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The field of vascular medicine has undergone a profound transformation in the 21 st century, transforming our approach to assessment and treatment. Atherosclerosis, a complex inflammatory disease that affects medium and large arteries, presents a major challenge for researchers and healthcare professionals. This condition, characterized by arterial plaque formation and narrowing, poses substantial challenges to vascular health at individual, national, and global scales. Its repercussions are far-reaching, with clinical outcomes including ischemic heart disease, ischemic stroke, and peripheral arterial disease-conditions with escalating global prevalence. Early detection of vascular changes caused by atherosclerosis is crucial in preventing these conditions, reducing morbidity, and averting mortality. This article underscored the imperative of adopting a holistic approach to grappling with the intricacies, trajectories, and ramifications of atherosclerosis. It stresses the need for a thorough evaluation of the vasculature and the implementation of a multidisciplinary treatment approach. By considering the entire vascular system, healthcare providers can explore avenues for prevention, early detection, and effective management of this condition, ultimately leading to improved patient outcomes. We discussed current practices and proposed new directions made possible by emerging diagnostic modalities and treatment strategies. Additionally, we considered healthcare expenditure, resource allocation, and the transformative potential of new innovative treatments and technologies., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To assess height and weight as possible sex-specific risk factors for bilateral myopia among young adults., Methods: We conducted a cross-sectional study including 101,438 pre-enlisted young adult males and females, aged 17.4 ± 0.6 and 17.3 ± 0.5 years, respectively, and born during 1971-1994. Categories of BMI (body mass index) were defined according to sex-related percentiles for 17-year-olds following U.S. Centers for Disease Control and Prevention growth charts, and subjects were divided into five height and weight categories according to sex-adjusted percentiles. Data included best-corrected visual acuity, diverse socio-demographic variables, anthropometric indices, and refractive errors, namely bilateral myopes and emmetropes., Results: The prevalence of bilateral myopia in males and females was 19.1% and 26.0%, respectively. Bilateral myopia displayed a J-shaped associated with BMI, achieving statistical significance only among males (p < 0.0001). Weight displayed a U-shaped association with bilateral myopia among both young males (p < 0.0001) and females (p < 0.005). A higher prevalence of bilateral myopia was observed only among males of the lower height category (p < 0.0001), even when controlling for BMI (from normal to obesity). In a multivariable regression model, obesity was associated with higher prevalence of bilateral myopia (OR: 1.21; 95% CI: 1.07-1.38, p = 0.002), only among males. There were no interactions of BMI with height or weight. Bilateral myopia was also associated with prehypertension among males (OR: 1.10, 95% CI: 1.04-1.15, p < 0.001)., Conclusions: A higher risk for bilateral myopia was associated with either BMI solely or height and weight, as well as pre-hypertension, in males. The possible association with low height requires further research., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Deciphering the origins of phenotypic variations in natural animal populations is a challenging topic for evolutionary and conservation biologists. Atypical morphologies in mammals are usually attributed to interspecific hybridisation or de-novo mutations. Here we report the case of four golden jackals (Canis aureus), that were observed during a camera-trapping wildlife survey in Northern Israel, displaying anomalous morphological traits, such as white patches, an upturned tail, and long thick fur which resemble features of domesticated mammals. Another individual was culled under permit and was genetically and morphologically examined. Paternal and nuclear genetic profiles, as well as geometric morphometric data, identified this individual as a golden jackal rather than a recent dog/wolf-jackal hybrid. Its maternal haplotype suggested past introgression of African wolf (Canis lupaster) mitochondrial DNA, as previously documented in other jackals from Israel. When viewed in the context of the jackal as an overabundant species in Israel, the rural nature of the surveyed area, the abundance of anthropogenic waste, and molecular and morphological findings, the possibility of an individual presenting incipient stages of domestication should also be considered., (© 2023. The Author(s).)

