Physical activity in wheelchair-using youth with spina bifida: an observational study

Background: Even though typically developing youth are already at risk for physical inactivity, youth with spina bifida may be even at higher risk as a consequence of their reduced mobility. No objective data is available for youth with spina bifida who use a manual wheelchair, so the seriousness of the problem is unknown. The purpose of this observational study was to quantify physical activity in wheelchair-using youth with spina bifida and evaluate the intensity of activities. Methods: Fifty-three children and adolescents (5–19 years) with spina bifida who use a manual wheelchair for daily life, long distances or sports were included. To assess time spent in several types of activities VitaMove data of 34 participants were used and were presented as time spent sedentary and time spent physically active. This was compared to reference data of typically developing youth. To assess time spent in several intensities Actiheart data of 36 participants were used. The intensities were categorized according to the American College of Sports Medicine, ranging from very light intensity to near to maximal intensity. Data of 25 participants were used to combine type of activity and intensity. Results: Children and adolescents with spina bifida who use a manual wheelchair were more sedentary (94.3% versus 78.0% per 24 h, p < 0.000) and less physically active (5.0% versus 12.2% per 24 h, p < 0.000) compared to typically developing peers. Physical activity during weekend days was worse compared to school days; 19% met the Guidelines of Physical Activity during school days and 8% during weekend days. The intensities per activity varied extensively between participants. Conclusions: Children and adolescents with spina bifida who use a manual wheelchair are less physically active and more sedentary than typically developing youth. The physical activity levels on school days seem to be more favorable than the physical activity levels on a weekend day. The low levels of physical activity need our attention in pediatric rehabilitation practice. The different intensities during activities indicate the importance of individually tailored assessments and interventions

Genetic defects in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations

Influences of levodopa on adipose tissue and skeletal muscle metabolism in patients with idiopathic Parkinson's disease

OBJECTIVE: The substantial weight loss in Parkinson's patients may be related to direct influences of levodopa treatment on fat mobilization/oxidation. We assessed systemic and local metabolic responses to levodopa/benserazide in patients with idiopathic Parkinson's disease. METHODS: We studied 10 Parkinson's disease patients and examined adipose tissue and skeletal muscle metabolism directly with microdialysis. We monitored dialysate concentrations of ethanol, glucose, lactate, pyruvate, and glycerol to assess tissue blood flow and metabolism before and after levodopa/benserazide intake. We also conducted in vitro studies on adipocytes from healthy women. RESULTS: Levodopa/benserazide increased serum levodopa, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine (P < 0.01). Serum adipose tissue and skeletal muscle glycerol did not change or decreased. Adipose tissue glycerol was inversely correlated with serum levodopa concentrations (P < 0.05). In isolated adipocytes, levodopa attenuated isoproterenol-induced glycerol release (P < 0.05). CONCLUSION: Levodopa/benserazide elicits pronounced metabolic changes in both adipose tissue and skeletal muscle with a switch from lipid to carbohydrate metabolism. In adipose tissue, levodopa/benserazide failed to activate lipolysis. Therefore, we suggest that levodopa/benserazide does not induce fat wasting through direct and acute influences on adipose tissue metabolism

Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.

Previous studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukemia remain largely unexplored. In this study, we characterized mutations in SRSF2, U2AF1, and SF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile which is highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline, we accurately detected aberrant splicing in splicing factor mutated samples. A large proportion of differentially used junctions were novel, including several junctions in leukemia-associated genes. In SRSF2(P95H) mutants, we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. Furthermore, we observed a validated impact on overall survival for two junctions overused in SRSF2(P95H) mutants. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes

Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

Item does not contain fulltextFetuin-A, also referred to as alpha2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 microg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 microg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer