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

The Retinoic Acid Receptor Agonist Am80 Increases Mucosal Inflammation in an IL-6 Dependent Manner During Trichuris muris Infection

PURPOSE: Vitamin A metabolites, such as all-trans-retinoic acid (RA) that act through the nuclear receptor; retinoic acid receptor (RAR), have been shown to polarise T cells towards Th2, and to be important in resistance to helminth infections. Co-incidentally, people harbouring intestinal parasites are often supplemented with vitamin A, as both vitamin A deficiency and parasite infections often occur in the same regions of the globe. However, the impact of vitamin A supplementation on gut inflammation caused by intestinal parasites is not yet completely understood. METHODS: Here, we use Trichuris muris, a helminth parasite that buries into the large intestine of mice causing mucosal inflammation, as a model of both human Trichuriasis and IBD, treat with an RARα/β agonist (Am80) and quantify the ensuing pathological changes in the gut. RESULTS: Critically, we show, for the first time, that rather than playing an anti-inflammatory role, Am80 actually exacerbates helminth-driven inflammation, demonstrated by an increased colonic crypt length and a significant CD4(+) T cell infiltrate. Further, we established that the Am80-driven crypt hyperplasia and CD4(+) T cell infiltrate were dependent on IL-6, as both were absent in Am80-treated IL-6 knock-out mice. CONCLUSIONS: This study presents novel data showing a pro-inflammatory role of RAR ligands in T. muris infection, and implies an undesirable effect for the administration of vitamin A during chronic helminth infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-013-9936-8) contains supplementary material, which is available to authorized users

Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.National Institutes of Health (U.S.) (grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (FA9950-04-1-0079

Complementary and alternative medicine use among US Navy and Marine Corps personnel

<p>Abstract</p> <p>Background</p> <p>Recently, numerous studies have revealed an increase in complementary and alternative medicine (CAM) use in US civilian populations. In contrast, few studies have examined CAM use within military populations, which have ready access to conventional medicine. Currently, the prevalence and impact of CAM use in US military populations remains unknown.</p> <p>Methods</p> <p>To investigate CAM use in US Navy and Marine Corps personnel, the authors surveyed a stratified random sample of 5,000 active duty and Reserve/National Guard members between December 2000 and July 2002. Chi-square tests and multivariable logistic regression were used to assess univariate associations and adjusted odds of CAM use in this population.</p> <p>Results and discussion</p> <p>Of 3,683 service members contacted, 1,446 (39.3%) returned a questionnaire and 1,305 gave complete demographic and survey data suitable for study. Among respondents, more than 37% reported using at least one CAM therapy during the past year. Herbal therapies were among the most commonly reported (15.9%). Most respondents (69.8%) reported their health as being very good or excellent. Modeling revealed that CAM use was most common among personnel who were women, white, and officers. Higher levels of recent physical pain and lower levels of satisfaction with conventional medical care were significantly associated with increased odds of reporting CAM use.</p> <p>Conclusion</p> <p>These data suggest that CAM use is prevalent in the US military and consistent with patterns in other US civilian populations. Because there is much to be learned about CAM use along with allopathic therapy, US military medical professionals should record CAM therapies when collecting medical history data.</p

Donepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkers

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement

Predictors of low cervical cancer screening among immigrant women in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Disparities in cervical cancer screening are known to exist in Ontario, Canada for foreign-born women. The relative importance of various barriers to screening may vary across ethnic groups. This study aimed to determine how predictors of low cervical cancer screening, reflective of sociodemographics, the health care system, and migration, varied by region of origin for Ontario's immigrant women.</p> <p>Methods</p> <p>Using a validated billing code algorithm, we determined the proportion of women who were not screened during the three-year period of 2006-2008 among 455 864 identified immigrant women living in Ontario's urban centres. We created eight identical multivariate Poisson models, stratified by eight regions of origin for immigrant women. In these models, we adjusted for various sociodemographic, health care-related and migration-related variables. We then used the resulting adjusted relative risks to calculate population-attributable fractions for each variable by region of origin.</p> <p>Results</p> <p>Region of origin was not a significant source of effect modification for lack of recent cervical cancer screening. Certain variables were significantly associated with lack of screening across all or nearly all world regions. These consisted of not being in the 35-49 year age group, residence in the lowest-income neighbourhoods, not being in a primary care patient enrolment model, a provider from the same region, and not having a female provider. For all women, the highest population-attributable risk was seen for not having a female provider, with values ranging from 16.8% [95% CI 14.6-19.1%] among women from the Middle East and North Africa to 27.4% [95% CI 26.2-28.6%] for women from East Asia and the Pacific.</p> <p>Conclusions</p> <p>To increase screening rates across immigrant groups, efforts should be made to ensure that women have access to a regular source of primary care, and ideally access to a female health professional. Efforts should also be made to increase the enrolment of immigrant women in new primary care patient enrolment models.</p

