Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, classic form: frequency evaluation of families with affected patients

OBJECTIVE: To analyze the frequency of affected patients, rate of parental consanguinity and clinical forms of the disease, according to sex in families with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, classic form (CAH-21-OHD-C). METHODS: 58 families with 79 patients (67 alive and 12 dead) with non-affected parents and at least one affected live patient with an established diagnosis of the disease by molecular analysis were studied. The frequency of affected siblings was evaluated according to Haldane and Hogben techniques by truncated selection. Data about parental consanguinity, frequency of CYP21A2 homozygosis gene mutation, clinical form of the disease and sex distribution were also evaluated. RESULTS: Ten families had parental history of consanguinity and other five had homozygosis in the molecular analysis. The frequency of affected children in the kindred was 23.5%, similar to the 25% expected, but the sample showed a heterogeneous distribution. Among the clinical forms, 56 (70%) patients had the salt wasting form (25 males and 31 females) and 23 (30%) the simple virilizing one (10 males and 13 females) without difference in sex distribution. CONCLUSIONS: These data confirm that CAH-21-OHD-C has an autosomal recessive monogenic inheritance, with a high rate of consanguinity, similar distribution in both sexes, but it has a heterogeneous distribution of cases among the kindred with predominance of the salt wasting form.OBJETIVOS: Analisar a freqüência de indivíduos afetados e das formas clínicas da doença, de acordo com o gênero e a taxa de consangüinidade, em famílias com hiperplasia adrenal congênita (HAC) por deficiência da enzima 21-hidroxilase, forma clássica (HAC-D21-OHC). MÉTODOS: A casuística foi composta por 58 famílias com 79 indivíduos afetados (67 vivos e 12 mortos) com pais normais e pelo menos um filho afetado vivo com diagnóstico comprovado da doença. A freqüência de indivíduos afetados foi avaliada pelas técnicas de Haldane e Hogben, com análise por seleção truncada. Também foram avaliadas a história parental de consangüinidade e a freqüência de homozigose de mutações no gene CYP21A2, bem como a forma clínica da doença e a distribuição por gênero. RESULTADOS: Dez famílias apresentaram história de consangüinidade entre os pais e mais cinco com homozigose no estudo molecular. A freqüência de indivíduos afetados nas irmandades avaliadas foi de 23,5%, semelhante à esperada de 25%; no entanto, com distribuição heterogênea. Quanto às formas clínicas, 56 (70%) eram perdedores de sal (25M:31F) e 23 (30%) virilizantes simples (10M:13F), não sendo observada diferença na distribuição entre os gêneros. CONCLUSÕES: Estes dados confirmam que a HAC-D21-OHC apresenta padrão de herança monogênica autossômica recessiva, com freqüência de 23,5% na irmandade de indivíduos afetados, elevada taxa de consangüinidade e proporção semelhante entre os gêneros, porém com distribuição heterogênea no número de casos nas irmandades e predomínio da forma clínica perdedora de sal.202206Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Quantitative ultrasonography measurements of the phalanges in adolescents: a mixed longitudinal study

This study examined the effect of pubertal development on Amplitude Dependent Speed of Sound (AD-SoS), accounting for the growth in stature among adolescents. A mixed-longitudinal design with 3 assessments across a 15-mo period in 439 adolescents (girls: 215; boys: 224) aged 9–16 y was used. Bayesian multilevel models were used to describe gender-specific AD-SoS variations among participants during pubertal years. Substantial increments in AD-SoS during pubertal years were observed in both genders. AD-SoS changes were positively related to stature, and the rate of stature growth per year. Quantitative ultrasonography was sensible to describe age-related changes of bone mass during pubertal development. It seemed clinically reliable to use AD-SoS in the study of bone growth and development43122934293

Assessment of total body water and its compartments in elite judo athletes: comparison of bioelectrical impedance spectroscopy with dilution techniques