Purpose: To assess the associations between the prevalence of congenital color vision deficiency (CVD) and genetics and environment, represented by place of origin (ethnic background) and place of birth, respectively., Methods: This is a retrospective study of the computerized database of the northern recruitment center of Israel of 53,895 consecutive male Jewish conscripts 16-19 years old, who completed the medical profiling process between 1988 and 2011. CVD was diagnosed using the 24-pseudo-isochromatic plate Ishihara test. Associations of CVD prevalence with sociodemographic variables, anthropometric indices, refractive errors, and mainly place of origin and place of birth were tested by both univariate analysis and multivariate regression models., Results: Elevated BMI (obesity) and blood pressure (hypertension), as well as myopia, were all positively associated with congenital CVD. The composition of the study population provides a unique opportunity to investigate the relationship between ethnicity and environment. The prevalence of CVD significantly differs among subpopulations of different ethnic background as well as among those who were born in different geographical locations. Additionally, differences in the prevalence of CVD (1.2-1.6%) were observed among conscripts from the same origin, who were born in Israel, compared to those who were born elsewhere. Both place of origin (p < 0.01) and place of birth (p < 0.05) were associated with the prevalence of CVD in a multivariable regression model., Conclusion: This study affirms previously established associations of CVD with certain variables and reveals a possible novel association of CVD with environmental factors., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abundant evidence strongly suggests that the condition of pregnancy makes women and their fetuses highly vulnerable to severe Corona-virus 2019 (COVID-19) complications. Here, two novel hypoxia-related conditions are proposed to play a pivotal role in better understanding the relationship between COVID-19, pregnancy and poor health outcomes. The first condition, "misattributed dyspnea (shortness of breath)" refers to respiratory symptoms common to both advanced pregnancy and COVID-19, which are mistakenly perceived as related to the former rather than to the latter; as a result, pregnant women with this condition receive no medical attention until the disease is in an advanced stage. The second condition, "silent hypoxia", refers to abnormally low blood oxygen saturation levels in COVID-19 patients, which occur in the absence of typical respiratory distress symptoms, such as dyspnea, thereby also leading to delayed diagnosis and treatment. The delay in diagnosis and referral to treatment, due to either "misattributed dypsnea" or "silent hypoxia", may lead to rapid deterioration and poor health outcome to both the mothers and their fetuses. This is particularly valid among women during advanced stages of pregnancy as the altered respiratory features make the consequences of the disease more challenging to cope with. Studies have demonstrated the importance of monitoring blood oxygen saturation by pulse oximetry as a reliable predictor of disease severity and outcome among COVID-19 patients. We propose the use of home pulse oximetry during pregnancy as a diagnostic measure that, together with proper medical guidance, may allow early diagnosis of hypoxia and better health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Machluf, Rosenfeld, Ben Shlomo, Chaiter and Dekel.)

Diverse populations worldwide are differentially affected by coronavirus disease 2019 (COVID-19). While socioeconomic background has been studied extensively, little is known about the genetic variation underlying this phenomenon. This study is aimed at examining the genetic basis behind the great discrepancies among diverse ethnic groups in terms of COVID-19 susceptibility for viral infection, disease prognosis, and mortality. To this end, in silico analysis of single-nucleotide polymorphisms (SNPs) within regulatory sequences of the human angiotensin-converting enzyme 2 ( ACE2 ) and transmembrane protease serine 2 ( TMPRSS2 )-the virus's gateway to host cells-and their plausible implications on expression levels was conducted. We provide indication that the variation in the human ACE2 and TMPRSS2 regulatory sequences is likely to be involved in and contribute to this phenomenon. SNPs that are abundant in the more susceptible populations introduce binding sites (BSs) for transcription factors or they may invalidate BSs for transcription repressor-both may enhance target gene ( ACE2 or TMPRSS2 ) expression in the relevant target tissues. SNPs that are abundant in the more resistant populations may invalidate BSs for a transcriptional repressor or they may introduce BSs for a transcriptional repressor or initiator of mRNA degradation, which may reduce target gene expression levels. This aspect, when added to the socioeconomic factors, can be a cause for the divergent prevalence of the disease and the different mortality rates within diverse populations. This demonstration may call for a shift in the paradigm of searching for COVID-19 biomarkers, such that SNPs within regulatory sequences should be of high importance., (Copyright © 2020 Barash, Machluf, Ariel and Dekel.)

Gender-specific differences in the prevalence, incidence, comorbidities, prognosis, severity, risk factors, drug-related aspects and outcomes of various medical conditions are well documented. We present a literature review on the extent to which research in this field has developed over the years, and reveal gaps in gender-sensitive awareness between the clinical portrayal and the translation into gender-specific treatment regimens, guidelines and into gender-oriented preventive strategies and health policies. Subsequently, through the lens of gender, we describe these domains in detail for four selected medical conditions: Asthma, obesity and overweight, chronic kidney disease and coronavirus disease 2019. As some of the key gender differences become more apparent during adolescence, we focus on this developmental stage. Finally, we propose a model which is based on three influential issues: (1) Investigating gender-specific medical profiles of related health conditions, rather than a single disease; (2) The dynamics of gender disparities across developmental stages; and (3) An integrative approach which takes into account additional risk factors (ethnicity, socio-demographic variables, minorities, lifestyle habits etc .). Increasing the awareness of gender-specific medicine in daily practice and in tailored guidelines, already among adolescents, may reduce inequities, facilitate the prediction of future trends and properly address the characteristics and needs of certain subpopulations within each gender., Competing Interests: Conflict-of-interest statement: The authors declare that there are no commercial or financial or any other relationships that could be construed or perceived by the academic or medical communities as representing a potential conflict of interest. The opinions expressed in this manuscript represent the consensus of the authors and do not necessarily reflect the formal position of the affiliated institutions., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Asthma is a multifactorial, heterogeneous, complex and common chronic respiratory disease driven by diverse mechanisms. Although asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question. Methods: This article presents a cross-sectional study of 113,671 Israeli adolescents. Univariate and multivariable logistic regression models were performed to analyze the independent associations between mild asthma and moderate-to-severe asthma phenotypes and coexistent medical conditions within each gender separately. Hierarchical clustering of the odds ratios of the diverse statistically significant medical conditions associated with asthma severity-gender groups was also performed. We focused on the allergic and neurological-cognitive-mental disorders. Results: Among males, two associations were common to both asthma groups (atopic dermatitis and allergic rhinitis), five unique to mild asthma (urticaria/angioedema, Hymenoptera/bee allergies, allergic conjunctivitis, epilepsy and migraine) and two unique to moderate-to-severe asthma (learning disabilities and ADD/ADHD (Attention-deficit disorder/Attention-deficit/hyperactivity disorder)). Among females, two associations were common to both clinical asthma groups (allergic rhinitis and urticaria/angioedema), and five unique to moderate-to-severe asthma (atopic dermatitis, learning disabilities, ADD/ADHD, anxiety/mood disorders and migraine). Allergic rhinitis was the only condition to be associated with all four groups. Learning disabilities and ADD/ADHD were only associated with moderate-to-severe asthma (but not with mild asthma), in both males and females. Hierarchical clustering analysis uncovered two prominent clusters, separating mild from moderate-to-severe asthma. Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to comorbidities, and indicate varied etiologies.

Background: Acute rheumatic fever (ARF) remains a major worldwide healthcare problem, despite its progressive decline in developed countries. The aims of our study were to estimate the prevalence of ARF among adolescents in Israel and to investigate risk factors. Methods: The study population consisted of 113,671 consecutive conscripts 16-19 years old, born during 1971-1993, who completed the medical profiling as part of the recruitment process to the IDF. ARF was diagnosed according to Jones criteria at time of illness, with confirmation relying on medical documentation and cardiologist evaluation including echocardiography. Results: The general prevalence rate of ARF was 0.12%. A downward trend was observed, from 0.19% among those born during 1971-1980 to 0.07% among those born during 1981-1993. Differences in prevalence of ARF were noted in sub-populations based on country of birth and origin-Israel, Ethiopia and the former soviet union (FUSSR). The prevalence rates of valvar disease among ARF+ and ARF- recruits were 15.7% and 0.95%, respectively. In multivariable logistic regression analyses, 4 variables were negatively associated with ARF: later birth year group, female gender, rural residence, youngest child; and 3 were positively associated with ARF: young parents, above normal BMI and valvar disease. Conclusion: Our study provides support for the documented decline in ARF prevalence and describes socio-demographic and anthropometric risk factors including the association with valvar disease and novel risk factors including above normal BMI and young parents, both warranting further investigation which might help in developing societal level prevention strategies., (Copyright © 2020 Machluf, Chaiter, Farkash, Sebbag and Fink.)

Purpose: To determine the trends in prevalence of myopia in Israeli young adults over approximately a generation, as well as associated factors and variation in the impact of these factors on myopia prevalence in this region over time., Design: Retrospective, cross-sectional study., Participants: One hundred four thousand six hundred eighty-nine consecutive persons 16 to 19 years of age born between 1971 and 1994 who had not yet enlisted in the Israeli Army but had completed the medical profiling process., Methods: Using data collected at a north Israel recruitment center, the prevalence of myopia over time was estimated, and a polynomial regression analysis was performed to assess significance of nonlinear trends. Associations of demographic and socioeconomic factors with myopia were assessed, and trends over time were analyzed using a factorial logistic regression., Main Outcome Measures: The primary outcome measure was factors associated with the prevalence of myopia over time. The secondary outcome measure was a description of the change in prevalence of myopia over time., Results: The prevalence of myopia increased 1.284-fold over 24 years from 20.4% among participants born between 1971 and 1982 to 26.2% among participants born between 1983 and 1994. A quite similar increase was observed among males (from 17.9% to 22.7%, respectively) and females (from 23.9% to 30.8%, respectively). The factors found to be associated with myopia were as follows: more recent date of birth, female gender, more years of education, being the eldest child, non-Israeli ethnic origin, and urban residence. However, there were significant trends over time in the effects of some of these factors, most notably an attenuation of the difference between participants of different religions in the recent birth-years period. Most of these associations and trends were observed in both males and females separately, with some gender-specific variations. Immigrants from Ethiopia who were raised in Israel were highly more likely to demonstrate myopia than those who arrived at an older age., Conclusions: This study demonstrated an increase in the prevalence of myopia and the possible associations of urbanization- and higher education-related factors among several subpopulations and the risk for myopia developing., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To evaluate the relationship between spherical equivalent (SE) refractive error and myopia-related peripheral retinal changes (MPRCs) and to find the optimal cutoff for screening myopic teenagers., Patients and Methods: The study included 2,286 myopic subjects who had a dilated fundus examination between 1998 and 2011 and SE of -4.0 diopters (D) or higher in both eyes., Results: Ninety-five subjects (4.16%) had MPRCs. Two subjects (0.09%) had moderate-to-severe MPRCs. A significant correlation (P < .0001) between SE and MPRC was found. The highest sum of sensitivity (72.63%) and specificity (73.44%) was achieved when a SE of -6.25 D in the more myopic eye was utilized as the cutoff., Conclusions: SE and MPRCs are highly associated. The optimal cutoff to detect MPRC in teenagers is -6.25 D. However, using a SE of -4.0 D as the cutoff may be the practical choice for screening due to the noninvasiveness nature and low cost of the examination. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e311-e319.]., (Copyright 2019, SLACK Incorporated.)

