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Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9–9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19–1.51); and OR 4.10, 95% CI 2.06–8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842–0.964] versus 0.745 [95% CI 0.668–0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available. © 2022 European Sleep Research Society.

Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. How-ever, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methy-lated β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-CD) was determined by X-ray crystallography. The structural investigation was complemented by molecular dynamics simulations. The cytotoxicity of CBD and its complexes with RM-β-CD and HP-β-CD was tested on two cell lines, the A172 glioblastoma and TE671 rhabdomyosarcoma cell lines. Methylated β-CDs exhibited the best inclusion ability for CBD. A dose-dependent effect of CBD on both cancer cell lines and improved efficacy of the CBD–CDs complexes were verified. Thus, cannabinoids may be considered in future clinical trials beyond their palliative use as possible inhibitors of cancer growth. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults. © The authors 2022.

Childhood obesity has been linked to physical and psychological comorbidities that can be carried into adulthood. A bidirectional link between body weight and the stress system appears to exist, as cortisol may affect the regulation of appetite, while adiposity can affect cortisol secretion. Among the biological tissues used to evaluate cortisol concentrations, scalp hair can provide retrospective measures. The aim of this systematic review was to investigate the difference in hair cortisol concentrations between obese and non-obese minors ≤ 19 years of age. Children and adolescents with genetic, somatic or psychiatric comorbidities were excluded. The work was conducted follow-ing the PRISMA guidelines, using prespecified search terms in the Pubmed database. The initial search yielded 56 studies, while the last step of the screening procedure concluded in 9 observational studies. Among them, the results could be characterized as inconclusive. Five of them demonstrated significantly higher hair cortisol concentrations in obese children and adolescents than normal weight subjects. On the contrary, the remaining four found no statistically significant differences in hair cortisol concentrations between obese and non-obese subjects. Different methodologies applied, and confounding factors could explain the inconsistency in the findings. Further research is needed to provide more solid results. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction. Prematurity is associated with increased cardiometabolic risk later in life. The adipomyokine irisin has been acknowledged as a modulator of energy metabolism and insulin sensitivity. The aim of this study was to investigate circulating levels of irisin and their relation to anthropometric measurements and cardiometabolic phenotype in a population of preterm-born children vs. full-term-born peers. Methods. A total of 160 children (87 born preterm aged 8.1-14.8 years and 73 born full-term of similar age and gender distribution) were studied. Arterial blood pressure, anthropometry, body composition assessments with dual energy X-ray absorptiometry (DXA) and skin fold measurements were performed. Blood biochemistry and circulating levels of irisin, insulin, cortisol, leptin, and adiponectin were also determined. Results. The preterm group had higher diastolic blood pressure, triceps skin fold, subscapular skin fold (SSF) and abdominal skin fold measurements and more central adiposity than the full-term group. Irisin was significantly lower (p=0.002), whereas leptin was higher (p=0.03), in the preterm than the full-term group. Irisin correlated positively with gestational age (r=0.19, p=0.01), birthweight (r=0.23, p=0.003) and high-density lipoprotein cholesterol (r=0.20, p=0.01), and negatively with SSSF (r=-0.25 p=0.003) and chronological age (r=-0.21, p=0.008). Conclusion. Lower levels of irisin and a slightly unhealthy adiposity and cardiometabolic pattern were detected in preterm-born children in comparison to their full-term-born peers. Whether low irisin levels in preadolescents and adolescents born prematurely could be of prognostic value for the development of cardiometabolic sequelae later in life remains to be further studied. © 2021 S. Karger AG, Basel. All rights reserved.

Background: There is an endless debate on whether androgens mediate testis descent through developmental changes in the gubernacular or the cranial suspensory ligament. Objective: To investigate the relation of any possible morphologic changes in the genital mesentery, that is, the system of genital peritoneal folds including the gubernacular and cranial suspensory ligaments, with the event of testis non-descent in rats prenatally exposed to the antiandrogen flutamide. Materials and methods: Time-pregnant Sprague Dawley rats received flutamide (100 mg/kg/d) or vehicle subcutaneously on gestational days 16-17. Flutamide-treated male offspring (n = 67), and vehicle-treated male (n = 34) and female (n = 28) offspring were surgically explored under microscope on postnatal day 50. Testicular position was examined bilaterally. Dimensions of genital mesentery parts were also assessed bilaterally. Association of flutamide-induced morphologic changes with descended (n = 61) and undescended (n = 50; 33 cryptorchid and 17 ectopic) testes was investigated with logistic regression analysis. Results: The male genital mesentery comprised a cranial and a caudal fold converging on the vas deferens. Flutamide resulted in enlarged cranial and reduced caudal folds. Of all flutamide-induced alterations, the increased length of the posterior fixation of the cranial fold and the decreased length of the gubernacular ligament of the caudal fold were found to independently increase the odds of testis non-descent. Testicular ectopy, unlike cryptorchidism, was associated with a short gubernacular ligament only. The female genital mesentery consisted of a cranial fold only. Conclusion: Our findings showed a combined contribution of both cranial and caudal folds of the genital mesentery to testis non-descent, through an abnormally long mesentery root and an abnormally short gubernacular ligament, respectively. Inhibition of male-specific development of the genital mesentery with flutamide did not result in a feminized architecture. © 2020 American Society of Andrology and European Academy of Andrology

