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Spondylometaphyseal dysplasia (SMD) is characterized by developmental changes in long bones and vertebrae. It has large phenotypic diversity and multiple genetic causes, including a recent link to novel variants in the extracellular matrix (ECM) protein fibronectin (FN), a regulator of ECM assembly and key link between the ECM and proper cell function. We identified a patient with a unique SMD, similar to SMD with corner fractures. The patient has been followed over 19 years and presents with short stature, genu varum, kyphoscoliosis, and pectus carinatum. Radiography shows metaphyseal changes that resolved over time, vertebral changes, and capitular avascular necrosis. Whole exome sequencing identified a novel heterozygous FN1 variant (p.Cys97Trp). Using mass spectroscopy, mutant FN was detected in plasma and in culture medium of primary dermal fibroblasts isolated from the patient, but mutant protein was much less abundant than wild‐type FN. Immunofluorescence and immunoblotting analyses show that mutant fibroblasts assemble significantly lower amounts of FN matrix than wild‐type cells, and mutant FN was preferentially retained within the endoplasmic reticulum. This work highlights the importance of FN in skeletal development, and its potential role in the pathogenesis of a subtype of SMD. [ABSTRACT FROM AUTHOR]

Backgrounds: Reports from the last decade suggest an epidemic of overweight and obesity in Western countries. Since obesity has been associated with increased blood pressure, we aimed to describe the secular trends in overweight and obesity and blood pressure among Israeli working adults. METHODS: Two cross-sectional studies were conducted in the setting of the Civil Servant Registry, Tel-Aviv District Health Office, Ministry of Health, Israel, including 1949 adults aged 17-69 years, who entered the Israeli civil service in 1993 and 2002. RESULTS: Compared with other reports, the overall prevalence rate (32.2%) of overweight and obesity was relatively low in our study population, however, an increase of 34% in the odds of being overweight or obese was noted during the study period (adjusted odds ratio: 1.34, 95% CI: 1.09-1.65). Despite this increase, the adjusted mean systolic blood pressure significantly fell from 119.3 (18.2) to 117.0 (14.3) mmHg (P < 0.001) during the 10-year period, and the respective mean diastolic blood pressure declined from 74.5 (9.0) mmHg to 73.2 (9.8) mmHg (P < 0.001). CONCLUSION: Israel joined the universal trend of increase in overweight and obesity. This study demonstrated a concomitant decline in blood pressure that could not be attributed to antihypertensive treatment. The decrease in blood pressure could partially explain the decrease in cardiovascular morbidity and mortality seen in Israel. [ABSTRACT FROM AUTHOR]

Introduction: Disparities in oral health are related to dental care knowledge, domestic oral hygiene practices and socioeconomic status. This cross-sectional study aimed to compare the oral hygiene and dental care practices of migrant, Arab, and Jewish children residing in Tel Aviv, Israel, and assess the influence of parental dental practices., Methods: Data were collected from parents of children aged 3 to 6 years. Parents completed their own and their children's oral health status, oral hygiene practices, dietary habits and dental care knowledge., Results: Of the 504 children, 153 (30.4%) were migrants, 117 (23.2%) were Arabs, and 234 (46.4%) were Jews. Twice-daily tooth brushing was reported by 57.5% of migrant children, 47% of Arab children, and 63.7% of Jewish children (p = 0.001). Compared with Arab and Jewish children, migrant children had higher rates of tooth filling and urgent dental interventions under general anesthesia (22.9%, 11.1%, and 9%, respectively; p < 0.001). The parent‒child association for twice-daily tooth brushing was strong overall (69.8%), particularly among migrants (70.9%) and Jews (72.3%), but weaker among Arabs (63.0%), p < 0.01., Conclusion: Migrant children exhibited better tooth brushing habits than Arab children did but required more urgent dental interventions, highlighting gaps in preventive care. The strong parent‒child link in oral hygiene, particularly among migrants and Jews, suggests that culturally sensitive, family-focused interventions could help reduce these disparities and improve dental health outcomes for underserved populations., Competing Interests: Declarations. Ethics approval and consent to participate: This study received ethical approval from the Ethics Committee of Ashkelon Academic College in accordance with the principles of the Helsinki Declaration. Approval for the distribution of questionnaires among parents was also granted by the Chief Scientist of the Ministry of Education. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background/Objectives: Mycoplasma genitalium ( MG ) infections and antibiotic resistance are increasing in prevalence while treatment options are limited. Limited data exist regarding MG resistance in Israel. Our aim was to study the prevalence of MG resistance in a sexually transmitted infection (STI) clinic in Israel. Methods: We performed a single-center retrospective study among patients attending an STI clinic during 2019-2020. MG isolates were tested to detect their resistance to azithromycin and fluoroquinolones (FQs) using commercial kits (Allplex™ MG & AziR Assay, Allplex™ MG & MoxiR Assay). We collected patient data regarding the risk factors for STIs and resistance. A multivariate logistic regression model was used to identify the risk factors for resistance. Results: Of the 142 patients who tested positive for MG , 50 (35.2%) and 22 (15.5%) had resistant mutations to azithromycin and FQ, respectively, and 13 (9.2%) showed resistance to both agents. In a multivariate logistic regression model, men who have sex with men (RR 7.01 95% CI 3.00-16.33) and past STIs (RR 2.33 95% CI 1.01-5.34) were independent risk factors for azithromycin resistance. Conclusions: We found a high prevalence of azithromycin resistance and, to a lesser degree, FQ resistance. These findings may help design the treatment guidelines and support routine resistance testing in high-risk populations.

This report describes an unusual surge of West Nile fever in Israel in June 2024, during which 125 cases were diagnosed, compared with 4 cases on average during June in previous years (2014-23). Of the cases, 64 (62.1%) had neuroinvasive disease and 12 (9.6%) died; the 2024 case fatality rate was not significantly elevated vs the average rate in 2014-23. The early rise could be related to a temperature increase in spring and early summer of 2024.

In October 2023, the Tel Aviv District was notified of ten cases of measles. The outbreak initiated in a preschool with high vaccination coverage with one dose of MMR vaccine. Serological testing was available for eight patients (six children and two adults). Among the six children vaccinated with one dose of MMR vaccine, primary vaccine failure was demonstrated. Among the adults, secondary vaccine failure was confirmed. The outbreak was successfully contained due to a combination of factors, notably its occurrence within a population characterized by high vaccination coverage in Tel Aviv, during a period of restricted public interactions due to the prevailing state of war in the country. Despite challenging wartime conditions, effective prophylactic measures were promptly executed, encompassing a 2-dose MMR vaccination schedule for close contacts and the broader community of children in the TA district, successfully curbing the outbreak and preventing widespread infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Between late 2023 and early 2024, two measles outbreaks occurred in Israel, each caused by importation of measles virus strains of respective B3 and D8 genotypes. In this study, we validate transmission pathways uncovered by epidemiological investigations using a rapid molecular approach, based on complete measles virus genomes. The presented findings support this rapid molecular approach in complementing conventional contact tracing and highlight its potential for informing public health interventions.

Aims: To outline the demographic, clinical, laboratory characteristics, and treatment outcomes of tuberculosis (TB) patients who used substances., Methods: This retrospective cohort study compared 50 TB patients who used substances with a matched random sample of 100 TB patients who did not use substances between 2007 and 2017. Treatment failure was defined as a sputum smear or culture that tested positive after 5 months of treatment, loss to follow-up, unevaluated patients, or death., Results: TB patients who used substances were typically younger, experienced homelessness, smokers, and had fewer chronic diseases than those who did not use substances. They also were hospitalized for longer periods, their treatment durations were longer, had higher rates of multidrug resistant strains, increased rates of treatment failure, and higher mortality. Individuals whose treatment failed predominantly originated from the former Soviet Union, experienced homelessness, and had chronic diseases compared with those whose treatment was successful. In the multivariate analysis, homelessness [odds ratios (OR) = 6.7], chronic diseases (OR = 12.4), and substance use (OR = 4.0) were predictors of treatment failures., Conclusions: TB patients who used substances were more likely to have treatment failure. Targeted interventions, including early diagnosis and enhanced support during treatment, are essential to achieve treatment success in this vulnerable population, in addition to TB-alcohol/drug collaborative activities., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Israeli Prison Services implemented a hepatitis C virus (HCV) elimination program in 2020. Inmates considered high risk for HCV were offered serology; HCV-seropositive participants were offered HCV RNA testing. Among participants, 7.0% had detectable HCV RNA and were offered antiviral drug therapy. This program reduced HCV burden among incarcerated persons.

Objectives: From May-September 2022, 203 cases of monkeypox (MPX) were reported in the Tel Aviv (TA) District, Israel. We aim to report the first ongoing local transmission of MPX in Israel., Methods: We analyzed the epidemiologic and clinical features of all cases of MPX notified to the TA District. Each case was contacted to verify the source of infection and locate potential contacts., Results: All cases were men; 195 (96%) were among men having sex with men, and 171 (84%) resided in the city of TA. Median age was 35 years. One case occurred in a healthcare worker. All cases had a self-limiting disease., Conclusion: A combined public health campaign with vaccination against MPX of high-risk individuals leads to a decrease in disease rates. Enhanced surveillance and prevention among susceptible populations are warranted., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Our study population consisted of all children and adolescents, with laboratory-confirmed SARS-Co-V-2 infection, hospitalised from February 2020 through February 2022, among residents of the Tel Aviv (TA) District, Israel. There were 491 children and adolescents hospitalised with Sars-CoV-2 infection. Among them, 281 (57%) admitted with coronavirus disease 2019 (COVID-19) as the primary cause of admission (rate of 39 per 100 000). Among all children and adolescents in the TA District, the highest hospitalisation rates were observed among infants and children below the age of 4 years (rate of 311 per 100 000 population). Severe disease was observed mostly among children with multiple underlying medical conditions. Admission rates were also elevated among residents of the ultra-orthodox community (rate ratio (RR) compared to the rest of the district; 95% confidence interval (CI) 2.38-3.82). Admission rates with COVID-19 as primary cause of admission were higher during Omicron compared to Delta predominance period (RR 1.7; 95% CI 1.22-2.32). Targeted social and public health policies should be put in place when rates of disease start to increase, such as encouraging vaccine uptake for eligible children and social distancing when necessary, taking into account already existing social and learning gaps, in order to reduce the burden of disease.

Background: Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1 ., Methods: We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families., Results: We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33*) in family 1 and c.850C>T; p.(Gln284*) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE., Conclusion: Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1 . All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Blue cone monochromacy (BCM) is an X-linked retinopathy caused by mutations in the red and green cone opsin genes. The aim of this study was to establish the clinical, genetic, and electrophysiological characteristics of a specific form of BCM., Methods: Patients harboring mutations in the OPN1LW/OPN1MW genes underwent a full clinical examination, including ocular examination, color vision, full-field electroretinography, color fundus and autofluorescence photography, and optical coherence tomography. Genetic analysis was performed using whole-exome sequencing, duplex PCR, PCR/restriction fragment length polymorphism, and Sanger sequencing. IBM SPSS Statistics v. 21.0 was used for the data analysis., Results: Twenty-five patients harboring various haplotypes in exon 3 of the OPN1LW/OPN1MW genes were recruited. They showed a milder incomplete phenotype of BCM than the typical BCM control group. They presented significantly better visual acuity (logarithm of the minimum angle of resolution [logMAR] 0.48 ± 0.26 vs. 1.10 ± 0.54; p < 0.0001) and a highly myopic refraction (-7.81 ± 5.81 D vs. -4.78 ± 5.27 D; p = 0.0222) compared with the BCM control group. The study group had higher 30-Hz cone flicker responses (28.60 ± 15.02 µv; n = 24), whereas the BCM group had none (0.66 ± 2.12 µv; n = 21; p < 0.0001). The Lanthony 15-HUE desaturated test was variable for the exon 3 haplotype group, with a tendency toward the deutan-protan axis., Conclusions: The present study included genetic and clinical data from the largest cohort of patients with exon 3 haplotypes that were previously shown to cause missplicing of the OPN1LW and OPN1MW genes. Analysis of the clinical data revealed better best-corrected visual acuity, more severe myopia, and higher 30-Hz cone flicker responses in the patients with exon 3 haplotypes than in those with typical BCM., (Copyright © 2022 Molecular Vision.)

Nuclear deubiquitinase BAP1 (BRCA1-associated protein 1) is a core component of multiprotein complexes that promote transcription by reversing the ubiquitination of histone 2A (H2A). BAP1 is a tumor suppressor whose germline loss-of-function variants predispose to cancer. To our knowledge, there are very rare examples of different germline variants in the same gene causing either a neurodevelopmental disorder (NDD) or a tumor predisposition syndrome. Here, we report a series of 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic NDD. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In matching peripheral blood mononuclear cells, histone H3 K27 acetylation ChIP-seq indicated that these BAP1 variants induced genome-wide chromatin state alterations, with enrichment for regulatory regions surrounding genes of the ubiquitin-proteasome system (UPS). Altogether, these results define a clinical syndrome caused by rare germline missense BAP1 variants that alter chromatin remodeling through abnormal histone ubiquitination and lead to transcriptional dysregulation of developmental genes., Competing Interests: Declaration of interests The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratory. K.Mc., R.E.S., and I.M.W. are employees of GeneDx, Inc., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)