Contrast Medium Controlled Injection in the Navicular Bursa and the Following Bursography in 23 Cases

Introduction

Equine palmar foot syndrome is a common cause of front limb lameness in the horse [1]. The podotrochlear apparatus is a special anatomic feature in the horse due to the deep digital flexor tendon needing a pulley before the insertion on the distal phalanx. The navicular bone (navicular bursa: NB), distal impar ligament (DIL), collateral sesamoidean ligaments (CSL) and the deep digital flexor tendon (DDFT) are part of the podotrochleat apparatus [2]. Alliterations of one of these structures alone or combined lead to pain [2]. Magnetic resonance imaging (MRI) is a favorable method to diagnose the different lesions [3–5]. Ultrasound is also an option to diagnose changes in the DIL and DDFT [6,7]. Due to lesions in the soft tissue, X-ray is sufficient to diagnose equine palmar foot syndrome [8]. Contrast radiography with palmaroproximal-palmarodistal oblique views seem to be helpful in diagnosing changes in the DDFT and the flexor surface cartilage [9,10]. Intrabursal medication is one of the widest use practices in navicular disease [11,12].
There are many ways to inject the bursa. The distal palmar approach to the “navicular position,” defined as a point on the lateral hoof wall, 1 cm distal to the coronary band, and halfway between the most dorsal and most palmar aspect of the coronary band [12], seems to be very successful. In cadaver limbs, 23/25 (92 %) were injected successful with 1.1 redirection per injection. However, there was also contrast medium (CM) in the distal interphalangeal joint (DIP) in 1/25 (4 %) and palmar to the DDFT in 1/25 (4 %) legs. There is also the possibility to show alliterations in navicular apparatus in cadaver limbs with bursography, especially with the dorsoproximal-palmarodistal oblique view [13]. There is a reported success of 14/17 for NB injections (82.35 %) in living horses [14]. There is no information currently about dorsoproximalpalmarodistal oblique radiographic projections with CM in the NB in living horses. Thus, this case study will show the first results of this technique in living horses.

Materials and Methods

Thirteen horses were chosen for a reason not connected to the study for injection of the NB. Patients were presented in the hospital from 2015 to 2020 and were all warmbloods. Nine horses were injected in both front feet. Only one foot was injected in each of four horses. The NB was injected twice in one horse. There was complete lameness examination data available in seven horses, including a positive distal digital nerve block. The data were collected retrospectively. All horses underwent a distal digital nerve block and a sedation with detomidine and butorphanol. The skin between the heel bulbs was shaved or clipped and washed for 5 min with antibacterial soap and swabbed several times with alcohol. The foot was placed on a standard DP 65° wooden block and held by staff, the same way as for the DPr-PaDiO radiographic projections. An amount of 3 ml Iomeprol 300 mg ID/ml (Imeron 300M© Bracco Imaging GmbH, Konstanz, Germany) and 5mg triamcinolonactenonide (TriamHexal©, Hexal AG, Holzkirchen, Germany) were injected directly into the NB using a spinal needle (BD© Spinal Needle, 0.9 *90 mm, Becton Dickinson GmbH, Karlsruhe, Germany) and a standard 5 ml syringe under sterile conditions.
The landmark for needle insertion was a point just proximal to the central sulcus of the frog, with the needle directed toward the apex of the frog and parallel to the ground surface of the hoof [10]. The correct placement of the needle was controlled with a latero-medial view. If the needle was not in place, it was redirected and also checked with an latero-medial view until it was correctly placed. The CM was then injected and another latero-medial view was taken to see whether the bursa was filled with CM. Holding the leg still in position, the DPr-PaDiO radiographic projection and a palmaroproximal-palmarodistal oblique (PaPr-PaDiO) radiograph on a standard block were made. All radiographs were acquired with a mobile X-ray tube (TR 90/30, Gierth®, Riesa, Germany) and a direct X-ray detector system (Mark 3 Sound-Eklin® Carlsbad, CA, USA or CXDI-801C, Canon®, Tokyo, Japan).
Findings in the DPr-PaDiO CE were a change in dimension of the proximal or distal border, which represents an adhesion formation. The rough shape of the NB might come from a chronic bursitis with hyperproliferation of the synovium. Additionally, there should be no CM abaxial to the border marked by the end of the navicular bone, which would be evidence of a rupture of the NB. A dorsal tendon tear would lead to a long, straight and radiopaque line. Therefore, if there is an irregularity in the surface of the DDFT communicating with the NB, CM would be able to fill the defect in the tendon. A defect in the flexor cortex (cartilage) would manifest as a round, radiopaque area. These lesions are typically roundshaped. An adhesion would be represented by a radiolucent area. As described above, there is a small amount of CM between the navicular bone and the DDFT. If there is an adhesion between those structures mentioned, the dye column will be interrupted. The radiological density of the scar tissue is like soft tissue, therefore, there will be radiolucency.

Results/Observations

Twenty-three legs were injected. The NB was successfully injected only in 20/23 (86.96 %). In the other three legs, the CM was injected completely palmar to the DDFT (Figure 1b). The NB and the DIP were filled with CM in one horse (4.35 %) (Figure 1a). The DPr-PaDiO CE showed alliterations in 7/9 (77.78 %) legs with a clinical history of lameness. There was CM palmar to the DDFT (Figure 1a) and the NB was filled with CM in 5/20 (25.00 %) legs. The findings are summarized in Table 1. There were two DDFT lesions, one full flexor cortex lesion, three suspected ruptures of the NB and five NB adhesions.

Figure 1:

a. There is contrast medium (CM) in the navicular bursa and the distal interphalangeal joint, and some CM palmar to the deep digital flexor tendon (DDFT)
b. The injection of the navicular bursa has failed. The CM is completely palmar to the DDFT.

Table 1: Table 1 shows the information about the horses, results of the injection and radiographic evaluation. + = positive and – = negative, n.a. = not available.

Special Cases

Horse 3 was presented at the hospital because of an acute onset of lameness in the right front two weeks previously. The referring vet made a DPr-PaDiO X-ray. There was a central radiolucent area in the navicular bone that was suspected of being an osseus cystlike lesion (OCLL). The lameness was alleviated by a distal digital nerve block in the clinic. The DPr-PaDiO was repeated and an additional PaPr-PaDiO X-Ray was done. The OCLL was seen again in both views. An intrabursal administration of corticosteroids was recommended and a systemic treatment with bisphosphonates as therapy. The DPr-PaDiO CE radiographs showed a radiopaque area exactly in the middle of the suspected OCLL. The proximal and distal border of the NB also seemed to be very irregular (Figure 2a). The finding could be revealed in the PaPr-PaDiO CE (Figure 2b). The diagnosis was a full thickness flexor cortex lesion including the subchondral bone and bursitis of the NB. The prognosis given was poor. The horse was three month better with the therapy. It was euthanized after three months because of the poor prognosis and the recurrent lameness.

Figure 2: Contrast-enhanced (CE) X-rays of horse 3; lateral is to the left.
a. Dorsoproximal-palmarodistal oblique (DPr-PaDiO) CE view; in the middle of the suspected osseus cyst-like lesion (OCLL) is a round-shaped radiopaque shadow arising from an accumulation of CM at the level of the navicular bone. The proximal border of the NB is very irregular, which is suspected of being a massive adhesion between the collateral sesamoidean ligament (CSL) and the DDFT. There also seems to be an adhesion on the lateral sight of the distal border.
b. DPr-PaDiO CE: the suspected focal pool of CM is in the middle of the navicular bone and, thus, proof of the suspected OCLL. There is an irregularity in the border of the CM medial to the ridge of the navicular bone. This finding is indicative of a lesion in the DDFT.

Horse 11 has a chronic right front limb lameness (3/5). The distal digital nerve block was positive. The radiographs and ultrasound of the tendon in the heel region (not transcuneal) were without significant findings. The owners reported a history of stumbling. Because they did not want to make an MRI, the NB was injected and the additional CE views were obtained. There were several longitudinal (proximo-distal) straight and radiopaque lines in the DPr-PaDiO CE (Figure 3a). The horse was diagnosed with a DDFT tendonitis. Additionally, there was an irregular proximal border of the dye column. The horse was given a poor prognosis for riding but a guarded prognosis for a pasture retirement. A special shoe for DDFT tendonitis was advised. The horse was sound for two months and returned with recurrent lameness after three months. The suspected tendon tear had enlarged enormously (Figure 3b) and was not visible in the ultrasound of the pastern region. The prognosis given was now poor. A neurectomy was performed even with the assessment that the chance was very poor and the tendon tear would be progressive. Three months later the horse was euthanized because of lameness when walking.

Figure 3: CE X-rays of horse 11, right front, lateral is to the left;
a. DPr-PaDiO CE view from May 28, 2019; there are several longitudinal (proximo-distal) straight radiopaque lines at the level of the NB. These lines were identified as dorsal DDFT lesions. The proximal border is very narrow to the proximal end of the navicular bone This seems to be a adhesion between the CSL and DDFT.
b. DPr-PaDiO CE view from August 21, 2019; the same findings as in a) but the lateral lesion of the DDFT has become much larger, reaching proximally an area where it could be easily seen in ultrasonography.

Horse 12 was lame (1-2/5) in the right front limb. After the positive distal digital nerve block with a shift of lameness to the left side and no findings in ultrasound and X-ray, a bursography was performed. The bursography showed an accumulation of CM medial to the navicular bone in both views (Figures 4a & 4b). In the DPr-PaDiO CE view, there was also a little bit of pooling of CM lateral to the ridge of the navicular bone. After the injection, the horse had acute lameness in a few steps (4/5). This lameness was gone after four hours and a single dose of flunixin-meglumin. The horse was diagnosed with a suspected traumatic rupture of the NB. The contralateral limb was also injected and showed no findings. It was given a good prognosis. After eight weeks rest and rehabilitation training, the horse was complete sound. There was a very clear end of the proximal dye column in the lateral and the DPr-PaDiO view (Figures 5a & 5b) in 4/23 (17.39 %) legs compared to the other legs (Figures 5c & 5d). In the lateral view, there was also a radiolucent area in the bursa, which seems to be air from the injection. Therefore, the air presents the proximal border of the NB. Three out of these four legs received 10 mg/1ml triamcinolonacetonide.

Figure 4: CE X-rays of horse 1,2 right front; lateral is to the left
a. The DPr-PaDiO X- ray shows that the proximal border of the NB has two outer pouches with normal invaginations, which represent the normal synovium of the NB. It is nearly the same in the distal border of the NB. Except for the pooling of CM on the medial site of the navicular bone, this seems to be a normal NB. The CM medial to the bursa has to be a small rupture of the NB;
b. The finding is reproducible in the DPr-PaDiO X-ray. In addition, a small pooling of CM lateral to the ridge of the navicular bone is visible

Figure 5:

A. a) DPr-PaDiO X- ray of horse 4; lateral is to the left. This shows a nearly horizontal and smooth proximal border of the CM;
B. b) lateral Image of the same horse as in a). The proximal border is also very sharp and nearly parallel to the ground. There is a radiolucent area in the estimated proximal border of the NB. The CM and the medication (1 ml/10 mg triamcinolone) are arranged in two phases. This makes an evaluation of the proximal border of the NB impossible.
C. c) and d) The same projections of a cadaver limb injected with 3 ml CM without medication. The proximal border has two outer pouches and is round-shaped in the lateral view.

Discussion

The injection of the bursa is a crucial part of treating navicular disease [11]. There has been a lot of discussion about whether it is necessary to inject the bursa because medication of the DIP joint will diffuse to the NB anyway [15,16]. Therefore, whether to inject the bursa or not should be considered every time [17]. There can be a case of DDFT tendonitis after injecting the bursa [18]. If the decision to inject the bursa has been made, a contrast study [12] for a successful injection seems to be necessary. In our study, the success rate in living horses with an X-ray-guided injection was successful in 20/23 (86.96 %) cases, which is nearly the same as that reported previously: 14/17 (82.35 %) [14]. The reason for the difference between 23/25 (92 %) [19] and (96/96) 100 % [13] seems to be the movement of a living horse. The horse is able to move in the time between making the lateral X-ray to check the needle placement and the injection. Even with the foot placed on the block, the lifted leg can fluctuate and the connected movement of the DDFT can move the needle.
The bursography revealed a diagnosis in 6/7 cases. In two cases (horse 3 and 11), the prognosis based on the bursography was correct, even though one of these cases did not show marked alliterations in the radiographs. In these cases, a MRI was not necessary and saved the owner money and stress for the horse. The communication between the NB and the DIP joint, as in horse 1, is also a finding which is perhaps not visible in the MRI. The same applies to the right front leg of horse 12. The rupture of the NB may only be visible in the MRI with CM [20]. The mixture of the CM with another medication could be a problem in evaluating bursographies, as shown in Figure 5. The CM based on iodine had a higher density than other drugs. In addition, it does not seem to be dilutable in other drugs. Therefore, there can be two phases in the bursa: distal the CM and proximal the medication (e.g. triamcinolone), and perhaps air. But no problems seem to occur when mixing the CM with local anesthetics and injecting them into synovial structures [21,22]. One horse in this study developed an acute onset of lameness after the injection. No horse had a septic inflammation. The injection of up to 6 ml in the bursa seems to be safe [20].

This is the first study on the DPr-PaDiO CE in living horses. No validated statistics could be made because of the low number of cases and the absence of a gold standard. The findings were compared with results from cadaver limbs [13]. Further research should be made to ensure these first results. This study shows that the injection of the NB should always be controlled with CM to be sure if the injection was successful. The bursography could lead to a diagnosis, a safer prognosis and a successful control for intrabursal treatment especially in cases where MRI or ultrasound examinations are not possible.

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A New Vision to Efficacy, Comparative Effectiveness and Cost-Effectiveness Research in Nursing

Introduction

Research possesses an important role in nursing practice development which can provide an opportunity to develop new knowledge and improve nursing care [1]. Recently, there is an increased focus on research conducted to compare clinical approaches [2]. Because the results of these studies are more patient-centred and generalizable [3]. Also nursing profession requires knowledge transfer from research to clinic [4] in order to utilize the obtained evidence regarding to implementations and interventions in practice. An important aim of clinical interventions research is to respond health care problems or needs of patients. Which can lead to produce clinical evidence and knowledge by identifying the effectiveness of the desired intervention [5]. However, nursing research activities have fewer focus on development of nursing interventions, while finding effective solutions to patient problems should be the primary motivation of nursing and its research community [5]. Therefore, it is necessary to mention on a more detailed information rather than effectiveness itself, that in which individuals and what circumstances the intervention is effective. Because it can develop clinical knowledge produced by interventions research and increase the level of theoretical knowledge related to different interventions [5].
In this study, two types of research that compares implementations, interventions and nursing cares, are referred to as efficacy and effectiveness research. They are both classified as intervention-based research that determine the impact of an intervention [6]. The two fundamental words of efficacy and effectiveness are different and should not be used mistakenly instead of each other [6]. Therefore, the research question determines the type of efficacy or effectiveness studies [2]. In terms of research design, to determine the impact of an intervention descriptive, correlation or observational designs, and to test the efficacy or effectiveness of an intervention the experimental or semi-experimental research designs are appropriate, respectively [6]. And the most used designs are clinical trials [6,7], which are widely welcomed by researchers, policy makers, stakeholders and journals in comparing clinical approaches. In the meantime, comparative effectiveness research and cost-effectiveness research provide opportunities to make change in health care delivery and improve patient outcomes [8]. Therefore, they can be considered as national health policies and provide the opportunity to identify the best evidence-based interventions which works in their target communities and settings [9]. Because the lack of comparative clinical data on effectiveness, costs of treatment, and care delivery models can be a major challenge in optimizing health care value [8]. The purpose of this study was to determine a new vision to efficacy, comparative effectiveness and cost-effectiveness research in nursing by an integrative review and Delphi technique in combination.

Method

This study was conducted in two phases, an integrated literature review and a Delphi technique to confirm or emphasize on the collected data in the review.

Phase One – Integrative Review

The framework of Whittemore and Knafl [2005] for integrated reviews was used to conduct the review [10]. This approach allows the review to contain diverse primary research methods, thus provides a comprehensive review needed for the topic of interest [10]. The Science Direct, Pub Med and Google Scholar databases were searched from 2000-2021 to identify the primary papers. The PubMed search strategy was ((((“Comparative Effectiveness Research”[Mesh]) OR “Cost-Benefit Analysis”[Mesh]) OR [“Treatment Outcome”[Mesh] OR “Therapeutic Equivalency”[Mesh])) AND “Nursing”[Mesh]). In other databases a full search strategy using the following terms were conducted: effectiveness research/study, comparative effectiveness research/ study, cost-effectiveness research/study, efficacy research/study and nursing/nurse led. Inclusion criteria consisted of any research or paper in the nursing field without methodological limitations about efficacy, comparative effectiveness, and cost-effectiveness research, with full text access in English or Persian. To access more papers and keep the maximum amount of data available, the publication time limit was not considered. Critical Appraisal Skills Program checklists were used to assess the quality of included papers [11] for their trustworthiness, relevance and results [12].
Papers were excluded if they were conducted using efficacy or effectiveness methods or a review of studies conducted with these methods, did not explicitly mention their use of these methods, and if they did not address the features of these types of research. The initial search result included 17096 papers and 6 additional records from other sources. Sixty-seven duplicate papers were removed. One of the authors screened the title and abstract of remaining 17033 papers based on inclusion criteria and excluded 16460 papers as irrelevant, abstract only, and inadequate quality. A review full text for eligibility resulted in 548 more excluded papers and 3 papers that were removed following critical appraisal. The outcomes were discussed with other authors at any stage and there was a full agreement with no conflict between them. Finally, 24 papers met the eligibility criteria to include in the integrative review that all were published in English (Figure 1).

Figure 1: The most feasible position of fetoscope.

Phase Two – Delphi Technique

As review conducted, a summary of the interested research definitions was prepared and a questionnaire consisting of 10 questions was designed to ask nursing experts about efficacy and effectiveness studies using Delphi technique. The Delphi technique was used to collect a variety of data from nursing experts who were distanced and dispersed throughout Iran, whose perspective to research was very important due to their familiarity with a variety of research methodologies used in nursing studies. Nursing experts including editors in chief of nursing journals and research assistants of their nursing schools were the research population. The list of “Medical Journal Commission” of Iran was used to obtain the nursing journals which resulted in 31 journals. The email addresses of the 3 journals were invalid, so 28 journals were listed. The email address of the editors and research assistants were also searched separately. Finally, 27 editors in chief and 21 research assistants were directly enrolled in the study. Based on snowball sampling method, two international nursing experts with high citation rates who were introduced by one of the participants were included, too. Because the number of nursing experts was limited, all individuals in the research population including a total number of 50 people enrolled in the study. The questionnaire was sent to the journals in two occasions and once directly to editors in chief, the research assistants and two international nursing experts, respectively. The results of Delphi technique were used to confirm or emphasize on extracted data from integrated review of literatures.

Results

Phase one: Integrative Review

A total of 24 papers were enrolled in the review including articles, editorials and reports, published in English between 2000 to 2021. The Federal Coordinating Council [FCC] [13] and Institute of Medicine of The National Academies [IOM] [14] reports both were published in 2009. Also, the American Recovery and Reinvestment Act [ARRA] of 2009 and the patient protection and Affordable Care Act [ACA] of 2010 have increased the considerations to comparative effectiveness type studies widely [15], Which resulted in more research conducted in effectiveness scope since 2009. In this integrative review findings are presented based on the research area, objectives, application, significant features, appropriate/ common research design, and the study classification in two tables. (Table 1) [ 6-7,16-18] indicates a comparison of efficacy and effectiveness studies. (Table 1) [ 6-7,16-18] Also considering two types of studies in effectiveness research scope that can play an important role in determining health policies at national levels, (Table 2) [6-9,13-14,19-32] presents comparative effectiveness and cost-effectiveness studies separately.

Table 1: A comparison of Efficacy and Effectiveness Studies.

Table 2: Comparative Effectiveness and Cost-Effectiveness Studies.

Phase Two: Delphi Study

A total of 7 nursing experts [14%] participated in this study, including 5 editors in chief, 1 managing editor and 1 executive manager. In spite of follow-ups, other experts did not reply to the e-mails which was justified by the coincidence of data collection period with the second semester’s examinations and the limited time of study duration. Therefore, outcomes of the conducted single round Delphi, which resulted in mindful comments and answers of participated experts, was used to confirm or emphasize on extracted data from integrated review of literatures. The Delphi phase data are classified in 6 finding areas about Efficacy, Comparative Effectiveness and Cost-Effectiveness research.

Knowledge of Experts About Efficacy, Comparative Effectiveness and Cost-Effectiveness Research

The methodology of these three studies is not mentioned explicitly in the curriculum and are not taught in detail, which results in poor knowledge and awareness of students, faculty members and nursing experts about differences and the nature of these studies (Participants No. 6 and 7). “… This lack of knowledge represents a training deficiency for nurses, journals and even the teachers …” (P.No. 6). On the other hand, the general information of individuals indicates that all three types of research usually take quantitative methods (P.No. 5) and are often conducted as a trial which assesses an impact, so differentiation between them may be difficult ([P.No. 2). Therefore, if the type of study was not explicitly mentioned, regard to the title or inappropriate use of vocabulary due to assessing the impact of an intervention or care, it may mistakenly be considered as effectiveness and usually comparative form of studies, while the underlying nature of the study is efficacy (P.No. 6 and 7).

Perspectives of Experts on Efficiency Studies, Comparative Effectiveness and Cost-Effectiveness Research

Considering the fact that nursing is an evidence-based discipline, and all of these three studies play an important role in evidence production, there should be a focus on the studies providing opportunities to produce accurate evidence in a comparative effectiveness or cost-effectiveness manner (P.No. 1, 2, 3 and 6). These studies possess high importance and offer applicable solutions as appreciated and valuable evidence that is capable of implementing an intervention with comparative accuracy and lower cost (P.No. 2 and 4).

Ideology of Experts About Nursing Research Priorities

Demonstrating the cost-effectiveness or cost-effectiveness of nursing, especially registered nursing is an imperative (P.No. 5, 6 and 7). Efficacy, comparative effectiveness, cost-effectiveness, or cost benefit of different implementations, interventions and nursing cares are appropriate priorities for nursing research (P.No. 1). Also, nursing beyond the acute care seems necessary (P.No. 5). Therefore, a wide range of actions can be mentioned for research conductions. For example, music therapy, heat/cold therapy, mental imagery, massage, etc. and comparing modern and traditional practices are notable (P.No. 1 and 2).

Perspectives of Experts on Obstacles and Strategies in Conducting Effectiveness Research

Effectiveness studies have considered throughout the world alongside efficacy studies (P.No. 5), but in Iran, despite the wide range of feasible research methods, yet they are not considered enough (P.No. 2), Which results due to the existing obstacles leading to obscurity and limited conducting of effectiveness studies, or even insufficient quality of conducted studies (P.No. 1). The mentioned obstacles, included lack of participation or inadequate power of nurses in healthcare policymaking (P.No. 3 and 6), inter and intradisciplinary conflicts or lack of cooperation (P.No. 1), unknown influence of journals and editors on research (P.No. 6), research criticizing efficaciously by stringent controls (P.No. 6 and 7), lack of research outcomes influencing the practice (P.No. 1), staff shortage either faculty members or clinical nurses (P.No. 3)and financial and time limitations (P.No. 1). “… In many medical universities, the lack of appropriate funding and, more importantly, the lack of time lead to less tendencies to conduct these types of studies timeconsuming studies. … Faculty members are busy with educational duties, so they do not have enough time to conduct these studies or because of the academic years increase in postgraduate students, such studies are not welcomed by colleagues or students. (P.No. 1).” The suggested strategies to reduce the existing obstacles, included providing clinical nursing specialties, Doctor of Nursing practice [DNP] and nurse practitioners, to achieve more power and position in healthcare (P.No. 2), making interests on studying health management alongside clinical services (P.No. 3) and providing information and support among colleagues (P.No. 1 and 4),

Ideology of Experts about Motivating Factors to Conduct Effectiveness Studies

In order to motivate nursing researchers to conduct effectiveness studies, it was recommended as necessary to increase the level of professional independence in nursing and raise the interdisciplinary coordination and partnership, which requires time and effort for nursing to reach its main position (P.No. 1 and 2). Other mentioned motivators included providing enough time and budget (P.No. 1), receiving support and information from colleagues (P.No. 1 and 4), more training in health economics and better collaboration with health economists [P.No. 5 and 7], and leading research projects and theses to effectiveness methodologies by nursing professors to make the administration context managerially (P.No. 3). “I think these studies would be suitable for PhD level study not undergraduate and masters as they will take a long time and require expertise and training not available at undergraduate level (P.No. 5).” The importance of effectiveness research could be identified by the implementation of the theses (P.No. 1-7). Also training workshops (P.No. 4) and qualitative methods (P.No. 2), emphasized on theses conductions. Despite this importance, research projects with more feasibility and less time limitations could make better research outcomes in effectiveness scope (P.No. 3).

The Role and Importance of Effectiveness Studies in Nursing Professional Development

Initially nursing professional development needs to be studied more and deeply (P.No. 4). In spite of this necessity, conducting effectiveness studies, can lead to nursing professional development if their outcomes are used in practice to solve nursing care problems (P.No. 1). These projects improve the quality of nursing care, which is the main fundamental feature of service providing professions such as nursing (P.No. 3, 6 and 7). Otherwise conducting effectiveness studies because of their possible distinctions or compulsory being, without interest and lack of adequate regulatory standard monitoring systems, reduces the motivation to use the results in practice (P.No. 1), Which is modified by ethical considerations, creation of advisory groups in health centres for researchers and assessment of clinical trials conducting process that can increase the quality of studies (P.No. 1). On the other hand, it should be noticed that effectiveness may be well represented, but there is a threat about weak point of alternative models which tends to need further exploration and search despite the proven positive results (P.No. 5).

Conducting such studies can express the profession, especially if they are published in valid journals (P.No. 2). Definitely there is no limitation for effective studies publication if they are conducted in a high quality with powerful research designs and well reported (P.No. 1-7). Among these three types of research, it seems that comparative effectiveness is preferable because of tangible evidence production, but the quality of study determines the publication priorities than methodology itself (P.No. 1-4). Publishing these types of strong studies in Iranian nursing journals can validate them, too (P.No. 4). Therefore, conducting more powerful studies by nursing professors can provide an opportunity to improve clinical conditions and create science production settings over time (P.No. 6 and 7).

