Down-regulation of MeCP2 in Hirschsprung's disease

Background/Purpose

Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells which are highly associated with impaired proliferation and migration of neural crest cells. Whether methyl CpG binding protein 2 (MeCP2) is related with HSCR still remains unknown. This study investigates the involvement of MeCP2 in HSCR.

Methods

Quantitative real time PCR and western blot were used to detect the expression level of MeCP2 both in the aganglionic/diseased segment and the ganglionic/normal segment. In vitro assays we used siRNAs to knock-down the expression of MeCP2 in SH-SY5Y cell lines, and furthermore, MTT and transwell assays were used to detect the proliferation and migration ability, respectively. In addition, bisulfite sequencing (BSP) and miRNA analysis were used to examine why MeCP2 is decreased in HSCR samples.

Results

MeCP2 exhibited a lower expression level in tissues of HSCR patients compared with the controls. The down-regulation may also suppress the proliferative ability of the cells. However, there was no significant difference in the MeCP2 methylation level between cases and controls. Similarly, there was no difference between cases and controls in miRNA-34b (miR-34b) which is predicted to regulate MeCP2 through complementary binding to the 3′-untranslated region of MeCP2.

Conclusion

Our results indicated that an aberrant decreased level of MeCP2 may play an important role in the pathogenesis of HSCR.     

Comorbidities,Treatment and Ensuing Survival in Men with Prostate Cancer

Background  

Comorbidity is poorly integrated into prostate cancer decision making.     

How transparent is behavioral intervention research on pathological gambling and other gambling‐related disorders? A systematic literature review

Aims To review the transparency of reports of behavioral interventions for pathological gambling and other gambling-related disorders. Methods We used the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) Statement to develop the 59-question Adapted TREND Questionnaire (ATQ). Each ATQ question corresponds to a transparency guideline and asks how clearly a study reports its objectives, research design, analytical methods and conclusions. A subset of 23 ATQ questions is considered particularly important. We searched PubMed, PsychINFO and Web of Science to identify experimental evaluations published between 2000 and 2011 aiming to reduce problem gambling behaviors or decrease problems caused by gambling. Twenty-six English-language reports met the inclusion criteria and were reviewed by three abstractors using the ATQ. Results The average report adhered to 38.4 (65.1%) of the 59 ATQ transparency guidelines. Each of the 59 ATQ questions received positive responses from an average of 16.9 (63.8%) of the reports. The subset of 23 particularly relevant questions received an average of 15.3 (66.5%) positive responses. Thirty-two of 59 (54%) ATQ questions were answered positively by 75% or more of the study reports, while 12 (20.3%) received positive responses by 25% or fewer. Publication year did not affect these findings. Conclusions Gambling intervention reports need to improve their transparency by adhering to currently neglected and particularly relevant guidelines. Among them are recommendations for comparing study participants who are lost to follow-up and those who are retained, comparing study participants with the target population, describing methods used to minimize potential bias due to group assignment, and reporting adverse events or unintended effects.     

Trajectories of femoral neck strength in relation to the final menstrual period in a multi-ethnic cohort

Summary

The purpose of this study was to describe the evolution of femoral neck strength relative to load across the menopause transition. It declined significantly over the 10 years bracketing the final menstrual period, and the rate of decline was modified by body mass index, race/ethnicity, and smoking status.

Introduction

Composite indices of femoral neck strength, which integrate dual energy X-ray absorptiometry (DXA)-derived bone mineral density and bone size with body size, are inversely associated with hip fracture risk. Our objective was to describe longitudinal trajectories of the strength indices across the menopausal transition.

Methods

Data came from the Study of Women’s Health Across the Nation; participants were pre- or early peri-menopausal, ages 42–53 at baseline, and were followed up for 9.1?±?1.8 years. Composite indices of femoral neck strength in different failure modes (compression, bending, and impact) were created in 921 women who had three or more hip DXA scans and had definable final menstrual period (FMP) dates. We used mixed effects models to fit piecewise linear growth curves to the baseline-normalized strength indices as a function of time to/after the FMP.

Results

Compression and impact strength indices did not decline until 1 year prior to the FMP, and declined rapidly thereafter, with some slowing of decline 1 year after the FMP. Bending strength index increased slightly until 2 years prior to the FMP, then plateaued, and began to decline at the FMP. Mean decline in strength indices over 10 years was 6.9 % (compression), 2.5 % (bending), and 6.8 % (impact). Women with higher body mass index had larger declines in two of the three indices. Other major modifiers of rates of decline were race/ethnicity and smoking status.

Conclusions

Femoral neck strength relative to load declines significantly during the menopausal transition, with declines commencing 1 to 2 years prior to the FMP.     

Orthodontic anomalies and malocclusions in Late Antique and Early Mediaeval period in Croatia

ObjectiveMalocclusions are relative infrequently analysed in bioarchaeological investigations and if investigated the samples are very small. This research provides analysis of orthodontic anomalies of even 1118 individuals from the Late Antique (LA) and Early Mediaeval (EM) period. Aims were to describe the prevalence of orthodontic anomalies in this historical period and to analyse which orthodontic anomalies are best suitable for bioarchaeological investigations.Methods1118 skulls were examined for anomalies of tooth number, tooth displacement (rotation, malposition, diastema and crowding) as well as for malocclusions.ResultsThe prevalence of hypodontia in the LA was 41.02% and 30.61% in the EM sample. Tooth displacement was noticed in 15.63% individuals from the LA and in 12.42% individuals from EM. About 26% of the LA sample and 7.19% of the EM sample were affected with tooth crowding and the difference was statistically significant.ConclusionOrthodontic anomalies affecting only one tooth or group of teeth are more suitable for examination in bioarchaeological investigations than orthodontic features requiring presence of both jaws and all or almost all teeth. Clinical investigation protocols and methodology should be adopted for bioarchaeological researches and international standards and recommendations should be established for this kind of investigation on skeletal remains.     

Associations of total and free 25OHD and 1,25(OH)<Subscript>2</Subscript>D with serum markers of inflammation in older men

Summary

Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.

Introduction

Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.

Methods

We tested serum total 25OHD, total 1,25(OH)₂D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)₂D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.

Results

IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)₂D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)₂D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)₂D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)₂D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)₂D).

Conclusions

Associations of 1,25(OH)₂D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)₂D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.