Bioelectrical impedance spectroscopy (BIS) is an inexpensive and non-invasive technique to measure total body water (TBW), extracellular water (ECW), and intracellular water (ICW). The purpose of this study was to validate TBW, ECW and ICW assessed by BIS, using dilution techniques as the reference method (REF) in elite judo athletes. Thirty-two Portuguese elite male judo athletes were evaluated during a period of weight stability. TBW, ECW and ICW were assessed by BIS (Xitron 4000). Deuterium and bromide dilution techniques were used as the criterion method for measuring TBW and ECW, while ICW was calculated as the difference between the two. BIS explained 96%, 77% and 94% of the total variability from REFs for TBW, ECW and ICW, respectively. BIS also demonstrated high precision (ρ ≥ 0.88) and accuracy (Cb = 0.98), with a minimum concordance coefficient correlation of 0.87 for ECW. The mean bias demonstrated that BIS slightly overestimated the REF in 1.1 kg (2.3%), 0.3 kg (1.6%) and 0.8 kg (2.7%) for TBW, ECW and ICW, respectively. The 95% limits of agreement ranged from −1.2 to 3.3 kg in TBW, from −1.8 to 2.4 kg in ECW and from −1.0 to 2.6 kg in ICW. A non-significant trend was found between the difference and the mean of reference and alternative methods. These findings highlight the efficacy of BIS as a valid non-biased tool for the assessment of TBW and its compartments in elite male judo athletes, during a period of weight stability.33663464

Citizenship, migration and the reassertion of national identity.

OBJECTIVE: To verify the influence of programmed physical activity on body composition among adolescent students during 1 school year. METHODS: The sample included 383 students (age range: 10 to 15years) separated into two groups: 186 cases (96 male and 90 female) and 197 controls (108 male and 89 female). This was an intervention study with pre- and post-test assessments in which interventions consisted of programmed physical activity; the control group had conventional school physical education. Body composition was assessed by anthropometric measurements, body mass index (BMI), body fat percentage and fat and lean body mass. RESULTS: In the case group, subscapular skinfold thickness, BMI, body fat percentage and fat body mass remained stable; there were significant reductions in tricipital skinfold thickness and in abdominal perimeter among girls and significant increases in arm, waist and calf perimeters and in lean body mass. In the control group, there were significant increases in BMI, tricipital skinfold thickness, abdominal perimeter and fat body mass among girls. At post-test, overweight and obesity significantly decreased among case group subjects, but not among controls. CONCLUSION: Programmed physical activity resulted in improvement or maintenance of body composition parameters and in reduction of overweight and obesity in the intervention group.OBJETIVO: Verificar o efeito da atividade física programada na escola sobre a composição corporal em escolares adolescentes durante 1 ano letivo. MÉTODOS: Amostra foi composta por 383 alunos, divididos em dois grupos: caso com 186 (96 meninos e 90 meninas) e controle com 197 (108 meninos e 89 meninas), com idade entre 10 e 15 anos. Trata-se de estudo de intervenção com pré e pós-teste, no qual o grupo caso foi submetido a atividade física programada e o grupo-controle a aulas convencionais de educação física escolar. A composição corporal foi avaliada por medidas antropométricas e cálculos de índice de massa corporal, percentual de gordura e massas gorda e magra. RESULTADOS: O grupo caso apresentou estabilidade na prega cutânea subescapular, índice de massa corporal, percentual de gordura e na massa gorda; redução significativa na prega cutânea triciptal, perímetro do abdome nas meninas e aumento significativo dos perímetros do braço, cintura e panturrilha e da massa magra. No grupo-controle houve aumento do índice de massa corporal, prega cutânea triciptal, perímetro do abdome e da massa gorda nas meninas. O grupo caso apresentou diminuição significativa na proporção de sobrepesos e obesos no pós em relação ao pré-teste, o mesmo não ocorrendo no grupo-controle. CONCLUSÃO: A atividade física programada resultou em melhoria e manutenção nas variáveis da composição corporal e redução da frequência de sobrepeso e obesidade no grupo que sofreu intervenção