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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-8-15)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-8-15)
    Abstract: An inactivating PHEX gene mutation with the resultant accumulation of several mineralization-inhibiting proteins (e.g., FGF23) causes skeletal and dental morbidity in X-linked hypophosphatemia (XLH). This prospective case-control study explored the effect of burosumab, an anti-FGF23 antibody, on dental health of children with XLH. Ten children (age 4.3-15 years) with XLH underwent burosumab treatment per protocol. Assessment of their dental status at treatment initiation and after 1 and 3 years of treatment included clinical, laboratory and radiographic evaluation of rickets and dentition. Orthopantomographic examinations of ten healthy sex- and age-matched controls were selected for comparison. Coronal and pulp dimensions of a selected permanent mandibular molar were measured with Planmeca Romexis ® software. One year of treatment led to improvement of height z-score ( p =0.019) and healing of the rickets ( p & lt;0.001) in the XLH patients, and those achievements were maintained after three years of treatment. Dental morphology of XLH patients, distinguished by increased pulp-coronal ratios compared to controls ( p =0.002), remained larger after the first year of treatment ( p & lt;0.001) and did not attain the decrease expected with age after three years of treatment. Five patients had a history of recurrent dental abscesses, with three having undergone at least one episode during the year before burosumab initiation. One patient sustained recurrent abscesses throughout three years of treatment. The persistence of the unique dental morphology of XLH patients undergoing burosumab therapy, as evidenced by excessively larger pulp dimensions, supports the role of other PHEX gene-related local mineralization inhibitors, such as osteopontin, in the pathogenesis of dental morbidity.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 2
    In: Fertility and Sterility, Elsevier BV, Vol. 114, No. 2 ( 2020-08), p. 374-378
    Type of Medium: Online Resource
    ISSN: 0015-0282
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 3
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-10-20)
    Abstract: Treated or untreated non-classic congenital adrenal hyperplasia (NCCAH) diagnosed in childhood could pose an increased risk of obesity and metabolic derangements in adolescence and early adulthood. We aimed to explore the interaction between muscle-to-fat ratio (MFR) and components of metabolic syndrome in pediatric subjects with NCCAH. Methods This retrospective observational study was conducted in the Tel Aviv Medical Center from January 2018 to January 2022. The study group comprised 75 subjects (26 males) with NCCAH (61 hydrocortisone-treated [21 males] and 14 untreated [5 males]) and 134 healthy sex- and age-matched subjects (41 males) with normal puberty served as controls. Body composition was measured by bioelectrical impedance analysis (BIA) and muscle-to-fat ratio (MFR) z-scores were calculated. Stepwise linear regression models were applied to evaluate explanatory variables for MFR z-scores, blood pressure percentiles, lipid profiles, and glucose metabolism. Results The median age [interquartile range] was 7.5 years [5.3, 8.8] at NCCAH diagnosis and 12.3 years [8.9, 15.4] at BIA. The median cumulative hydrocortisone dose was 7620 mg/m 2 [2547, 12903]. Subjects with NCCAH had higher mean BMI z-scores and lower median MFR z-scores compared to controls [(0.47 ± 0.97 vs. -0.19 ± 1.04, p & lt;0.001) and (-0.74 [-1.06, -0.14] vs.-0.37 [-0.99, 0.15] , p =0.045), respectively]. The linear regression models dependent variables and their explanatory variables were: MFR z-score (R 2 = 0.253, p & lt;0.001) - socioeconomic position index (β=0.348, p =0.003), birthweight z-score (β=-0.258, p =0.013), and duration of hydrocortisone treatment in years (β=0.048, p =0.023); systolic blood pressure percentile (R 2  = 0.166, p & lt;0.001) - MFR z-score (β=-9.75, p & lt;0.001); TG/HDL ratio (R 2  = 0.116, p =0.024) - MFR z-score (β=-0.300, p =0.024). No significant variables were found for glucose. Conclusions Children and adolescents with NCCAH have a body composition characterized by an imbalance between muscle and fat tissues, which may place them at increased risk for early-onset cardiometabolic derangements. It is reassuring that glucocorticoid therapy aimed to alleviate androgen overproduction does not appear to adversely affect their body composition.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  BMC Pediatrics Vol. 21, No. 1 ( 2021-12)
    In: BMC Pediatrics, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published. Methods In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy ( 〈  2 years), early childhood (2–6 years), and childhood/adolescence (6–18 years). Results The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [ p  = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [ p   〈  0.001], hypertriglyceridemia 71 % vs. 40 % [ p  = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [ p  = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [ p   〈  0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients ( p  = 0.008, p  = 0.001, and p  = 0.037, respectively), and higher triglyceride levels during early childhood ( p  = 0.050), with no significant group differences during childhood/adolescence. Conclusions Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation.
