Pubertad normal y variantes de la normalidad

La pubertad es un periodo de transición entre la infancia y la vida adulta, regulada por complejos mecanismos biológicos que, a su vez, están controlados por la interacción entre redes nodales de genes y el ambiente. Aunque ha existido una notable tendencia secular en el inicio de la pubertad, desde el siglo XIX hasta mediados del siglo XX, esta se ha estabilizado en las últimas décadas. De esta forma, se define como pubertad normal aquella que acontece entre los ocho y los trece años en las niñas y entre los nueve y catorce en los niños. El principal signo físico a tener en cuenta para la valoración del desarrollo puberal, es la aparición de telarquia progresiva en las niñas y el incremento del tamaño testicular en los niños. Seguidamente, se desarrollarán otros caracteres sexuales secundarios y se objetivará un incremento de la velocidad del crecimiento. En el diagnóstico diferencial de trastornos de la pubertad, aparte de conocer los límites normales de la pubertad, deberemos tener en cuenta una serie de variantes de la normalidad, como son: la adrenarquia prematura idiopática, la telarquia prematura aislada, la pubertad adelantada y el retraso constitucional del crecimiento y pubertadPuberty is a transition period between childhood and adulthood regulated by complex biological mechanisms, which in turn are controlled by the interaction between gene networks and environment. Although there has been a significant secular trend in onset of puberty from the XIX century to the mid XX century, it has been stabilized in recent decades. Thus, it is defined normal puberty as that occurs between eight and thirteen years old in girls and between nine and fourteen years old in boys. The main physical sign to be considered for assessment of pubertal development is the emergence of progressive thelarche in girls and increased testicular size in boys. Then, other secondary sexual characteristics will develop and increased growth velocity will be observed. In the differential diagnosis of puberty disorders, apart from knowing the normal limits of puberty, we must consider a number of variants of normality such as idiopathic premature adrenarche, premature thelarche, early puberty and constitutional delay of growth and pubert

Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases

Gestational diabetes mellitus (GDM) is defined as the presence of high blood glucose levels with the onset, or detected for the first time during pregnancy, as a result of increased insulin resistance. GDM may be induced by dysregulation of pancreatic β-cell function and/or by alteration of secreted gestational hormones and peptides related with glucose homeostasis. It may affect one out of five pregnancies, leading to perinatal morbidity and adverse neonatal outcomes, and high risk of chronic metabolic and cardiovascular injuries in both mother and offspring. Currently, GDM diagnosis is based on evaluation of glucose homeostasis at late stages of pregnancy, but increased age and body-weight, and familiar or previous occurrence of GDM, may conditionate this criteria. In addition, an earlier and more specific detection of GDM with associated metabolic and cardiovascular risk could improve GDM development and outcomes. In this sense, 1st–2nd trimester-released biomarkers found in maternal plasma including adipose tissue-derived factors such as adiponectin, visfatin, omentin-1, fatty acid-binding protein-4 and retinol binding-protein-4 have shown correlations with GDM development. Moreover, placenta-related factors such as sex hormone-binding globulin, afamin, fetuin-A, fibroblast growth factors-21/23, ficolin-3 and follistatin, or specific micro- RNAs may participate in GDM progression and be useful for its recognition. Finally, urine-excreted metabolites such as those related with serotonin system, non-polar amino-acids and ketone bodies, may complete a predictive or earlydiagnostic panel of biomarkers for GDMThis work was supported by the grant PI17/01495, from the Fondo de Investigación Sanitaria (ISC-III) and Fondo Europeo de Desarrollo Regional (FEDER) (for EJ), and grant SAF2017-84776-R, from Ministerio de Educación y Ciencia (for PC)

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children

Objective: To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR). Materials and Methods: We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP). Results: SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls. Discussion: The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation

Ether-linked lipids of Dermabacter hominis, a human skin actinobacterium

Valero-Guillén PL, Fernández-Natal I, Marrodán-Ciordia T, Tauch A, Soriano F. Ether-linked lipids of Dermabacter hominis, a human skin actinobacterium. Chemistry and Physics of Lipids. 2016;196:24-32.Dermabacter hominis is a medically important actinobacterial inhabitant of human skin, although it is rarely implicated in infections. The lipid composition of D. hominis is revisited in this study in the context of its natural resistance to daptomycin, an antibiotic whose activity is influenced by membrane lipids. Thin layer chromatography and mass spectrometry revealed that this species contains phospholipids and glycolipids. Using electrospray ionization time of flight mass spectrometry (exact mass) and gas chromatography-mass spectrometry, the major phospholipid of D. hominis was identified as plasmanyl-phosphatidylglycerol (pPG), because it presented one alkyl chain and one acyl chain in the glycerol moiety of the molecule. The structure of the major glycolipid (GL1) was studied by combined gas-liquid chromatography, mass spectrometry and nuclear magnetic resonance, and was established as galactosyl-alpha-(12)-glucosyl-alkyl-acyl-glycerol. Lipid analyses showed differences between one daptomycin-resistant (DAP-R) strain and one daptomycin-sensitive (DAP-S) strain growing in the presence of the antibiotic: DAP-R tended to accumulate GL1 and to reduce pPG, whereas DAP-S maintained high proportions of pPG. The results demonstrate the existence of ether-linked lipids in D. hominis and reveal a differential distribution of phospholipids and glycolipids according to the sensitivity or resistance to daptomycin, although the mechanism(s) operating in the resistance to the antibiotic remain(s) to be elucidated. Copyright 2016 Elsevier Ireland Ltd. All rights reserved