonable growth and yield components. However, the maximum fruit diameter and fruit length (3.63 and 5.8cm) were recorded from 75%ETc and control (100%ETc) respectively. On the other hand, the minimum fruit diameter and fruit lengths were 3.58 and 5.7cm recorded in the application of 50%ETc respectively, (Table 6). According to (Berihun, et al. [39]), amount of water applied did not have a significant effect on the growth and yield components of tomatoes. This results consistent with the findings of Shahein, et al. [40]) who reported that water stress for the whole growing season does not significantly affect fruit length and diameter compared to fully irrigated treatment. A similar result was also reported by Selamawit (Bekele, et al. [41]) who reported that deficit levels had no significant effect on growth and yield components. No significant difference in fruit diameter was observed under full irrigation and 70%ETc (Randhe et al., [42]).

Table 6: Analysis of chemical properties of soil and water.

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The Effects of Deficit Irrigation on Yields and Water Productivity of Tomato: The analysis of variance (ANOVA) results showed that the marketable yield of tomato was significantly (p < 0.05) affected by irrigation levels. the highest and the lowest marketable yield of tomato (37.7t/ha) and (29.5t/ha) were obtained from the 75%ETc and 50%ETc respectively. This shows that the marketable yield of tomato in 75%ETc was 27.8% higher than 50%ETc and 4.1 % higher than 100%ETc, i.e., 75%ETc could save 25% of water without affecting yield (Table 6). This result is consistent with the suggestion of (Biswas, et al. [43]) reported that the yield of tomatoes with the increasing amount of irrigation water. The trend was reversed when irrigation was coupled with mulches there was a decrease in tomato yield with the increase in irrigation regime. This result was in line with (Audu, et al. [44]) who reported that the high tomato yield was obtained at 80%ETc than 100ETc. A similar result was also (Randhe, et al. [42]) stated that, the yield of tomatoes was higher under 70%ETc than full irrigation. For tomatoes production applying 85% and 70% of ETc was recommended with a minimum reduction of yield (Kifle, 2018). This result was also in line with (Ya-dan, et al. [45]) reported that tomato yield increased with the amount of applied irrigation water at 75%ETc and then decreased at 100%ETc. Similarly, the highest WP of tomato 12.7 and 11.2kg/m3 was obtained from 50%ETc and 75%ETc respectively while the lowest WP 8.3kg/m3 was obtained from 100%ETc (Table 7). This shows that the WP of tomato in 50%ETc was 13.4% higher than 75%ETc and 53.0 % higher than 100%ETc. This shows that WP in 100%ETc was lower than 50% and 75%ETc. The 100%ETc had a significantly different on WP from all other deficit treatments. This was because the amount of water applied in the full irrigation treatment was significantly higher than the deficit treatment. WP for tomato was increased in deficit treatment compared to non-stressed treatment. This result was in line with (Guangcheng, et al. [46]) who stated that DI significantly increased the WP compared to the full irrigation regime. A similar result was also reported by (Ragab, et al. [47]) that DI improved WP for tomatoes. This result was also in line with Selamawit Bekele, (2017) reporting that the maximum WP was recorded from 50%ETc and the minimum was recorded at 100%ETc. The highest WP of tomato was found at 50%ETc, while 100%ETc showed the least WP (Asmamaw, et al. [22]). The highest WP of tomatoes were obtained in 50%ETc (Yadan, et al. [45]). The highest WP was observed at 60%ETc while the lowest was observed at 100%ETc (Sang, et al. [48]).

Table 7: Seasonal irrigation water applied to tomato.

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The Effects of Mulch Types on Yield and Water Productivity of Tomato

The Effects of Mulch on Yield Components of Tomato: The analysis of variance showed that the fruit diameter of tomato was significantly affected by the main effects of mulch type (p < 0.05), while the fruit length of tomato was not significantly affected by the mulch type. The highest fruit diameter was obtained from rice straw mulch 3.66cm and plastic mulch 3.60cm while the lowest fruit diameter was obtained from no mulched treatment 3.56cm (Table 8). Whereas the fruit length of tomato was not significantly different among treatments. This result agreed with the results of (Karaer, et al. 49]) who stated fruit diameter was found to be higher in mulch applications. This result agreed with the results of (Goel, et al. [50]) reported that the trend of the favorable effect produced by mulches on growth parameters was rice straw mulch higher than no mulch. The application of different mulch types had no significant effect on the growth and yield parameters of tomatoes (Mn, et al. [51]).

Table 8: Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at a 5% level of significance. ** =significant at P <0.01.

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The Effects of Mulch Types on Yields and Water Productivity of Tomato: The analysis of variance showed that the marketable yield of onion and tomato was significantly affected by mulch type at (p < 0.01). The marketable yield of tomatoes was 36.9, 35.1, and 31.1 t/ha, respectively, in RSM, WPM, and NM treatments. This implies that the marketable yield in RSM was 17.1% higher than NM and 5.1% higher than WPM treatment. The result indicated that mulch application significantly improves the yield of the tomato. This result was in line with the result of (Audu, et al. [44]) reported that the yields of tomatoes obtained from RSM were higher than the yield obtained from WPM. The results were also consistent with the findings reported in (Goel, et al. [50]) that increase in tomato yield with mulches RSM was 25.6% as compared to NM. RSM increased the fruit yield of tomatoes (Pandey, et al. [52]). These results agree with (Robel Admasu, et al. [53]) who reported that the maximum marketable yield was obtained due to plastic mulch than no mulch for tomatoes. The application of straw mulch is found to be economically and agronomically feasible (Berihun, et al. [39]). The application of mulch types significantly influences tomato fruit yield (Tegen, et al. [54]). Crop yield significantly increased with the application of rice straw mulch (Dossou-yovo, et al. [55]). These results suggest that straw mulching has great potential for improving onion yield (Tao, et al., [56]). Similarly, the WP of tomatoes was 11.4, 11.0, and 9.8 kg/m3 in RSM, WPM, and NM treatments, respectively (Table 9). It implies that the WP in RSM treatment was 16.3% higher than NM and 3.6% higher than WPM treatment. The results indicated that mulching applications significantly improve the WP of the tomato. This result was in line with the result of (Goel, et al. [50]) who reported that RSM increased WP by 26.6 % over no mulch. The results were also consistent with the findings reported in tomato Robel Admasu and Zelalem Tamiru, (2019) that the maximum WP was obtained due to PM than NM for tomatoes. The result indicated that mulching was one of the important water management strategies used to improve WP. This result showed that straw mulch increased WP, and decreased evapotranspiration.

Table 9: The effects of deficit irrigation on yield and water productivity of tomato.

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance. ** =significant at P < 0.01.

The interaction effects of deficit irrigation and mulch types on yield and water productivity of tomato

The Effects of Deficit Irrigation and Mulch on Yield Components of Tomato: The analysis of variance showed that the fruit diameter and fruit length of tomatoes were not significantly affected by the interaction effects of deficit irrigation and mulch types (p < 0.01). There was no significant difference was observed between treatments in fruit diameter and fruit length of tomato at all deficit irrigation and mulch types (Table 10). Even we applied minimum amount of water to get the reasonable fruit size of tomato. This may be due to the canopy covers of tomato use as a mulch. This result agreed that the results of (Kere, et al. [57]) the yield attributes of tomato were not significantly affected by either irrigation amount and mulch type. According to (Berihun, et al. [39]), the interaction effect of the amount of water and mulch was not significant in fruit length and fruit diameter. According to (Aliabadi, et al. [58]) the interaction effect of mulch and amount of water on fruit length and diameter was not significant. A similar result was also reported by (Selamawit Bekele, et al. [41]) who reported that deficit levels have no significant effect on plant and fruit height. No significant difference in fruit diameter was observed under full irrigation and 70%ETc (Randhe, et al. [41]).

Table 10: The effects of deficit irrigation on yield and water productivity of tomato.

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance.
** =significant at P < 0.01.

Combine Effects of Mulch and Deficit Irrigation on Yields and Water Productivity of Tomato: The ANOVA results showed that the marketable yield of tomato was significantly affected by the interaction effects of deficit irrigation and mulch types at (p < 0.05). the highest marketable yield of tomato (41.7t/ha and 38.6 t/ha) were achieved from 75%ETc and 100%ETc with RSM treatments, respectively. However, no significant yield difference was observed between 75%ETc with WPM, and 100%ETc with RSM treatment combinations. The lowest marketable yield obtained from 50%ETc with NM treatment was 26.6t/ha. The marketable yield of tomato was 41.7, 38.6, and 38.0, t/ha, respectively, in 75% and 100%ETc with RSM, and 75%ETc with WPM treatment combinations. This implies that marketable yield of tomato in 75%ETc with RSM was 8.0% higher than 100%ETc with RSM and 9.7% higher than 75%ETc with WPM treatment combinations (Table 11). This result showed that RSM and WPM increased the yield of tomatoes by 21.2% and 10.5% compared with NM treatment. These results also showed that there was no yield advantage observed using 100ETc with NM. RSM improves the yield of tomatoes compared to WPM and NM treatments. All the deficit treatments with mulch resulted in significantly higher yields than unmulched irrigation level treatments. The yield of tomatoes increased with the increase in water supply without mulch. The effect was reversed when the irrigation level was coupled with either plastic or straw mulch; there was a decrease in tomato yield with the increase in irrigation regime. Irrigation at the same level without mulch produced the lowest yield.

Table 11: The effects of mulch type on marketable yield tomato.

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance.
** =significant at P < 0.01.

