Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

BackgroundMerosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES).MethodsIn the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants.ResultsWe identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis.ConclusionsIn general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.     

The effects of vitamin D treatment on glycemic control,serum lipid profiles,and C-reactive protein in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

Purpose

Insulin resistance, dyslipidemia and increased systemic inflammation are important risk factors for chronic kidney disease (CKD). Hence, vitamin D administration might be an appropriate approach to decrease the complications of CKD. Randomized controlled trials assessing the effects of vitamin D supplementation or treatment on glycemic control, lipid profiles, and C-reactive protein (CRP) among patients with CKD were included.

Methods

Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science in November 2018 with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneity was estimated using the Cochran’s Q test and I-square (I²) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size.

Results

Of the 1358 citations identified from searches, 17 full-text articles were reviewed. Pooling findings from five studies revealed a significant reduction in fasting glucose (WMD:???18.87; 95% CI:???23.16,???14.58) and in homeostatic model assessment of insulin resistance (HOMA-IR) through three studies (WMD:???2.30; 95% CI:???2.88,???1.72) following the administration of vitamin D. In addition, pooled analysis revealed a significant reduction in triglycerides (WMD:???32.52; 95% CI:???57.57,???7.47) through six studies and in cholesterol concentrations (WMD:???7.93; 95% CI:???13.03,???2.83) through five studies, following vitamin D supplementation or treatment, while there was no effect on insulin, HbA1c, LDL and HDL cholesterol, and CRP levels.

Conclusions

This meta-analysis demonstrated the beneficial effects of vitamin D supplementation or treatment on improving fasting glucose, HOMA-IR, triglycerides and cholesterol levels among patients with CKD, though it did not influence insulin, HbA1c, LDL and HDL cholesterol, and CRP levels.

     

Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta‐analysis of randomized controlled trials

This systematic review and meta‐analysis of randomized controlled trials was performed to determine the effect of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until August 30, 2018. Nine studies with 10 effect sizes out of 357 selected reports were identified eligible to be included in current meta‐analysis. The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment‐estimated insulin resistance, and hemoglobin A1c levels. In subgroup analysis, quercetin supplementation significantly reduced FPG in studies with a duration of ≥8 weeks (weighted mean difference [WMD]: ?0.94; 95% confidence interval [CI; ?1.81, ?0.07]) and used quercetin in dosages of ≥500 mg/day (WMD: ?1.08; 95% CI [?2.08, ?0.07]). In addition, subgroup analysis revealed a significant reduction in insulin concentrations following supplementation with quercetin in studies that enrolled individuals aged <45 years (WMD: ?1.36; 95% CI [?1.76, ?0.97]) and that used quercetin in dosages of ≥500 mg/day (WMD: ?1.57; 95% CI [?1.98, ?1.16]). In summary, subgroup analysis based on duration of ≥8 weeks and used quercetin in dosages of ≥500 mg/day significantly reduced FPG levels.     

The effects of mobile health interventions on lipid profiles among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of mobile health (m-health) interventions on lipid profiles among patients with metabolic syndrome and related disorders.MethodsCochrane Library, EMBASE, PubMed, and Web of Science databases were searched to indentify the relevant randomized clinical trials published up April 30^th, 2018. Two reviewers examined study eligibility, extracted data, and assessed risk of bias of included clinical trials, individually. Heterogeneity was measured using I-square (I²) statistic and Cochran's Q test. Data were pooled the standardized mean difference (SMD) effect size by the random-effect model.Results18 trials of 1681 citations were identified to be appropriate for the current meta-analysis. Findings random-effects model indicated that m-health interventions significantly decreased total- (SMD ?0.54; 95% CI, ?1.05, ?0.03) and LDL-cholesterol levels (SMD ?0.66; 95% CI, ?1.18, -0.15). M-health interventions had no significant effect on triglycerides (SMD ?0.14; 95% CI, ?0.56, 0.28) and HDL-cholesterol levels (SMD ?0.35; 95% CI, ?0.81, 0.11).ConclusionOverall, the current meta-analysis demonstrated that m-health interventions resulted in an improvement in total- and LDL-cholesterol, but did not affect triglycerides and HDL-cholesterol levels.     

Value of Polyclonal Human Immunoglobulin Tagged With 99mTc for Detecting Acute Appendicitis in Patients With Intermediate Probability of Appendicitis

Background

The aim of this study was to assess the value of a technetium (^99mTc)-polyclonal antibody to detect acute appendicitis in patients with intermediate probability of appendicitis.

Methods

A total of 40 patients with mean age of 24.6?±?6.9?years with intermediate probability of appendicitis according to the Alvarado scoring system (score 5 or 6) were studied. After intravenous injection of 740?MBq of ^99mTc?Cimmunoglobulin G (IgG), a flow and blood pool image was obtained followed by two planar images and single photon emission tomography (SPECT) scan from the lower abdominal and pelvic regions. The images were subjected to visual and quantitative analysis. Patients were followed clinically, and the surgeon decided to operate on or observe the patient depending on the clinical findings. The pathology results were considered the gold standard if patients underwent an operation. If patients improved without surgery, it was considered negative for appendicitis.