Discussion

This study was conducted to determine a new vision to efficacy, comparative effectiveness and cost-effectiveness research in nursing. For this purpose, an integrative review in combination with Delphi technique was conducted. The emphasized and important role of efficacy and effectiveness research in producing clinical evidence [6,13,14,16,17], mentioned by nursing experts, considers the evidence-based nursing values. So, it is an imperative to transfer knowledge and evidence to practice [4], which results in leading the research to real practice settings as clinical outcomes research. Other possible results include making strong and reliable evidence, conducting any type of research considering the needed priorities for each nation based on health policies and validating the existing body of knowledge or making new knowledge infrastructures. The integrative review indicated that evidence made by efficacy; comparative effectiveness and cost-effectiveness research are complementary to each other, so more training workshops are needed to make theoretical sensibilities in nursing research. The efficacious intervention in an Ideal, selective and controlled setting [6,16,17] should be translated to a real-world setting to prove their effectiveness [6,13,14,16,17] in comparison to the routine care [8,13,14,16,31] in real community populations [13,14,16] with the least possible exclusion criteria [17]. This is a research process to confirm evidence and make them applicable in nursing practice as evidence-based nursing cares.
The patient-centred evidence resulted from comparative effectiveness research [3,16,21,22,25] can increase the cost, because it considers the effectiveness independently without noticing its costs [19]. While increased costs of healthcare services which results in financial burden for both patients and their families and the government itself, makes the healthcare policies to determine effective evidence with lower costs; that is also mentioned by nursing experts. So, using cost-effectiveness analysis is indeed to reduce the healthcare costs [7,19,31]. But the usefulness of comparative effectiveness research is agreed [15], and in serious diseases even cost-effectiveness research recommend the effective intervention without considering its costs while this is vice versa in less serious diseases and costs of intervention is prior to their effectiveness [19]. So, everything about making clinical evidence depends on the purpose of researcher and existing policies, also efforts on nursing professional development with increased influencing power on healthcare policies are noticeable. Nursing profession as an independent discipline needs its own strong body of knowledge. As expectations increase for comparative effectiveness research, more gaps appear in body of knowledge and research infrastructures that should be addressed in order to achieve informed decisions and better outcomes [14]. But despite the increased use of this patientcentred research method, controlled trials are more published [33] while the clinical outcome research can provide a stronger body of knowledge in nursing [2,6]. Also nursing experts claimed that there are a lot of gaps in nursing, but the existing obstacles fetter these studies. In order to modify the research obstacles, it is necessary to introduce methodologies in detail, which will motivate the faculty members, researchers and students conduct more patient-centred research to make strong body of knowledge for nursing. Therefore, there is a need for standard rules and monitoring systems to conduct high quality studies. Moreover, the effort to strengthen the nursing profession tends to take part in healthcare policy making. Generally determining that which evidence-based intervention, in whom and where is more effective [9], needs more patient involvement in the study [21], according to the community drive, healthcare policies and stakeholders’ penetration [9]. And it totally is dependent to the purpose of knowledge translation to practice, because inter and intra-disciplinary collaborations guarantee the research support, funding and evidence-based nursing practice. Yet the least information of nursing experts about the existing differences between efficacy, comparative effectiveness and costeffectiveness research is a challenging issue. And it is still possible to use these two words mistakenly [6]. Therefore, providing information especially for faculty members and nursing journals is so imperative.

Limitations

The study limitations include lack of access to some databases, limited access to full text of all papers, failure to achieve sufficient with methodological-focused approaches especially in efficacy scope and emerging effectiveness studies in health and nursing in recent decade since 2009. In order to reduce the impact of limitations abstract only papers were reviewed, to prepare their full text if they were appropriate to be enrolled in the integrative review, but none met the eligibility criteria. Instead, the editorials and reports which emphasized on methodologies enrolled to the review.

Conclusion

The efficacy and effectiveness research are important in producing complementary evidence to improve patient care outcomes. Recently, due to the need for comprehensive and accurate information to be more applicable in clinical practice, comparative effectiveness research is more considered and seems to be more important across the world. The effectiveness outcomes origin in the real clinical practice settings and can be extracted using diverse study designs depended on research question and aims. Therefore, the efficacious implementations or interventions should be studied for their effectiveness in real-world settings to become applicable. The obtained evidence needs to be reviewed to make a body of knowledge. The health policies should provide opportunities to test the new knowledge in implementation research in practice. The main conclusion of completing this research process leads to reduce the gap between theory and practice in nursing and its professional development. In spite of the increased consideration to effectiveness research, both in terms of comparative effectiveness and cost-effectiveness, still efficacy studies are more welcomed than effectiveness studies in Iran which demonstrates a controlled impact of an intervention in an ideal setting which is not necessarily applicable in real-world settings. But according to the economic constraints and the high costs of health services, cost-effectiveness studies are increasingly considered in Iran; because costeffectiveness research, determines both costs and effectiveness of two or more interventions correspondingly.

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Effects of Low Electromagnetic Waves on Thymus Size, Testis and Body Weight and Therapeutic Role of Vitamin C in Mice

Introduction

During last years, increased use of devices producing electromagnetic wave, has attracted researcher’s attention to possible effects of them on human health. Electromagnetic waves have different shapes, they are classified according to their frequencies and wavelength [1]. Today, effects of electromagnetic waves with low frequency (ELF) have been attracted researcher’s attention [2,3]. Electromagnetic waves with different intensities influence on prevalence of embryo evolution disorders, infertility, neuronal/sleep disorders, gastro-intestinal, heart disorders and several neoplasms including hematopoietic, lymphoma [4,5]. Thymus is behind of sternum between lungs, often it contains 2 parts. Each part of thymus is divided to smaller parts. Cortex contains compacted lymphocytes. Medulla constructed from sporadic epithelial and lymphocytes. Epithelial cells in thymus produce its hormones, possibly it incorporates in T lymphocyte evolution; however, its effect is not clear. Thymus is large in childhood but during growth it will be replaced by connective and adipose tissues. During maturation, thymus will be smaller, but it incorporates in T cell evolution. Thymus produces many hormones like thymosin, thymic humoral factor, thymopoietin, mentioned hormones induce proliferation and differentiation of T cells. Some evidence reveals that thymus hormones can delay aging [6].
Testis produces hormones and spermatozoon. Testes are wrapped by tunica albuginea. Tunica albuginea thickens at posterior of testis and constructs mediastinum which is a fibrous connective tissue diffuses to gland and divides it to pyramid structures called testis lobules. These walls are not complete, often there are connections between them. Each lobule contains 1-4 seminiferous tubules. They locate in a fragile connective membrane which is full of blood vessels, lymphocytes, neurons and leydig cells. Seminiferous tubules produce male reproductive cells, spermatozoon. While leydig cells produce androgenic hormones, sperms are produced in seminiferous tubules. Seminiferous tubules are connective tissues contain a basal and a germ epithelial layers. Fibrous tunica properia encompasses seminiferous tubules and has several fibroblast layers. Innermost layer attached to basal layer is constructed from semi-muscular flat cells. These cells function as smooth muscles. Leydig cells occupy most part of space between seminiferous tubules. Epithelial seminiferous tissue has 2 cells; sertoli or supportive cells and cells which construct spermatogene antecedent cells. Spermatogene antecedent cells are distributed in 4-8 layers, they produce spermatozoids. Process of producing spermatozoids is called spermatogenesis. This includes cells divisions via mitosis/meiosis and final differentiation of spermatozoids which is called spermiogenesis [7].
Vitamin C or L-ascorbate is a vital micronutrient for many species like human, monkeys and few number of other mammals, especially guinea pigs and some bird/fish species. Amount of vitamin C is a critical index for commercial value of fruits and vegetables. Vitamin C is a solid, white, water soluble, safe component which has s circular ester, it is hydrolyzed in aqueous medium and convert to acid [8]. This vitamin which attacks to electrons in body reactions, is most important antioxidant in neutralizing free radicals and inhibiting oxidative stress [9]. Antioxidant mechanism of action: free radical/reactive oxygen species production is an inevitable issue in metabolism process. These compounds because of high potential in damaging biological macro molecules like fats, DNAs function as major agents of ageing and cause several diseases. Organisms have various mechanisms to defend and neutralize these reactive species including defensive anti-oxidant immune systems. These systems have enzymes like superoxide dismutase, catalase. Glutathione peroxidase and macro molecules like albumin, ceruloplasmin, ferritin and micro molecules like carotene, alphatocopherol, ascorbate, methionine, uric acid, bilirubin, and reduced glutathione (GSH) [10].
There are several reports about role of this vitamin in prevention DNA damages and occurrence cancer or heart diseases [11]. Large amount of vitamin C aggregates in ovaries and other endocrine tissues. In ovaries, vitamin C aggregation occurs in granulosa, luteal and theca cells, these cells relate closely to fertility. Studies on luteal granulosa cells demonstrated that vitamin C can increase progesterone production/concentration [12]. this relation is strong negative feedback, where high levels of progesterone reduces vitamin C concentration and its metabolism is inhibited [9]. Fritze, et al. [13] exposed rats to 900 Hz electromagnetic waves, they observed that these waves increased Hsp7z mRNA replication at brain cortex [13]. In Louis studies, pregnant CD-1 mice exposed to 2.45 GHz waves for 100 minutes from 1-17 pregnancy days, rats were dissected at 18th day and their embryos were evaluated in terms of disorders. Results showed that weight of experimental embryos was less than control [14]. In another study, few Spagu- Dawley rats were exposed to microwaves from 6-20 pregnancy day. Weight of test group was less that control [15].
Occonnor exposed mice to 2450 MHz and found that weight of embryos was reduced significantly because of maternal thermal stress [16]. Kolomiytseva, et al. [17] investigated muridae, they reported that unionizing electromagnetic waves caused lipid storage in adipose tissue and weight gain. Results of several studies on different effects of electromagnetic waves reveal that change of field intensity, even milli tesla has various biological effects, therefore investigation on electromagnetic effects can be done in very wide range [18]. In this research, amount of these effects on biomass, thymus, testis and therapeutic role of vitamin C in improvement of changes caused by electromagnetic field, have been studied.

Material and Methods

This experiment was done in research electrophysiology laboratory of biochemistry-biophysics department of Mashhad Azad University. In order to evaluate effects of 50 Hz electromagnetic waves on biomass, testis, thymus and therapeutic effect of vitamin C on mature male mice, 3-2.5 month Balb/C mice with average weight 20-25 grams were used. Mature mice have been stored in animal room with 60-70% humidity, 23±1 centigrade temperature and 12 hours light/12 hours overnight. Room light was adjusted alternatively by automatic electrical timer and temperature was controlled by radiators and cooler at winter and summer respectively. Cages were cleansed every other day. For smoothness of cage, wood chips were used. Mice feed was special prepared pellets (Khorasan Javaneh dam company), water delivered by flasks. Mice were purchased from Razi Vaccine and Serum research Institute of Mashhad, for being adapted with new environment and eliminating stress of changing environment, mice were kept one week in animal room before experiment. Electromagnetic producing machine includes 35 cm diameter and 60 cm length PVC tube equipped with 1900 copper coils which coiled 3 times around tube. This machine could produce 0.5-4 mT/25-100 Hz electromagnetic field. In order to evaluate therapeutic role of vitamin C, commercial 250 Osveh vitamin C tablets (chewable scored tablets) were used. In order to inject tablet, it was dissolved in 50 cc physiologic serum. Intraprotaneal vitamin C was injected by disposable syringe.
Study groups in this 15 day research were 15 day old ( 24 mature 2.5-3 month mice) distributed in 3 groups:
1) Control: 8 mice stored in animal room with normal conditions,
2) Exposed to electromagnetic waves group: in this group, 8 mice exposed to 50 Hz/4 mT electromagnetic waves for 15 days, 4 hours per day(12-16 hours),
3) Exposed to electromagnetic waves receiving vitamin C: in this group, 8 mice exposed to 50 Hz/4 mT electromagnetic waves for 15 days whom were treated with 0.5 cc intra protaneal vitamin C 7 times. This injection was done weekly, 3 times per week. During experiment, mice were weighted 3 times weekly by 0.01 resolution scale and their weights noted. In order to be sure about weighting, this process repeated 3 times. After required time, mice were anesthetized by chloroform, following careful dissection, organs splited over. Then these organs exposed to physiologic serum for 3 seconds, dried on paper for 3 seconds. Organs were located separately on glass to weight. Statistical analysis was done by Spss16 and plots were illustrated by Excel. Data were represented by mean±SEM. Comparison between control and test was done by statistical T-test and P˂0.05 was considered statistical significant difference (Figures 1-4).

Figure 1: Weighing of mice.

Figure 2: Dissection of mice.

Figure 3: Weighing mice organs.

Figure 4: Intra-protaneal vitamin C injection.

Results

Evaluation of Thymus Weight

Mean weight of thymus in control group is 0.055 ±0.0120 and in exposed electromagnetic fields is 0.115±0.0066, there is significant difference P˂0.01 between them. Mean weight of thymus in exposed electromagnetic receiving vitamin C group is 0.0131±0.0081 which is not significant difference to exposed field group.
• Diagram 1: comparison weight of thymus between control, electromagnetic field exposed and electromagnetic field exposed receiving vitamin C groups.
++ refers to significant difference between control and electromagnetic field exposed groups with P˂0.01.
NS refers to un-significant statistical difference (Figure 5).

Figure 5: Evaluation of thymus weight.

Evaluation of Testis Weight

Mean weight of testis in control group is 0.0916 ±0.0079 and in exposed electromagnetic fields is 0.045±0.0104, there is significant difference P˂0.01 between them. Mean weight of testis in exposed electromagnetic receiving vitamin C group is 0.068±0.0102 which is not significant difference to exposed field group.
• Diagram 2: comparison weight of testis between control, electromagnetic field exposed and electromagnetic field exposed receiving vitamin C groups.
++ refers to significant difference between control and electromagnetic field exposed groups with P˂0.01.
NS refers to un-significant statistical difference (Figure 6).

Figure 6: Evaluation of testis weight.

Evaluation of Body Weight

Mean weight of body in control group is 33.615±0.8700 and in exposed electromagnetic fields is 23.542±0.4068, there is significant difference P˂0.001 between them. Mean weight of testis in exposed electromagnetic receiving vitamin C group is 26.422±0.8551 which is significant difference to exposed field group with P˂0.05.
• Diagram 3: comparison weight of body between control, electromagnetic field exposed and electromagnetic field exposed receiving vitamin C groups.
++ refers to significant difference between control and electromagnetic field exposed groups with P˂0.001.
*refers to significant statistical difference between electromagnetic field exposed and electromagnetic field Balb/c male mice exposed receiving vitamin C groups with P˂0.05 (Figure 7).