Weight-loss intervention using implementation intentions and mental imagery: A randomised control trial study protocol

Background: Overweight and obesity are major health problems worldwide. This protocol describes the HEALTHI (Healthy Eating and Active LifesTyle Health Intervention) Program, a 12-week randomised-controlled weight-loss intervention that adopts two theory-based intervention techniques, mental imagery and implementation intentions, a behaviour-change technique based on planning that have been shown to be effective in promoting health-behaviour change in previous research. The effectiveness of goal-reminder text messages to augment intervention effects will also be tested. The trial will determine the effects of a brief, low cost, theory-based weight-loss intervention to improve dietary intake and physical activity behaviour and facilitate weight-loss in overweight and obese individuals. Methods/Design: Overweight or obese participants will be randomly allocated to one of three conditions: (1) a psycho-education plus an implementation intentions and mental imagery condition; (2) a psycho-education plus an implementation intentions and mental imagery condition with text messages; or (3) a psycho-education control condition. The intervention will be delivered via video presentation to increase the intervention's applicability in multiple contexts and keep costs low. We hypothesise that the intervention conditions will lead to statistically-significant changes in the primary and secondary outcome variables measured at 6 and 12 weeks post-intervention relative to the psycho-education control condition after controlling for baseline values. The primary outcome variable will be body weight and secondary outcome variables will be biomedical (body mass, body fat percentage, muscle mass, waist-hip circumference ratio, systolic and diastolic blood pressure, low-density lipoprotein, high-density lipoprotein, total cholesterol, triglycerides, blood glucose and insulin levels), psychological (quality of life, motivation, risk perception, outcome expectancy, intention, action self-efficacy, maintenance self-efficacy, goal setting and planning), and behavioural (self-reported diet intake, and physical activity involvement) measures. We also expect the intervention condition augmented with text messages to lead to statistically significant differences in the primary and secondary outcome variables at the follow up periods after controlling for baseline values. Discussion: The planned trial will test the effectiveness of the theory-based HEALTHI program intervention to reduce weight and salient psychological, biomedical, and behavioural outcomes in overweight and obese adults. The study has been designed to maximise applicability to real world settings and could be integrated into existing weight management practices

Bats, Bat Flies, and Fungi: Exploring Uncharted Waters

Bats serve as hosts to many lineages of arthropods, of which the blood-sucking bat flies (Nycteribiidae and Streblidae) are the most conspicuous. Bat flies can in turn be parasitized by Laboulbeniales fungi, which are biotrophs of arthropods. This is a second level of parasitism, hyperparasitism, a severely understudied phenomenon. Four genera of Laboulbeniales are known to occur on bat flies, Arthrorhynchus on Nycteribiidae in the Eastern Hemisphere, Dimeromyces on Old World Streblidae, Gloeandromyces on New World Streblidae, and Nycteromyces on Streblidae in both hemispheres. In this chapter, we introduce the different partners of the tripartite interaction and discuss their species diversity, ecology, and patterns of specificity. We cover parasite prevalence of Laboulbeniales fungi on bat flies, climatic effects on parasitism of bat flies, and coevolutionary patterns. One of the most important questions in this tripartite system is whether habitat has an influence on parasitism of bat flies by Laboulbeniales fungi. We hypothesize that habitat disturbance causes parasite prevalence to increase, in line with the “dilution effect.” This can only be resolved based on large, non-biased datasets. To obtain these, we stress the importance of multitrophic field expeditions and international collaborations