Results

Altogether, 31 patients were operated on, and 21 patients had acute appendicitis. Nine patients were discharged from hospital and had no symptoms during follow-up. The sensitivity of the planar images for diagnosing appendicitis was 19?C24% and specificity was 100%. The sensitivity of SPECT for diagnosis of appendicitis was 62%, the specificity was 68%, and the negative predictive value (NPV) was 62%. Quantitative analysis showed that using a cutoff of >1.2 for the mean right-to-left count per voxel ratio, the sensitivity of the test for detection of appendicitis was 54%, and the specificity was 86%.

Conclusions

^99mTc?Cpolyclonal IgG scanning has low sensitivity and moderate NPV for detecting appendicitis. Therefore, it is not a suitable tracer for excluding appendicitis.     

The effect of zinc and vitamin E cosupplementation on metabolic status and its related gene expression in patients with gestational diabetes

Abstract

Objective: The aim of this study was to determine the effects of zinc and vitamin E cosupplementation on metabolic status and gene expression related to insulin and lipid metabolism in women with gestational diabetes mellitus (GDM).

Methods: Fifty-four women, in the age range of 18–40 years, diagnosed with GDM were recruited for this randomized, double-blinded, placebo-controlled trial. Subjects were randomly allocated into two intervention groups to either taking 233?mg/day Zinc Gluconate plus 400-IU/day vitamin E supplements or placebo (n?=?27 each group) for 6 weeks. Gene expression related to insulin and lipid metabolism was evaluated in peripheral blood mononuclear cells (PBMCs) of women with GDM using RT-PCR method.

Results: Participants who received zinc plus vitamin E supplements had significantly lower serum insulin levels (β?=??3.81; 95% CI, ?5.90, ?1.72; p?=?.001), homeostasis model of assessment-insulin resistance (β?=??0.96; 95% CI, ?1.54, ?0.38; p?=?.002), serum total-cholesterol (β?=??8.56; 95% CI, ?16.69, ?0.43; p?=?.03) and low density lipoprotein-cholesterol (LDL)-cholesterol (β?=??8.72; 95% CI, ?15.27, ?2.16; p?=?.01), and higher quantitative insulin sensitivity check index (β?=?0.01; 95% CI, 0.005, 0.02; p?=?.007) compared with the placebo. Moreover, zinc and vitamin E cosupplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ; p?=?.03) and low-density lipoprotein receptor (LDLR; p?=?.04) compared with the placebo. Though, zinc and vitamin E combination did not affect other metabolic parameters.

Conclusions: Overall, zinc and vitamin E cosupplementation for 6 weeks in women with GDM significantly improved insulin metabolism, lipid profile, and the gene expression levels of PPAR-γ and LDLR.     

Exploiting osmosis for blood cell sorting

Blood is a valuable tissue containing cellular populations rich in information regarding the immediate immune and inflammatory status of the body. Blood leukocytes or white blood cells (WBCs) provide an ideal sample to monitor systemic changes and understand molecular signaling mechanisms in disease processes. Blood samples need to be processed to deplete contaminating erythrocytes or red blood cells (RBCs) and sorted into different WBC sub-populations prior to analysis. This is typically accomplished using immuno-affinity protocols which result in undesirable activation. An alternative is size based sorting which by itself is unsuitable for WBCs sorting due to size overlap between different sub-populations. To overcome this limitation, we investigated the possibility of using controlled osmotic exposure to deplete and/or create a differential size increase between WBC populations. Using a new microfluidic cell docking platform, the response of RBCs and WBCs to deionized (DI) water was evaluated. Time lapse microscopy confirms depletion of RBCs within 15 s and creation of > 3 μm size difference between lymphocytes, monocytes and granulocytes. A flow through microfluidic device was also used to expose different WBCs to DI water for 30, 60 and 90 s to quantify cell loss and activation. Results confirm preservation of ∼ 100% of monocytes, granulocytes and loss of ∼ 30% of lymphocytes (mostly CD3⁺/CD4⁺) with minimal activation. These results indicate feasibility of this approach for monocyte, granulocyte and lymphocyte (sub-populations) isolation based on size.     

Importance of gated imaging in both phases of myocardial perfusion SPECT: myocardial stunning after dipyridamole infusion

We present the case report of a 72-y-old woman who underwent (99m)Tc-sestamibi gated myocardial perfusion SPECT with a 2-d protocol. SPECT images revealed ischemia of the apical, anteroapical, apicoseptal, and septal walls. Postdipyridamole gated SPECT revealed significant deterioration in the left ventricular ejection fraction (LVEF), wall motion, and systolic wall thickening relative to the findings obtained with rest gated SPECT. Myocardial stunning is a lingering contractile dysfunction that occurs after a brief ischemic insult. Myocardial stunning after dynamic exercise or pharmacologic stress tests has been demonstrated. Thus, the use of gated SPECT in both phases of perfusion studies may add useful information about cardiac function, as a poststress study alone probably reflects stunned myocardium in some patients undergoing ischemic stress tests. The difference between poststress LVEF and rest LVEF may have a powerful impact on prognosis, as it seems to depend on the extent and severity of induced ischemia.