Figure 7: Evaluation of body weight.

Discussion and Conclusion

Analysis the Results of 50 Hz/4 Mt Electromagnetic Wave Effects on Thymus Weight of Mature Balb/C Male Mice

According to this research, 50 Hz/4 mT electromagnetic waves reduce thymus weight of mature Balb/C male mice which shows significant relation.

Analysis the Results of 50 Hz/4 mT Electromagnetic Effects on Thymus Weight of Mature Male Balb/C Mice Receiving Vitamin C

According to this research, 50 Hz/4 mT electromagnetic waves did not change signifantly thymus weight of mature male Balb/C mice receiving vitamin C.

Analysis the Results of 50 Hz/4 mT Electromagnetic Wave Effects on Testis Weight of Mature Balb/C Male Mice

According to this research, 50 Hz/4 mT electromagnetic waves reduce testis weight of mature Balb/C male mice which shows significant relation. Studies on total weight of testis and epididymis showed significant weight reduction after exposure to electromagnetic field which is in agreement with current study and reveals the discharge of sperms at seminiferous tubules or epididymis; because a semi-muscular layer surrounds seminiferous layer in mice which has erectile property. Electromagnetic waves produce electrical current in animal body, this current changes cellular function directly/indirectly, therefore contraction/sperm discharge will be increased. In addition, local secretion of oxytocin after exposure to electromagnetic waves has been demonstrated. This protein factor increases contractile property in seminiferous tubules [19].

Analysis the Results of 50 Hz/4 mT Electromagnetic Effects on Testis Weight of Mature Male Balb/C Mice Receiving Vitamin C

According to this research, 50 Hz/4 mT electromagnetic waves did not change signifantly testis weight of mature male Balb/C mice receiving vitamin C.

Analysis the Results of 50 Hz/4 mT Electromagnetic Wave Effects on Body Weight of Mature Balb/C Male Mice

According to this research, 50 Hz/4 mT electromagnetic waves reduce body weight of mature Balb/C male mice which shows significant relation.
In Louis experiments, CD-1 pregnant mice were exposed to 2/45 GHz waves from 1-17 day of pregnancy for 100 min/day, they were dissected at 18th day and fetus were analyzed in terms of abnormalities. Louis results showed that experimental fetus weight was lower than control [20]. In another study, few Spagu- Dawley rats were exposed to microwaves from 6-20 pregnancy day. Weight of test group was less that control [21]. Occonnor exposed mice to 2450 MHz and found that weight of embryos was reduced significantly because of maternal thermal stress [22]. Some researchers investigated neonate weight of female physiotherapists and concluded that their weights were less than control. They also explained thermal stress of electromagnetic waves for this weight reduction, increased temperature not only kills fetus but also delays fetus development. This phenomenon explains less weight of test neonates than control in mentioned study [23].
Dasdage, et al. [24] investigated mobile phone waves on rats which showed decreased weight of exposed fetus [24]. In another study, invertebrate embryos exposed to low frequency electromagnetic waves lowered fertility in females and inhibited embryo development at bi cellular phase [25]. In another study, it was reported that exposure of embryonic cells to electromagnetic waves decreased cell cleavage and in harsh cases, stopped cleavage, the reason was chromosomal damage induction by electromagnetic waves [26]. It was reported that exposure of Inner Cell Mass to electromagnetic waves inhibited mitosis and pluripotency in these cells. Reason of this was free radical production in these cells [27]. mIn study by Rahbarian and Sadughy, it was demonstrated that development percentage of fetus exposed daily to 50 Hz and 200 Gauss electromagnetic waves was reduced significantly in comparison to fetus exposed to 10 Gauss waves [28].
Balanejad reported inhibitory effects of low frequency electromagnetic waves with 400 Gauss intensity on angiogenesis at chorioallantotic membrane of chick embryo. Balanejad believes that high intensity electromagnetic waves can reduce weight of chick embryo in early phases of growth [29]. Huuskonen claimed that exposure of pregnant wistar rats to low frequency electromagnetic waves leads to sever body weight and occur of abnormality in motor organs, in addition, high intensities lead to mortality of rats [30]. Canseven exposed embryonic cells of guinea pigs to 50 Hz with1,2,3 T electromagnetic waves for 5 days (4 to 8 hours/day) and investigated their development. Results showed that electromagnetic radiation degenerated embryonic cells by DNA damage, influencing on membrane enzymes and changing its permeability [31]. Cieslar studied development phases of embryonic heart cells of rats (in vitro) exposed to 50 Hz with 78.3 Gauss electromagnetic waves for 30 minutes. Results showed that length, diameter and size of heart in samples exposed directly to electromagnetic waves decreased significantly in comparison to control [32].
In a study Valles showed that low frequency/high intensity electromagnetic waves could affect cell cleavage and mitotic spindle orientation, even they could inhibit cell division by damaging mitotic spindles [33]. Low frequency electromagnetic waves decrease adrenal weight and inhibit sympatho-adneral system in hypertension rats [34]. According to Jelodar and Beizai studies, leakage waves of microwave oven reduced growth, increased T3, T4, cortisol, triglyceride and HDL levels [35].

Analysis the Results of 50 Hz/4 mT Electromagnetic Effects on Body Weight of Mature Male Balb/C Mice Receiving Vitamin C

According to this research, 50 Hz/4 mT electromagnetic waves increase body weight of mature Balb/C male mice which shows significant relation.

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What is the Level of Awareness of Novel Coronavirus (SARS-CoV-2) Among Greek Students in the Days of School Reopening?

Introduction

Severe acute respiratory syndrome due to coronavirus 2 (SARSCoV- 2) and the resultant coronavirus disease 2019 (COVID-19) has raised worldwide health concern since December 2019. As of March 11th, 2020, the World Health Organization (WHO) characterized it as a pandemic [1]. Governments all over the world have taken actions to minimize the risk of infection and the spread of the virus [2]. In the context of the social distancing strategies, schools, universities and colleges have closed, in a nationwide or local basis in 190 countries, affecting approximately 73.5% of the world’s student population [3]. Being on the same wavelength, and based on evidence and assumptions from influenza outbreaks that school closures reduce social contacts between students and therefore interrupt transmission, the Greek authorities took the decision to also implement this measure [4]. However, as Greece was highlighted among the countries with the less cases and victims from COVID-19, this measure was taken back and the schools were reopened for the last class of high school in May 4th and one week later for secondary and the rest of the classes of high school. This descriptive study aimed to determine the level of information about the COVID-19 among students of Athens, aged 13 to 18 years. More specifically, we attempted to assess the level of knowledge, as well as their preparedness and ability to react efficiently during the pandemic.

Methods

Study Design and Sample

The study was conducted in schools of Athens Area, with a total population of 3,74 million people. The study was approved by the Hospital ethics committee and executed in accordance with the Declaration of Helsinki (1989). Inclusion criteria were voluntary involvement of students living in the Attika area. Common exclusion criteria include the presence of a severe and uncorrectable cognitive, visual, or hearing impairment that would preclude a participant’s ability to complete interviews. Participants were not required to record their personal details, nor to answer all questions in the questionnaire. Data were collected from 13 through 20 March 2020. Surveys took less than 10 minutes. In total, 1200 students aged 13 to 18 years were selected, sub-divided in two groups, 13-15 years old and 16-18years old, respectively

Questionnaire

Survey items were adapted from questionnaires used to study prior outbreaks [5,6]. The questionnaire consisted of 12 items (9 dichotomous questions, and 3 multiple choice) designed to assess students’ knowledge of SARS-CoV-2 characteristics, for example: What is COVID-19? How is COVID-19 transmitted? Which are the symptoms and the protection measures? What is the quarantine? Is there a vaccine? Has there ever been a COVID-19 case in Greece?

Statistical Analysis

Categorical variables were presented as a percentile. Descriptive statistics were calculated for all participant characteristics and survey responses and were presented as valid percentages and as numerical values were appropriate. The chi square test was used to determine statistically significant differences among subgroups of the study’s participants. A p value <0.05 was considered as statistically significant. SPSS 24 for Windows (SPSS 23 Armonk, NY: IBM Corp) was used for the analysis.

Results

General Knowledge about SARS-CoV2

From the total group of 1,200 teenagers aged between 13 and 18 years, 658 (54,8%) were female. Among the participants, 1,044 (87%) knew what the coronavirus is, and 744 (62%) were aware that the outbreak began from China. When the survey was conducted, the virus had spread to all regions of Italy, while on March 12th the first victim was reported in Greece. Therefore, when participants were asked if the virus had infected people in Europe and Greece, 79,5% and 74,7% respectively, answered positively. Interestingly, most of the responders (85%) were informed by their families or teachers; only 180 of the students (15%) said that the source of their information about COVID-19 was media and the web.

Symptoms and Transmission of Covid-19

Study participants were asked about the symptoms of COVID-19; 774 (64,5%) said the symptoms are similar to those of a common cold-like illness, while 198 (16%) were unaware. Regarding the ways of transmission 54,1% of them answered through coughing and human contact while 15,9% of them were not aware. On average one third of responders (30,5%) claimed that there is no need for an urgent visit at the hospital if someone is suspected to be infected by the SARS-CoV-2.

Awareness of Ways of Protection

The study aimed to determine how informed students were about protection measures. Of note, only 66 (5,5%) and 138 (11,5%) recognized the social distancing and avoidance of contacts as effective precaution measures, respectively. More than half of them (53%) answered that hand washing should be followed. Interestingly, nearly one third agreed that all the above-mentioned measures should be applied by general population to avoid the spread of the disease. Furthermore, only 222 (18,5%) of the participants knew what quarantine is; 390 (32,5%) claimed that there is no need for a mask if the person is not infected. Regarding whether an effective vaccine exists, 330 (27,5%) reported falsely that a vaccine already exists. (Table 1) summarizes respondents’ estimations according to their age group.

Table 1: Knowledge level of participants about COVID-19.

Data Stratified According to Sex or Age

After multivariable adjustment, male subjects were more aware that COVID-19 has been come to Greece (78% vs. 71%, p=0.01). Older students were more aware that COVID-19 has come to Greece compared to younger ones (82% vs. 67%, p=0.01), while they were also aware that if they are suspected of having the disease there is no need to go immediately to hospital (73% vs. 66%, p=0.01). Nevertheless, the younger compared to older students were more informed that no vaccine exists (79% vs. 66%, p<0.001) and that the mask should be applied even if the person has not the disease (36% vs. 29%, p<0.01) (Figure 1).

Figure 1.

Discussion

In a survey of more than 1,200 sociodemographically diverse teenagers, we found that most respondents perceived that they have heard of the coronavirus (COVID-19). However, many are not properly aware about the symptoms and the ways of protection; the one forth could not identify symptoms and almost the one third were totally informed about the proper prevention measures. Another critical point is the use of mask by healthy individuals as two thirds answered that is not necessary. That facts may reflect the blurred image given by the experts regarding the use of the mask. In our study, disparities by sex and age were presented. During the pandemic, Greece managed to react early and effectively. The number of the cases (2,892) and the victims (173) rank Greece in 78th position [7]; international mass media praise Greece’s handling of outbreak as a surprising success story. As a consequence, from the beginning of May, most activities gradually return to normal, employees go back to work, various public restrictions ceased, bar and restaurant reopened. Whilst pandemic globally exists, Greek government outweighing the benefits for children’s education and mental health, decided to reopen schools in 7th September. Several studies of COVID-19 hint that children are less likely to catch the novel coronavirus, and they don’t often transmit it to others [8,9]. Relying on those encouraging data and the reassuring knowledge that very few children get severely ill from COVID-19 other governments, amongst then Denmark, Germany and Israel have already reopened schools.
The measures are tentative as most schools are resuming with reduced class sizes, shortened school days, and extra handwashing, while spots, which outbid about social distancing are flooding the media. However, some scientists worry about the risks, as even if the possibilities of transmission are low, the web of contacts makes the tracking process difficult. Our study, working to quickly capture the opportunity to investigate the level of awareness in teenagers, has clear limitations. First, the survey was conducted among a selected group of students only in the Attika region. Therefore, there is no knowledge how semi-urban and rural areas are informed regarding coronavirus. However, our study samples purposefully include girls and boys from schools socioeconomically diverse. Prior research on virus outbreaks guided our selection and creation of survey items [5,6]. However, items followed best practices for the design of assessments for use among persons with lower literacy [10]. Third, our outcomes capture only initial awareness of COVID-19, fundamental knowledge, attitudes, and a limited set of behaviors. However, understanding of the virus has since quiete evolved, and we could not expand on those developments. Items included in planned follow-up waves of the survey will adapt accordingly. Finally, public health messages about new policies and restrictions dramatically change day to day. Regardless, our findings depict the initial lack of clarity in understanding and perceived susceptibility, among teenagers regarding pandemic. Bearing in mind our findings, actions and cooperation are needed amongst local authorities, health boards, trade unions, public health, disease control experts, and schools, to ensure that as long as the pandemic exists, all teenagers are adequately made aware of the gravity of the threat.

Conclusion

The level of information about COVID-19 among Greek students aged 13 to 18 years was found to be not ideal but adequate. Although the students were found informed on some aspects, they were unfamiliar with other important issues. In the light of a potential second wave of COVID-19 pandemic, our findings highlight the need for intensified health education programs in Greek schools in order to deal with this serious emerging health problem.

