Insights into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.

CONTEXT: Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. OBJECTIVES: To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. DESIGN: Multicenter cross-sectional retrospective chart review. SETTING: Nine pediatric endocrine units throughout Israel. PATIENTS: Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. RESULTS: CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. CONCLUSIONS: Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.

Muscle-to-fat ratio in children and adolescents with type 1 diabetes in predicting glycaemic control and partial clinical remission.

BACKGROUND: Advances in treatment could mitigate the expected adverse changes in the body composition of children and adolescents with type 1 diabetes (T1D). OBJECTIVES: To examine the evolution of weight status and body composition and their association with glycaemic control and partial clinical remission in youth with T1D. METHODS: Ninety-nine participants with T1D (median age 9.5 years [interquartile range 7.3, 12.9], 59.6% boys) were longitudinally followed for 3 years since diagnosis. Data at seven pre-determined time points were extracted from medical files. Outcome measures included body mass index (BMI) z-scores, muscle-to-fat ratio (MFR) z-scores, haemoglobin A1c (HbA1c) levels, continuous glucose monitoring metrics, and insulin dose-adjusted HbA1c (IDAA1c) levels. RESULTS: The BMI z-scores increased significantly (p < 0.001) for both sexes, with no significant change in MFR z-scores over time. The girls had higher BMI z-scores (p < 0.001) and lower MFR z-scores than the boys (p = 0.016). The mean HbA1c levels decreased during the first month and at 3 months since diagnosis (p < 0.001), then plateaued and achieved a median overall HbA1c of 7.1% for the entire cohort. At 12 months, 37 participants (37.6%) were in partial clinical remission, as evidenced by IDAA1c ≤ 9. The odds of partial clinical remission at 2 years increased by 2.1-fold for each standard deviation increase in the MFR z-score (p < 0.001). Higher MFR z-scores were associated with better metabolic control. CONCLUSIONS: Integration of body composition assessments could mitigate adverse body changes in paediatric patients with T1D.

Polyethylene glycol thyroid-stimulating hormone (PEG-TSH) testing in the management of pediatric thyroid dysfunction.

PURPOSE: The polyethylene glycol (PEG) methodology is used for investigating incongruities in laboratory assays, such as thyroid-stimulating hormone (TSH) measurements. The aim of the study is to investigate the practical application of PEG-TSH testing in cases of discrepancies between elevated TSH and normal free thyroxine (FT4) levels. METHODS: A real-life observational study conducted in a tertiary medical center. The hospital's electronic database was queried for TSH tests performed in pediatric patients between 2015 and 2023. Of those, PEG-TSH were identified. Patients' clinical and biochemical characteristics and PEG-TSH-guided management were assessed. RESULTS: In total, 2949 TSH tests were performed in 891 children and adolescents for various indications. Among them were 61 (2.1%) PEG-TSH results, mean age 7.1 ± 5.3 years, of 38 patients (4.3%), comprised of 16 with congenital hypothyroidism, 16 with subclinical hypothyroidism, and 6 with Hashimoto thyroiditis. Both the TSH and the PEG-TSH levels of patients with congenital hypothyroidism were higher than those of the other two groups (P = 0.021 and P = 0.009, respectively), with no group differences in FT4 levels. Spearman's correlation analysis revealed a strong association between TSH and PEG-TSH levels: r = 0.871, P < 0.001. In nearly one-half of the cases, clinical decisions made by clinicians (decreasing the dose or not initiating L-thyroxine treatment) were affected by the PEG-TSH results. CONCLUSION: Our findings support PEG-TSH testing for determining appropriate TSH levels and avoid unnecessary thyroid hormone treatment among children and adolescents. We propose the suitability of managing their clinical condition based upon age-appropriate clinical parameters and FT4 levels when their PEG-TSH levels are within the normal range.

Imaging the field inside nanophotonic accelerators.

Controlling optical fields on the subwavelength scale is at the core of nanophotonics. Laser-driven nanophotonic particle accelerators promise a compact alternative to conventional radiofrequency-based accelerators. Efficient electron acceleration in nanophotonic devices critically depends on achieving nanometer control of the internal optical nearfield. However, these nearfields have so far been inaccessible due to the complexity of the devices and their geometrical constraints, hampering the design of future nanophotonic accelerators. Here we image the field distribution inside a nanophotonic accelerator, for which we developed a technique for frequency-tunable deep-subwavelength resolution of nearfields based on photon-induced nearfield electron-microscopy. Our experiments, complemented by 3D simulations, unveil surprising deviations in two leading nanophotonic accelerator designs, showing complex field distributions related to intricate 3D features in the device and its fabrication tolerances. We envision an extension of our method for full 3D field tomography, which is key for the future design of highly efficient nanophotonic devices.

Early exposures and inherent factors in premature newborns are associated with type 1 diabetes.

BACKGROUND: Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. METHODS: This is a multicenter, matched case-control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. RESULTS: Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92-9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69-14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. -0.27 ± 0.97, OR = 2.03 (1.19-3.49), p = 0.01), longer duration of glucose infusion (3 (1-5) days vs. 2 (0-4), OR = 1.23 (1.03-1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32-20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11-0.88), p = 0.027). CONCLUSIONS: A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. IMPACT: Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Sex differences in body composition in youth with type 1 diabetes and its predictive value in cardiovascular disease risk assessment.