Background: Epidemiological studies have reported an association between asthma and migraine, mainly in adults., Objective: To examine the association between specialist-diagnosed asthma and migraine among adolescents., Methods: The electronic database of a recruitment center was retrospectively searched for all 17-year-old draftees during the years 1987-2010. Diagnoses of asthma and migraine were made by certified specialists. The prevalence of migraine was compared among draftees with and without asthma. Covariate data on socio-demographics and associated medical conditions were recorded., Results: A total of 113 671 adolescents were available for analysis. Asthma was diagnosed among 4.0% and migraine among 1.9%. Migraine was significantly more prevalent among adolescents with asthma [174 of the 4581 subjects (3.8%)] compared to those without asthma [1946 of the 109 090 (1.8%)] [OR = 2.17 (95% CI 1.86-2.55; P < 0.001)]. Rates of migraine among subjects with and without allergic rhinitis were 6.3% and 1.7%, respectively [OR = 4.04 (95% CI 3.58-4.56; P < 0.001)]. On multivariate analysis, there was a significant association between migraine and both asthma [OR = 1.42 (95% CI 1.19-1.68)] and allergic rhinitis [OR = 3.18 (95% CI 2.80-3.63)]. Other factors significantly associated with migraine were female gender, urban area of residence, recent immigration to Israel, having three or fewer siblings, and abnormal body mass index., Conclusion: Clinicians should be aware that asthma and allergic rhinitis are potential risk factors for migraine in adolescents. A combined finding of these conditions and recurrent headache is highly suggestive of migraine and warrants a different diagnosis and treatment approach from sinusitis., (© 2018 John Wiley & Sons Ltd.)

Objectives: While asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question., Methods: This paper presents a cross-sectional study of 113,671 Israeli adolescents. Prevalence rates of mild and moderate-to-severe asthma over a 24-year period were calculated and multivariate regression models (outcomes: different asthma severity, reference: subjects without asthma) were performed to analyze associations with anthropometric indices and socio-demographic variables, in males and females separately., Results: The prevalence of mild asthma increased until birth years 1976-1980 and then steadily decreased. In contrast, the prevalence of moderate-to-severe asthma was relatively stable until birth years 1976-1980, then rose steeply until 1986-1990 and subsequently plateaued in the early 1990s. Obesity was positively associated with both mild and moderate-to-severe asthma in males (Odds Ratio (OR) [95%CIs]: 1.61 [1.37-1.89] and 1.63 [1.34-1.98], respectively) and females (1.54 [1.10-2.16] and 1.54 [1.20-1.98], respectively). Family size greater than three siblings was negatively associated with both mild and moderate-to-severe asthma in males (0.62 [0.56-0.68] and 0.59 [0.52-0.68]) and females (0.71 [0.60-0.83] and 0.73 [0.63-0.83]). In contrast, in males, underweight was only associated with mild asthma (1.54 [1.22-1.94]) but not with moderate-to-severe asthma. In females, overweight was only associated with moderate-to-severe asthma (1.21 [1.00-1.46]) and rural residence was only associated with mild asthma (1.26 [1.09-1.47])., Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to secular trends and associated variables, and indicate varied etiologies.

Background: Rheumatic heart disease (RHD) among Ethiopian school children was recently found to be 1.4%. Immigration of the Jewish population from the Gondar region to Israel created an opportunity for further enquiry., Methods: A cross-sectional study of the cardiac status of 113,671 adolescent recruits aged 16-19 years from the northern district of Israel who completed the medical profiling process over a 22-year period., Results: 140 recruits had a history of rheumatic fever (0.12%), although none from an Ethiopian origin ( n  = 1,719). The prevalence of valvular heart disease clinically and confirmed echocardiographically in Ethiopian recruits was not different from the total population (0.81 and 0.93%, respectively). However, the prevalence was higher in those migrating to Israel in their 13th year or older (2.09%), compared to those migrating at a younger age or born in Israel (0.49%)., Conclusion: The Ethiopian teenage Israeli population from Gondar had a high rate of auscultation positive and echocardiographically confirmed valvular disease that suggested a high rate of RHD (~1.6%), despite no relevant past history. Our findings also suggested that for the younger Ethiopian immigrants or Israeli born subjects of Ethiopian origin, the improved medical care may well reduce the prevalence of valvular heart disease to that of the rest of the local population.

Aims: To estimate the prevalence of amblyopia, present strabismus and amblyopia risk factors (ARFs) among young adults in Israel and to analyse trends over time of prevalence rates., Methods: We conducted a cross-sectional study including 107 608 pre-enlistees aged 17.4±0.6 years born between 1971 and 1994. Across the birth years, the following trends of prevalence rates among young adults were analysed: prevalence of amblyopia, prevalence of strabismus, severity of amblyopia and prevalence of ARFs (strabismsus, anisometropia and isoametropia). Unilateral amblyopia was defined as best corrected visual acuity (BCVA) of <0.67 (6/9) in either eye or as an interocular difference of two lines or more. Bilateral amblyopia was defined as BCVA of <0.67 (6/9) in both eyes. The severity of amblyopia was classified as mild (BCVA ≥0.5 [6/12]), moderate (BCVA <0.5 [6/12] and ≥0.25 [6/24]) or severe (BCVA <0.25 [6/24])., Results: The prevalence of young adulthood amblyopia declined by 33%, from 1.2% to 0.8% (R 2 =0.87, p<0.001) across 24 birth years. This decline may be due to a drop in unilateral amblyopia from 1% to 0.6% (R 2 =0.93, p<0.001), while the prevalence of bilateral amblyopia remained stable (0.2%, p=0.12). The decline in amblyopia was apparent in mild and moderate amblyopia, but not in severe amblyopia. Strabismus and anisometropia were detected in 6-12% and 11-20% of subjects with unilateral amblyopia, respectively, without significant trends. Strabismic amblyopia remained constant in the entire population across years. Isoametropia was detected in 46-59% of subjects with bilateral amblyopia without a significant trend across birth years. Prevalence of strabismus in the study population decreased by 50%, from 1.2% to 0.6% (R 2 =0.75, p<0.001). In subjects with present strabismus, the prevalence of mild unilateral amblyopia increased, while moderate or severe unilateral amblyopia remained relatively stable., Conclusion: Among young adults, the prevalence of unilateral amblyopia, as well as the prevalence of present strabismus, decreased significantly over a period of a generation. The prevalence of strabismic, bilateral or severe (both unilateral and bilateral) amblyopia remained stable. The establishment of the national screening programme for children and the improved utility of treatment for amblyopia and strabismus coincide with these trends. Thus, it is possible that these early interventions resulted in modification of the 'natural history' of these conditions and their prevalence in adolescence., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Study Question: Is there an association between spermatozoon genomic stability and vacuolar morphology and location?, Summary Answer: The genomic stability of spermatozoa is associated with specific characteristics of vacuolar morphology (depth) and location (cellular compartment, i.e. nucleus and equatorial region)., What Is Known Already: Genetic anomalies in sperm are correlated with semen abnormalities, yet the advantage of morphologically based selection of spermatozoa for IVF according to current criteria is controversial. Selection criteria based on the number of vacuoles and their size have been proposed and are widely applied. Nevertheless, it has not improved the ICSI success rates, suggesting the currently used vacuole criteria are incomplete., Study Design, Size, Duration: Normal sperm according to Motile Sperm Organelle Morphology Examination criteria (MSOME) and common vacuole grading were evaluated. An additional evaluation of sperm vacuole morphology according to novel vacuole criteria (i.e. location and depth) was conducted. An assessment to align these specific vacuolar morphology features with genomic stability was conducted among spermatozoa from infertile patients and healthy fertile donors aged 24-38 between June 2015 and July 2016., Participants/materials, Setting, Methods: Single spermatozoa (n = 53) from 16 infertile patients and 14 fertile donors were morphologically and genetically evaluated. Each spermatozoon was examined morphologically, by ultra-magnification ×6300, and genetically by a novel comparative genomic hybridization protocol, without the use of reference DNA, to assess chromosomal instability as evident by copy number variations (CNV)., Main Results and the Role of Chance: We established an association between genomic stability and vacuolar morphology as a base for a new classification according to novel vacuolar criteria, specifically depth and location. Genomic instability was found to be related to these two main features of vacuoles and, surprisingly not to the number and size of vacuoles as in the previously proposed classifications. High CNV spermatozoa were characterized by vacuoles located in the nucleus and/or equatorial segment or by deep vacuoles, while, low CNV spermatozoa were characterized by a complete lack of vacuoles or non-deep vacuoles not located in the nucleus/equatorial segment. A putative threshold of ~265 CNV was deduced to distinguish between genetically stable and unstable spermatozoa, and 94% of the tested spermatozoa segregated accordingly., Limitations Reasons for Caution: A relatively small sample of spermatozoa were examined-53 in total. However, the association between vacuoles location and morphology and genomic stability was significant. This is the first study evaluating spermatozoon genomic stability with respect to vacuole morphology according to novel vacuole criteria (i.e. location and depth) and further investigation is warranted to verify the value of these criteria in larger sample size clinical studies., Wider Implications of the Findings: Our results, which are based on spermatozoon vacuoles morphological classification and genomic parameters, indicate an association between vacuoles morphology and location and genomic stability. The data presented herein suggest the existence of subpopulations of spermatozoa potentially appropriate for IVF-ICSI, as they appear normal according to the current MSOME and vacuoles classification, however they are almost certainly genetically damaged. As current criteria have yet to achieve an unequivocal evaluation of the implantation potential of a given spermatozoon, we propose novel criteria, based on specific vacuolar morphological traits; depth and location, as these were found aligned with genomic findings., Study Funding/competing Interest(s): No funding was received for this study. The authors have no conflict of interest to declare., Trial Registration Number: N/A.

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment., Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions., Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied., Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity., Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.

