Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism

Metabolic Brain Disease - Cytoplasmic FMRP interacting proteins 1 and 2 (CYFIP1/2) have been previously shown to be associated with central nervous system (CNS) disorders such as autism spectrum...     

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.     

Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized,double‐blinded clinical trial

BackgroundThis study aimed to investigate the effect of melatonin supplementation on endothelial function in patients with heart failure with reduced ejection fraction (HFrEF).MethodsThis is an analysis of the MeHR trial, a randomized double‐blinded placebo‐controlled clinical trial with two parallel arms of 1:1. Oral 10 mg melatonin tablets or placebo was administered for 24 weeks. Deference in the percentage of flow‐mediated dilatation (FMD) after the intervention was the primary outcome.ResultsNinety‐two patients were included in the study (age: 62.7±10.3 years, 87.0% male, ejection fraction (EF): 28.6±8.1). After adjustment for baseline FMD and age, a statistically significant difference in post‐treatment FMD in favor of the melatonin group was seen (estimated marginal means [95%CI], melatonin: 7.84% [6.69–8.98], placebo: 5.98% [4.84–7.12], p = .027). There was no significant difference in the mean of post‐treatment systolic/diastolic blood pressure, serum total antioxidant capacity, and serum malondialdehyde (MDA) between groups. Subgroup analysis showed significant improvement in FMD and MDA in the melatonin group in nondiabetic patients, while no difference was seen between study groups in diabetic patients.ConclusionsMelatonin supplementation in HFrEF might improve endothelial function; however, this beneficial effect might not be seen in diabetic patients.     

Prevalence and risk factors of gastroesophageal reflux disease in Qashqai migrating nomads, southern Iran

AIM： To investigate the prevalence and risk factors of gastroesophageal reflux disease （GERD） symptoms in Qashqai migrating nomads with a different life style in Fars province, southern Iran. METHODS： In summer 2006, 748 Qashqai migrating nomads aged 25 years or more were enrolled using a multiple-stage stratified cluster random sampling method. A questionnaire consisting of demographic characteristics, lifestyle and GERD symptoms （heartburn, regurgitation, chest pain, dysphagia, hoarseness and cough） as completed for each subject. RESULTS： The questionnaire was completed in 717 subjects. The prevalence rate of GERD, defined as reflux occurring at least one time per week in the preceding year, was 33% （237 subjects）. The prevalence was higher in older individuals （36.0% vs 28.9%, P 〈 0.05） and in those with other gastrointestinal complaints （51.0% vs 27.8%, P 〈 0.001）, but not different in obese and non-obese subjects. It was also higher in those consuming fruits and vegetables more than once a week （36.2% vs 17.3%, P 〈 0.001）. GERD had a positive correlation with smoking （42.1% vs 27.8%, P 〈 0.001）, but a negative relation with non-alcoholic beverages. The association between GERD and non-steroidal antiinflammatory drugs （NSAIDs） consumption was also significant （40.2% vs 25.4%, P 〈 0.001）. CONCLUSION： The prevalence of GERD （33%） is very high in Qashqai migrating nomads which may be due to a lower socioeconomic and educational level of these people and difference in the life style. Older age, frequent consumption of fruits and vegetables, smoking and NSAIDs are risk factors for GERD in this population.     

Determination of sensitivity and specificity of a novel gene dosage assay for prenatal screening of trisomy 21 syndrome

ObjectiveTo compare the gene dosage results achieved by a novel multiplex quantitative assay with cytogenetic and quantitative fluorescent polymerase chain reaction (QF-PCR) analysis for prenatal screening of trisomy 21 syndrome on corresponding fetal samples.Design and methodsFetal samples (n = 134) were collected from pregnant women considered high risk for having trisomy 21 affected fetus. Cytogenetic analysis and QF-PCR were performed. Then, the relative gene dosage of DSCAM and DYRK1A2 genes was determined on corresponding samples using comparative delta cycle of threshold (ΔC_T) method.ResultsThe mean gene dosage ratio was 1.55 ± 0.11 (95% CI:1.51–1.58) in trisomy 21 cases and 1.01 ± 0.12 (95% CI:0.98–1.03) in normal samples (p value < 0.001). The results were in agreement to the results of cytogenetic and QF-PCR analysis with the overall specificity of 0.96 (95% CI:0.91–0.98) and the sensitivity of 0.80 (95% CI:0.49–0.94).ConclusionsThis gene dosage assay is appropriate for the screening of high risk pregnant women and is readily amenable to automation.