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Experimental Cerebral Ischemia Causes Disturbances in Mitochondrial Respiration of Neurons

Introduction

Energy exchange in the cell is associated with mitochondria, which play an important role in vital processes, participating not only in the formation of ATP, but also in the storage and transmission of hereditary information, apoptosis and plastic processes [1-3]. Mitochondria are very mobile and plastic organelles that constantly change their shape, have the ability to fusion and subsequent separation. The movement of mitochondria in the cytoplasm is associated with microtubules, which determines their orientation and distribution in the cell. In some cells, mitochondria form long mobile filaments or chains, while in others they are fixed near the places of consumption of ATP [4-6]. Neurons need a constant supply of ATP for their stability and maintaining the level of potassium ions K + inside the cell, and sodium and calcium ions outside. At rest, the brain consumes up to 20% of the oxygen received by the body. Under normal conditions, effective biological oxidation is the main source of energy-rich phosphate compounds required for the renewal of structures corresponding to the functional activity of cells [5-7]. Elucidation of the mechanisms of development of energy deficiency in ischemic damage is advisable for detailing the pathogenesis, the ratio of damage and compensation processes in this pathology.

Materials and Research Methods

The experiments were carried out on 88 male outbred white rats weighing 260 ± 20 g in compliance with the Directive of the European Parliament and of the Council No. 2010/63/EU of 22.09.2010 on the protection of animals used for scientific purposes. The studies used models of total (TCI) and subtotal (SCI) cerebral ischemia. Cerebral ischemia (CI) was modeled under conditions of intravenous thiopental anesthesia (40-50 mg/kg). Total cerebral ischemia was modeled by decapitation of animals. Subtotal cerebral ischemia was modeled by simultaneous ligation of both common carotid arteries (CCA). The sampling of material for the study of tissue respiration of mitochondria was carried out 1 hour and 24 hours after decapitation or ligation of the CCA. The control group consisted of sham-operated rats of the same sex and weight. To study mitochondrial respiration, the brain was removed in the cold (0-4°C), dried with filter paper, weighed and homogenized in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4 (in the ratio 1:10) using a Potter-Evelheim homogenizer with a Teflon pestle according to the modified method [8]. Mitochondria were isolated by differential centrifugation.
The nuclear fraction was separated by centrifugation at 600g for 10min (4°C). The resulting supernatant was centrifuged at 8500g for 10min (4°C), the mitochondrial pellet was washed twice in the isolation medium and resuspended to a protein concentration of 35-40mg/ml in the isolation medium and stored in a short tube on ice. Protein concentration was determined by the Lowry method. To study mitochondrial respiration, a concentrated suspension of mitochondria was introduced into a thermostated sealed polarographic cell with an incubation medium in an amount providing a final protein concentration in the cell of 1mg/ml. The incubation medium for recording mitochondrial respiration includes 0.17 M sucrose, 40 mM KCl, 10 mM Tris-HCl, 5 mM KH2PO4, 8 mM KHCO3, 0.1 mM EDTA, pH 7.4. The principle of operation of a 3.0 ml polarographic cell is based on the registration of oxygen uptake by mitochondria using a built-in Clarke electrode at a temperature of 25°C (Figure 1).

Figure 1: Polarographic cell for studying the respiratory activity of mitochondria
1. Cell;
2. Thermostatically controlled chamber;
3. Clarke electrode;
4. Mmagnetic stirrer;
5. Sealing plug;
6. Channels for dosed anaerobic administration of substrates and ADP;
7. A sealing ring;
8. Channel for removing air and excess liquid;
9. Fitting for connection to an ultrathermostat.

Registration of changes in oxygen tension (pO2) in the mitochondrial suspension was carried out using an electronic recorder KSP-4. The Clarke electrode was calibrated by successively blowing air (pO2 of air) and gaseous nitrogen (pO2 = 0 mmHg) through the cell. After recording the rate of basal (endogenous) respiration in the absence of a substrate (V1), respiration substrates (malate – 2 mM/glutamate – 5 mM or succinate – 5 mM) are alternately introduced into the mitochondrial suspension, and then ADP in an amount of 200 nmol/ml. The obtained polarograms are used to calculate the respiration rate of mitochondria in different metabolic states and the coefficients characterizing the conjugation of oxidation and phosphorylation processes. The following indicators of mitochondrial respiration were recorded: V1 – the rate of basal respiration, V2 – the rate of substrate-dependent respiration, V3- – the rate of respiration coupled with phosphorylation (after the addition of ADP), V4 – the rate of respiration after the completion of phosphorylation of the added ADP.
The indicators characterizing the conjugation of oxidation and phosphorylation processes in mitochondria were determined: the acceptor control coefficient (AK = V3/V2), the respiratory control coefficient (DC = V3/V4) and the phosphorylation coefficient – ADP/O. The use of solutions of substrates of the complex “malate/ glutamate” and succinate makes it possible to assess the degree of functional activity of the electron transfer chain (ETC) in mitochondria in general, in particular I and II of the ETC complex [9,10]. To prevent systematic measurement errors, brain samples from the compared control and experimental groups of animals were studied under the same conditions. As a result of research, quantitative continuous data were obtained. Since the experiment used small samples that had an abnormal distribution, the analysis was carried out by methods of nonparametric statistics using the licensed computer program Statistica 10.0 for Windows (StatSoft, Inc., USA). Data are presented as Me (LQ; UQ), where Me is the median, LQ is the value of the lower quartile; UQ is the upper quartile value. Differences between groups were considered significant at p<0.05 (Kruskell-Wallis test with Bonferoni’s correction).

Results

Compared with the control, at 1-hour TCI in the presence of the substrate “malate/glutamate”, which characterizes the state of the first (NADH-dehydrogenase) complex, the electron transport chain V1 decreased by 65 (58; 67)%, p<0.05, V2 – by 41 (38; 48)%, p<0.05, V3 – by 25 (22; 38)%, p<0.05, and the phosphorylation coefficient – by 78 (71; 84)%, p<0,05. The rest of the indicators (V4, the coefficient of acceptor control and the coefficient of respiratory control) did not change (p>0.05), (Table 1). In the presence of succinate substrate, which reflects the work of complex II (succinate dehydrogenase) of the electron transport chain, a decrease in the parameters of energy exchange was established: the rate of basal respiration V1 – by 44 (38; 52)%, p<0.05, the rate of substratedependent respiration V2 – by 60 (48; 64)%, p<0.05, respiration rate associated with V3 phosphorylation – by 59 (38; 65)%, p<0.05, respiration rate after completion of phosphorylation of added V4 ADP – by 32 (28; 46)%, p<0.05 [9].

Table 1: Respiration indices of the mitochondrial fraction of rat brain homogenates with total cerebral ischemia when using the substrates “malate/glutamate” and “succinate”, Me (LQ; UQ).

Note: p<0.05 compared with the control group, + – p<0.05 compared with 1-hour TCI, TCI – total cerebral ischemia.

The respiratory control coefficient (V3/V4) decreased by 45 (42; 48) % (p<0.05), the phosphorylation coefficient (ADP/O) at 1-hour CTI was zero. The acceptor control coefficient (V3/V2) did not change (p>0.05). The decrease in the rate of basal respiration V1 was more pronounced when using the substrate succinate (by 21%, p<0.05), which indicates a greater damage to the II complex (succinate dehydrogenase) of the electron transport chain (ETC) during TCI. There were no differences between other indicators (p>0.05). Under conditions of 1-day TCI in the presence of the substrate “malate/glutamate” at 1-day TCI, V1 decreased by 90 (82; 96) %, p<0.05, V2 – by 46 (42; 55) %, p<0,05, and V3 – by 45 (39; 56) % (p<0.05), the respiratory control coefficient – by 35 (31; 42) % (p<0.05). Indicators V4 and the coefficient of acceptor control did not change (p>0.05). The phosphorylation coefficient (ADP/O) when using both succinate and malate/glutamate with 1-day TCI, as with 1-hour TCI, was equal to zero. Compared to 1-hour TCI, the respiratory control coefficient with 1-day TCI was 41 (35; 47) % less (p<0.05).
There were no differences in other indicators (V2, V3¬, V4, acceptor coefficient and phosphorylation coefficient) (p>0.05), (Table 2). In the presence of succinate, there was a more significant decrease in V1 than with 1-hour TCI – by 90 (84; 95) %, p<0.05, V2 – by 65 (54; 70) %, p<0.05, V3 – by 78 (54; 87) %, p<0.05, V4 – by 67 (59; 81) %, p<0.05. The respiratory control coefficient decreased by 45 (41; 49) %, p<0.05. Compared with 1-hour TCI, the V1 index was 80 (75; 86) % less (p<0.05) Changes in mitochondrial respiration in relation to the control level when using both substrates were equivalent (p>0.05). In the SCI group lasting 1 hour, compared with the control group, in the presence of malate/ glutamate, V2 increased by 24 (18; 27) %, p<0.05, and the acceptor control coefficient and phosphorylation coefficient decreased by 25 (17; 29) %, p<0.05. Other indicators (V1, V3, V4, respiratory control coefficient) did not change (p>0.05). In the presence of the substrate “malate/glutamate” at 1-hour SCI, the mitochondrial respiration indices V1, V2, V3 and V4 were 89 (82; 93) % higher than at 1-hour TCI, p<0.05, 58 (55; 63) %, p<0.05, 24 (21; 29) %, p<0.05 and 32 (27; 37) %, p<0.05, respectively [10-19].

Table 2: Respiration indices of the mitochondrial fraction of rat brain homogenates in subtotal cerebral ischemia when using the substrates “malate/glutamate” and “succinate”, Me (LQ; UQ).

Note: p<0.05 – in relation to the control level, + – p<0.05 compared to 1-hour SCI, SCI – subtotal cerebral ischemia

The respiratory control coefficient did not change (p>0.05), while the acceptor control coefficient was 34 (24; 43) % less, p<0.05, and the phosphorylation coefficient was 66 (58; 73) % more, p<0.05. The decrease in the phosphorylation coefficient with SCI was less significant by 53% (p<0.05). In the presence of succinate substrate, an increase in the rate of basal respiration V1 was noted – by 38 (34; 42) %, p<0.05, the rate of substratedependent respiration V2 – by 13 (9; 18) %, p<0.05, rate respiration associated with V3 phosphorylation – by 26 (21; 32) %, p<0.05. These changes indicate a significant decoupling of oxidation and phosphorylation. The respiration rate after the completion of phosphorylation of the added ADP (V4) did not change (p>0.05). At the same time, the acceptor control coefficient, the respiratory control coefficient and the phosphorylation coefficient decreased by 35 (31; 39) %, p<0.05, 20 (18; 28) %, p<0.05 and by 36 (30; 41) %, p<0.05, respectively, which indicates a decrease in energy production.
Compared with 1-hour TCI, with 1-hour SCI in the presence of the substrate “succinate” the rates V1, V2¬, V3 and V4 were 67 (62; 71) % higher, p<0.05, 64 (58; 68) %, p<0.05, 46 (39; 52) %, p<0.05 and 35 (31; 41) %, p<0.05, respectively. The respiratory control coefficient increased by 30 (24; 36) %, p<0.05. The phosphorylation coefficient at 1-hour TCI was zero. When using succinate, the decrease in the respiratory control coefficient was less pronounced with SCI (by 10%, p<0.05). When using succinate, when using malate/glutamate, in relation to the control level, the phosphorylation coefficient was lower by 11% (p<0.05). Other indicators (V1, V3¬, V4, respiratory control coefficient, acceptor control coefficient) did not differ (p>0.05). An increase in V1 and V2 and a decrease in the phosphorylation coefficient (ADP/O) indicates proton transfer bypassing the ATP synthase complex. Enzymes of the mitochondrial matrix and cytochrome in this model of CI do not yet have pronounced damage, as evidenced by the high rates of V1 and V2, however, a decrease in the coefficients of acceptor control, respiratory control and phosphorylation indicates the separation of oxidation and phosphorylation processes and a decrease in the production of ATP during SCI.
More pronounced disturbances with the use of succinate than with the use of malate/glutamate indicate a greater damage to the succinate dehydrogenase complex of ETC, as in TCI. In the presence of the substrate “malate/glutamate” at 1-day SCI, compared with 1-day TCI, V1 decreased by 66 (60; 71)%, p<0.05, V2 – by 45 (41; 50)%, p<0.05, V3 – by 47 (39; 52)%, p<0.05, V4 – by 34 (27; 39)%, p<0.05, which is more significant than with 1-hour SCI by 87 (72; 94) %, p<0.05, 61 (58; 73)%, p<0.05 and by 46 (41; 52)%, p<0.05, respectively, except for the value of the V4 indicator, which did not change, p>0.05. The coefficients of acceptor control, respiratory control and phosphorylation decreased by 42 (37; 51) %, p<0.0; by 12 (9; 18) %, p<0.05 and by 25 (21; 32) %, p<0.05, respectively. In the presence of the “malate/glutamate” substrate, the basal respiration rate V1 was 67% higher (p<0.05), the acceptor control coefficient was 39% lower (p<0.05), and the phosphorylation coefficient at 1-day TCI was zero. Under the conditions of daily SCI in the presence of succinate substrate, a decrease in V1 was noted – by 47 (39; 51)%, p<0.05, V2 – by 62 (54; 66)%, p<0.05, V3 – by 64 (59 ; 68)%, p<0.05, which is more pronounced than with 1-hour SCI by 67 (62; 72)%, p<0.05; by 66 (63; 74)%, p<0.05 and by 55 (49; 59)%, p<0.05, respectively.
The acceptor control coefficient and the respiratory control coefficient decreased by 35 (29; 41) %, p<0.05 and by 44 (38; 49) %, p<0.05, respectively. The phosphorylation coefficient with 1-day SCI, as well as with 1-day TCI, was equal to zero. Compared with TCI lasting 1 day, with 1-day SCI in the presence of succinate substrate, the V1 rate was 78% higher (p<0.05), and the V3 and V4 rates were higher by 43% (p<0.05). while other parameters did not change (p>0.05). The use of a mixture of malate with glutamate as a substrate for 1-day SCI showed similar changes in mitochondrial respiration parameters as with succinate, with the exception of a higher phosphorylation coefficient – 1.4 (0.6; 1.6), p<0,05. The decrease in the V1, V2, and V3 indices with 1-day SCI is a consequence of a decrease in the oxygen content for mitochondrial respiration.
The suppression of energy processes was more pronounced than with 1-hour SCI, which reflects an extremely low phosphorylation coefficient. Changes in V1, V2 and V3 indicators at 1-hour SCI and 1-hour TCI were multidirectional. Their increase in SCI is associated with the uncoupling of oxidation and phosphorylation, while a decrease in TCI is associated with a lack of substrates for mitochondrial respiration. The decrease in the rate of basal respiration V1 with 1-day SCI was less pronounced than with TCI: in the presence of succinate – by 43% (p<0.05), and in the presence of malate/glutamate – by 24% (p<0.05).

