Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial

Introduction  

Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA.     

XcisClique: analysis of regulatory bicliques

Background  

Modeling of cis-elements or regulatory motifs in promoter (upstream) regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions.     

Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models

Background

Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine.

Methods

We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope.

Results

We applied our method to ID₅₀ neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF)?>?6), a subset of which were experimentally confirmed using site-directed mutagenesis.

Conclusions

Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.

     

Comparative Estimation of Genetic Diversity in Population Studies using Molecular Sampling and Traditional Sampling Methods

Entomopathogenic nematodes (EPN) are efficient biological pest control agents. Population genetics studies on EPN are seldom known. Therefore, it is of interest to evaluate the significance of molecular sampling method (MSM) for accuracy, time needed, and cost effectiveness over traditional sampling method (TSM). The study was conducted at the Mohican Hills golf course at the state of Ohio where the EPN H. bacteriophora has been monitored for 18 years. The nematode population occupies an area of approximately 3700 m² with density range from 0.25-2 per gram soil. Genetic diversity of EPN was studied by molecular sampling method (MSM) and traditional sampling method (TSM) using the mitochondrial gene pcox1. The MSM picked 88% in compared to TSM with only 30% of sequenced cox 1 gene. All studied genetic polymorphism measures (sequence and haplotype) showed high levels of genetic diversity of MSM over TSM. MSM minimizes the chance of mitochondrial genes amplification from non target organisms (insect or other contaminating microorganisms). Moreover, it allows the sampling of more individuals with a reliable and credible representative sample size. Thus, we show that MSM supersedes TSM in labour intensity, time consumption and requirement of no special experience and efficiency.     

Ocean acidification and the loss of phenolic substances in marine plants

Rising atmospheric CO(2) often triggers the production of plant phenolics, including many that serve as herbivore deterrents, digestion reducers, antimicrobials, or ultraviolet sunscreens. Such responses are predicted by popular models of plant defense, especially resource availability models which link carbon availability to phenolic biosynthesis. CO(2) availability is also increasing in the oceans, where anthropogenic emissions cause ocean acidification, decreasing seawater pH and shifting the carbonate system towards further CO(2) enrichment. Such conditions tend to increase seagrass productivity but may also increase rates of grazing on these marine plants. Here we show that high CO(2) / low pH conditions of OA decrease, rather than increase, concentrations of phenolic protective substances in seagrasses and eurysaline marine plants. We observed a loss of simple and polymeric phenolics in the seagrass Cymodocea nodosa near a volcanic CO(2) vent on the Island of Vulcano, Italy, where pH values decreased from 8.1 to 7.3 and pCO(2) concentrations increased ten-fold. We observed similar responses in two estuarine species, Ruppia maritima and Potamogeton perfoliatus, in in situ Free-Ocean-Carbon-Enrichment experiments conducted in tributaries of the Chesapeake Bay, USA. These responses are strikingly different than those exhibited by terrestrial plants. The loss of phenolic substances may explain the higher-than-usual rates of grazing observed near undersea CO(2) vents and suggests that ocean acidification may alter coastal carbon fluxes by affecting rates of decomposition, grazing, and disease. Our observations temper recent predictions that seagrasses would necessarily be "winners" in a high CO(2) world.     

Young Adults' Performance in a Low‐Intensity Weight Loss Campaign

Young adults (YA) are underrepresented in behavioral weight loss programs and achieve poorer outcomes than older adults (OA). There has been a call to develop programs specifically targeting this age group. This study examined the performance of YA enrolled in a low‐intensity, team‐based weight loss campaign and compared their outcomes to OA to determine the utility of such an approach for weight loss in this population. Shape Up Rhode Island (SURI) 2009 was a 12‐week online team‐based weight loss and exercise competition (N = 6,795, 81% female, 94% white, age = 44.7 ± 11.2, BMI = 29.4 ± 5.9). YA was defined as 18–35 years and OA as >35 years; YA and OA were compared on enrollment, retention, weight loss, and change in steps. A total of 1,562 YA enrolled and 715 completed the program. Fewer YA completed compared with OA (46 vs. 62%, P < 0.001). However, among completers, YA achieved greater percent weight loss (‐4.5 ± 4.0 vs. ?3.8 ± 3.2%) and greater daily step change (+1,578.2 ± 3,877.2 vs. +1,342.2 ± 3,645.7) than OA (P's < 0.001). Further, more YA completers achieved a ≥5% weight loss (40 vs. 29%, P < 0.001). Findings were consistent in the overweight/obese (OW/OB) subsample, and using ≤25 years of age as the cut off for YA. Weight losses among YA in this low‐intensity weight loss campaign were quite promising, with over 700 YA completing the program and on average achieving a 4.5% weight loss. Indeed, the potential public health impact of such an approach is substantial; future efforts to develop programs for this age group may benefit from using a low‐intensity, team‐based approach.     

Teammates and social influence affect weight loss outcomes in a team-based weight loss competition

Team-based internet interventions are increasing in popularity as a way of promoting weight loss in large numbers of individuals. Given that social networks influence health behavior change, this study investigated the effects of teammates and social influence on individual weight loss during a team-based weight loss competition. Shape Up Rhode Island (SURI) 2009 was a 12-week online program open to adult residents of Rhode Island. Participants joined with a team and competed with other teams on weight loss and/or physical activity. Overweight/obese (OW/OB) individuals (N = 3,330; 76% female; age = 46.1 ± 10.8; BMI = 31.2 ± 5.3 kg/m(2)), representing 987 teams, completed the weight loss program. Multilevel modeling was used to examine whether weight loss clustered among teammates and whether percentage of teammates in the weight loss division and reported teammate influence on weight loss were associated with individual weight outcomes. OW/OB completers reported losing 4.2 ± 3.4% of initial body weight. Weight loss was similar among teammates (intraclass correlation coefficient (ICC) = 0.10, P < 0.001). Moreover, having a greater percentage of teammates in the weight loss division and reporting higher social influence for weight loss were associated with greater percent weight loss (P's ≤ 0.002). Similarly, achieving a clinically significant (5%) weight loss tended to cluster within teams (ICC = 0.09; P < 0.001) and having more teammates in the weight loss division and higher social influence for weight loss were associated with increased likelihood of achieving a 5% weight loss (odds ratio (OR) = 1.06; OR = 1.20, respectively). These results suggest that teammates affect weight loss outcomes during a team-based intervention. Harnessing and maximizing teammate influence for weight loss may enhance weight outcomes in large-scale team-based programs.     

Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

Background

Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome.

Methods

Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously) and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue.

Results

Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day) significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH).

Conclusion

Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary inflammatory response, fibrin deposition and RVH, and stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic lung injury and continued during room air recovery improves alveolarization and restores pulmonary angiogenesis and RVH in experimental BPD.