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0–16 years) with suspected meningitis–encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1–60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

It has been established, worldwide, that non-communicable diseases such as obesity, diabetes, metabolic syndrome, and cardiovascular events account for a high percentage of morbidity and mortality in contemporary societies. Several modifiable risk factors, such as sedentary activities, sleep deprivation, smoking, and unhealthy dietary habits have contributed to this increase. Healthy nutrition in terms of adherence to the Mediterranean diet (MD), rich in fruits, legumes, vegetables, olive oil, herbs, spices, and high fiber intake may contribute to the decrease in this pandemic. The beneficial effects of the MD can be mainly attributed to its numerous components rich in anti-inflammatory and antioxidant properties. Moreover, the MD may further contribute to the improvement of reproductive health, modify the risk for neurodegenerative diseases, and protect against depression and psychosocial maladjustment. There is also evidence highlighting the impact of healthy nutrition in female people on the composition of the gut microbiota and future metabolic and overall health of their offspring. It is therefore important to highlight the beneficial effects of the MD on metabolic, reproductive, and mental health, while shaping the overall health of future generations. The beneficial effects of MD can be further enhanced by increased physical activity in the context of a well-balanced healthy lifestyle. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Social media platforms have gained ground in the day-to-day life of the vast majority of people globally. Growing evidence suggests that social media overuse can take a pathological form, and users can exhibit behaviors similar to those appearing in several types of addiction. The aim of this study was to validate the Greek version of the Social Media Disorder Scale (SMDS) among young adults. An online survey was conducted among Greek adults, aged 18–29 years old. A total of 251 respondents voluntarily participated. Internal consistency, criterion, and construct validity were examined. Results suggest that the Greek version of SMDS shows good psychometric properties. Internal consistency was above the acceptable margin, with a satisfying Cronbach’s α coefficient. Correlations with other addiction-related constructs were found to be moderate. Construct validity of the scale was evaluated with exploratory factor analysis. Exploratory factor analysis resulted in a single factor model, which explained almost half of the total variance. The Greek version of SMDS is a psychometrically sound and valid instrument, which researchers and practitioners can use to assess social media addiction in young adults. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Purpose: The aim of this study was to investigate the oral health status of overweight and obese children compared to normal weight children and to explore the effect of risk indicators, including stress, on the oral health of the children. Methods: For this cross-sectional study, 7–15-year-old children were enrolled: divided into a group of overweight and obese and a group of normal weight children. Parent-reported questionnaires were used to for data collection demographic data, children’s medical and developmental history, brushing frequency and dietary habits. Participants’ state and trait anxiety levels were evaluated using STAIC questionnaires while saliva cortisol was measured as a biomarker of stress. Dental Caries (DMFT/dmft), periodontal health (plaque index–PI and gingival index–GI), saliva flow rate and buffer capacity were recorded at the dental clinic by two calibrated examiners. Student’s t-test, Pearson’s r and Fisher’s exact test were used for bivariate associations and backward stepwise multivariate regression analysis for each oral health outcome was performed (P ≤ 0.05). Results: Overweight and obese children had significantly higher DMFT (3.92 ± 4.69 vs. 1.30 ± 2.49, P < 0.001), PI (0.9 ± 0.5 vs. 0.45 ± 0.52, P < 0,001) and GI (0.38 ± 0.39 vs. 0.18 ± 0.47, P < 0,001), salivary cortisol AUC (128.3 ± 55.5 vs. 99.4 ± 35.7, P = 0.004), lower saliva flow rate and decreased “high” saliva buffer capacity. There were no differences for the STAIC measures between the groups. Child’s weight affected periodontal parameters but not dental caries, when controlling for other risk indicators. Conclusion: Oral status of overweight and obese children was worse compared to normal weight children and this did not correlate to stress variables. © 2021, European Academy of Paediatric Dentistry.

Congenital Hyperinsulinism (CHI) is the most common cause of persistent hypoketotic hypoglycaemia in neonates and infants. It is a genetic disorder with both familial and sporadic forms. In this study, we examined two unrelated infants of diabetic mothers (IDMs) presented with HH. DNA sequencing (Sanger and NGS panel) identified pathogenic variants of the Hepatocyte Nuclear Factor 4A (HNF4A) gene in both families. Pathogenic variants of HNF4A gene are reported to cause HH in the newborn period and Maturity Onset Diabetes of the Young (MODY) later in life. The diagnosis of MODY was made in retrospect for the two mothers, thus improving the management of their diabetes. Genetic testing for CHI is strongly recommended if neonatal hypoglycemia persists. A family history of MODY or presumed type II diabetes can support that the affected gene is HNF4A. © 2020 2020 Walter de Gruyter GmbH, Berlin/Boston.

Context: Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency. Objective: To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency. Design: Clinical and molecular study. Setting: Tertiary academic Children's Hospital, Center for Rare Pediatric Endocrine Diseases. Patients and Methods: Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out to evaluate protein stability and potential pathogenicity. Results: CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, 6 of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The 6 novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C, and the donor splice site variant of intron 8, c.1398 + 1G > A. Conclusion: Molecular diagnosis was achieved in 62 patients with aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene. © 2020 The Author(s).

Background: Children with type 1 diabetes (T1D) are at much higher risk of developing celiac disease (CD) than the general population. The aim of the study was to assess the prevalence and differences in clinical presentation of CD in T1D in different regions of the world. Methods: This study is based on the Better control in Pediatric and Adolescent diabeteS: Working to crEate cEnTers of Reference (SWEET) database. There were 57 375 patients included in the study, aged ≤18 years from 54 SWEET centers. Only centers with screening for celiac disease were included. Regression models adjusted for age, diabetes duration, and gender and a fixed effect in the models for region was used. Diabetes duration, age at diabetes onset, and sex were presented as unadjusted results. Results: CD was present in 2652 subjects (4.5%), with different prevalence among regions: from 1.9% in Asia/Middle East to 6.9% in Australia/New Zealand. CD was observed more often among females. Comparing children with and without CD, characteristics for those with CD were younger age at diabetes onset (6.3 [3.3; 9.8] vs 8.1 [4.6; 11.3], P < 0.001) and had longer diabetes duration (6.4 [3.6; 9.8] vs 4.8 [2.1; 8.2], P < 0.001). Further, they had lower glycosylated hemoglobin (HbA1c) in Europe and North America/Canada; lower body mass index (BMI)-SD score (BMI-SDS) in southern Europe, North America, and Canada; In most regions daily insulin dose was lower, height-SDS was lower, and the percentage of insulin pump users was higher in children with T1D and CD. Conclusions: The prevalence and the anthropometric and metabolic consequences of CD in children with T1D differ around the world. © 2020 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd

Adolescent suse internet via several devices to gather information or communicate. Sleep, as a key factor of adolescents’ development, contributes to their physical and mental health. Over the past decades insufficient sleep among adolescents has been wide spread, and one of its attributing factors is the increased availability of technology. This review aims to investigate the body of evidence regarding the impact of problematic internet use on adolescent sleep. Extensive search of databases was performed according to PRISMA guidelines for studies published within the last decade, regarding subjects aged 10-19. The final step of the search yielded 12 original studies. The quality of extracted data was evaluated with the AXIS tool, in order to estimate the risk of bias. All studies showed a negative correlation between adolescent sleep and problematic internet use. It was found to affect sleep quality and quantity and provoke insomnia symptoms. Interestingly, adolescent’s sex, parental educational level, type of family and use for leisure or academic reasons appeared as affecting factors of the problematic internet use-sleep relationship. Problematic internet use has several effects on adolescents’ sleep. Results of relevant studies should be embedded in educational interventions addressed to adolescents as well as parents, to eliminate the negative outcomes of problematic internet use on sleep and adolescence’s health in general. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Myocarditis represents a potential complication of various infectious and noninfectious agents and a common diagnostic challenge for clinicians. Data regarding Campylobacter-associated myocarditis are limited. Here, a case of a 13-year-old female with Campylobacter jejuni gastroen-teritis complicated by myocarditis is presented, followed by a literature review in order to retrieve information about Campylobacter-associated carditis in the pediatric population. A search on MED-LINE/PubMed yielded 7relevant cases in the last 20 years. Most of them (six/seven) were males and the mean age was 16.1 years. All patients presented with gastrointestinal symptoms followed in six/seven cases by chest pain within two to seven days. Campylobacter was isolated from stool cultures in six patients; abnormal electrocardiographic findings were detected in six; and abnormal echocardiographic findings in three of the cases. Five patients were treated with antibiotics. Full recovery was the clinical outcome in six patients, whereas one patient died. Concerning the nonspecific symptoms of patients with myocarditis, high clinical suspicion of this complication is necessary in cases where patients with a recent infection present with chest pain and elevated cardiac biomarkers. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Pediatric cancer and its treatment may have an impact on the neurocognitive functions of childhood cancer survivors (CCS). The aim of the present meta-analysis was to compare the intelligence quotient (IQ) scores between CCS of acute lymphoblastic leukemia (ALL) and controls. A compre- hensive electronic search identified original research articles that reported scores of the Wechsler Intelligence Scale (WISC; WISC-III, WISC-IV and WISC-R) for children and adoles- cents, aged 6-16 years at evaluation, survivors of ALL and healthy controls. The included CCS had completed anticancer treatment and were in remission at the time of assessment. A total of 16 studies were included in the meta-analysis, out of 128 extracted studies, and involved a total of 1,676 children and adolescents: 991 CCS (ALL) and 685 healthy controls. Among the studies, a random effects model revealed a moderate estimate of effect size [standardized mean differ- ence (SMD), -0.78; 95% CI, -1.05 to -0.50], indicating that the WISC scores for total IQ were significantly lower in the CCS than in the controls. The mean total IQ range was 85.2-107.2 in the CCS and 88.4-114.1 in the controls. The difference in the mean total IQ between controls and CCS ranged from -13.8 to 20.6. As regards the WISC scores for verbal IQ, 11 studies were included. A random effects model revealed a moderate estimate of effect size (SMD, -0.71; 95% CI, -1.05 to -0.38), indicating that the WISC scores for verbal IQ were signifi- cantly lower in the CCS than in the controls. Among the 9 studies that had available data for performance IQ scores, a fixed effect model revealed a moderate estimate of effect size (SMD, -0.80; 95% CI, -1.09 to -0.52), indicating that the WISC scores for performance IQ were significantly lower in the CCS than in the controls. As the survival rates of children and adolescents with ALL are steadily increasing, regular, lifelong follow-up for neurocognitive late effects is imperative in order to improve their education and employment prospects and overall, their quality of life. © 2021 Spandidos Publications. All rights reserved.

This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated. © 2021, The Author(s).

Background Aquagenic wrinkling of the palms (AWP) is an excessive and early palmar wrinkling occurring after Brief Immersion to Water (BIW), and has been reported as a frequent finding among cystic fibrosis (CF) patients. Objectives To evaluate and assess the diagnostic performance of BIW test as an initial screening tool for CF diagnosis. Methods We measured AWP in CF patients, CF-heterozygotes (CF-het) and normal controls. The AWP parameters of palmar wrinkling, oedema, papules, pruritus and pain were assessed at 3, 7 and 11 min after a BIW test was performed for all the participants. Statistical analyses explored the progression of AWP in time for the three groups and assessed the diagnostic performance of BIW test as a diagnostic screening tool for CF. Results A total of 250 individuals (100 CF patients, their 50 CF-het parents, 100 healthy controls) were included in the analysis. The average age in years (mean +/- SD) was 10.4 +/- 4.0 for CF, 35.9 +/- 6.1 for CF-het and 10.5 +/- 4.0 for controls. The rate of positives for AWP at 3 min among CF patients, CF-het and controls was 68%, 8% and 0%, respectively (P < 0.01). Kaplan-Meier analysis showed a clear trend towards earlier appearance of all five parameters in the direction controls < hetCF < CF (P values

Recently, a novel syndrome of combined immune deficiency, infections, allergy, and inflammation has been attributed to mutations in the gene encoding actin-related protein 2/3 complex subunit 1B (ARPC1B), which is a key molecule driving the dynamics of the cytoskeleton. Homozygous mutations in the ARPC1B gene have been found to result in the disruption of the protein structure and cause an autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation, increased levels of immunoglobulin E (IgE) and immunoglobulin A (IgA), and thrombocytopenia. To date, only a few individuals have been diagnosed with the ARPC1B deficiency syndrome worldwide. In this case series, we report the wide spectrum of phenotype in 3 siblings of a consanguineous family from Afghanistan with a novel homozygous synonymous pathogenic variant c.783G>A, p. (Ala261Ala) of the ARPC1B gene that causes a similar syndrome but no thrombocytopenia. Targeted RNA studies demonstrated that the variant affects the splicing process of mRNA, resulting in a marked reduction of the levels of primary (normal) RNA transcript of the ARPC1B gene in the affected patients and likely premature termination from the abnormally spliced mRNA. The next generation sequencing (NGS) studies facilitated the diagnosis of this rare combined immunodeficiency and led to the decision to treat the affected patients with hematopoietic cell transplant (HCT) from an human leukocyte antigen (HLA)-matched healthy sibling. © Copyright © 2021 Papadatou, Marinakis, Botsa, Tzanoudaki, Kanariou, Orfanou, Kanaka-Gantenbein, Traeger-Synodinos and Spoulou.

