The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p_a = 0.02; Taq, p_g = 0.02, p_a = 0.02; BsmI, p_g = 0.02, p_a = 0.04; ApaI, p_g = 0.008, p_a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p_g = 0.01, p_a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p_corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.     

Quantitative myotonia assessment with a commercially available dynamometer in myotonic dystrophy types 1 and 2

Introduction: The objective of this study was to develop a simple method for quantitative assessment of myotonia in patients with myotonic dystrophy type 1 (DM1) and DM2, to compare the myotonia severity, and to correlate this objective outcome with a subjective scale, the Myotonia Behaviour Scale (MBS). Methods: A commercially available dynamometer was used for all measurements. The relaxation time after voluntary contraction was measured in 20 patients with DM1, 25 patients with DM2, and 35 healthy controls. Results: The average relaxation time was 0.17 s in controls, 2.96 s in patients with DM1, and 0.4 s in patients with DM2. The correlation between relaxation time and MBS score was significant, 0.627 in patients with DM1 and 0.581 in patients with DM2. Discussion: Our method provides a valid and reliable quantitative measure of grip myotonia suitable as an outcome measure in clinical trials and as part of routine examinations to gather data on the natural history of myotonic disorders. Muscle Nerve 59:431–435, 2019     

Altered leptin,adiponectin, resistin and ghrelin secretion may represent an intrinsic polycystic ovary syndrome abnormality

Abstract

The aim of the study was to investigate whether altered adipose tissue secretion of various adipokines is secondary to obesity, hyperandrogenism, and hyperinsulinemia or intrinsic to polycystic ovary syndrome (PCOS). This cross-sectional study included 151 women diagnosed with PCOS by the Rotterdam criteria and 95 healthy women matched by age, body mass index (BMI), and waist-to-hip ratio (WHR). Clinical, biochemical, and hormonal characteristics were assessed. Serum concentrations of ghrelin and adiponectin were found to be significantly lower and concentrations of leptin and resistin significantly higher in women with PCOS than in healthy women matched by age, BMI, and WHR. A PCOS diagnosis made the largest contribution to predicting serum levels of leptin, adiponectin, resistin, and ghrelin in all stepwise multiple regression models, which included PCOS diagnosis, BMI, WHR, luteinizing hormone, total testosterone, free testosterone and homeostatic model assessment of insulin resistance as independent predictors. Leptin, adiponectin, ghrelin and resistin levels may serve as independent biomarkers for the diagnosis of PCOS.     

Anatomical site differences of sodium lauryl sulfate-induced irritation: randomized controlled trial

Sodium lauryl sulphate (SLS) is a chemical used to induce skin irritation that mimics irritant contact dermatitis (ICD). ICD is a condition where direct contact with certain substances causes rash, redness, blistering, itching, dryness and cracking of the exposed skin. It is a common occupational disease and accounts for 4-7% of all dermatological consultations in U.K. This SLS induced irritation is often used to test the effectiveness of different treatments that could be used to alleviate the ICD symptoms. Irritation is usually induced on the forearms but other locations such as upper back have been used. The extent of the irritation might be different between different anatomical locations. Those differences could affect the results of the treatment testing. That means that the beneficial effects achieved by the treatment on one location may not be achieved on the other. This study, from Croatia, aimed to investigate variations in skin response to irritation and its effects on treatment in an SLS induced ICD. The irritant was applied on the forearms and the upper back of the healthy volunteers. Emollient (moisturising) cream was chosen as a treatment. One forearm and one side of the back were treated with the emollient for nine days while others were left untreated. The skin parameters that indicate the extent of the irritation and the recovery were measured using skin probes. The authors found that the upper back had stronger reaction to the irritant and faster recovery of the skin than the forearms. Also, the tested emollient cream did not improve the skin recovery. In conclusion, the anatomical location is an important factor influencing the results of the studies testing treatment effectiveness. Future studies should always accurately report the testing location. The results of the studies using this irritation model, but on different anatomical locations, are not necessarily directly comparable.     

Primary leiomyosarcoma of the thyroid gland with prior malignancy and radiotherapy:A case report and review of literature

BACKGROUND Leiomyosarcoma(LMS) of the thyroid gland is a rarely presented tumor that offers poor prognosis. To the best of the authors' knowledge, there currently exist only 28 known cases described in the literature(limited to English).CASE SUMMARY Herein a case is reported of a 60-year-old female patient who had an LMS of the thyroid, which was accompanied by periodic dysphonia and breathing disorder as well as the feeling of pressure in the chest and neck. At the time the disease was diagnosed, no metastases were detected. Prior to the diagnosis, the patient experienced a uterine adenocarcinoma that had been treated by surgical procedure and radiotherapy. For the LMS, a total thyroidectomy was performed,followed by radiotherapy. Since metastases were also discovered in the lungs,sternum, and femur, chemotherapy was administered as well.Immunohistochemically, the tumor cells in the thyroid indicated positively for alpha smooth muscle actin, calponin, and H-caldesmon, but were negative for CD34, p63, estrogen receptor, progesterone receptor, and Epstein-Barr virus.CONCLUSION Although the etiology of the LMS is as of yet unknown, prior malignancy and radiation should be considered as risk factors.     

Depletion of BAFF cytokine exacerbates infection in Pseudomonas aeruginosa infected mice

BackgroundCystic fibrosis (CF) is a genetic disease characterized by chronic inflammation of the lungs that is ineffective at clearing pathogens. B-cell activating factor (BAFF), a cytokine involved in the development of B-cells, is known to be elevated in CF patients with subclinical infections. We postulate that the elevated BAFF levels in CF patients might be triggered by Pseudomonas aeruginosa infection and it might play a protective role in the regulation of lung responses to infection.MethodsTo address this hypothesis, we used a well characterized model of CFTR.KO mice infected with a clinical strain of P. aeruginosa (PA508). We quantified cell types with flow cytometry, concentration of cytokines by ELISA tests, bacterial load by colony counting and lung physiology by metacholine-induced lung resistance.ResultsOur data demonstrates that BAFF is not elevated in uninfected CF mice, and infection with Pseudomonas leads to significant induction of this regulatory cytokine. We also demonstrate that the maintenance of BAFF levels and its induction during the infection is important for clearance of Pseudomonas infection as its depletion during the course of infection leads to decrease in the resolution of infection both in WT and CFTR-KO mice. Interestingly, the depletion of BAFF not only results in a depletion of B cells numbers but also to a significant decrease in the number of regulatory T cells in the non-infected lungs.ConclusionsOverall, our data demonstrate for the first time that BAFF is an important regulatory molecule helping to maintain the immunological response to infection and clearance of lung infection.