However, 100%ETc irrigation supply produced a lower yield than 75%ETc when mulched with plastic and mulched with straw. This may be due to excessive watering that has been shown to increase flower drops and reduce fruit set. Also, this may cause excessive vegetative growth and a delay in ripening. The water supply during and after the fruit set must be limited to a rate that will prevent the stimulation of new growth at the expense of fruit development (Doorenbos, et al. [59]). This result is in line with the findings of (Audu, et al. [44]) recommended that tomato producers to adopt water application at 80%ETc and use RSM. These results were also consistent with the findings of (Biswas, et al. [43]) reported that with 100%ETc water application, the plastic-mulched treatment produced a lower yield than the straw-mulched treatment. The maximum marketable yield of tomatoes was observed at 80%ETc with mulch (Alebachew, et al. [60]). The maximum fruit yield was recorded from the plants receiving deficit irrigation at 80%ETc with a straw mulching treatment combination (Samui, et al. [61]). The best level of irrigation for tomato crop is 80%ETc and this correspond to mulching practice of rice straw mulch (Zakari et al. 2020). Similarly, the highest WP of tomatoes (13.59 and 13.08 kg/m3) were achieved from 50%ETc with WPM and with RSM respectively (Table 11). There was no significant difference observed between 50%ETc with WPM and with RSM treatment combinations. The lowest WP was obtained from 100%ETc with no mulch. However, there were no significant differences observed between in WP of 100%ETc with NM and 100%ETc with WPM treatment combinations. The WP of tomatoes was 13.59, 13.08, and 12.44, kg/m3, respectively, at 50%ETc with WPM, RSM, and 75%ETc with RSM treatment combinations. This implies that WP in 50%ETc with WPM was 3.2% higher than 50%ETc with RSM and 8.5% higher than 75%ETc with RSM treatment combinations. These results showed that RSM and WPM combined with DI improved tomato WP without yield penalty. At irrigation level of 50%ETc, irrigated to tomato plot mulched with WPM produced better WP than that of NM and NM treatment. The NM treatment remained always behind the mulched treatment. At a high irrigation level of 100%ETc, all mulched and un-mulched treatments performed almost similarly to produce WP. Mulches reduced the rate of water loss through evaporation from the soil surface. So, the soil-water-plant relationship was better in a low irrigation level than in a high irrigation level which might help produce higher WP. These results were consistent with the findings of (Biswas, et al. [43]) reported that the higher WP were obtained from mulch treatments with a 50%ETc. This result is in line with the findings of (Goel, et al. [50]) who explained that mulching increased irrigation water use efficiency by 26.6 % in rice straw mulch over no mulch. The tomato WP under the interactive effect of deficit irrigation and mulch was determined to be highest at 60%ETc with mulch and lowest at 100%ETc (Sang, et al. [48]).

The Effect of Mulch and Deficit Irrigation on Yield Response Factor

The study revealed that a lower yield response factor (ky) of 0.0 was achieved from 75%ETc with RSM for tomato. The result indicated that the ky was associated with deficit level and mulch types. At 100%ETc were no recorded yield response factors. Because the actual amount of water applied at 100%ETc was similar to ETm, the result was one. In this study, the Ky of the tomato crop under no mulch condition was 1.0. The Ky values of the no mulch treatment were higher than the mulched treatment which implies that the proportional decrease in yield under the no mulch condition was much higher than in the mulched condition. Ky, which indicates the level of tolerance of a crop to water stress, approaching unity when yield declines proportionally to ET deficit (the greater Ky the lower the tolerance), was higher in no mulch compared to mulched treatment. This reveals a greater tolerance of this mulched treatment to water shortage. In this respect, Ky may be a valuable tool for water deficit tolerance and, thus, for deficit irrigation adaptability evaluation in tomato and onion production. Results among the treatments showed as the deficit increased, the sensitivity of yield increased [62-67] (Tables 12-14).

Table 12: The interaction effects of mulch and deficit on yield components of tomato.

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance.
** =significant at P < 0.01.

Table 13: The interaction effects of mulch and deficit on marketable yield tomato (t/ha).

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance.
** =significant at P < 0.01.

Table 14: Effect of mulch type and deficit irrigation levels on tomato yield response factor.

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Note: Where, LSD = Least Significant Difference at 5% level; CV = Coefficient of Variation. Means in columns followed by the same letters are not significantly different at 5% level of significance.
** =significant at P < 0.01.

Conclusion and Recommendations

Conclusion

Water scarcity is the main challenge in current sub-Saharan African countries including Ethiopia. To mitigated those challenge on farm water saving strategies should be implemented to increase yield and water productivity. The marketable yield of tomato in 75%ETc was 27.8% higher than 50%ETc and 4.1% higher than 100%ETc treatment. While the IWUE in 50%ETc treatment was 13.4% higher than 75%ETc and 53.0% higher than 100%ETc treatment. The marketable yield of tomato in RSM was 17.1% higher than NM and 5.1% higher than WPM treatment while the IWUE of tomato in RSM was 16.3% higher than NM and 3.6% higher than in the WPM treatment. In the combination effects of mulch and deficit irrigation, the marketable yield of tomatoes in 75%ETc with RSM was 8.0% higher than 100%ETc with RSM and 9.7% higher than 75%ETc with WPM treatment combinations. Similarly, the water productivity of tomatoes in 50%ETc with WPM was 3.2% higher than 50%ETc with RSM and 8.5% higher than 75%ETc with RSM treatment combinations. Deficit irrigation strategies are recommended for use by farmers and extension workers to achieve optimum tomato yield and maximize WP by applying at 75%ETc through growth phases while saving water 25% of the water requirement. Smallholder farmers should apply RSM practices to increased tomato yields and savings water under conservation agriculture. Tomato growers are highly advised to cover their crop with RSM and apply 25%deficit irrigation instead of full irrigation to achieve higher tomato yields and better WP. Adoption of water-saving strategies by smallholder farmers during the water scarcity time has economic benefits because less production cost was required for diesel, and labor for irrigation water application, and the saved water can potentially increase farm income to be used for bringing new areas under irrigation. Additional research is needed on the effect of mulch types on soil nutrient dynamics, soil temperature, and the occurrence of pests and disease while different irrigation levels of moisture stress to determine conclusively the influence of the same study on yields and water productivity. Such studies may result in a further improvement of the yield of tomato in water shortage areas of the country.

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Life and Work Satisfaction in Literature from 2020 to 2024

Introduction

The history of life satisfaction is a concept that has evolved over time, reflecting changes in cultural, philosophical, and scientific perceptions about well-being and happiness (Vallejo, et al. [1]). While there is no single narrative of the history of life satisfaction, we can identify some important milestones and perspectives throughout history: In ancient Greece and Rome, thinkers such as Aristotle and Epicurus addressed questions related to happiness and well-being. welfare. Aristotle proposed that happiness (eudaimonia) was achieved through the realization of human virtues, while Epicurus associated happiness with the absence of pain and the satisfaction of moderate desires. During the Middle Ages, the conception of life satisfaction was strongly influenced by Christian religious teachings, which promoted the idea of happiness as a spiritual state based on salvation and the fulfillment of divine will (Carrillo-García, et al. [2]). With the Enlightenment, new ideas about happiness emerged based on the use of reason and the search for the common good. Philosophers such as John Locke and Jeremy Bentham explored concepts of utility and pleasure as fundamental components of human happiness. In the 20th century, the field of psychology began to systematically study life satisfaction and psychological well-being (Rodríguez-Rey, et al. [3]). Figures such as Abraham Maslow and Carl Rogers developed theories about human needs and self-development as essential ingredients of a satisfying life.

Currently, life satisfaction is understood in a multidimensional way, incorporating psychological, social, economic, and cultural aspects. The science of happiness and well-being has become an interdisciplinary field that studies how various factors contribute to people’s subjective and objective well-being. The search for life satisfaction today involves a comprehensive approach that considers factors such as quality of life, social relationships, sense of purpose, physical and mental health, as well as the connection with nature and the environment (Juárez – Adauta, [4]). There is growing interest in understanding what factors promote lasting and meaningful happiness over time, beyond momentary satisfaction or ephemeral pleasure. The history of life satisfaction is a complex and evolving story that reflects the interaction between philosophical, religious, scientific, and cultural concepts over the centuries. The contemporary understanding of life satisfaction remains a topic of ongoing research and debate in the social sciences and the study of human well-being. Life satisfaction theory is an area of study within psychology and social sciences that focuses on understanding the factors that contribute to people’s subjective well-being and sense of satisfaction with life (Duche-Pérez, et al. [5]). This theory explores how experiences, emotions, beliefs, and behaviors influence a person’s overall evaluation of their own life. Here I present some important theories about life satisfaction.

Hedonic Adaptation Theory

This theory suggests that people have a relatively stable level of well-being over time, despite changes in external circumstances (Peña Cárdenas, et al. [6]). It is postulated that individuals tend to adapt to positive or negative changes in their lives, meaning that after a time, the emotional impact of an event (whether good or bad) tends to decrease, and the level of satisfaction returns to normal. a point close to the initial state.

Human Needs Theory

Based on Maslow’s hierarchy of needs, this theory postulates that people experience life satisfaction when their fundamental needs are satisfied in a hierarchical order (Pienkowski, et al. [7]). Basic needs include food, shelter, and safety, followed by needs for social relationships, self-esteem, and self-actualization. When these needs are met, people tend to experience greater satisfaction and well-being.

Self-Determination Theory

This theory proposes that life satisfaction is associated with the degree to which people experience autonomy, competence, and meaningful social relationships in their lives (Martínez, et al. [8]). Life satisfaction is maximized when people can make autonomous decisions that are aligned with their personal values and goals, when they feel competent in the activities they perform, and when they have satisfying social connections.

Attachment and Social Relationships Theory

This theory emphasizes the importance of social and emotional relationships in life satisfaction (Sanchez -García, et al. [9]). According to this perspective, secure and supportive relationships, particularly in childhood and young adulthood, promote greater life satisfaction in adulthood. People with close, positive relationships tend to report higher levels of well-being and global satisfaction.

Flow Theory

This theory refers to the mental state of flow , which occurs when a person is completely immersed in a challenging but achievable activity (Özcan, [10]). During flow, people experience a sense of total concentration, enjoyment, and satisfaction, which contributes significantly to their well-being and life satisfaction. In addition to these specific theories, there are also multidimensional approaches that consider multiple aspects of human life (such as physical health, quality of relationships, purpose and meaning in life, among others) to comprehensively understand life satisfaction (Schnettler, et al. [11]). Together, these theories and approaches offer a holistic view of life satisfaction, showing that it is the result of a complex interaction between internal and external factors that affect people’s perception and evaluation of their own existence. There are several models and approaches to understand life satisfaction from different perspectives (Portero de la Cruz, et al. [12]). These models provide conceptual frameworks for understanding how the various dimensions of human life contribute to overall well-being and satisfaction. The World Health Organization Quality of Life Model (WHOQOL, [13]) addresses life satisfaction from a broad and multidimensional perspective (Bellini, et al. [14]). This model considers four main domains that influence quality of life and satisfaction. The WHOQOL provides a comprehensive framework for assessing and improving life satisfaction from multiple perspectives.

Life Satisfaction Model

Richard E. Diener, one of the pioneers in the study of happiness and life satisfaction, proposed a life satisfaction model that considers multiple components (Vela Quintero, et al. [15]). This model recognizes that life satisfaction is influenced by the subjective evaluation of life as a whole and by the emotions and meanings associated with daily experiences.

Self-Determination Model

The Self-Determination Theory proposed by Deci and Ryan posits that life satisfaction is related to the degree to which people experience autonomy, competence, and satisfactory social relationships (Fernández-Portero, et al. [16]). This model emphasizes the importance of meeting basic psychological needs to promote well-being and personal satisfaction.

Life Satisfaction Levels Model

This model considers that life satisfaction can be influenced by individual, contextual and cultural factors (Vallbona, et al. [17]). There are several levels of satisfaction.

Attachment and Social Relationships Model

This model highlights the importance of social and emotional relationships in life satisfaction (Wright, [18]). Secure and supportive relationships are postulated to contribute significantly to people’s overall well-being and satisfaction.

Agency and Opportunity Capacity Model

This approach, developed by Amartya Sen and Martha Nussbaum, considers that life satisfaction is related to people’s ability to choose and pursue valuable opportunities in life (such as education, health, work significant, etc.) (Mutiu, [19]). These models show the diversity of theoretical and practical perspectives to understand and evaluate life satisfaction, recognizing that it is a complex construct that encompasses multiple interrelated dimensions of the human experience (Loewe, et al. [20]). Life satisfaction is a multidimensional concept that encompasses several important dimensions that influence well-being and the global perception of happiness and personal fulfillment (Huertas-Delgado, et al. [21]). These dimensions represent different aspects of life that contribute significantly to overall satisfaction.

Health and Physical Well-being

Physical health plays a fundamental role in life satisfaction (García, et al. [22]). This dimension includes the subjective evaluation of one’s own health, the ability to perform daily activities without difficulty, the absence of chronic diseases or significant disabilities, and the general perception of physical well-being.

Emotional and Mental Well-being

The emotional and mental dimension refers to the ability to experience positive emotions and effectively manage stress and negative emotions (Addabbo, et al. [23]). It includes aspects such as self-esteem, emotional resilience, the ability to experience joy and satisfaction in everyday life, and emotional balance.

Social Relationships and Social Support

The quality of interpersonal relationships and social support are important determinants of life satisfaction (Pena, et al. [24]). This dimension considers the presence and quality of meaningful relationships with family, friends, partners, and the community, as well as the sense of belonging and the ability to receive and offer emotional support.

Personal Achievement and Development

Life satisfaction is influenced by personal achievement and the sense of personal development (Echenique, et al. [25]). This dimension includes the achievement of personal and professional goals, a sense of personal progress and growth, self-direction, and the ability to pursue activities that are meaningful and rewarding.

Material Quality of Life

Although it is not the only factor, life satisfaction can also be affected by the economic situation and material conditions (Carmona, et al. [26]). This dimension includes factors such as income level, financial security, access to basic resources (housing, food, medical care), and job stability.