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.

Objectives: Evidence for nocturnal oximetry interpretation in patients with abnormal neuromuscular function is limited. We aimed to compare children with neuromuscular disease (NMD) or Prader-Willi syndrome (PWS) to otherwise healthy subjects with obstructive sleep-disordered breathing (SDB) or without respiratory disorder (controls) regarding nocturnal oximetry parameters. Methods: We analyzed recordings from children with: (a) NMD; (b) PWS; (c) snoring and adenotonsillar hypertrophy and/or obesity (SDB); and (d) controls. Outcomes included: (a) basal SpO2; (b) proportions of subjects with McGill oximetry score (MOS) >1 (clusters of desaturations); and (c) desaturation index (SpO2 drops ≥3%/h-ODI3). Results: Data of 12 subjects with NMD (median age, 5.2 years; IQR, 2.7, 8.2), 14 children with PWS (5 years; 2.3, 6.9), 21 children with SDB (5.8 years; 4.6, 9.6), and 20 controls (6.2 years; 5.4, 11.2) were analyzed. Children with NMD, PWS, and SDB had lower basal SpO2 than controls (95.6% [94.5%, 96.9%], 96.2% [95.1%, 97.4%], 96.1% [95.8%, 97.5%] vs 97.8% [97.2%, 97.9%], respectively; (P 1 than patients with NMD (OR, 25.9 [95% CI, 3.4-200.4] and 9.5 [1.5-62.6]). NMD, PWS, and SDB were similar regarding ODI3, which was elevated compared to ODI3 in controls (P

Background: Maturity Onset Diabetes of the Young (MODY) constitutes a genetically and clinically heterogeneous type of monogenic diabetes. It is characterized by early onset, autosomal dominant inheritance and a defect in pancreatic β-cell insulin secretion. To date, various MODY subtypes have been reported, each one of a distinct genetic etiology. Objective: The aim of this study was to identify the molecular defects of 50 patients with MODY employing the methodology of next generation sequencing (NGS) targeted gene panel. Methods: A panel of seven MODY genes was designed and employed to screen 50 patients fulfilling the MODY diagnostic criteria. Patients with no pathogenic, likely pathogenic or uncertain significance variants detected, were further tested by multiplex ligation-dependent probe amplification (MLPA) for copy number variations (CNVs). Results: Eight different pathogenic or likely pathogenic variants were identified in eight MODY patients (diagnostic rate 16%). Five variants of uncertain significance were also detected in seven MODY patients. Five novel pathogenic and likely pathogenic variants were detected in the genes GCK; p.Cys371X, HNF1A; p.Asn402Tyr, HNF4A; p.Glu285Lys, and ABCC8; p.Met1514Thr and p.Ser1386Phe. Two de novo heterozygous deletions of the entire HNF1B gene were detected in two patients, raising the diagnostic rate to 20%. Conclusions: Although many MODY patients still remain without exact MODY type identification, the application of NGS methodology provided rapid results, increased diagnostic accuracy, and was cost-effective compared to Sanger sequencing. Accurate genetic diagnosis of the MODY subtype is important for treatment selection, disease prognosis, and family counseling. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background: Thalassemia Major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients suffer from various health conditions, including endocrinopathies and low bone mineral density. Aim: The aim of the present study was to evaluate the fracture incidence regarding the markers of bone metabolism, bone mineral density and treatment of osteoporosis as well as the treatment of comorbidities. Methods: Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from “Aghia Sofia” Children’s Hospital and evaluated using dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results: The statistical analysis of markers of bone metabolism in relation to fractures revealed no statistical significance. However, statistical analysis of bone mineral density and markers of bone metabolism in relation to fractures was also not significant. Conclusions: In TM patients, fractures are not related to bone mineral density. Maybe some other conditions are the cause, haemosidirosis, drugs, comorbid conditions. © 2020 Bentham Science Publishers.

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM). Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m2 vs. 21.9 ± 2.0 kg/m2 vs. 21.4 ± 1.9 kg/m2; P>.05) were prospectively recruited. Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiAândrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androÂgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P.05). Conclusion: Menstrual disorders and androgen-relatAêd traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations. © Copyright © 2020 AACE.