Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing.

OBJECTIVE: To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. STUDY DESIGN: For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. RESULTS: Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. CONCLUSIONS: The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.

Quality of sleep and excessive daytime sleepiness among medical students in a Brazilian private university.

OBJECTIVE: The aim of this study was to assess medical students' quality of sleep and excessive daytime sleepiness in different graduation cycles. METHODS: A cross-sectional study was carried out at a private university in Maceió, Brazil, from August 2021 to March 2022. The sample was composed of medical students aged 18 years and above from years 1-2 (basic cycle), 3-4 (clinical cycle), and 5-6 (internship) of Medical School who were invited to answer two validated questionnaires: the Pittsburgh Sleeping Quality Index and the Epworth Sleepiness Scale. RESULTS: A total of 179 students participated; most of them were female (78.2%), aged 19-25 years (73.7%), and with a body mass index<25 kg/m2 (73.7%), with smaller participation from students from the basic cycle (21.2%). Analyzing the Pittsburgh Sleeping Quality Index, 55.9% of the students were classified as having poor sleep quality, with no difference in sleep category between gender, age, body mass index, and graduation cycle. Students with a body mass index of ≥25 kg/m2 had longer sleep latency (p=0.016) and shorter sleep duration (p=0.027). The Epworth Sleepiness Scale assessment showed that 44.1% of the students exhibit daytime sleepiness. Women had more daytime sleepiness than men (p=0.017), with no difference between age, body mass index, and graduation cycle. CONCLUSION: About half of the medical students experience poor sleep quality and daytime sleepiness, regardless of the graduation cycle. This should trigger a targeted institutional intervention to promote better mental and physical health, as well as sleep hygiene, to reduce future health issues.

Quality of sleep and excessive daytime sleepiness among medical students in a Brazilian private university

SUMMARY OBJECTIVE: The aim of this study was to assess medical students' quality of sleep and excessive daytime sleepiness in different graduation cycles. METHODS: A cross-sectional study was carried out at a private university in Maceió, Brazil, from August 2021 to March 2022. The sample was composed of medical students aged 18 years and above from years 1-2 (basic cycle), 3-4 (clinical cycle), and 5-6 (internship) of Medical School who were invited to answer two validated questionnaires: the Pittsburgh Sleeping Quality Index and the Epworth Sleepiness Scale. RESULTS: A total of 179 students participated; most of them were female (78.2%), aged 19-25 years (73.7%), and with a body mass index<25 kg/m2 (73.7%), with smaller participation from students from the basic cycle (21.2%). Analyzing the Pittsburgh Sleeping Quality Index, 55.9% of the students were classified as having poor sleep quality, with no difference in sleep category between gender, age, body mass index, and graduation cycle. Students with a body mass index of ≥25 kg/m2 had longer sleep latency (p=0.016) and shorter sleep duration (p=0.027). The Epworth Sleepiness Scale assessment showed that 44.1% of the students exhibit daytime sleepiness. Women had more daytime sleepiness than men (p=0.017), with no difference between age, body mass index, and graduation cycle. CONCLUSION: About half of the medical students experience poor sleep quality and daytime sleepiness, regardless of the graduation cycle. This should trigger a targeted institutional intervention to promote better mental and physical health, as well as sleep hygiene, to reduce future health issues.

ESR1 polymorphism (rs2234693) influences femoral bone mass in patients with Turner syndrome.

Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.

Prevalence of reported incidental adrenal findings in chest computerized tomography scans performed during the COVID-19 pandemic in a single center in Northeast Brazil

ABSTRACT Objective: We investigated the prevalence of adrenal incidentalomas (AIs) in a nonselected Brazilian population in chest computed tomography (CT) performed during the COVID-19 pandemic. Materials and methods: This was a retrospective cross-sectional observational study using chest CT reports from a tertiary in- and outpatient radiology clinic from March to September 2020. AIs were defined by changes in the shape, size, or density of the gland initially identified in the released report. Individuals with multiple studies were included, and duplicates were removed. Exams with positive findings were reviewed by a single radiologist. Results: A total of 10,329 chest CTs were reviewed, and after duplicate removal, 8,207 exams were included. The median age was 45 years [IQR 35-59 years], and 4,667 (56.8%) were female. Thirty-eight lesions were identified in 36 patients (prevalence 0.44%). A higher prevalence was observed with age, with 94.4% of the findings in patients aged 40 years and over (RR 9.98 IC 2.39-41.58, p 0.002), but there was no significant difference between the sexes. Seventeen lesions (44.7%) had more than 10 HU, and five lesions (12.1%) were more than 4 cm. Conclusions: The prevalence of AIs in an unselected and unreviewed population in a Brazilian clinic is low. The impact on the health system caused by AIs discovered during the pandemic should be small regarding the need for specialized follow-up.

Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child.

INTRODUCTION: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients' fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. PATIENT AND RESULTS: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient's growth pattern. CONCLUSIONS: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.

Retraction Note: Fatal factitious Cushing syndrome (Münchhausen's syndrome) in a patient with macroprolactinoma and silent corticotrophinoma: case report and literature review.

[This retracts the article DOI: 10.1186/s40842-015-0002-8.].