Conclusion

During cerebral ischemia, damage to the inner mitochondrial membrane occurs due to the activation of free radical oxidation processes [5]. Damage to the inner mitochondrial membrane, in turn, leads to an increase in its permeability and a decrease in the level of the proton gradient due to the transition of protons along the concentration gradient through the formed nonspecific pores into the mitochondrial matrix [13,19,18]. As a result, the efficiency of ATP synthesis decreases, and to maintain the intermembrane potential under these conditions, more substrates and oxygen are required [14-18]. Thus, the most pronounced decrease in the respiration indices of the mitochondrial fraction of brain homogenates occurs in total cerebral ischemia due to the complete cessation of the blood supply to the brain neurons.
With this method of modeling cerebral ischemia, the appearance of hyperchromic shriveled neurons with pericellular edema is characteristic. In their cytoplasm, the destruction of organelles occurs, the disintegration of neurofibrils and neuropil, which indicates their low functional activity. Simultaneous subtotal ischemia also leads to severe irreversible damage to neurons: at the morphological level, this is manifested by a significant increase in the number of hyperchromic shriveled neurons. Their predominance in the population of neurons in the SCI group corresponds to the inhibition of respiration of the mitochondrial fraction of brain homogenates.

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COVID-19 Pandemic and Horticultural Sector: An Investigation of Cause & Effect Relationship in J&K

Introduction

Despite radical structural changes over the years, the agricultural sector consistently continued to remain an important activity supporting J&Ks’ economy. Although the domestic product generated in this sector has increased by 25.94 cr. since 1980-81 (DE&S, various issues) but it could not keep pace with the growth of other sectors of economy. The proportionate decline in the role of this sector towards states’ domestic product seems discouraging given the huge dependence of labour force on this sector. The concentration of poor and landless labourers has given a strategic place to this sector in the process of economic progress for whom it is the only option for sustenance and livelihood. Agriculture has played an important role in ensuring inclusive growth and providing food security to its populace [1] despite huge urban pressure on land resources. The development of this sector seems more relevant in spite of shrinking land resources, depletion of water resources, climate change, costlier farm-inputs and instability in global markets. To overcome these issues, quality research and skill development would be required to develop technologies that are relevant to the region and could be put in use to achieve rational resource use efficiency. But it will require strengthening of infrastructure which could intern result in and better governance/ management to make delivery of services better.

Switching over to Horticulture

The agro-climatic diversity of the union territory of Jammu and Kashmir favors diversification towards horticultural crops. The capacities of the territory are being increasingly shifted towards the production of horticultural crops as driven by market demands and in turn profitability. The reason for this switchover may be attributed to the less remunerative production of field crops like rice and maize. Horticulture crops occupy an area of 3.31 lakh hectares (2018-19) in J&K, of which a whopping1.64 lakh hectares is under apple cultivation [2]. 20 and 24 lakh metric tons annually of fresh and dry fruits, respectively of which apple alone constitutes 80 per cent. Horticultural sector is the largest employment provider in the region engaging over 23 lakh people, depending directly or indirectly on this sector [3]. Kashmir has rightly been described as the land of fruits, producing 24.15 lakh mt of fruits from 332 lakh ha of land. Its land, environment and salubrious climate provides greater facilities for rapid growth of horticulture industry. The fruit production is highly capital and labour intensive activity, thus become the most dominant factor for changing the social and economic status of rural Kashmir.
The vibrant fruit sector of Kashmir holds key to the economic growth as well as sustenance by containing the widespread unemployment in the union territory. The fruit sector has strong backward and forward linkages which involve such activities that have significant multiplier effects. From the input market to the final destination of produce, this sector has a long supply/ value chain. The market functionaries and various marketing logistics/infrastructures including cold storages, market yards, loading, weighing facilities involved in long supply/value chain constitute the basics of an efficient supply chain management. Any permanent or temporary changes that disrupt its supply/value chain to any extent have long lasting multiple negative implications on the performance of the fruit economy. In accordance with this the political disturbances, climate change, price fluctuations, availability of labour or inputs, etc. may have undesirable effects on the desired performance of the horticultural sector. Undoubtedly the ongoing covid-19 pandemic and associated lockdown are expected to have some implications on horticultural economy necessitating assessment in terms of their magnitude which forms an objective of this study.

Status of Covid-19 Pandemic Across States & in J&K, UT

Table 1: District wise status of corona virus cases in Jammu and Kashmir.

There is hardly any place on the earth which is not infected by this dreadful virus. Covid-19 pandemic that spread in every part of the world. This virus was first detected in Kerala (state of India) on January 30, 2020 and then gradually kept on spreading across all the states and UTs of the country. As of now the country has reported 4.47 million infected cases of which 3.47 million have recovered (MHFW, India). This covid-19 infection has taken about 75,062 lives. All the health centers across the country are involved in prevention as well as arresting further spread of the disease. In India, Maharashtra recorded highest number of cases compared to other states (Figure 1). The other highly affected states/UT’s in India include Tamil Nadu, Gujarat and Delhi. The situation is J&K, UT is also grim as the numbers of cases are adding to the infected patients with every single passing day. Within Kashmir province of Jammu and Kashmir UT the first covid-19 case was reported from Khanyar area of Srinagar city, and the case was having a travel history. Since then every nook and corner of the Union Territory was put on high alert with demarcation of district with Red, green and Orange zones. The capital of the UT, district Srinagar, witnessed highest number of infected persons (Table 1). A total of 671 people (614 in Kashmir and 57 in Jammu) have died of the virus in the Union Territory so far. The infection is spreading at an exponential rate and is yet to see its peak in the territory which calls for necessary measures to neutralize the effects of this pandemic.

Figure 1: State wise covid-19 confirmed cases and deaths recorded in India.
Ministry of Health & Family Welfare, Govt. of India, 10 September, 2020

Restricting Corona Spread with Lockdown

The novel coronavirus has wreaked havoc across the globe, killing and infecting millions and in turn affecting world economy. Since the virus is highly communicable, the only option to prevent or slow down its spread is to prohibit contacts and maintain social distancing. Therefore, like other economies, lockdown was taken as a measure to restrict its spread across India which has over 1.35 billion population. Lockdown is considered one of the harsh steps to combat the coronavirus pandemic as it is novel in nature and no vaccine is available till date despite a lot of ongoing research. Lockdown is the best available option for India considering it less advanced and less equipped health sector. J&K UT also observed like rest of the country a strict lockdown with prohibitory orders and all the economic activities of the territory were stopped. During this period government took a number of measures like opening up of dedicated covid-19 test centers, provision of support to the poor sections and relief package to few economic activities. Although the lockdown has reduced contacts and spread of virus significantly but the closure of economy definitely has broken the network of its various activities which is expected to have short as well as long term implication on the livelihood of different sections of the population and wellbeing of the national economy.

Lockdown Features and Impact on Growth Indicators of Horticulture

Lockdown in Kashmir valley of J&K was imposed to restrict the spread of covid-19. Barricades, barbed J-hock wires and even trunks of popular trees were used to block all the roads connecting cities, towns and villages. The restrictions imposed on internet, transport, and communication subsequent to the abrogation of Article 35A and 370 was further carried forward with strict prohibitions. The implication of the lockdown has impacted the already limping economic activities of the territory along with its relevant sectors. Of these, agricultural sector owing to its biological nature was expected to get drastically influenced by the lockdown, since the impact on this sector is complex and varies across diverse segments that form its value chain. Farming is gradually diversifying in favour of fruits especially apple which has strong linkages in pre-production and post-production. Apple cultivation is the main farming activity employing more than 23 lakh people in the valley and is the predominant activity of small and marginal growers. Apple production has long value chain between input markets and consumers of final products which necessarily has to be integrated. Through its value chain horticultural production and processing requires diverse inputs and services and any distortion in this chain would have drastic unfavorable impact on its productivity and growers net returns.
The restriction on transport, mobility, administration, financial sector, etc. under lockdown is an add-on hurdle inflicted on different segments of long value chain of horticultural sector of J&K. During the first phase of lockdown which coincided with leaflet and first fruit development stage of apple and the application of dose of nitrogen, potassium, phosphate, fungicides, acaricides, insecticides and sprays of other micro-nutrients which is highly crucial for plant health and prevention of infestation of pests got affected badly. Since the restrictions were imposed on all the activities, it has resulted in immobility of factors of production that delayed the application of inputs at stage specific for their execution. The complete shutdown of all Universities, Research institutions, KVK’s led to the communication gaps between apple growers and the extension functionaries resulting in no or poor percolation of advisories to the growers. The technological disseminations activities like farm visits, training/workshops and exhibitions could not be organized by the Agricultural institutions. Moreover, scientists and Subject Matter Specialists (SMS’s) were not able to attend experimental field that drastically affected field demonstration. The response to huge technological gaps owing to poor extension system was reported by 21.0 and 7.3 per cent of growers and SMSs, respectively. This duration has taken apple cultivation far from scientific package of practices in absence of the role of extension activities, financial institutions, etc. (refer Figure1 for details of implications).
The horticultural economy got severely hit when lockdown halted transportation that suspended the movement of the previous year’s harvest kept in the CA stores. March and April is considered the peak season for the stored apple to be transported to the mandis outside the state, but due to transport restriction, the fruit is expected to rot in the stores and the growers may not be in a position to meet the production cost including CA store charges and has been also disrupting the supply chain (Raashid Hassan and Ishtiaq Wani, 2020). As per reports approximately 4 per cent of Kashmir’s’ apple produce of 23 lakh metric tons was in cold storage units. The growers had to pay an amount of Rs 30 per box per month as cold storage charge and the apple which is stored for seven months costed around Rs 215 for a 16 kilogram box which amounts to an additional Rs 100 crore cold storage charges for one lakh tons of apples. Within CA stores the quality of apple gets gradually deteriorated raising the concerns for its sale but despite this fact the growers still paid the charges. As per official records apple worth Rs 900 crores were still in the valleys’ CA stores up to ending May, 2020 that imply, the loss of such a huge amount raised havoc among the farming community. The closing up of corporate or the functioning of private players has put manufacturing of fertilizers, pesticides, and packaging material to a complete halt and this problem intensified with the non-availability and immobility of raw material to these units.
The apple/vegetable growers faced lot of inconveniences in purchasing the chemicals and fertilizers due to closure of shops in the valley besides all the government offices and functionaries remained closed which inflicted indirect costs to growers in terms of non-availability of timely credit for performing capital intensive intercultural operations and purchase of inputs. In consideration to the severity of lockdown, a good proportion of worried growers were apprehensive of possible sale of their apple produce which apprehensions forced them to reduce the application of fungicides and other chemicals, further resulted in intense pest infestation. A proportion of growers preferred fungicides which are not prescribed in package of practices to save money to meet the expenses on basic necessities [4]. Since the vegetable and fruit cultivation is highly labour intensive, therefore, unavailability of laborer’s contributed too negatively to the apple economy. Labour demand in Kashmir broadly depends on out-side state labour force. Political disturbances that arose due to scrapping of Article 370 had already forced migration of laborer to return to their native places which had created scarcity of skilled/unskilled laborer’s in apple growing belt of the valley. The non-availability of laborer’s due to COVID-19 further aggravated the problems in production of fruits particularly apple and vegetable. The standing vegetable crop could not be harvested skillfully on time and there was a delay in transplanting of vegetables nurseries, which reduced the returns from vegetables further by an amount of Rs 22000 per kanal (Table 2). Apiculturists rent out beehives to apple growers for pollination of their apple orchards. Since these apiculturists are migratory, they were yet to return to the valley when covid-19 lockdown was announced. The mis-managed pollination not only caused loss to the apiculturists but is expected to decrease the productivity of apple by 20-25 per cent.

Table 2: Lockdown features and possible implications on horticulture (%).

The poor execution of various economic activities relating to the value chain of apple and vegetables leads to an increase in the cost of cultivation. Farmers could not attend their fields in a crucial fruit development stage that resulted in pest/weed/disease infestation and an additional amount of Rs 450.0 were spent on this input. More demand in relationship with the supplies resulted in more wage rate of available labour. Agriculture land is being shifted to horticultural crops especially apple at alarming rate and nearly 2.5 lakh hectare apple area is in non-bearing stage. Farmers raise intercrops for home consumption thus increase their real income but owing to strict restriction there have been dis-economies worth of Rs 24000.00 per hectare as no intercropping has been done within non-bearing orchards. During the second phase of Covid-19 lockdown, the transporting fare escalated from Rs 15,000 per truck to around Rs 35,000 and even then, only few trucks were available for transporting the apple to the other mandis. Though the restriction on mandis was relaxed to open the outlets but the out of CA store apple produce could not see the buyers and the produce spoiled in a bad way. Similarly an additional amount was spent by growers in different items to resolve the added problems due to lockdown (Table 3).

Table 3: Additional costs due to lockdown (Rs/ha-1).