Background: Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan., Results: The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds., Conclusions: This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.

Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab). These Abs were examined for their ability to self-assemble and form ordered aggregates, by several biophysical methods. Atomic force microscopy analyses revealed the formation of multimeric nanostructures. The biological activity of multimeric IgG or IgY particles was retained and restored, in a dilution/time-dependent manner. IgG activity was confirmed by a binding assay using HER2 + human breast cancer cell line, SKBR3, while IgY activity was confirmed by ELISA assay using the VP2 antigen. Competition assay with native Herceptin antibodies demonstrated that the binding availability of the multimer formulation remained unaffected. Under long incubation periods, IgG multimers retained five times more activity than native IgG. In conclusion, the multimeric antibody formulations can serve as a storage depositories and sustained-release particles. These two important characteristics make this formulation promising for future novel administration protocols and altogether bring to light a different conceptual approach for the future use of therapeutic proteins as self-delivery entities rather than conjugated/encapsulated to other bio-compounds.

Background: In the era of big data, the medical community is inspired to maximize the utilization and processing of the rapidly expanding medical datasets for clinical-related and policy-driven research. This requires a medical database that can be aggregated, interpreted, and integrated at both the individual and population levels. Policymakers seek data as a lever for wise, evidence-based decision-making and information-driven policy. Yet, bridging the gap between data collection, research, and policymaking, is a major challenge., The Model: To bridge this gap, we propose a four-step model: (A) creating a conjoined task force of all relevant parties to declare a national program to promote collaborations; (B) promoting a national digital records project, or at least a network of synchronized and integrated databases, in an accessible transparent manner; (C) creating an interoperative national research environment to enable the analysis of the organized and integrated data and to generate evidence; and (D) utilizing the evidence to improve decision-making, to support a wisely chosen national policy. For the latter purpose, we also developed a novel multidimensional set of criteria to illuminate insights and estimate the risk for future morbidity based on current medical conditions., Conclusion: Used by policymakers, providers of health plans, caregivers, and health organizations, we presume this model will assist transforming evidence generation to support the design of health policy and programs, as well as improved decision-making about health and health care, at all levels: individual, communal, organizational, and national.

Objective: To determine the prevalence, secular trends and associations of heart disease in a large unscreened, otherwise basically healthy, adolescent population., Subjects and Methods: Cross-sectional study of the cardiac status of 113,694 adolescents from the northern district of Israel, who completed the profiling process between the ages of 16 and 19, including all essential measures over a 22-year period. Results of imaging were categorized as either isolated valvar or structural abnormalities, and their clinically significant subgroups defined prospectively. The findings were correlated with the socio-demographic and anthropometric data and non-cardiac health conditions., Results: Of those sent for echocardiography, 1257 (0.93% of the total population) had isolated valvar disease and 216 (0.19%) had structural abnormalities, with 20% of both groups considered significant. Females had lower prevalence of heart disease. There was peak prevalence in the second 5-year period. Tall subjects or a past history of rheumatic fever had more valvar abnormalities. Thin subjects or those with skeletal anomalies had more structural abnormalities. Significant valvar and structural anomalies were more common in subjects with learning disorders, endocrine disorders and diabetes mellitus. Fewer valvar abnormalities were diagnosed in obese subjects. Heart disease was more common in those with non-solid tumors., Conclusion: Appreciable numbers of potentially healthy adolescents were found to have heart disease. There appeared to be an association with body size, skeletal abnormalities and relatively common medical disorders, the cause of which remains to be determined in prospective studies that could change the way common adolescent disease should be followed.

Despite the central place held by bioinformatics in modern life sciences and related areas, it has only recently been integrated to a limited extent into high-school teaching and learning programs. Here we describe the assessment of a learning environment entitled 'Bioinformatics in the Service of Biotechnology'. Students' learning outcomes and attitudes toward the bioinformatics learning environment were measured by analyzing their answers to questions embedded within the activities, questionnaires, interviews and observations. Students' difficulties and knowledge acquisition were characterized based on four categories: the required domain-specific knowledge (declarative, procedural, strategic or situational), the scientific field that each question stems from (biology, bioinformatics or their combination), the associated cognitive-process dimension (remember, understand, apply, analyze, evaluate, create) and the type of question (open-ended or multiple choice). Analysis of students' cognitive outcomes revealed learning gains in bioinformatics and related scientific fields, as well as appropriation of the bioinformatics approach as part of the students' scientific 'toolbox'. For students, questions stemming from the 'old world' biology field and requiring declarative or strategic knowledge were harder to deal with. This stands in contrast to their teachers' prediction. Analysis of students' affective outcomes revealed positive attitudes toward bioinformatics and the learning environment, as well as their perception of the teacher's role. Insights from this analysis yielded implications and recommendations for curriculum design, classroom enactment, teacher education and research. For example, we recommend teaching bioinformatics in an integrative and comprehensive manner, through an inquiry process, and linking it to the wider science curriculum., (© The Author 2016. Published by Oxford University Press.)