Sense of Purpose and Meaning

Feeling that life has a purpose and meaning is essential for life satisfaction (Ríos, et al. [27]). This dimension relates to clarity of personal values and goals, connection to something larger than oneself (such as spiritual or community beliefs), and a sense of meaningful contribution to the world.

Environment and Quality of Life

Life satisfaction is also influenced by the physical and social environment in which a person lives (Kucel, et al. [28]). This dimension considers factors such as the quality of the natural environment (air, water, landscapes), the safety and accessibility of the community, and the quality of available public and cultural services. These dimensions interact with each other and jointly contribute to a person’s overall evaluation of their life satisfaction (Brioso, et al. [29]). It is important to recognize that life satisfaction is a subjective and multifaceted concept, and that different people may value these dimensions differently based on their individual values, experiences, and circumstances. However, life satisfaction has not been reviewed at the organizational level. Therefore, the comparison between life satisfaction and job satisfaction at a global and local level is the objective of this work. Are there significant differences between life satisfaction and job satisfaction at global and local levels with respect to public universities? The premise that guides this work suggests that life satisfaction has its correlation in job satisfaction observable in organizations and institutions. In this way, differences inherent to the context in which the literature has been published are expected.

Method

Selection of Measurement Instruments: Validated and reliable instruments to measure life satisfaction and its dimensions. Standardized questionnaires such as the Satisfaction with Life Index (SWLS), the Subjective Well-being Scale (SWB) or the WHOQOL-BREF Quality of Life Questionnaire. Data collection using appropriate methods, such as online surveys, structured interviews or focus groups. Obtaining informed consent from participants and guaranteeing the confidentiality and anonymity of the data.

Statistical Analysis

Use of techniques to analyze the data collected. Conducting descriptive analyzes to summarize life satisfaction scores and inferential analysis to explore relationships between predictor variables and life satisfaction. Identification of predictive factors that most influence life satisfaction according to the results of the analysis. This may include variables such as physical health, emotional well-being, social relationships, socioeconomic level, and other aspects relevant to your study. Interpretation and discussion of results in the context of existing literature and discuss the practical implications of your results. Ethical considerations at each stage of your research, including informed consent, privacy and confidentiality of participants, and responsible use of the data collected.

Results

A comparative table that contrasts typical findings related to life satisfaction and job satisfaction (Table 1). These two concepts are closely related but represent different aspects of a person’s well-being and quality of life: Autonomy and Participation in Decision Making: Employees who have a certain degree of autonomy and participation in decision making related to their work tend to be more satisfied in their work roles. Fostering a positive and supportive organizational climate, where diversity is valued and open communication is promoted, can significantly improve job satisfaction. The perception of fair compensation and the availability of additional benefits (such as health insurance, bonuses, etc.) are determining factors in job satisfaction in Mexico.

Table 1: Comparison of the findings of life satisfaction and job satisfaction.

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Note: Source: Prepared with the literature review

Professional Development

The opportunity for professional growth and development within the organization influences job satisfaction. Employees value opportunities for training, promotion, and skill development. Access to development and professional growth opportunities is valued by Mexican employees. Lack of development prospects can negatively affect job satisfaction. Designing jobs that promote autonomy, task variety, and a sense of purpose is crucial to improving job satisfaction. The ability to achieve a satisfactory balance between job demands and personal responsibilities is positively associated with job satisfaction in many cultures.

Improvement Strategies

The results suggest that organizations should implement effective strategies to improve job satisfaction, such as promoting a supportive culture, offering development opportunities, and ensuring fair and equitable compensation. To improve job satisfaction, organizations must implement effective strategies that address the key factors identified. This may include human resources policies focused on employee well-being, professional development programs, improving the organizational climate, and appropriate recognition for work performed.

Determinants of Job Satisfaction

Findings show that factors such as work environment, work-life balance, career development and recognition are critical to job satisfaction across cultures. Studies have identified several determinants of job satisfaction, including the work environment, the quality of interpersonal relationships, work-life balance, professional development opportunities, and recognition for work performed.

Impact of Organizational Culture

Organizational culture in Mexico, which can include values such as hierarchy and loyalty, influences job satisfaction. Organizations that promote an environment of respect and collaboration tend to have more satisfied employees. Job satisfaction is closely related to the personal and emotional well-being of individuals. Employees spend a significant part of their lives at work, so it is important that this experience is positive and rewarding. Job satisfaction can be influenced by specific cultural aspects of each country or region, such as the importance of hierarchy, interpersonal relationships, and organizational norms. Global studies suggest that the work environment, including the relationship with coworkers and superiors, has a significant impact on job satisfaction.

Productivity and Performance

Satisfied employees tend to be more productive and engaged in their work tasks, which contributes to the overall performance of the organization. There is a positive relationship between job satisfaction and organizational performance. Satisfied employees tend to be more engaged, productive, and less likely to leave the organization, which positively impacts business results. Organizations must invest in training and development programs to enable the professional growth of employees and meet their development needs. The perception of being recognized and rewarded appropriately for work performed is critical to job satisfaction around the world.

