Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1) SIT and NO3--depleted beetroot juice as a placebo (SIT+PL); 2) SIT and NO3--rich beetroot juice (∼13 mmol NO3-/day; SIT+BR); or 3) no training and NO3--rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR (P 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only (P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT. NEW & NOTEWORTHY We investigated the influence of nitraterich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training.PepsiC

Muscle metabolic and neuromuscular determinants of fatigue during cycling in different exercise intensity domains.

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.The lactate or gas exchange threshold (GET) and the critical power (CP) are closely associated with human exercise performance. We tested the hypothesis that the limit of tolerance (Tlim) during cycle exercise performed within the exercise intensity domains demarcated by GET and CP is linked to discrete muscle metabolic and neuromuscular responses. Eleven males performed a ramp incremental exercise test, 4-5 severe-intensity (SEV; >CP) constant-work-rate (CWR) tests until Tlim, a heavy-intensity (HVY; GET) CWR test until Tlim, and a moderate-intensity (MOD; 0.05) muscle metabolic milieu (i.e., low pH and [PCr] and high [lactate]) was attained at Tlim (~2-14 min) for all SEV exercise bouts. The muscle metabolic perturbation was greater at Tlim following SEV compared to HVY, and also following SEV and HVY compared to MOD (all P0.05). Neural drive to the VL increased during SEV (4±4%; P0.05). During SEV and HVY, but not MOD, the rates of change in M-wave amplitude and neural drive were correlated with changes in muscle metabolic ([PCr], [lactate]) and blood ionic/acid-base status ([lactate], [K(+)]) (P<0.05). The results of this study indicate that the metabolic and neuromuscular determinants of fatigue development differ according to the intensity domain in which the exercise is performed

Muscle metabolic and neuromuscular determinants of fatigue during cycling in different exercise intensity domains.

Lactate or gas exchange threshold (GET) and critical power (CP) are closely associated with human exercise performance. We tested the hypothesis that the limit of tolerance (Tlim) during cycle exercise performed within the exercise intensity domains demarcated by GET and CP is linked to discrete muscle metabolic and neuromuscular responses. Eleven men performed a ramp incremental exercise test, 4-5 severe-intensity (SEV; >CP) constant-work-rate (CWR) tests until Tlim, a heavy-intensity (HVY; GET) CWR test until Tlim, and a moderate-intensity (MOD; 0.05) muscle metabolic milieu (i.e., low pH and [PCr] and high [lactate]) was attained at Tlim (approximately 2-14 min) for all SEV exercise bouts. The muscle metabolic perturbation was greater at Tlim following SEV compared with HVY, and also following SEV and HVY compared with MOD (all P 0.05). Neural drive to the VL increased during SEV (4 ± 4%; P 0.05). During SEV and HVY, but not MOD, the rates of change in M-wave amplitude and neural drive were correlated with changes in muscle metabolic ([PCr], [lactate]) and blood ionic/acid-base status ([lactate], [K(+)]) (P < 0.05). The results of this study indicate that the metabolic and neuromuscular determinants of fatigue development differ according to the intensity domain in which the exercise is performed.NEW & NOTEWORTHY The gas exchange threshold and the critical power demarcate discrete exercise intensity domains. For the first time, we show that the limit of tolerance during whole-body exercise within these domains is characterized by distinct metabolic and neuromuscular responses. Fatigue development during exercise greater than critical power is associated with the attainment of consistent "limiting" values of muscle metabolites, whereas substrate availability and limitations to muscle activation may constrain performance at lower intensities

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions

Sparse canonical correlation analysis for identifying, connecting and completing gene-expression networks

<p>Abstract</p> <p>Background</p> <p>We generalized penalized canonical correlation analysis for analyzing microarray gene-expression measurements for checking completeness of known metabolic pathways and identifying candidate genes for incorporation in the pathway. We used Wold's method for calculation of the canonical variates, and we applied ridge penalization to the regression of pathway genes on canonical variates of the non-pathway genes, and the elastic net to the regression of non-pathway genes on the canonical variates of the pathway genes.</p> <p>Results</p> <p>We performed a small simulation to illustrate the model's capability to identify new candidate genes to incorporate in the pathway: in our simulations it appeared that a gene was correctly identified if the correlation with the pathway genes was 0.3 or more. We applied the methods to a gene-expression microarray data set of 12, 209 genes measured in 45 patients with glioblastoma, and we considered genes to incorporate in the glioma-pathway: we identified more than 25 genes that correlated > 0.9 with canonical variates of the pathway genes.</p> <p>Conclusion</p> <p>We concluded that penalized canonical correlation analysis is a powerful tool to identify candidate genes in pathway analysis.</p

EDTA chelation therapy for cardiovascular disease: a systematic review

BACKGROUND: Numerous practitioners of both conventional and complementary and alternative medicine throughout North America and Europe claim that chelation therapy with EDTA is an effective means to both control and treat cardiovascular disease. These claims are controversial, and several randomized controlled trials have been completed dealing with this topic. To address this issue we conducted a systematic review to evaluate the best available evidence for the use of EDTA chelation therapy in the treatment of cardiovascular disease. METHODS: We conducted a systematic review of 7 databases from inception to May 2005. Hand searches were conducted in review articles and in any of the trials found. Experts in the field were contacted and registries of clinical trials were searched for unpublished data. To be included in the final systematic review, the studies had to be randomized controlled clinical trials. RESULTS: A total of seven articles were found assessing EDTA chelation for the treatment of cardiovascular disease. Two of these articles were subgroup analyses of one RCT that looked at different clinical outcomes. Of the remaining five studies, two smaller studies found a beneficial effect whereas the other three exhibited no benefit for cardiovascular disease from the use of EDTA chelation therapy. Adverse effects were rare but those of note included a few cases of hypocalcemia and a single case of increased creatinine in a patient on the EDTA intervention. CONCLUSION: The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease. Although not considered to be a highly invasive or harmful therapy, it is possible that the use of EDTA chelation therapy in lieu of proven therapy may result in causing indirect harm to the patient

New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Appropriateness of acute admissions and last in-patient day for patients with long term neurological conditions

<p>Abstract</p> <p>Background</p> <p>To examine the appropriateness of admissions and in-patient stay for patients with long term neurological conditions (LTNCs). To identify variables predictive of appropriateness and explore management alternatives.</p> <p>Methods</p> <p>Adults admitted as acute patients to Derby Hospitals NHS Foundation Trust (England). Data were collected prospectively and examined by a multi-disciplinary expert panel to determine the appropriateness of admission and length of stay (LoS). Management alternatives were discussed.</p> <p>Results</p> <p>A total of 119 participants were recruited. 32 admissions were inappropriate and 83 were for an inappropriate duration. Whether a participant lived in their own home was predictive of an inappropriate admission. The number of LTNCs, number of presenting complaints and whether the participant lived alone in their own home were predictive of an inappropriate LoS. For admissions judged to be inappropriate, the panel suggested management alternatives.</p> <p>Conclusion</p> <p>Patients with LTNCs are being admitted to hospital when other services, e.g. ambulatory care, are available which could meet their needs. Inefficiencies in hospital procedures, such as discharge planning and patient transfers, continue to exist. Recognition of the need to plan for discharge at admission and to ensure in-patient services are provided in a timely manner may contribute towards improved efficiency.</p

Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment.</p> <p>Methods</p> <p>Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses.</p> <p>Results</p> <p>Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication.</p> <p>Conclusions</p> <p>The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.</p