Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in non-alcoholic fatty liver disease (NAFLD).

AIMS: Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease risk, in non-alcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised exercise program, patients would maintain longer-term improvements in cardiorespiratory fitness, liver fat and endothelial function. MATHERIALS AND METHODS: Ten NAFLD patients [5/5 males/females, age 51±13years, BMI 31±3 kg.m(2) (mean±s.d.)] underwent a 16-week supervised moderate-intensity exercise intervention. Biochemical markers, cardiorespiratory fitness (VO2peak), subcutaneous, visceral and liver fat (measured by magnetic resonance imaging and spectroscopy respectively) and brachial artery flow-mediated dilation (FMD) were assessed at baseline, after 16 weeks supervised training and 12-months after ending supervision. RESULTS: Despite no significant change in body weight, there were significant improvements in VO2peak [6.5 ml.kg(-1).min(-1) (95% CI 2.8, 10.1); P=0.003], FMD [2.9% (1.5, 4.2); P=0.001], liver transaminases (P0.05) and liver fat [1.4% (-13.0, 15.9); P=0.83] were not significantly different from baseline. CONCLUSIONS: Twelve months following cessation of supervision, exercise-mediated improvements in liver fat and other cardiometabolic variables had reversed with cardiorespiratory fitness at baseline levels. Maintenance of high cardiorespiratory fitness and stability of body weight are critical public health considerations for the treatment of NAFLD.International Journal of Obesity accepted article preview online, 21 July 2016. doi:10.1038/ijo.2016.123

Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability

Mutations in the ATP13A2 (PARK9) and FBXO7 (PARK15) genes are linked to different forms of autosomal recessive juvenile-onset neurodegenerative diseases with overlapping phenotypes, including levodopa-responsive parkinsonism, pyramidal disturbances, cognitive decline, and supranuclear gaze disturbance. However, the associated genotypes and phenotypes are poorly characterized due to the small number of patients described. Here, we report clinical, instrumental, and genetic findings in an Italian family with novel PARK9 and PARK15 mutations. The proband developed a severe progressive phenotype including juvenile-onset parkinsonism, pyramidal disturbances, cognitive decline, and oculomotor abnormalities. On the contrary, his brother only shows mild abnormalities (pyramidal, cognitive, and oculomotor) on the neurological examination at the age of 31 years. These two brothers both carry a novel homozygous PARK9 missense (p.G877R) and a novel heterozygous PARK15 mutation (p.R481C). The PARK9 mutation replaces a crucial residue for the ATPase activity, and is therefore most likely a loss-of-function mutation and disease-causing in homozygous state. The pathogenic significance of the PARK15 single heterozygous mutation remains unclear. In both sibs, DaTSCAN single photon emission computed tomography showed marked nigrostriatal dopaminergic defects, and transcranial magnetic stimulation detected prolonged central motor conduction time. MRI, including T2*-weighted imaging, detected no evidence of brain iron accumulation. This family, the third reported with homozygous PARK9 mutations and the first with mutations in two genes for atypical juvenile parkinsonism, illustrates that PARK9-linked disease might display wide intra-familial clinical variability and milder phenotypes, suggesting the existence of strong, still unknown, modifiers

PI3Kδ and primary immunodeficiencies.

Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy

RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia

RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnos

Maternal Knowledge and Practice in Mashhad City about Breast-feeding in First 6 -Month of Infant's Life

Introduction: Breastfeeding is an important principle in pediatric health. It decreases their mortality and protect them fromm diseases in the first 6-month of life. This study aimed to determined Maternal Knowledge and practice in Mashhad City about Breast-feeding in first 6 -month of Infant's life.   Materials and Methods: This Analytic study was conducted on 105 mothers who had a child between 6 to 12 months,and selected by the cluster sampling and simple random, completed the Knowledge and Practic questionnaire who was made by researchers. Information were analyzed by descriptive- analytical test (ANOWA,T-test,corelation) in spss software in version11.5.   Results: This findings showed that 72/4% of infants have had exclusive until end of the first 6-month.  breast-feeding. Average of maternal knowledge about exclusive breast-feeding was 19/818+4/545 of total score 28 and average of maternal practice was 7/106+2/338 of total score 12. Status of growth infants at 4/8% was very good and in 42/9% was good. There was a significant relationship between maternal practice about Breast-feeding and fathers' education, number of children, status of growth (