Relaxation in Lockdown have Aggravated Problems

In the first phase of relaxation all the farm operation were permitted which made all the stakeholders like growers, traders, and custom hiring activities restarted. Growers came out to start spraying, fertilization and other intercultural operations but they face trouble in finding skilled labour services, quality critical inputs and other material. The abrupt increase in the demand in relationship with inelastic supplies in short period resulted in the rise in price of inputs. Although manufacturing sector was allowed to start their activities but they could not come up the spike in demands for pesticides and fertilizers for three main reasons viz. one that they could not use their unit to full capacity while observing social distancing and other relaxation guidelines, second a good chunk of laborer’s were on way to or reached to their native place and third was the dearth of transport to ship the consignments. The pesticides, which may not be as per scientific recommendation, are purchased at higher prices and growers have to bear the additional costs on these items (Table 3).
The Covid-19 further aggravated the mayhem created after repealing of article 35A and 370 of Indian constitution. Only a few laborer’s available in the valley took ways back to their native places though a part of local laborer’s returned to the valley. The non-local labors did not wish to come back to the valley, given the unpredictable corona related situation following the lockdown [5-8]. This resulted in the less or no availability of labour services bringing asymmetry in the execution of farm operations. As high as Rs 9000 ha additional amount was spent on labour wages contributing to heavily for horticulture industry especially apple (Table 4). The associated implication of lockdown resulted in the limited production of packaging material for fruits like cherry. Although the cherries were harvested with available family laborer’s but the poor transportation facilities and irregular marketing activities in wholesale markets within and outside the valley resulted in the wastage of produce and sale of some surpluses at lower rates in domestic markets. The rising demands for inputs and labors and deficit supplies led to the overall rise in the prices of factors of production. After lockdown, the economy is expected to take time to balance the markets, however, the institutions has to play an important role with safety cover and financial support.

Table 4: Additional costs on intercultural operations in apple in relaxing lockdown (Rs/ha-1).

Climate and Covid-19

Scholars across the globe were of the opinion that the severity of corona virus infestation may reduce gradually with each degree rise in temperature and this notion says that the territory would have a virtual exit from pandemic in summers. The temperature (max., min., and average) experienced a gradual rise as the territory has been through spring towards summer season with an ideal normal behaviour with occasional rains with maximum spike of only 55mm in the beginning of May (Figure 2). The covid-19 pandemic finds no end rather the positive cases kept on rising consistently with steeper upward slope in recent days (Figure 3) thereby explaining the regressive increase in corona virus affected cases wherein community has got involved. The evolving scenario of covid-19 pandemic exhibits positive correlation with temperature as both progresses towards same direction (Table 5). There appears no significant association of corona virus infection with rainfall. Given these findings we can foresee only uncertain behaviour of covid-19 pandemic which directs towards building up health care facilities in the region. It would apparently cost fairly a good amount to adhere medical guidelines to be followed in horticultural farms. Institutional role with a kind of safety cover could inevitably find its place in avoiding further deviations from scientific management of orchards and vegetable farms.

Figure 2: Behaviour of covid-19 cases between 22/03/20 and 14/7/20

Figure 3: Behaviour of climate variables between 22/03/20 and 14/7/20.

Table 5: Climate in correlation with corona virus infections.

Lasting Impacts of Covid-19 Pandemic on Horticulture in Kashmir

The covid-19 related lockdown has affected all the farm activities like the entire economy. There as a huge delay in the execution of intercultural operations and application of input. The inputs available within the approach of growers, could be substandard but were purchased at much higher costs and applied on apple crop. The delayed pest management due to unavailability of quality pesticides encouraged pest/disease/weed infestation which not only increased the cost of their management but also expected to reduce the productivity of apple/vegetables and deteriorate the quality of produce. During relaxation the orchards are suffering from scab, sanjose scale and other pests, which may be much worse in the coming months. Estimated 40-50 per cent of the apple orchards and 25-35 per cent of vegetable fields are suffering from pest/diseases of various kinds. The delayed management of orchards and poor pollination is expected to reduce the yield level to a great extent (Table 6). These manifestations of impact are considered to last for a longer time period.

Table 6: Expected decline in productivity (kg/ha-1).

The supply chain of apple and vegetables starts from the purchase of inputs and their application on crops. The nonavailability of transportation made growers to act as a part of closed economy wherein the inputs whatsoever available with whosoever traders were applied on the crops resulted in the complete distortion of supply chain. The produce of other fruits like cherries at farm of apple orchardist were due to be harvested by ending May. However, due to non-availability of skilled laborer’s the cherries were harvested by the family laborer’s but the surplus fruit could not be sold outside the state incurring a huge loss to the producers accompanied by less net price received. This scenario obviously shall have a long-term self-perpetuating negative implications on farm economy in general and horticultural economy in particular. Growers were not able to sell off their vegetable produce during the first phase of lockdown and could not earn from subsidiary occupations like shop-keeping, handicraft, driving services, etc. that reduced their purchasing power drastically.
Poor role of financial institutions coupled with poor resource position of grower are expected to reduce their spending on critical inputs in future and may further reduce productivity on account of increasing technological gaps and unscientific cultivation of apple. Moreover, the small holders with limited resources in consideration of unforeseen corona situations were seen to spend lesser amount on family consumption of food and nutrients (Table 7) which may inflict undesirable influence on the health status. The uncertainties about the persistence of Corona Virus related disease is expected to have negative impact on the sale proceeds of apple in domestic as well as international markets. The demand of apple by traders, processors and export houses is likely to reduce further in consideration of poor business returns in the current season. Moreover, our importing partners would possibly prefer to consume their domestic produce. The slackening of working capital and poor employment of laborer’s may lead to less derived demands and in turn would make the multiplier to operate in a reverse order. Unless this situation is taken seriously, it is rather impossible to put apple economy back on the trajectory of steady growth.

Table 7: Dietary intake of small holders during and after lockdown (g/capita/day).

Conclusion and Policy Suggestions

Even though relaxations for agricultural activities have been announced after the first lockdown in J&K, impact of the lockdown still can be seen in terms of difficulties in marketing perishables, transporting farm inputs, institutional closure, credit availability, closure of Government offices and basic necessities for the apple growers. Following policy suggestion would help to bring up horticultural economy to the steady growth level: Farming community, especially horticulturist’s, with small holders and landless laborer’s should be brought under the benefits of economic packages. There is a pent up need to conceive a special insurance coverage scheme including damage to the crop in terms of quality and quantity both in view of climate uncertainties and for not attending farms due to geopolitical conditions and pandemic like that of covid-19. E-crediting system with easy procedures find their importance in advancing loan to small holders at the time when it is highly required. These options could help retention of farmers in farming and prevent them from selling out land or abandoning of farming as a commercial activity. There is a need to integrate production with marketing through value addition so as to achieve various economies and utilities. This way grower can utilize his farm produce efficiently if markets are not available immediately and the skilled/unskilled laborer’s would find employment for major part of the year.
There is a dire need to make a demand assessment of inputs well in advance, consistent with regional crop plans, to ensure full stock of required quantity well before the commencement of crop season. This will provide information to the industries Moreover, the timely warehousing and creation of CA storage facilities in PPP mode with necessary logistics around each production centre would help to hoard inputs and outputs for their timely availability. Additional 10-20 CA stores would be required in the valley for which government and corporate sector should chain up with pooled resources. In light of unforeseen abrupt distortions in supply chain, there is a need of a properly conceived procurement policy so that farmers may not face glut or price fluctuations. Additionally this policy may be converged with MSP system to add security to the farming community by avoiding market and price uncertainties. Labour scarcity is considered to be one of the persistent problems to confront horticultural sector in view of male outmigration and other significant reasons. There is a need for automation and mechanization of farm operation to enhance work and input use productivity in horticultural crops.

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Influence of iSGLT-2 on Lipid Profile in Patients with Diabetic Nephropathy

Introduction

Diabetes mellitus (DM) is a global medical and social problem of our time, which is faced by medical science and healthcare in almost all countries of the world. The World Health Organization (WHO) for the first time recognized this disease as a new non-infectious epidemic of the 21st century, since in recent years the growth rate of patients has become alarming [1]. The current constant increase in the number of patients with type 2 diabetes unambiguously affects the incidence of microvascular complications, including diabetic nephropathy (DN). DN increases morbidity, disability and mortality in type 2 diabetes patients. DN in parallel with diabetes is a risk factor for the onset and progression of cardiovascular diseases and one of the main factors of end-stage renal failure [2,3]. Type 2 diabetes increases the risk of chronic kidney disease (CKD) 2.6 times, and the risk of death due to kidney pathology – 3 times. According to statistics, CKD develops in about 15% of individuals in the general population and in every second patient with diabetes mellitus (DM). In Uzbekistan, 118026 patients with CKD were registered, in 2020 the number of patients with CKD was 23773 with CKD, of which 5146 are on hemodialysis, about 40% are patients with diabetes [2]. The leading role in the development of CKD in patients with diabetes is played by permanent hyperglycemia.
Advances in the treatment of patients with diabetes mellitus (DM) in recent years do not reduce the risk of chronic kidney disease (CKD), but provide a delay in its development. Obesity and the associated lipid metabolism disorder is a factor in the progression of any kidney disease, including DN. Along with damage to the mesangial and paramesangial regions of the glomerulus, lipids filtered into the primary urine can also cause damage to the cells of the renal tubules [3-5]. It has been shown that the lipid profile shift characteristic of T2DM is chronologically ahead of the development of carbohydrate metabolism disorders and confirms the fact that lipotoxicity pathogenically precedes glucose toxicity [6,7]. The most pronounced anti-lipolytic effect is possessed by representatives of the gliflozin classes (iSGLT-2). Meanwhile, the action of hypoglycemic drugs should also be considered from the point of view of renoprotection and correction of cardiovascular insufficiency [7].

Purpose of the Study

To study the effect of iSGLT-2 on the parameters of carbohydrate metabolism, lipid spectrum in patients with diabetic nephropathy.

Material and Research Methods

The prospective study included 80 patients with type 2 diabetes with DN. The duration of diabetes mellitus was on average 9.7 ± 0.9 years. To study the effect of iSGLT-2 on carbohydrate metabolism, lipid profile in type 2 diabetes mellitus, 2 groups were identified. Group 1 40 patients with type 2 diabetes with CKD G3a diabetic nephropathy, average GFR 56 ± 0.9 ml / min 72 m2, patients’ age was 56.8 ± 2.8 years, of which 18 were men and 22 women, as hypoglycemic therapy received metformin and a sodium-glucose cotransporter type 2 inhibitor (iSGLT-2) empagliflozin. Group 2 of 40 patients with diabetic nephropathy, the average age of patients was 58.3 ± 2.9 years, including 21 men and 19 women with CKD G3b, the average GFR was 40 ± 0.9 ml / min 72 m2. The studied groups of patients were comparable in terms of sex, age, duration and severity of diabetes mellitus. The patients were on a constant diet, and they were not prescribed hypolipidemic therapy. Glomerular filtration rate was determined using the CKD-EPI formula. Glycemia was determined on an automatic biochemical analyzer BS-380 “Mindray” by glucose oxidase method in venous blood on an empty stomach using HUMAN Glucose reagents (Germany). HbA1c was determined on a Huma Nex A1c analyzer. The lipid spectrum of blood was determined using kits from Cypress Diagnostics (Belgium) using a Hospitex Diagnostics spectrophotometer. Total cholesterol and triglycerides in blood serum were determined by a standard enzymatic method, HDL cholesterol in the supernatant was determined after precipitation of lipoproteins of other classes with dextran sulfate. LDL cholesterol values were calculated according to the formula of W. Friedwald (1972): LDL cholesterol = total cholesterol – (TG / 2.2 + HDL cholesterol), mol / l. Control studies of the studied parameters were carried out after 3 and 6 months.

Research Results and their Discussion

Studies have shown that the baseline indicators characterizing glycemia (fasting glycemia, postprandial glycemia and HbA1c%) in the studied groups were comparable (Table 1). By the 3rd month of treatment, there was a significant decrease in HbA1c in the 1st and 2nd groups of patients. The decrease in HbA1c in the 1st group occurred by 9.2% (P <0.05), in the 2nd group by 8.8% (P> 0.05), which is almost 2% lower. The initial indicators of fasting glycemia and postprandial glycemia in the 1st group did not significantly exceed the indicators of the 2nd group (8.7 ± 0.84 mmol /l and 8.10 ± 0.82 mmol /l, respectively; 12.1 ± 0, 21 mmol /l and 11.49 ± 0.31 mmol /l, respectively), after 3 months these indicators significantly decreased in the 1st group by 24.9% and 19.8%, respectively, in relation to the initial data, in the 2nd group, the decrease was significantly lower – 14.1% and 16.8%, respectively. In the dynamics of treatment, after 3 and 6 months, there was a pre-delivery decrease in the studied parameters of carbohydrate metabolism in both groups of patients. So, the level of postprandial glycemia within 6 months in both the 1st and 2nd groups significantly decreases in relation to the initial data, in the 1st group – by 25.6% and by 19.9% (P < 0.05). The HbA1c content after 6 months decreased by 25% in the 1st group of patients with type 2 diabetes and by 10.2% in the 2nd group (P <0.05). Episodes of hypoglycemia were not observed in both groups. By the 6th month of observation, it should be noted that the glycated hemoglobin indicators reached the target values in patients with diabetic nephropathy (Table 2).

Table 1: Dynamics of carbohydrate metabolism indicators in the treatment groups at baseline and after 3 (M ± m).

Note: * p <0.001, ** p <0.05

Table 2: Influence of the appointment of sodium glucose cotransporter type 2 inhibitors (iSGLT-2) on the lipid profile in DN.