The increasing prevalence of abnormal body mass index (BMI), mainly obesity, is becoming a significant public health problem. This cross-sectional study aimed to provide a comprehensive view of secular trends of BMI, and the associated socio-demographic variables and comorbidities among adolescents with abnormal BMI. Individuals of the study population were born mainly between 1970 and 1993, and were examined at 16 to 19 years of age during the years 1987 to 2010, at 1 conscription center in the northern district of Israel.The study population included 113,694 adolescents. Univariate and multivariable logistic regression models were used to investigate the associations between BMI categories, socio-demographic variables, and medical conditions.A downward trend in the prevalence of normal BMI among both male and female adolescents was obtained, while trends of overweight and obesity (in both genders) and underweight (only among females) rose. Socio-demographic variables such as religion, education, family-related parameters, residential environment, country of birth, and origin were all associated with different risks for abnormal BMI. Obesity was associated with higher risk for hyperlipidemia, endocrine disorders (only in males), knee disorders, and hypertension type I + II (in both genders). Overweight was associated with knee disorders (only in females). Underweight, exclusively in males, was associated with increased risk for endocrine disorders, proteinuria, and cardiac disorders. Hierarchical clustering analysis revealed the intricate relations between gender, BMI, and medical signatures. It brought to light novel clusters of diseases that were abundant among populations having above-normal BMI or underweight males. Furthermore, above-normal BMI was associated with a lower rate of cardiac anomalies and scoliosis/kyphosis, whereas being underweight was associated with a lower risk for hypertension and flat foot.This study provides a reliable and in-depth view of secular trends in height, weight, and BMI of male and female adolescents. It supports previous associations between abnormal BMI and demographic variables and comorbidities, while uncovering novel associations, mainly regarding medical signatures of each gender-BMI group. This might lead to better monitoring, early detection, prevention, and treatment of various conditions associated to abnormal BMI categories and gender groups., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background: In recent years, the perception of transposable genetic elements has changed from "junk DNA" to a focus of interest when appearing near or inside genes. Bov-A2 is a short interspersed nuclear element (SINE) that was first found in Bovidae and later in other ruminants. This retroposon is mostly used as a marker for phylogenetic analysis., Results: We describe insertions of Bov-A2 in the promoter region of TP53, a key tumor suppressor gene that is indispensable for diverse developmental processes, in Antilopinae and Tragelaphini (belonging to the Bovinae subfamily). In Tragelaphini two Bov-A2 elements were inserted sequentially, whereas in 5 tribes of Antilopinae only one Bov-A2 element was inserted, in a different site and reverse orientation. The entrance site in both cases employed short palindromes that can form hairpin secondary structures. Interestingly, mutations that create or disrupt base pairing in the palindrome sequence dictated the presence or absence of Bov-A2, such as in the domestic cow and buffalo, which lack Bov-A2. Transcription factor binding site analysis revealed unique binding sites for STAT3 and NFκB within the Bov-A2 sequence, which together with TP53 itself are known to play a crucial role in mammary involution., Conclusions: This report demonstrates how short palindromes serve as hot spots for Bov-A2 retroposon insertion into the mammalian genome. The strict correlation between point mutation in the palindromes and the presence/absence of Bov-A2 retroposon insertions, questions the use of singular insertion events as valid phylogenetic markers inside families. Bov-A2 insertion into the TP53 promoter in Antilopinae and Tragelaphini may not only provide a genetic network that regulates mammary involution, but can also answer the need for rapid mammary involution in Savanna antelopes after weaning, partially in response to predation stress. The absence of Bov-A2 in domestic bovids may constitute the molecular background for greater lactation persistency.

Purpose: As part of the routine work of the medical committees in the Israel Defense Forces, a unique nationwide computerized control system is being implemented to assess and manage medical processes. The purpose of this paper is to report on that implementation., Design/methodology/approach: The computerized system consists of three main components: a specific status indicating the processes in each file, an appointment system, and an internal computerized system that uses a magnetic card for the regulation of the local waiting lists., Findings: The combined computerized system improves the control and management of the medical processes and informatics from the point-of-view of both the patients and system operators. Different parameters of quality control regarding the medical and administrative processes are assessed (such as efficiency), and solutions are sought. Computerized system-based design and re-allocation of human and medical resources were implemented according to the capacities and limitations of the medical system. A reduction in the daily number of invited recruits improved the quality of the medical encounters. Specific combined status codes were introduced for the efficient planning of the medical encounters. Implementation and automation of medical regulations and procedures within the computerized system make the latter play a key role and serve as a control tool during the decision-making process., Originality/value: The computerized system allows efficient follow-up and management of medical processes and informatics, led to a better utilization of human and medical resources, and becomes a component of the decision making by the system operators and the administrative staff. Such a system could be used with success in clinics, hospitals, and other medical facilities.

Hypothalamic neurons regulate fundamental body functions including sleep, blood pressure, temperature, hunger and metabolism, thirst and satiety, stress, and social behavior. This is achieved by means of the secretion of various hypothalamic neuropeptides and neurotransmitters that affect endocrine, metabolic, and behavioral activities. Developmental impairments of hypothalamic neuronal circuits are associated with neurological disorders that disrupt both physiological and psychological homeostasis. Hypothalamic cell specification and morphogenesis can be uniquely studied in zebrafish, a vertebrate organism readily amenable to genetic manipulations. As embryos are optically transparent and develop externally, they provide a powerful tool for in vivo analyses of neurons and their circuits. Here, we discuss the current knowledge regarding the neuroanatomy of the zebrafish hypothalamus and recent studies identifying critical determinants of hypothalamic differentiation. Taken together, these reports demonstrate that the molecular pathways underlying development of the hypothalamus are largely conserved between zebrafish and mammals. We conclude that the zebrafish has proved itself a valuable vertebrate model for understanding the patterning, specification, morphogenesis, and subsequent function of the hypothalamus., (© 2011 New York Academy of Sciences.)

Purpose: This paper seeks to examine an intervention program which was developed in order to improve the performance and skills of technical medical personnel at the military recruitment medical committees., Design/methodology/approach: Evaluation of the technician soldiers' performance was carried out by the usage of a specifically farmed survey, comprising a designed questionnaire, and direct observation of their work, including appraisal of their measurements and interpretation skills., Findings: Prior to intervention, analysis revealed: insufficient knowledge of normal range of blood pressure and pulse values, visual acuity of color vision, urinalysis and their relation to the classification process at medical committees; and inadequate technicalities such as incorrect weight and height measurements., Originality/value: The model of the intervention program could be modified and adopted by medical committees, sports medicine examinations, periodic screening procedures, and primary care medicine in order to improve the quality of medical records and medical care.

Examination of spatial and temporal gene expression pattern is a key step towards understanding gene function. Therefore, in situ hybridization of mRNA is one of the most powerful and widely used -techniques in biology. Recent advances allow the reliable and simultaneous detection of mRNA transcripts, or combinations of mRNA and protein, in zebrafish embryos.Here we describe a standard protocol for visualizing the precise expression pattern of a single transcript or multiple gene products. The procedure employs fixation and permeabilization of embryos, followed by hybridization with tagged antisense riboprobes. Excess probes are then washed and hybrids are detected by enzyme-mediated immunohistochemistry utilizing either chromogenic or fluorescent substrates.

Purpose: The paper aims to focus on a unique quality control system that was set up ten years ago to evaluate Medical Classification Committee decision-making processes at the Israel Defense Forces (IDF) conscription center., Design/methodology/approach: Two main approaches were deployed by the control system to assess medical classification committees' performance. The first was direct assessment of the medical committees' clinical work and decision-making processes. The second applied data mining procedures to the computerized medical databases. The functional classification codes (FCCs)--codes for the most common medical disorders assigned to male recruits from the central computerized central IDF database, the sub-districts comprising the recruitment centers, and the chairmen assigning the FCCs to recruits--were all analyzed., Findings: A total of 26 FCCs, each indicating a common medical problem and its severity, constituted approximately 90 percent of all FCCs assigned at recruitment centers between 2001 and 2006. Major contributors to medical profiling outcomes were underweight, asthma, chronic headache, mental illness, symptomatic scoliosis, hypnosis, chronic back pain, knee joint disorders, allergic rhinitis and sinusitis. Evaluating the computerized medical database revealed significant differences in: medical profile prevalence; recruitment center FCCs; different sub-districts in a given recruitment center; and profiling by medical committee chairmen., Practical Implications: Findings indicate disparities between recruitment centers and their chairmen in the medical profiling process owing to variations in recruitment center working methods and medical history taking, physical examinations, interpreting medical information and individual differences in the chairmen's decision-making process. Other reasons include technician and laboratory staff inaccuracies. These significant discrepancies highlighted the need for an intervention program. To minimize variations and create a uniform work platform, an orderly instruction system and training programs for the committee chairmen, technicians and laboratory staff were established. These actions resulted in improved performance in 2007 as confirmed by a decreased variability in the assignment of medical FCCs., Originality/value: The paper highlights methods that can be used to assess disability screening, sports medicine committees and primary care setting procedures.

Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF-kappaB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-kappaB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-kappaB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response.

Ligand-dependent endocytosis of the epidermal growth factor receptor (EGFR) involves recruitment of a ubiquitin ligase, and sorting of ubiquitylated receptors to lysosomal degradation. By studying Hgs, a mammalian homolog of a yeast vacuolar-sorting adaptor, we provide information on the less understood, ligand-independent pathway of receptor endocytosis and degradation. Constitutive endocytosis involves receptor ubiquitylation and translocation to Hgs-containing endosomes. Whereas the lipid-binding motif of Hgs is necessary for receptor endocytosis, the ubiquitin-interacting motif negatively regulates receptor degradation. We demonstrate that the ubiquitin-interacting motif is endowed with two functions: it binds ubiquitylated proteins and it targets self-ubiquitylation by recruiting Nedd4, an ubiquitin ligase previously implicated in endocytosis. Based upon the dual function of the ubiquitin-interacting motif and its wide occurrence in endocytic adaptors, we propose a ubiquitin-interacting motif network that relays ubiquitylated membrane receptors to lysosomal degradation through successive budding events.