Language Predictors in Autism Spectrum Disorder: Insights from Neurodevelopmental Profile in a Longitudinal Perspective.

Language outcome in individuals with autism spectrum disorder (ASD) is predicted by early developmental milestones and cognitive abilities. The development and acquisition of expressive language (particularly the onset of first phrases) is a relevant clinical milestone by school age, since its early presentation is associated to better long-term life outcomes and to lower core clinical severity of ASD. Focusing on predictors of language in ASD children, a number of outstanding questions remain to be answered, namely, whether there are differences in the early key neurodevelopmental abilities and whether those differences in a specific period of time might predict verbal development and acquisition of expressive language. We aim to understand how the neurodevelopmental profile of ASD children evolves from the preschool to the school age and if and which subarea can better predict acquisition of expressive language. Children with ASD (N = 205) were evaluated with a structured assessment of neurodevelopment in two different age periods: 1) preschool period (mean age four years) and 2) reassessment in the school period (mean age seven years). Our findings demonstrate that in nonverbal preschool children with ASD normal or near normal Performance Developmental Quotient (superior to 73.5) evaluated at preschool age is a good predictor of later language development in ASD, which has important implications for intervention programs targeting this population and family information.

mTOR Signaling Pathway Regulates Sperm Quality in Older Men.

Understanding how age affects fertility becomes increasingly relevant as couples delay childbearing toward later stages of their lives. While the influence of maternal age on fertility is well established, the impact of paternal age is poorly characterized. Thus, this study aimed to understand the molecular mechanisms responsible for age-dependent decline in spermatozoa quality. To attain it, we evaluated the impact of male age on the activity of signaling proteins in two distinct spermatozoa populations: total spermatozoa fraction and highly motile/viable fraction. In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. On the contrary, when considering the entire spermatozoa population (including defective/immotile/apoptotic cells) our findings support an active mTORC1 signaling pathway in older men. Additionally, total spermatozoa fractions of older men presented increased levels of apoptotic/stress markers (e.g., cellular tumor antigen p53-TP53) and mitogen-activated protein kinases (MAPKs) activity. Moreover, we established that the levels of most signaling proteins analyzed were consistently and significantly altered in men more than 27 years of age. This study was the first to associate the mTOR signaling pathway with the age impact on spermatozoa quality. Additionally, we constructed a network of the sperm proteins associated with male aging, identifying TP53 as a central player in spermatozoa aging.

Study on the short-term effects of increased alcohol and cigarette consumption in healthy young men's seminal quality.

Many studies have reported a negative impact of lifestyle factors on testicular function, spermatozoa parameters and pituitary-gonadal axis. However, conclusions are difficult to draw, since studies in the general population are rare. In this study we intended to address the early and late short-term impact of acute lifestyle alterations on young men's reproductive function. Thirty-six healthy male students, who attended the Portuguese academic festivities, provided semen samples and answered questionnaires at three time-points. The consumption of alcohol and cigarette increased more than 8 and 2 times, respectively, during the academic festivities and resulted in deleterious effects on semen quality: one week after the festivities, a decrease on semen volume, spermatozoa motility and normal morphology was observed, in parallel with an increase on immotile spermatozoa, head and midpiece defects and spermatozoa oxidative stress. Additionally, three months after the academic festivities, besides the detrimental effect on volume, motility and morphology, a negative impact on spermatozoa concentration was observed, along with a decrease on epididymal, seminal vesicles and prostate function. This study contributed to understanding the pathophysiology underlying semen quality degradation induced by acute lifestyle alterations, suggesting that high alcohol and cigarette consumption are associated with decreased semen quality in healthy young men.

New Insights on the Impact of Statin Therapy in the Susceptibility to Hypovitaminosis D Through Serum Lipidome Profiling.

Hypovitaminosis D is a worldwide clinical problem, affecting populations in numerous ways. Several factors seem to affect vitamin D metabolism, including the suggestion that therapy with the lipid lowering HMG-CoA inhibitors might modulate vitamin D levels. However, the relationship between statins intake and serum levels of vitamin D is still controversial. The present work aimed to add new insights on the association between statins therapy, and more specifically the generation of statins, and the lipid profile in a population of 106 subjects treated with these HMG-CoA inhibitors. Data showed that despite a higher prevalence of hipovitaminosis D in subjects treated with statins, there is no association between statin generation, total and LDL cholesterol and vitamin D levels. Moreover, second generation statins, the most common treatment of hypercholesterolemia in the studied population, promoted the remodelling of serum fatty acids that was characterized by the increase of arachidonic acid (AA) relative levels without affecting eicosapentaenoic acid (EPA) levels. Among statin treated subjects, vitamin D levels did not affect serum fatty acid profile. The statin-related increased ratio AA/EPA suggests a pro- inflammatory status, whose long-term impact should be better clarified in the future.

Profiling signaling proteins in human spermatozoa: biomarker identification for sperm quality evaluation.

OBJECTIVE: To determine the correlation between semen basic parameters and the expression and activity of signaling proteins. DESIGN: In vitro studies with human spermatozoa. SETTING: Academic research institute. PATIENT(S): Thirty-seven men provided semen samples for routine analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Basic semen parameters tracked included sperm DNA fragmentation (SDF), the expression levels of 75 protein kinases, and the phosphorylation/cleavage patterns of 18 signaling proteins in human spermatozoa. RESULT(S): The results indicated that the phosphorylated levels of several proteins (Bad, GSK-3ß, HSP27, JNK/SAPK, mTOR, p38 MAPK, and p53), as well as cleavage of PARP (at D214) and Caspase-3 (at D175), were significantly correlated with motility parameters. Additionally, the percentage of morphologically normal spermatozoa demonstrated a significant positive correlation with the phosphorylated levels of p70 S6 kinase and, in turn, head defects and the teratozoospermia index (TZI) showed a significant negative correlation with the phosphorylated levels of Stat3. There was a significant positive correlation between SDF and the teratozoospermia index, as well as the presence of head defects. In contrast, SDF negatively correlated with the percentage of morphologically normal spermatozoa and the phosphorylation of Akt and p70 S6 kinase. Subjects with varicocele demonstrated a significant negative correlation between head morphological defects and the phosphorylated levels of Akt, GSK3ß, p38 MAPK, and Stat1. Additionally, 34 protein kinases were identified as expressed in their total protein levels in normozoospermic samples. CONCLUSION(S): This study contributed toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters.