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Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features.  相似文献   
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Background and aimsDeterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort.Methods and resultsRetrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan–Meier curves were used to identify factors associated with developing abnormal glucose tolerance.Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29–0.69]) and HbA1c (HR: 2.43; CI 95% [1.86–3.18]) in years preceding ascertainment were associated with the risk of developing CFRD.ConclusionChildren who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.  相似文献   
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The gut and its bacterial colonizers are now well characterized as key players in whole-body metabolism, opening new avenues of research and generating great expectation for new treatments against obesity and its cardiometabolic complications. As diet is the main environmental factor affecting the gut microbiota, it has been suggested that fruits and vegetables, whose consumption is strongly associated with a healthy lifestyle, may carry phytochemicals that could help maintain intestinal homeostasis and metabolic health. We recently demonstrated that oral administration of a cranberry extract rich in polyphenols prevented diet-induced obesity and several detrimental features of the metabolic syndrome in association with a remarkable increase in the abundance of the mucin-degrading bacterium Akkermansia in the gut microbiota of mice. This addendum provides an extended discussion in light of recent discoveries suggesting a mechanistic link between polyphenols and Akkermansia, also contemplating how this unique microorganism may be exploited to fight the metabolic syndrome.  相似文献   
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Cross‐sectional associations between objectively‐measured sleep duration, sleep efficiency and sleep timing with adiposity and physical activity were examined in a cohort of 567 children from Ottawa, Canada. Five‐hundred and fifteen children (58.8% female; age: 10.0 ± 0.4 years) had valid sleep measurements and were included in the present analyses. Physical activity, sedentary time and sleep parameters were assessed over 7 days (actigraphy). Height, weight and waist circumference were measured according to standardized procedures. Percentage body fat was assessed using bioelectric impedance analysis. Light physical activity and sedentary time were greater in children with the shortest sleep durations (< 0.0001), whereas children with the highest sleep efficiencies had lower light physical activity and more sedentary time across tertiles (< 0.0001). In multivariable linear regression analyses, and after adjusting for a number of covariates, sleep efficiency was inversely related to all adiposity indices (< 0.05). However, sleep duration and sleep timing were not associated with adiposity indices after controlling for covariates. Inverse associations were noted between sleep duration and light physical activity and sedentary time (< 0.0001). Sleep efficiency (< 0.0001), wake time and sleep timing midpoint (< 0.05) were negatively associated with light physical activity, but positively associated with sedentary time. In conclusion, only sleep efficiency was independently correlated with adiposity in this sample of children. Participants with the shortest sleep durations or highest sleep efficiencies had greater sedentary time. More research is needed to develop better sleep recommendations in children that are based on objective measures of sleep duration, sleep efficiency and sleep timing alike.  相似文献   
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