The study of the lipid spectrum in the observed patients showed that when using hypoglycemic therapy (metformin + iSGLT-2) after 3 and 6 months of therapy, a decrease in the level of triglycerides by 9.8 and 14.1%, respectively, in total cholesterol by 15.4 and 9,8%, respectively, LDL-C – by 11.0 and 12.4%, respectively, and an increase in cholesterol in HDL-C – by 32.0 and 41.8%, respectively (p <0.05). At the same time, the TG level was slightly changed and remains within the normal range in all the studied groups. The data obtained indicate that TG should be determined with reference or slightly increased levels of TG and LDL in patients with type 2 diabetes in patients with DN. In the 1st group of patients, there is a decrease in TG 8,6%, and HDL 38,1% increases. In group 2, the dynamics of TG, HDL was less pronounced: TG decreased 9,2%, HDL increased 11,1%. Thus, it should be emphasized that the first group of patients with type 2 diabetes with CKD G3a achieved a more favorable lipid spectrum in general, TG and HDL parameters were close to the target values in this category of patients. In the second group, patients with type 2 diabetes with CKD G3b also showed a decrease in TG, but less pronounced, the level of HDL was achieved the target values in this category of patients. The lack of significant dynamics of LDL in both groups is possibly due to the lack of special lipid-lowering therapy.

Discussion

Advances in the management of patients with DM in recent years do not reduce the risk of CKD, but provide a delay in its development [4,5]. Along with damage to the mesangial and paramesangial regions of the glomerulus, lipids filtered into the primary urine can also damage the cells of the renal tubules. Lipoproteins deposited in the renal tissue bind negatively charged glycosaminoglycans, there by neutralizing its negative charge and increasing its permeability to proteins [7,8]. Damage to the renal tubules is associated with intense lipid reabsorption and metabolism by nephrocytes, which leads to the release of lysosomal enzymes, cytotoxic effect and subsequent sclerosis. In turn, proteinuria is one of the most studied risk factors for the progression of renal disease [7]. The strategy and therapeutic goals, including those for indicators of lipid metabolism in patients with diabetes, have been determined. In recent years, special attention in diabetology has been paid to inhibitors of the sodium-glucose cotransporter 2 (iSGLT-2). These drugs, in addition to successful glycemic control, have a positive effect on renal function in individuals with type 2 diabetes and CKD [9], they also have positive metabolic effects, but also the ability to correct hemodynamic disorders, reducing intraglomerular hypertension and systemic arterial pressure, which can potentially have a nephroprotective effect. The mechanism of the effect of iSGLT-2 on lipid metabolism is not fully understood, according to the data, a potential mechanism of action of SGLT2 inhibitors may be an increase in the metabolism of LDL, but this fact has been shown in rats [9,10]. So, the main mechanism for reducing the fat content in the liver under the action of iSGLT2 inhibitors is a decrease in de novo lipid synthesis by reducing the level of glycemia and insulin and an increase in beta-oxidation of fatty acids.

Conclusion

Thus, in patients with type 2 diabetes with CKD G3, the combination of metformin and iSGLT-2 a had a positive effect on the main indicators of carbohydrate and lipid metabolism. This combination was more effective in improving lipid metabolism in type 2 diabetes patients with CKD G3a compared with type 2 diabetes patients with CKD G3b.

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Cardiac Fibroma Revealed at Adulthood….!!

A 37-year-old man without known comorbid conditions or cardiovascular risk factors presented with lipothymia. The neurological and cardiovascular examinations were normal. The brain magnetic resonance imaging was normal. Electrocardiogram (EKG) showed LV hypertrophy with T waves inversion in inferolateral leads (A). 24-hours EKG Holter showed a sinusal rhythm with no further abnormalities. Transthoracic echocardiography (TTE) revealed a left ventricular hypertrophy localized in the inferior wall suggestive of myocardial mass (B) with normal left ventricle ejection fraction. In the subsequent cardiac magnetic resonance (CMR) imaging, a 7.6×2.6 cm mass was found. The mass was well demarcated, lined with normal myocardial tissue, hyperintense on T1 weighted images (C), hypointense on T2 weighted images (D), and showed extensive late gadolinium hyperenhancement (E; F). Those CMR findings were consistent with cardiac fibroma. Despite of the known risk for arrhythmias of cardiac fibroma, the decision was made to closely follow this patient without excisional surgery given the normal sinus rhythm, the absence of history of syncope or resuscitated sudden death and the patient preference. Cardiac fibroma is the second most common primary pediatric cardiac tumor after rhabdomyoma. It remains a rare entity, especially in the adult population. Clinical presentation of patients with cardiac fibroma depends on the location and size of the tumor. CMR imaging is an excellent tool for evaluation of patients with suspected cardiac masses as it provides excellent tissue characterization and may give information about the possible etiology of cardiac mass thus foregoing the need for myocardial biopsy (Figure 1).

Figure 1:

a) EKG showing LV hypertrophy (Sokolow index at 39 mm) and T waves inversion in infero-lateral leads
b) TTE 2-chamber view showing the myocardial mass in the inferior wall of the left ventricle
c) T1-weighted imaging 2-chamber view showing a hyperintense cardiac mass
d) T2-weighted imaging short-axis view showing a hypointense cardiac mass. Delayed enhanced imaging (2-chamber view at 2 min)
e) Short axis at 10 min
f) Showing marked late hyperenhancement of the mass with gadolinium, which is a hallmark of cardiac fibroma.

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Predicting Delays in Acute Ischemic Stroke Care with Machine Learning

Introduction

Machine learning with neural networks have demonstrated remarkable success in finding patterns in structured, as well as unstructured data. It has been applied to various aspects of health care including early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation [1]. Process optimization is another application of machine learning, as it can find intricate trends from historical data. With 15-year historical data from the stroke thrombolysis program at a tertiary care center, an attempt was made to design a neural network with the aim of predicting team performance, in terms of door to needle time (defined as the time interval from arrival at the hospital to administration of the thrombolytic drug). Such information could be of help to warn of potential delay when a particular patient arrives, and the team armed with this information will be better enabled to pre-empt the delay [2].

Methods

Historical records of acute stroke thrombolysis were available from 2003 – 2018. The data was first split into training, validation sets. Data from 2003 – 201, consisting of 221 cases, was used as the training data, and the last 2 years’ data of 61 cases was used for validation. Identification of feature and target measures. (The inputs parameters fed to a machine learning model are called features, and the output it is trained to optimize on, the target). It has been reported from various centers that the door to needle time in acute ischemic stroke tends to have an inverse relation to duration of stroke at presentation [3], and this was replicated from data in our center as well. Similarly, regression and scatter plots were used to identify that: severity of stroke by NIH Stroke Score (NIHSS) scale, age of the patient in years, time of the day (rounded to the nearest hour) were also showing an association with the door to needle time, though individually the effects were weak (Figure 1). Thus, these four features were selected to train the network. The target parameter was the door to needle time, parametrized as above or below 45 minutes, as this was the cut off that showed the best predictive performance. Cases with delay <= 45 minutes were labelled as 0 and others as [1] (Table 1).

Table 1: Features and target.

Neural Network Architecture

A 3-layered fully connected architecture was used and implemented using the open source Tensor Flow framework [4]. The number of neurons in each layer were 4, 6 and 1, from input to output. The first two layers consisted of rectified linear activation units (Re LU), and the final unit used the sigmoid activation function, to give output in the range of 0 to 1. (Figure 1). The source code of the implementation is available at https://github.com/mlnoone/ nnstroketeamperf/

Training

The network was trained using batch gradient descent, with total iterations of 1500. Sigmoid cross entropy cost of the 45 min delay prediction (ranging 0 to 1) vs actual status (0 vs 1) was used as the minimization target. The learning rate was optimized based on performance on the training set and a value of 0.15 achieved the best result as shown in (Figures 2 & 3).

Figure 1: Scatter plots showing the (weak) correlations with door to needle time in minutes (on the vertical axis in all) of duration (A), Age(B), Severity (C) and Hour of day (D)

Figure 2: The neural network architecture.

Figure 3: Plot of cost vs iterations as the network was being trained at a learning rate of 0.15

Hyper Parameter Tuning

Based on performance in the training and the validation sets, the hyper parameters of the network were optimized. Performance on the validation set was assessed using the following parameters:
a) Accuracy, defined as percentage of delay > 45 min correctly predicted.
b) Sensitivity and positive predictive value (also called recall and precision in machine learning parlance) which were combined into the F1 score, defined as: 2 x precision x recall / (precision + recall).
These were then used to select the optimum hyper parameters for the network which, in addition to the learning rate of 0.15, included:
a) The number of neurons in each layer as mentioned above was set at 4, 6 and 1 which resulted in optimum performance on the training set (accuracy 60%, precision 68%, recall 71%, F1 0.68).
b) L2 Regularization was used to minimize overfitting which was observed initially, a regularization parameter (lambda) of 0.02 was chosen based on observing the result over a range of parameters to minimize error on the validation set.

Results

The network after optimization showed precision (positive predictive value) 63%, recall (sensitivity) 67% and F1 0.64 on the validation set, with an overall accuracy of 60% (Table 2).

Table 2: Performance measures on the validation set.

Discussion

Neural networks are capable of extracting intricate patterns from complex data, which are otherwise nearly impossible to delineate. They have been applied with remarkable success in fields like advertising and manufacturing to optimize performance based on structured data. Though the success of neural network with unstructured data like computer vision, speech and language are more widely appreciated, they are also remarkably effective in analyzing structured data. As seen here, with four weakly associated parameters it was possible to develop a reasonable prediction model for stroke team performance with 60% accuracy and 63% positive predictive value. Application of neural network in this context of optimizing acute care based on a predictive model has not so far been reported in literature. With increasing application of care pathways, neural networks could be a natural choice to build predictive models to identify potential for errors and delays.

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Pneumothorax Associated with Thoracic Endometriosis: Current Knowledge

Introduction

Endometriosis is a condition in which endometrial-like glands and stroma are located outside of the uterine cavity. The ectopic endometrium is encountered most commonly pelvic structures such as ovary, uterine ligaments, pelvic peritoneum, and genital structures [1-4]. The usual site of endometriosis outside of the abdominopelvic cavity is in or around the lung (intrathoracic cavity) (Figure 1). Although endometriosis in general can affect up to 15% of women of reproductive age, thoracic endometriosis remains a very rare condition [5-9]. Thoracic endometriosis produces a broad range of clinical and radiological manifestations, including catamenial pneumothorax (80%), catamenial hemothorax (15%), hemoptysis (5%), and rarely pulmonary nodules [5-9]. The age of onset in patients with thoracic endometriosis (a mean of 35 years) is higher compared to a mean age at presentation of 25 to 30 years in patients with only pelvic endometriosis [5-9]. The exact mechanism of catamenial pneumothorax associated with thoracic endometriosis remains unclear, but several hypotheses have developed to explain this condition.

Figure 1: Endometriosis involving the pleural surface of diaphragm (arrows). The clinical and laboratory findings have been reported previously [32].

Retrograde Menstruation through Diaphragmatic Fenestrations

The endometrial tissue is thought to move through the fallopian tubes to the peritoneal cavity by retrograde menstruation backflow [4]. The endometrial cells in peritoneal fluid may follow clockwise peritoneal circulation and pass through the right paracolic gutter towards the right sub-diaphragmatic region. The phrenicocolic ligament on the left side and falciform ligament form barriers that prevent cells and fluids from reaching the left sub-diaphragmatic area [10,11]. Implantation of endometrial cell leads to the formation of endometriotic nodules on the ventral side of the diaphragm [10]. The nodules cause cyclical necrosis and induce diaphragmatic fragility, leading to the formation of the usual diaphragmatic fenestrations. After endometrial tissue enters the pleural space, it may form colonies in other part of the diaphragm or in the pleural space. Air leaks from vagina may occur during the menstrual cycle when the cervical mucus plug is deleted [10-14]. This hypothesis may be in good agreement with the observation that endometriosis occurs nine times frequently on the right hemidiaphragm than on the left [4,6,14,15].

Coelomic Metaplasia

The second proposes the coelomic metaplasia mechanism that causes endometriosis by metaplasia of mesothelial cells lining the pleura and peritoneal surfaces into endometrial stroma and gland [9,16,17]. Transformation of these cells may be affected by physiological stimuli such as estrogen [18]. Support for this hypothesis is observed in endometriosis patients with Mayer- Rokitansky-Küster-Hauser syndrome who lack a functional endometrium [19,20]. Rare cases of endometriosis can also occur in men receiving high-dose estrogen. The coelomic metaplasia hypothesis provides an explanation for pleural cases of thoracic endometriosis. However, this fails to explain the right-sided predominance seen in patients with thoracic endometriosis.

Prostaglandin

The third is a bioactive substance-mediated mechanism in which high levels of prostaglandins, in particular prostaglandin F2α. Prostaglandins are detectable in the plasma of women during menstruation. Circulating prostaglandins increase with menstruation [21,22-25] and causes vascular and bronchiolar vasoconstriction, leading to the vasospasm and associated ischemia within the lung [23,25,26]. This may result in alveolar rupture of previously formed subpleural blebs and bullae, and subsequent air leaks [23,25-27].

Hematogenous or Lymphatic Metastasis

An interesting hypothesis of metastasis suggests that endometrial transplantation occurs through lymphatic or hematogenous dissemination of endometrial cells, explaining both the thoracic and other sites of implantation, in an analogous manner to cancer metastasis [7,28,29]. Review of autopsy data of humans with thoracic endometriosis shows that patients with bronchopulmonary endometriosis usually have bilateral lesions, whereas diaphragmatic and pleural diseases are predominantly right sides [17]. Perhaps the most compelling evidence for the benign metastasis hypothesis is derived from the investigations of ectopic endometriosis lesions occurring in remote parts of the body including the bone or brain [8,21,30-32].

Comment

Thoracic endometriosis is characterized by the presence of endometrial-like glands and stroma within the lung parenchyma or on the diaphragm and pleural surfaces. It remains unclear how endometrial tissue migrates to the thoracic cavity, but it is often associated with abdominal endometriosis. As none of the theories proposed alone can account for all clinical manifestations of this condition, so the etiology of thoracic endometriosis development is likely multifactorial and closely intertwined with each other hypothesis.

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