Genetic susceptibility to invasive pneumococcal disease.

Background: The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF).

Objectives: The aim of the present study was to investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on IPD susceptibility.

Methods: Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls.

Enhancing interactions during daily routines: A randomized controlled trial of a web-based tutorial for parents of young children with ASD.

Unlabelled: Children with Autism Spectrum Disorder (ASD) often experience difficulty participating in everyday home routines, such as bed time or bath time. This randomized controlled trial examined the efficacy of an interactive, web-based parenting tutorial for improving children's engagement in daily routines (i.e.

Transient effects in π-pulse sequences in MAS solid-state NMR.

Dipolar recoupling techniques that use isolated rotor-synchronized π pulses are commonly used in solid-state NMR spectroscopy to gain insight into the structure of biological molecules. These sequences excel through their simplicity, stability towards radio-frequency (rf) inhomogeneity, and low rf requirements. For a theoretical understanding of such sequences, we present a Floquet treatment based on an interaction-frame transformation including the chemical-shift offset dependence.

Antibodies Directed toward Neuraminidase N1 Control Disease in a Mouse Model of Influenza.

There is increasing evidence to suggest that antibodies directed toward influenza A virus (IAV) neuraminidase (NA) are an important correlate of protection against influenza in humans. Moreover, the potential of NA-specific antibodies to provide broader protection than conventional hemagglutinin (HA) antibodies has been recognized. Here, we describe the isolation of two monoclonal antibodies, N1-7D3 and N1-C4, directed toward the N1 NA.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels.

Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels.

Background: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained.

Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation.

Background/aims: Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America.

GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition.

Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood. Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may, in part, influence this risk. Formula-fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants.

Perirenal fat is related to carotid intima-media thickness in children.

Background/objectives: It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking.

Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.

Objective: To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD).

Methods: Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk.

Results: We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD.

Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat.

Background And Objective: The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume.

Subjects/methods: The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.

Developmental sequelae and neurophysiologic substrates of sensory seeking in infant siblings of children with autism spectrum disorder.

It has been proposed that early differences in sensory responsiveness arise from atypical neural function and produce cascading effects on development across domains. This longitudinal study prospectively followed infants at heightened risk for autism spectrum disorder (ASD) based on their status as younger siblings of children diagnosed with ASD (Sibs-ASD) and infants at relatively lower risk for ASD (siblings of typically developing children; Sibs-TD) to examine the developmental sequelae and possible neurophysiological substrates of a specific sensory response pattern: unusually intense interest in nonsocial sensory stimuli or "sensory seeking." At 18 months, sensory seeking and social orienting were measured with the Sensory Processing Assessment, and a potential neural signature for sensory seeking (i.

Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.

Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome-wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine-induced agranulocytosis and 5,170 population controls. Sulfasalazine-induced agranulocytosis was significantly associated with the HLA region on chromosome 6.

Reduced Prenatal Weight Gain and/or Augmented Postnatal Weight Gain Precedes Polycystic Ovary Syndrome in Adolescent Girls.

Objective: Hepato-visceral fat excess is a feature of polycystic ovary syndrome (PCOS). Risk factors for such excess include low prenatal weight gain and high postnatal weight gain. This study examined whether adolescent PCOS was preceded by a relatively low birth weight and/or a relatively high BMI at diagnosis.

Effects of All-Oral Anti-Viral Therapy on HVPG and Systemic Hemodynamics in Patients With Hepatitis C Virus-Associated Cirrhosis.

Background & Aims: Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH.

Methods: We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain.

Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome.

Purpose: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment.

Methods: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23.

Neural Correlates of Sensory Hyporesponsiveness in Toddlers at High Risk for Autism Spectrum Disorder.

Altered patterns of sensory responsiveness are a frequently reported feature of Autism Spectrum Disorder (ASD). Younger siblings of individuals with ASD are at a greatly elevated risk of a future diagnosis of ASD, but little is known about the neural basis of sensory responsiveness patterns in this population. Younger siblings (n = 20) of children diagnosed with ASD participated in resting electroencephalography (EEG) at an age of 18 months.

Differences in dietary and lifestyle habits between pregnant women with small fetuses and appropriate-for-gestational-age fetuses.

Aim: The purpose of this study was to determine differences in lifestyle and dietary habits between pregnant women with small for gestational age (SGA) fetuses and those appropriate for gestational age (AGA).

Methods: This cross-sectional, prospective study was conducted over 14 months and included 46 mothers with SGA and 81 with AGA fetuses. Fetal growth was assessed by a routine third trimester scan.

The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans.

Background: The developmentally important DLK1-DIO3 imprinted domain on human chromosome 14 is regulated by 2 differentially methylated regions, the intergenic differentially methylated region and the MEG3 differentially methylated region.

Objective: The aim was to determine the natural variation in DNA methylation at these differentially methylated regions in human placentas, and to determine its link to gene expression levels at the domain. The second goal was to explore whether the domain's methylation and gene expression correlate with prenatal and early postnatal growth of the conceptus.

A new risk of bias checklist applicable to randomized trials, observational studies, and systematic reviews was developed and validated to be used for systematic reviews focusing on drug adverse events.

Objectives: The objective of the study was to develop and validate an adequate tool to evaluate the risk of bias of randomized controlled trials, observational studies, and systematic reviews assessing drug adverse events.

Study Design And Setting: We developed a structured risk of bias checklist applicable to randomized trials, cohort, case-control and nested case-control studies, and systematic reviews focusing on drug safety. Face and content validity was judged by three experienced reviewers.

TMEM230 in Parkinson's disease.

A study on familial Parkinson disease (PD) described 4 variants in the gene TMEM230 (Chr. 20p13) as the cause of PD. The aim of this study was to test if variants in the TMEM230 gene are associated with PD in 2 independent American European data sets.

Dysregulation of Placental miRNA in Maternal Obesity Is Associated With Pre- and Postnatal Growth.

Context: Human placenta exhibits a specific microRNA (miRNA) expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders such as preeclampsia and intrauterine growth restriction and are potential biomarkers for these pathologies.

Objective: To study the placental miRNA profile in pregnant women with pregestational overweight/obesity (preOB) or gestational obesity (gestOB) and explore the associations between placental miRNAs dysregulated in maternal obesity and prenatal and postnatal growth.