The Effects of Heavy Backpack Carriage on Hand Strength

Force production in upper limb muscles could be affected following exercise that involves carrying a heavy backpack load. In lower limb muscles, previous study has demonstrated that there is muscle force depression after several different regimens of metabolically and mechanically demanding exercise. PURPOSE: The aim of this study is to examine pinch strength after exercising while carrying a heavy backpack with straps that compress the nerves and blood vessels of the upper limb. We hypothesized that backpack load carriage at 15% body weight and 30% body weight will lead to changes in upper limb lateral pinch strength as compared to a no-load condition. METHODS: To date, eleven participants (5 female, 6 male; mean ± SD of 25.8 ± 6.3 yrs, 81.9 ± 18 kg mass, 11 right handed) have completed 3 load conditions on separate days: 1) no backpack, 2) 15% body weight (BW) backpack, and 3) 30% BW backpack. Load condition order was randomized. Maximum lateral pinch strength was measured bilaterally using a pinch dynamometer before and after participants walked on a treadmill at 1.1 m/s for 30 minutes for each load condition. Pinch strength was measured every 5 minutes for 30 minutes after exercise. RMANOVA with Bonferroni post-hoc testing was used to compare among backpack conditions and among timepoints. RESULTS: Mean pinch strength on the dominant hand before backpack carriage was 10.8 ± 2.7 kg for male participants and 8.0 ± 1.2 kg for female participants. Pinch strength on the non-dominant hand before load carriage averaged 9.9 ± 1.7 kg for male participants and 7.5 ± 1.0 kg for female participants. Mean pinch strength on the dominant hand after 30% BW backpack carriage ranged from 10.6-10.9 kg for male participants and from 7.8 - 8.3 kg for female participants. There were no significant differences in pinch strength on either hand when comparing among backpack load conditions or timepoints for male or female participants. CONCLUSION: The compression of backpack straps and the exercise of walking with a backpack load did not affect pinch strength in the first 30 minutes after backpack carriage

IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD

A tetraspecific VHH-based neutralizing antibody modifies disease outcome in three animal models of Clostridium difficile infection

Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd

Stoking the flame: Subsistence and wood energy in rural Alaska, United States

Energy costs are large and increasing in rural Alaska communities, so communities are turning to renewable energy. While, many of these communities have a mixed subsistence-cash economy, the relationship between renewable energy and subsistence has not been studied. Tanana, Alaska has a biomass program and we conducted interviews with 61 households in 2017 to understand how residents perceive the program and its association with subsistence activities. We analyzed Alaska Department of Fish & Game subsistence surveys from 89 communities to estimate differences in subsistence harvest between households that harvest wood and those that do not. Interviews indicated that people who harvest wood for the biomass program were six times more likely to engage in subsistence. Subsistence harvests were nearly double (184 kg/per capita) in households that harvested wood for personal use versus those that did not (101 kg/per capita). Equipment used for both activities was similar, and 57% respondents combined wood harvesting with other activities (e.g. subsistence, travel, etc.). Higher household incomes and employment were positively associated with subsistence participation (p < 0.001) while only household incomes was positively associated with wood harvest through the biomass program (p < 0.001). Overall, the program was perceived as having a positive effect (69%) for the community because it has created jobs (36%), saved people money (23%), promoted sharing (16%), and reduced fuel use by the community (15%). Our research shows that biomass programs have the potential to complement subsistence activities and enhance the sustainability of communities in rural Alaska that are faced with high energy costs

Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms

Vasomotor symptoms (VMS) may be associated with an increased risk of cardiovascular disease. One candidate mechanism may involve alterations in physiological responses to stress. The current study therefore examined the relationship between self-reported VMS bother and cardiovascular, hemodynamic, neuroendocrine and inflammatory responses to an acute psychosocial stress protocol

Potent antitrypanosomal activities of 3-aminosteroids against African trypanosomes: investigation of cellular effects and of cross-resistance with existing drugs. Molecules

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against Trypanosoma brucei brucei. The in vitro activity of selected compounds of this series against T. congolense (Savannah-type, IL3000), T. b. brucei (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Studies on mode of antitrypanosomal activity of some selected 3-aminosteroids against Tbb 427WT were also carried out. The tested compounds mostly showed moderate-to-low in vitro activities and low selectivity to mammalian cells. Interestingly, a certain aminosteroid, holarrhetine (10, IC50 = 0.045 ± 0.03 µM), was 2 times more potent against T. congolense than the standard veterinary drug, diminazene aceturate, and 10 times more potent than the control trypanocide, pentamidine, and displayed an excellent in vitro selectivity index of 2130 over L6 myoblasts. All multi-drug resistant strains of T. b. brucei tested were not significantly cross-resistant with the purified compounds. The growth pattern of Tbb 427WT on long and limited exposure time revealed gradual but irrecoverable growth arrest at ≥ IC50 concentrations of 3-aminosteroids. Trypanocidal action was not associated with membrane permeabilization of trypanosome cells but instead with mitochondrial membrane depolarization, reduced adenosine triphosphate (ATP) levels and G2/M cell cycle arrest which appear to be the result of mitochondrial accumulation of the aminosteroids. These findings provided insights for further development of this new and promising class of trypanocide against African trypanosomes

NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy

&lt;b&gt;Aims:&lt;/b&gt; Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. &lt;b&gt;Results:&lt;/b&gt; Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. &lt;b&gt;Innovation:&lt;/b&gt; Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. &lt;b&gt;Conclusions:&lt;/b&gt; Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie

Ireland's Rejection of the Lisbon Treaty and the EU's Impasse.

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