A whole-genome sequencing study implicates GRAMD1B in multiple sclerosis susceptibility

While the role of common genetic variants in multiple sclerosis (MS) has been elucidated in large genome-wide association studies, the contribution of rare variants to the disease remains unclear. Herein, a whole-genome sequencing study in four affected and four healthy relatives of a consanguineous Italian family identified a novel missense c.1801T \u3e C (p.S601P) variant in th

Impact of Age and Heart Rate on Strain-Derived Myocardial Work in a Population of Healthy Subjects

The influence of age and gender on strain-imaging-derived myocardial work (MW) was recently investigated in healthy subjects. No information is available on the impact of heart rate (HR) on MW

Management of Congenital Diaphragmatic Hernia (CDH): role of molecular genetics

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery

Pyridostigmine in pediatric Intestinal pseudo-obstruction. case report of a 2-year old girl and literature review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility

Realistic and Spherical Head Modeling for EEG Forward Problem Solution: A Comparative Cortex-Based Analysis

The accuracy of forward models for electroencephalography (EEG) partly depends on head tissues geometry and strongly affects the reliability of the source reconstruction process, but it is not yet clear which brain regions are more sensitive to the choice of different model geometry. In this paper we compare different spherical and realistic head modeling techniques in estimating EEG forward solutions from current dipole sources distributed on a standard cortical space reconstructed from Montreal Neurological Institute (MNI) MRI data. Computer simulations are presented for three different four-shell head models, two with realistic geometry, either surface-based (BEM) or volume-based (FDM), and the corresponding sensor-fitted spherical-shaped model. Point Spread Function (PSF) and Lead Field (LF) cross-correlation analyses were performed for 26 symmetric dipole sources to quantitatively assess models' accuracy in EEG source reconstruction. Realistic geometry turns out to be a relevant factor of improvement, particularly important when considering sources placed in the temporal or in the occipital cortex

Update on Febrile Neutropenia in Pediatric Oncological Patients Undergoing Chemotherapy

: Febrile neutropenia (FN) is a common complication of chemotherapy in oncological children and one of the most important causes of morbidity and mortality in these patients. The early detection of a bacteremia and the rapid therapeutic intervention are crucial to improve the outcome. We analyzed the literature in order to clarify the epidemiology of FN in children undergoing chemotherapy, the specific factors associated with a negative outcome, the most common etiology, and the value of biological markers as a tool to make an early diagnosis or to monitor the evolution of the infection. Several studies have tried to identify specific factors that could help the clinician in the detection of an infection and in its microbiological identification. However, due to the heterogenicity of the available studies, sufficient evidence is lacking to establish the role of these risk factors in clinical practice and future research on this topic appear mandatory. Determinations of risk factors, etiology, and markers of febrile episodes in these patients are complicated by the characteristics of the underlying illness and the effects of treatments received. Although some studies have tried to develop an evidence-based guideline for the empiric management of FN in pediatrics, validated predictive scores and algorithms are still lacking and urgently needed

Biogenic Amines in Meat and Meat Products: A Review of the Science and Future Perspectives

Biogenic amines (BAs) can be found in a wide range of meat and meat products, where they are important as an index for product stability and quality, but also for their impact on public health. This review analyzes the scientific evidence gathered so far on the presence and role of biogenic amines in meat and meat products, also considering the effect of technological conditions on BAs accumulation or decrease. The data provided can be useful for developing solutions to control BAs formation during the shelf-life, for example by novel starters for dry cured products, as well as by packaging technologies and materials for fresh meats. Further research, whose trends are reviewed in this paper, will fill the knowledge gaps, and allow us to protect such perishable products along the distribution chain and in the home environment

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and endometrial cancer risk: a multicentric case-control study

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published evidence-based recommendations for cancer prevention focusing on body weight, physical activity, and diet. Our aim is to evaluate whether adherence to the WCRF/AICR recommendations could reduce endometrial cancer risk. We used data from a multicentric, Italian hospital-based case-control study (1992-2006) including 454 endometrial cancer cases and 908 age-matched controls. Adherence to the WCRF/AICR recommendations was measured using a score (range: 0-7) based on seven components: body mass index (BMI), physical activity and five dietary items; higher scores indicated higher adherence. Odds ratios (OR) were estimated by multiple (adjusted) conditional logistic regression models including terms for major confounders and energy intake. Adherence to the WCRF/AICR recommendations was inversely related to endometrial cancer risk (OR = 0·42, 95 % confidence interval (CI) 0·30, 0·61 for the highest compared with the lowest score quartile), with a significant trend of decreasing risk with increasing adherence. An inverse association was also observed for a score including only dietary recommendations (OR = 0·67, 95 % CI 0·46, 0·96 for the highest compared with the lowest score tertile). In stratified analyses, the association was stronger among women with a normal weight, those who were older, and consequently those in post-menopause, and those with ≥ 2 children. In conclusion, high adherence to the WCRF/AICR recommendations has a favourable role in endometrial cancer risk, which is not fully explained by body weight