Interpersonal Relationships

Relationships with colleagues and superiors play an important role in job satisfaction in Mexico. The sense of community and support at work contributes positively to employee well-being. Job satisfaction is associated with higher employee retention. Workers who feel valued and satisfied are less likely to leave the organization.

Health and Wellbeing: Job dissatisfaction can have negative effects on employees’ physical and mental health, including stress, anxiety, and burnout. Given the economic and social context in Mexico, job stability and job security are key aspects that affect job satisfaction. The perception of job satisfaction may vary depending on the cultural context and social norms of each country or region. It is important to consider these differences when developing strategies to improve job satisfaction in multicultural environments.

Discussion

Job satisfaction is a complex phenomenon that is influenced by a variety of contextual and personal factors (Barba-Sánchez, et al. [30]). Findings both globally and in Mexico highlight the importance of creating healthy work environments, promoting professional development, and ensuring equity and recognition at work to improve employee satisfaction and well-being. The discussion of the findings on job satisfaction is crucial to understand the importance of this concept in the organizational and social context (Aliabadi, et al. [31]). To advance the understanding of job satisfaction, it is important to explore innovative approaches and study cultural differences in the perception of job satisfaction (Bălţătescu, [32]). Furthermore, future research could focus on specific strategies to improve job satisfaction in different organizational and social contexts. Findings on job satisfaction highlight the importance of creating positive and stimulating work environments that promote employee well-being and engagement (Polo-Vargas, et al. [33]). Addressing job satisfaction effectively can benefit both individuals and organizations as a whole (Madrid-Solorza, et al. [34]). Job satisfaction is a crucial factor that influences the emotional well-being, commitment, and productivity of employees in any organization (Çetinkaya, et al. [35]). It is a fundamental aspect to promote a healthy and effective work environment (Vieira, et al. [36]). Although significant progress has been made in the study of job satisfaction, there are still areas that require additional research (Loewe, et al. [37-44]). Continued studies are needed to better understand the factors that influence job satisfaction and to develop effective workplace interventions.

Conclusion

The conclusions on job satisfaction highlight the main ideas and findings obtained from the research and study of this topic. Here are some key takeaways about job satisfaction: Findings on job satisfaction emphasize the importance of promoting work environments that foster employee well-being and satisfaction. Improving job satisfaction not only benefits individuals, but also contributes to the success and sustainability of organizations in a competitive business environment.

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Journals on medical research |BJSTR

Hormonal Characteristics of Patients with Arterial Hypertension with Various Tumors of the Adrenal Glands

Relevance

Adrenal tumors occur in approximately 4–10% of the general population, and their incidence increases with age [1-4] as a result because of spread use of imaging techniques. They are most often discovered incidentally during imaging performed as part of the diagnosis of unrelated conditions. The peak incidence occurs in the seventh decade of life [4,5]. All patients found to have an adrenal tumor should undergo a detailed clinical, biochemical, and radiological examination to select those who require surgical treatment [1-4]. Many adrenal tumors (about 80%) are adrenal adenomas, hypertrophy, or nodular adrenal hyperplasia. Other lesions include pheochromocytomas (PHEC) (3–6%), adrenocortical carcinomas (ACC) (2–5%), adrenal metastases (1–2%), mesenchymal tumors (myelolipomas, lipomas, hemangiomas, sarcomas), lymphomas, cysts. , ganglioneuromas [6- 14], other rare tumors [15] or collision tumors consisting of at least two different histopathological types [7,16]. Purpose of the study– to study the hormonal characteristics of patients with arterial hypertension with various tumors of the adrenal glands.

Material and Research Methods

The material for the study was the analysis of 89 cases of hypertension of adrenal origin according to retrospective data for 2 years (from 2021 to 2024) in the clinic of the Russian National Research Medical Center of Endocrinology of the Ministry of Health of the Republic of Uzbekistan in various departments: neuroendocrinology, endocrine surgery. The following groups of patients were formed: 1 gr.–patients with corticosteroma (13patients), 2 g.–patients with aldosteroma (8patients), 3gr.–patients with pheochromocytoma (21 patients), 4 gr. – adrenal incidentaloma (17 patients), 5 gr.–patients with adrenal hyperplasia (comparison group-30 patients).

Research Methods Included

1. General clinical (examination of endocrine and ocular status)
2. Instrumental – ECG, CT/MRI of the Sella turcica and adrenal glands
3. Ultrasound of internal and genital organs, etc.)
4. Hormonal blood tests (STH, IGF-1, LH, FSH, PRL, TSH, ACTH, prolactin, testosterone, estradiol, progesterone, cortisol (IKLA method) and others. In addition, the postoperative material was subjected to histological diagnosis at the Republican Specialized Medical Center of the Ministry of Health of Uzbekistan named after Academician Y. Kh. Turakulova (Histology Department, candidate of medical sciences Issaeva S.S.).

Research Results

Thus, out of 89 patients, 22 (24.7%) were patients aged 13 to 29 years. There were 26 patients (29.2%) aged 30 to 44 years. From 45 to 59 years old–33 (37.0%), and over 60–only 8 patients (8.9%). So, among the tumors of the adrenal glands (H) with hypertension, the most common was pheochromocytoma-21 patients (23.6%), in 2nd place were patients with incidentaloma H-17 cases (19.0%), in 3rd place in frequency were patients with corticosteroma-13 (14.6%) and in last place were patients with aldosteroma-8 cases (8.9%). Patients with hyperplasia made up the control group, although their number was dominant-30 patients (33.7%). According to the analysis of retrospective data from hormonal studies (basal levels taken in the morning on an empty stomach), the following data were obtained for the groups. In the Table 1 shows the average hormone values in 1 group of patients. As can be seen from Table 1, in patients with corticosteroma there was a significant increase in the average values of cortisol and prolactin (P<0.05), while the basal levels of ACTH, renin and aldosterone were not significantly changed. Table 2 shows the average value of blood plasma hormones in patients of group 2 (n=8). As can be seen from Table 2, in patients with aldosteroma there was a significant increase in the average values of plasma renin and aldosterone (P<0.05), while the basal levels of ACTH, cortisol, and testosterone were not significantly changed. Table 3 shows the average value of blood plasma hormones in patients of group 3 (n=21).

Table 1: Average value of blood plasma hormones in patients of group 1 (n=13).

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Note: P – Significance of differences compared to the control group.

Table 2: Average value of blood plasma hormones in patients of group 2 (n=8).

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Note: P – significance of differences compared to the control group.

Table 3: Average value of blood plasma hormones in patients of group 3 (n=21).

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Note: P – Significance of differences compared to the control group.

As can be seen from Table 3, in patients with pheochromocytoma, the basal levels of ACTH, cortisol, prolactin, testosterone and cortisol were not significantly changed (P>0.05), since for these patients the most informative determination of catecholamines in daily urine (see below in subchapter 3.2). Table 4 shows the average value of blood plasma hormones in patients of group 4 (n=17). As can be seen from Table 4, in patients with adrenal incidentaloma, the basal levels of ACTH, cortisol, prolactin, testosterone and cortisol were not significantly changed (P>0.05). Table 5 shows the average value of blood plasma hormones in patients of group 5 (n=30). As can be seen from Table 5, in patients with adrenal hyperplasia, the basal levels of ACTH, cortisol, prolactin, testosterone and cortisol were not significantly changed (P>0.05). So, according to the analysis of retrospective hormonal data (basal levels taken in the morning on an empty stomach), the following data were obtained by group. In patients with corticosteroma, there was a significant increase in the average values of cortisol and prolactin (P<0.05), while the basal levels of ACTH, renin and aldosterone were not significantly changed. In the group of patients with aldosteroma, there was a significant increase in the average values of plasma renin and aldosterone (P<0.05), while the basal levels of ACTH, cortisol, and testosterone were not significantly changed. It was typical for patients with pheochromocytoma that the basal levels of ACTH, cortisol, prolactin, testosterone, and cortisol were not significantly changed (P>0.05), since for these patients the most informative determination of catecholamines in 24-hour urine.

Table 4: Average value of blood plasma hormones in patients of group 4 (n=17).

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Note: P – Significance of differences compared to the control group.

Table 5: Average value of blood plasma hormones in patients of group 1 (n=30).

biomedres-openaccess-journal-bjstr

Note: P – Significance of differences compared to the control group.

In patients with adrenal incidentaloma, basal levels of ACTH, cortisol, prolactin, testosterone, and cortisol were not significantly changed (P>0.05). In patients with adrenal hyperplasia, basal levels of ACTH, cortisol, prolactin, testosterone, and cortisol were not significantly changed (P>0.05). At the same time, patients in group 3 had a significant increase (P<0.05) in the level of cortisol in daily urine. In patients of group 3 there was a significant increase (P<0.05) in the levels of catecholamines in daily urine (adrenaline, norepinephrine, dopamine). Thus, hormonal blood tests have shown how informative they are in diagnosing adrenal diseases. In the case of hormonally active mass formations of the adrenal glands, assessment of basal hormone levels can be of great diagnostic value in case of corticosteromas, aldosteromas, since these patients have significantly increased values of plasma cortisol and aldosterone, respectively. For patients with adrenal hyperplasia and incidentaloma, these studies turned out to be of little information.

Conclusion

According to the analysis of retrospective data on hormonal parameters of blood plasma (basal levels taken in the morning on an empty stomach) and urine, the most significantly significant differences in their content were found in patients with corticosteroma, aldosteroma and pheochromocytoma (P < 0.05).

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