Exercise-induced abdominal muscle fatigue in healthy humans

Exercise-induced abdominal muscle fatigue in healthy humans. J Appl Physiol 100: 1554–1562, 2006. First published January 19, 2006; doi:10.1152/japplphysiol.01389.2005.—The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (V˙ O2 peak) 50.0 1.9 (SE) ml kg 1 min 1] cycled at 90% V˙ O2 peak to exhaustion (14.2 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1–25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean 25 4%; P 0.001) that persisted up to 30 min postexercise ( 12 4%; P 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 13 before vs. 145 10 cmH2O after exercise; P 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 6 before vs. 64 2% after exercise; P 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms

Age adjustment in ecological studies: using a study on arsenic ingestion and bladder cancer as an example

<p>Abstract</p> <p>Background</p> <p>Despite its limitations, ecological study design is widely applied in epidemiology. In most cases, adjustment for age is necessary, but different methods may lead to different conclusions. To compare three methods of age adjustment, a study on the associations between arsenic in drinking water and incidence of bladder cancer in 243 townships in Taiwan was used as an example.</p> <p>Methods</p> <p>A total of 3068 cases of bladder cancer, including 2276 men and 792 women, were identified during a ten-year study period in the study townships. Three methods were applied to analyze the same data set on the ten-year study period. The first (Direct Method) applied direct standardization to obtain standardized incidence rate and then used it as the dependent variable in the regression analysis. The second (Indirect Method) applied indirect standardization to obtain standardized incidence ratio and then used it as the dependent variable in the regression analysis instead. The third (Variable Method) used proportions of residents in different age groups as a part of the independent variables in the multiple regression models.</p> <p>Results</p> <p>All three methods showed a statistically significant positive association between arsenic exposure above 0.64 mg/L and incidence of bladder cancer in men and women, but different results were observed for the other exposure categories. In addition, the risk estimates obtained by different methods for the same exposure category were all different.</p> <p>Conclusions</p> <p>Using an empirical example, the current study confirmed the argument made by other researchers previously that whereas the three different methods of age adjustment may lead to different conclusions, only the third approach can obtain unbiased estimates of the risks. The third method can also generate estimates of the risk associated with each age group, but the other two are unable to evaluate the effects of age directly.</p

Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies

Micro-RNAs (miRs) are important regulators of mRNA and protein expression; the ability of miR expression profilings to distinguish different cancer types and classify their sub-types has been well-described. They also represent a novel biological entity with potential value as tumour biomarkers, which can improve diagnosis, prognosis, and monitoring of treatment response for human cancers. This endeavour has been greatly facilitated by the stability of miRs in formalin-fixed paraffin-embedded (FFPE) tissues, and their detection in circulation. This review will summarize some of the key dysregulated miRs described to date in human epithelial malignancies, and their potential value as molecular bio-markers in FFPE tissues and blood samples. There remain many challenges in this domain, however, with the evolution of different platforms, the complexities of normalizing miR profiling data, and the importance of evaluating sufficiently-powered training and validation cohorts. Nonetheless, well-conducted miR profiling studies should contribute important insights into the molecular aberrations driving human cancer development and progression

ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17×10-9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10-9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions

Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants

Summary Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4+ T-cell subsets, regulatory T-cells, CD8+ T-cells, B-cells, and monocytes. We find that ~90% of causal variants are noncoding, with ~60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10–20% directly alter recognizable transcription factor binding motifs. Rather, most noncoding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models

Encapsulation with a complex of acidic/alkaline polysaccharide-whey protein isolate fibril bilayer microcapsules enhances the stability of β-carotene under acidic environments

Background: Recent studies have highlighted the potential of protein fibrils for the microencapsulation of lipophilic bioactive molecules. Given their biocompatible and biodegradable properties, as well as their enhanced material stability, proteins are ideal for this purpose. However, β-carotene, a common antioxidant, degrades in acidic environments. In light of this, the present study explored the stability and antioxidant properties of acidic/alkaline polysaccharide–whey protein isolate fibril (WPF) bilayer microcapsules containing β-carotene under acidic conditions. Methods: WPFs were prepared and then homogenized with a β-carotene/limonene solution to form microcapsules. The addition of pectin and chitosan created polysaccharide–WPF bilayer microcapsules. Zetasizer was used to analyze the microcapsules’ size and stability, while confocal microscopy was used to observe their morphology under acidic conditions. The β-carotene concentration was determined via heptane/ethanol extraction. Significant findings: The results show that the pectin–WPF bilayer microcapsules exhibited excellent stability under acidic conditions, which can enhance stability and retain the antioxidant activity of β-carotene. Thus, this work suggests pectin–WPF bilayer microcapsules to be promising carriers for lipophilic bioactive molecules due to enhancing their bioavailability