    Type of Medium: Online Resource
    ISSN: 1471-2431
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041342-7
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  • 5
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background The intrauterine environment affects growth and adiposity acquisition from the fetal period until adulthood. Mild sleep disordered breathing (SDB) during pregnancy is a common underdiagnosed medical condition in healthy women. We aimed to investigate the interaction between maternal isolated SDB during the third trimester of pregnancy and the offspring’s growth and adiposity during the first three years of life. Methods Healthy pregnant women in the third trimester of an uncomplicated singleton pregnancy who were followed at the low-risk obstetric surveillance clinic of our hospital were recruited between 4/2013 and 5/2016. They were followed from enrollment until their offspring was three years old. During their third trimester of pregnancy, they underwent an ambulatory overnight sleep study by means of a validated sleep technology [SDB defined as apnea hypopnea index (AHI) ≥5]. Fasting blood samples were drawn on the following morning for glucose, insulin, HbA1c, lipid profile and C-reactive protein (CRP) levels. The offspring’s growth (length, weight and head circumference) and adiposity (subscapular and triceps skinfolds) parameters were measured at birth, 1 and 4 months, and 1, 2, and 3 years of age. Growth parameters were presented as standard deviation scores using the CDC growth charts. A general linear model was used to evaluate the interaction between maternal SDB and her offspring’s growth and adiposity measurements, after controlling for gestational week at delivery and maternal and paternal body mass index (BMI). Results Fourteen of 58 women (24.1%) were diagnosed with SDB (AHI range 5.3–14.7). They had a significantly higher mean BMI during the third trimester of pregnancy (30.1 ± 3.9 vs 27.2 ± 3.5, P = 0.011), elevated CRP levels, and decreased HDL-cholesterol levels (6.39 ± 2.29 mg/L vs 4.28 ± 2.15 mg/L, P = 0.003 and 67 ± 14 mg/dl vs 82 ± 19 mg/dl, P = 0.009, respectively) compared to women with normal sleep study results. Offspring of mothers with SDB had a smaller mean head circumference SDS at birth (-0.95 ± 0.70 vs -0.30 ± 0.71, P = 0.004), with a distinctive pattern of catchup growth by the end of the first year of life (P = 0.018). They also had increased mean adiposity at birth measured by triceps and subscapular skinfolds (6.8 ± 1.8 mm vs 5.4 ± 1.2 mm, P =0.002 and 5.8 ± 1.3 mm vs 5.0 ± 1.0 mm, P =0.019, respectively), with a distinctive pattern of increased triceps thickness at age 3 years (P = 0.001). There was no significant difference in offspring length or weight between groups. Conclusions Our findings suggest that isolated maternal SDB during pregnancy affected longitudinal head circumference growth and adiposity acquisition in the fetus and during the first three years of life.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
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  • 6
    In: Cells, MDPI AG, Vol. 12, No. 19 ( 2023-09-22), p. 2333-
    Abstract: The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in Drosophila larvae carrying a temperature-sensitive mutation in the shibire (shi1) gene was induced to mimic sedentary behavior during early life and study its transcriptional outcome. Our findings indicated a significant change in the epigenetic profile, as well as the genomic profile, of RNA Pol II binding in the inactive muscles relative to control, within a relatively short time period. Whole-genome analysis of RNA-Pol II binding to DNA by muscle-specific targeted DamID (TaDa) protocol revealed that muscle inactivity altered Pol II binding in 121 out of 2010 genes (6%), with a three-fold enrichment of genes coding for lncRNAs. The suppressed protein-coding genes included genes associated with longevity, DNA repair, muscle function, and ubiquitin-dependent proteostasis. Moreover, inducing muscle inactivation exerted a multi-level impact upon chromatin modifications, triggering an altered epigenetic balance of active versus inactive marks. The downregulated genes in the inactive muscles included genes essential for muscle structure and function, carbohydrate metabolism, longevity, and others. Given the multiple analogous genes in Drosophila for many human genes, extrapolating our findings to humans may hold promise for establishing a molecular link between sedentary behavior and metabolic diseases.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 7
    In: Bone Abstracts, Bioscientifica, ( 2019-07-31)
    Type of Medium: Online Resource
    ISSN: 2052-1219
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Neuromuscular Disorders Vol. 30, No. 4 ( 2020-04), p. 270-276
    In: Neuromuscular Disorders, Elsevier BV, Vol. 30, No. 4 ( 2020-04), p. 270-276
    Type of Medium: Online Resource
    ISSN: 0960-8966
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2008287-3
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  • 9
    In: Acta Paediatrica, Wiley, Vol. 110, No. 2 ( 2021-02), p. 711-717
    Abstract: To explore corticosteroid prescription practices and knowledge among paediatricians. Methods The Paediatricians Corticosteroids Survey, a cross‐sectional, web‐based survey distributed to Israeli paediatricians between February and July 2018. Results Three hundred and forty‐nine paediatricians (105 general paediatricians, 207 subspecialists and 37 paediatric endocrinologists) participated. Two hundred and three (58.2%) had 〉 10 years of paediatric clinical experience and treated 〉 60 patients/wk on average, 175/318 (55%) prescribed corticosteroids to 〉 10% of their patients. On knowledge items, 11/266 (4.1%) responded ‘not sure’ when tapering of steroids is required, 22/268 (8.2%) to what ‘stress dose’ meant and 27/268 (10.1%) when a stress dose is required. Multivariate linear analysis showed higher scores were associated with training in paediatric endocrinology (β = 2.271, P  = 0.032); medical practice only in a subspecialty (β = 1.909, P  = 0.041) or in both general paediatrics and a subspecialty (β = 2.023, P  = 0.014), compared to general paediatrics alone and medical studies in Israel (β = 1.059, P  = 0.035). Overall, 96.2% thought continued medical education (CME) sessions would be helpful. Conclusion Our findings suggest that despite clinical experience with corticosteroid usage, respondents demonstrated gaps in knowledge for potentially life‐threatening situations. Corticosteroid‐based CME programs are warranted to improve paediatricians' knowledge and patient management.
    Type of Medium: Online Resource
    ISSN: 0803-5253 , 1651-2227
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1492629-5
    detail.hit.zdb_id: 1501466-6
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  • 10
    Online Resource
    Online Resource
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Previous phase I studies demonstrated that alpha-1 antitrypsin (AAT) was safe and well tolerated in type 1 diabetes (T1D) patients. This multicenter, randomized, placebo-controlled phase II trial was designed to test whether AAT could preserve C-peptide secretion in new-onset T1D patients aged 8-25 years. Seventy patients (37 males; mean age 13.1 ± 4.1 years) were randomized (1:1:1) to treatment with 22 IV infusions − 60 mg/kg AAT, 120 mg/kg AAT or placebo administered over 1 year. The primary end point of the study was the change in C-peptide area under the curve (AUC) from a 2-h mixed-meal tolerance test (MMTT) after 1 year. Secondary endpoints were HbA1c and safety parameters. Post-hoc sub-group analysis by age was performed. At 1 year, the decrease in C-peptide AUC was not different in AAT vs. placebo groups (P = 0.66 and 0.96, for 60 and 120 mg/kg AAT). Within 12-18 years subgroup (n=35), C-peptide AUC in placebo-treated and 60 mg/kg AAT-treated patients decreased significantly from baseline (-0.34 and -0.55 pmol/mL, respectively, P & lt; 0.01) while no significant decrease was observed in the 120 mg/kg AAT-treated patients (-0.18 pmol/mL, P = 0.20). At 1 year, mean HbA1c levels were higher in placebo-treated patients and 60 mg/kg AAT-treated patients vs. 120 mg/kg AAT-treated patients (8.24 ± 1.42% and 7.85% ± 1.67% vs. 6.66% ± 1.01%, respectively, P = 0.for 120 mg/kg AAT vs. placebo); a lower percentage of patients attained HbA1c ≤ 7% in the placebo and 60 mg/kg AAT groups compared to 120 mg/kg AAT (25% and 28.6% vs. 70%, P = 0.07). The infusions were well tolerated with a similar safety profile in the AAT and placebo groups. Two patients in the 60 mg/kg treatment group had allergic reactions after 4 and 17 infusions. Although AAT intervention shows promise with a favorable safety profile, the efficacy of AAT in T1D patients is inconclusive. Further studies should be undertaken with appropriate patient stratification pre-randomization and implementation of biomarkers to determine whether AAT has a beneficial effect on beta cell preservation. Disclosure Y. Lebenthal: Speaker's Bureau; Self; Novo Nordisk Inc.. Consultant; Self; Kamada. A. Brener: None. E. Hershkovitz: None. N. Shehadeh: None. S. Shalitin: None. S. Gai-Castro: Employee; Self; Kamada. M. Stein: Employee; Self; Kamada. N. Tov: Employee; Self; Kamada. M. Rachmiel: Advisory Panel; Self; Novo Nordisk Inc.. Other Relationship; Self; Medtronic MiniMed, Inc.. Research Support; Self; Kamada.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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