Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

OBJECTIVE: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. METHODS: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development

Association between Eating Disorder and Depression among Medical Students of Islamic Azad university of Yazd in 2013

Introduction: Eating disorder is one of the most prevalent psychiatric disorders that cause various problems for physical health, psychological functioning and quality of life. The purpose of this study was to evaluate and determine the association between eating disorder and depression among medical students of Free University of Yazd, Iran in 2013. Methods: In a descriptive study, a total of 400 medical students were selected via convenient sampling. Students were assessed by 2 questionnaires: Eat-26 and Beck. The data was analyzed using chi square, fisher exact and ANOVA tests. Results: According to the results,7/5% of students suffered from eating disorder , 25/8% from moderate, and 22% from severe depression. The relative frequency of eating among the participants according to age, gender, state of residence, and marital status were identical. However there was a significant correlation between the relative prevalence of eating disorder and depression severity among the medical students. Conclusion: The findings of the present study imply that eating disorder had a significant association with severity of depression. Thus, educating of medical students by consulting centers can be effective for early diagnosis and treatment

Effect of both uncoated and coated calcium carbonate on fracture toughness of HDPE/CaCO3 nanocomposites

The main goal of this research is to investigate the effect of nano-CaCO3 coated with different content of stearic acid on fracture toughness of HDPE/CaCO3 nanocomposite. For this purpose, HDPE/10 vol % CaCO3 nanocomposites were made using a twin-screw mixer-single-screw extruder. Nanocomposite standard samples were prepared via injection molding method. Three-point bending tests and microscopic evaluations were performed. The results of fracture toughness test showed that the addition of uncoated nano-CaCO3 to HDPE causes to decrease fracture toughness, but it can be increased slightly as stearic acid content added. Also the results showed that the stress whitening zone width depends strongly on both CaCO3 and stearic acid content

Modeling of electrical conductivity in the proton conductor Ba0.85K0.15ZrO3-delta

The electrical conductivity of Ba0.85K0.15ZrO3-delta (BKZ) has been studied as a function of both oxygen and water vapor partial pressure in the temperature range of 550-700 degrees C, to determine the partial conductivities of protons, holes, and oxygen vacancies from the defect model. It is shown that p-type conduction is dominant in dry oxidative atmospheres, while in wet oxidative atmospheres, a conduction transition from proton to hole conduction is found with increasing temperature. On the contrary, in wet nitrogen atmosphere, proton conduction is dominant over the whole temperature range. The calculated activation energies for oxide-ion, electron-hole and proton conduction are 0.86, 1.36 and 0.59 eV, respectively. The standard solution enthalpy for water dissolution is -90 kJ/mol, which is lower in absolute terms than that typically reported for doped barium cerates but very close to that reported for BaZr0.85Y0.15O3-delta. (C) 2015 Elsevier Ltd. All rights reserved

Oxybutynin reduces sweating in depressed patients treated with sertraline: a double-blind, placebo-controlled, clinical study

Ali Ghaleiha,1 Leila Jahangard,1 Zahra Sherafat,1 Mohammad Ahmadpanah,1 Serge Brand,2 Edith Holsboer-Trachsler,2 Hafez Bajoghli,3 Mohammad Haghighi11Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran; 2Psychiatric Hospital of the University of Basel, Center for Affective, Stress and Sleep Disorders, University of Basel, Basel, Switzerland; 3Psychiatry and Psychology Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, IranBackground: Selective serotonin reuptake inhibitors are primarily used in the pharmacological treatment of patients experiencing a major depressive disorder. However, one of the common unwanted effects is excessive sweating or hyperhidrosis. Oxybutynin is an anticholinergic medication which reduces sweating. The aim of this double-blind study was to examine the effect of administration of oxybutynin on subjective sweating in patients treated with sertraline.Methods: A total of 140 patients experiencing a major depressive disorder (mean age 37.69 ± 10.44 years, 86 females [61.4%]) treated with sertraline (mean dose 83 mg/day) were consecutively enrolled in the study, and all reported excessive sweating as a side effect. Thereafter, the patients were randomly assigned to either an oxybutynin 5 mg/day group or to a placebo group. At the beginning and end of the 2-week trial, the patients completed questionnaires related to sweating and medication-related side effects.Results: Over time, subjective sweating reduced significantly in the treatment group as compared with the control group. Oxybutynin-induced side effects were uncommon. Relative to male patients, female patients reported less subjective sweating.Conclusion: Administration of oxybutynin successfully reduced excessive sweating in patients experiencing a major depressive disorder and treated with sertraline. However, possible gender effects should be taken into account.Keywords: oxybutynin, sweating, sertraline, major depressive disorder

Enhanced BaZrO3 mechanosynthesis by the use of metastable ZrO2 precursors

The current work assesses the impact of structural differences between stable and metastable ZrO2 precursors on the mechanochemical preparation of BaZrO3. Monoclinic (m-ZrO2) and tetragonal (t-ZrO2) zirconia polymorphs were prepared without stabilizing additives by slow alkaline precipitation. High-energy milling of the individual ZrO2 precursors induced different partial transformations in each case. The as-synthesized m-ZrO2 powders showed partial conversion to the tetragonal polymorph on mechanical activation, reaching about 10% t-ZrO2 after 420 min accompanied by increases in strain. In contrast, the as synthesized t-ZrO2 powders underwent the inverse transformation to the monoclinic phase, producing about 50% m-ZrO2 after 120 min with the liberation of strain. The t-ZrO2 precursor was shown to exhibit the higher reactivity with barium peroxide, yielding significantly earlier formation of barium zirconate under room-temperature mechanosynthesis. The progress of the mechanochemical formation of BaZrO3 has been discussed with respect to the differing behaviour of the ZrO2 precursors upon mechanical activation and associated thermodynamic perspectives