BACKGROUND: Women with type 1 diabetes (T1D) are more susceptible than men to cardiovascular disease (CVD). Signs of increased risk may already appear among adolescent girls. OBJECTIVES: We explored the contribution of body composition to the development of CVD risk factors among youth with T1D. METHODS: One hundred and eighty nine subjects with T1D (mean age 15.3 ± 5.1 years, 55% boys) followed between January 2018-January 2022 were included in this observational study. Sociodemographic and clinical data were extracted from medical files. Body composition was measured by bioelectrical impedance analysis, and muscle-to-fat ratio (MFR) z-scores were calculated. Logistic regression model assessed the association between body composition (MFR z-scores) and evidence of CVD risk factors. RESULTS: Females were characterised by higher median BMI z-scores (0.47 vs. 0.04, p = 0.012), higher fat and truncal fat percentage levels (p ≤ 0.001) and lower median MFR z-scores (-0.64 vs. -0.25, p ≤ 0.001), higher median triglyceride (TG) levels (71 vs. 61 mg/dl, p = 0.05), longer disease duration to initiation of insulin pump therapy (p = 0.041), and more time spent in marked hypoglycemia (1 vs. 0.2%, p = 0.007) than males. Males' MFR z-scores were associated with several diabetes-related parameters (age at diagnosis, CGM metrics, HbA1c and insulin dose), while the females'' MFR z-scores were linked to the atherogenic dyslipidemia index (TG:HDL ratio). The odds for CVD risk factors were doubled for every 1 SD decrease in MFR z-score (OR = 0.50, CI [0.30-0.84], p = 0.009) and also increased with age (OR = 1.07, CI [1.004-1.148], p = 0.038). CONCLUSIONS: Body composition measurement has a predictive value in CVD risk assessment in youth with T1D, with unique characteristics and influences in each sex.

Body composition in children and adolescents with non-classic congenital adrenal hyperplasia and the risk for components of metabolic syndrome: An observational study.

Background: 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/m2 [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<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 (R2= 0.253, p<0.001) - socioeconomic position index (ß=0.348, p=0.003), birthweight z-score (ß=-0.258, p=0.013), and duration of hydrocortisone treatment in years (ß=0.048, p=0.023); systolic blood pressure percentile (R2 = 0.166, p<0.001) - MFR z-score (ß=-9.75, p<0.001); TG/HDL ratio (R2 = 0.116, p=0.024) - MFR z-score (ß=-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.

Imprinting the quantum statistics of photons on free electrons.

The interaction between free electrons and light stands at the base of both classical and quantum physics, with applications in free-electron acceleration, radiation sources, and electron microscopy. Yet to this day, all experiments involving free-electron­light interactions are fully explained by describing the light as a classical wave. We observed quantum statistics effects of photons on free-electron­light interactions. We demonstrate interactions that pass continuously from Poissonian to super-Poissonian and up to thermal statistics, revealing a transition from quantum walk to classical random walk on the free-electron energy ladder. The electron walker serves as the probe in nondestructive quantum detection, measuring the second-order photon-correlation g(2)(0) and higher-orders g(n)(0). Unlike conventional quantum-optical detectors, the electron can perform both quantum weak measurements and projective measurements by evolving into an entangled joint state with the photons. These findings inspire hitherto inaccessible concepts in quantum optics, including free-electron­based ultrafast quantum tomography of light.

Association between age at type 1 diabetes diagnosis and metabolic outcome at young adulthood: a real-life observational study.

BACKGROUND: Younger age at diagnosis of type 1 diabetes (T1D) may affect the clinical course and outcome. We examined whether age at diagnosis was associated with glycemic control and metabolic outcome in young adulthood. METHODS: This observational study included 105 young adults with T1D (current mean age: 21.2 ± 3.0 years, mean age at diagnosis 12.0 ± 4.0 years) followed during 2012 to 2019. Data on HbA1c, glucose variability, continuous glucose monitoring (CGM) metrics, body mass index (BMI), blood pressure (BP), and body composition were collected from medical records from age 18 years until last visit, and the association between age at diagnosis and outcomes was assessed. RESULTS: Age at T1D diagnosis was negatively associated with HbA1c levels (r = -0.368, P = .001), BMI (r = -0.218, P = .026), and diastolic BP (r = -0.215, P = .028). Younger age at diagnosis predicted poorer glycemic control after controlling for T1D duration, sex, socioeconomic status, BMI, and CGM use (r2 = 0.19, P = .002). There was a 0.1% greater HbA1c reduction for every yearly increase in age at diagnosis (ß = -0.090, P = .042). The mean metabolic age of females diagnosed at <10 years of age was older than their chronological age (P = .049). CONCLUSIONS: Younger age at T1D diagnosis predicts worse glycemic control at young adulthood, independent of recognized confounding risk factors (disease duration, sex, socioeconomic status, weight, and use of diabetes technology). Female patients diagnosed at a young age have an older metabolic age, indicating the need for lifestyle alteration to improve their basal metabolic rate.