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.     

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.     

Image reconstruction using filtered backprojection and iterative method: effect on motion artifacts in myocardial perfusion SPECT

Patient motion during myocardial perfusion SPECT is a common source of errors. The extent and severity of motion artifacts have been described for filtered backprojection (FBP) reconstruction. In recent years, iterative reconstruction has been used increasingly in reconstruction of myocardial perfusion SPECT images and has been shown to be more accurate than FBP even in cases of incomplete datasets. This study evaluated the effect of iterative reconstruction on the extent and severity of motion artifacts. METHODS: Six normal, motion-free, and nongated (99m)Tc myocardial perfusion SPECT scans were selected, and simulated motion of 3 pixels was applied to the early, middle, and late phases of acquisition in 2 types of movement, returning and nonreturning. The images were acquired by a single-head gamma-camera in 32 steps at 30 s per step and in a 180 degrees arc from right anterior oblique to left posterior oblique. All original and shifted images were reconstructed using FBP and ordered-subset expectation maximization (OSEM) techniques and interpreted by 2 nuclear medicine specialists qualitatively and semiquantitatively (using 17 segments and a 5-point scoring system). RESULTS: Overall, 68.1% and 70.8% of shifted images were categorized as definitely abnormal in the FBP and OSEM reconstructions, respectively (P > 0.5). The mean summed score was 11.9 (+/-5.7) and 11.3 (+/-5.2) for nonreturning shifted images (P = 0.13) and 5.2 (+/-2.4) and 3.9 (+/-2.0) for returning shifted images (P < 0.001) in the OSEM and FBP reconstructions, respectively. The incidence of defects in different myocardial segments was similar with the 2 reconstruction methods. The summed score was higher with shifting in the middle phase of acquisition than in the late or early phase. CONCLUSION: Our study showed that the incidence of abnormal findings and the location of defects were not different between the 2 reconstruction types; however, with semiquantitative assessment, the severity of defects increased with OSEM reconstruction. Although OSEM reconstruction has been reported to be more tolerant to missing data than is FBP reconstruction, our study showed that OSEM reconstruction may be less tolerant to motion artifacts than is FBP reconstruction.     

The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials

Objective

This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders.

Methods

We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I²) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size.

Results

Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD?=???1.80; 95% CI ??3.27, ??0.32; P?=?0.01; I²: 95.2) and interleukin 6 (IL-6) concentrations (SMD?=???2.02; 95% CI ??3.57, ??0.47; P?=?0.01; I²: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD?=???1.87; 95% CI ??3.81, 0.07; P?=?0.05; I²: 94.4).

Conclusions

In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.