Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change

Development and evaluation of a patient centered cardiovascular health education program for insured patients in rural Nigeria (QUICK - II)

<p>Abstract</p> <p>Background</p> <p>In Sub Saharan Africa, the incidence of hypertension and other modifiable cardiovascular risk factors is growing rapidly. Poor adherence to prescribed prevention and treatment regimens by patients can compromise treatment outcomes. Patient-centered cardiovascular health education is likely to improve shortcomings in adherence. This paper describes a study that aims to develop a cardiovascular health education program for patients participating in a subsidized insurance plan in Nigeria and to evaluate the applicability and effectiveness in patients at increased risk for cardiovascular disease.</p> <p>Methods/Design</p> <p><it>Design: </it>The study has two parts. Part <it>1 </it>will develop a cardiovascular health education program, using qualitative interviews with stakeholders. Part <it>2 </it>will evaluate the effectiveness of the program in patients, using a prospective (pre-post) observational design.</p> <p><it>Setting: </it>A rural primary health center in Kwara State, Nigeria.</p> <p><it>Population: </it>For part 1: 40 patients, 10 healthcare professionals, and 5 insurance managers. For part 2: 150 patients with uncontrolled hypertension or other cardiovascular risk factors after one year of treatment.</p> <p><it>Intervention: </it>Part <it>2</it>: patient-centered cardiovascular health education program.</p> <p><it>Measurements: </it>Part 1: Semi-structured interviews to identify stakeholder perspectives. Part 2: Pre- and post-intervention assessments including patients' demographic and socioeconomic data, blood pressure, body mass index and self-reporting measures on medication adherence and perception of care. Feasibility of the intervention will be measured using process data.</p> <p><it>Outcomes: </it>For program development (part 1): overview of healthcare professionals' perceptions on barriers and facilitators to care, protocol for patient education, and protocol implementation plan.</p> <p>For program evaluation (part 2): changes in patients' scores on adherence to medication and life style changes, blood pressure, and other physiological and self-reporting measures at six months past baseline.</p> <p><it>Analysis: </it>Part 1: content analytic technique utilizing MAXQDA software. Part 2: univariate and multilevel analysis to assess outcomes of intervention.</p> <p>Discussion</p> <p>Diligent implementation of patient-centered education should enhance adherence to cardiovascular disease prevention and management programs in low income countries.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN47894401">ISRCTN47894401</a></p

Antihyperlipidemic effects of Pleurotus ostreatus (oyster mushrooms) in HIV-infected individuals taking antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Antiretroviral treatment (ART) regimens in HIV patients commonly cause significant lipid elevations, including increases in both triglycerides and cholesterol. Standard treatments for hypercholesterolemia include the HMG CoA reductase inhibitors, or "statins." Because many ART agents and statins share a common metabolic pathway that uses the cytochrome P450 enzyme system, coadministration of ART with statins could increase statin plasma levels significantly. The oyster mushroom, <it>Pleurotus ostreatus</it>, has been shown in animal models to decrease lipid levels - a finding that has been supported by preliminary data in a small human trial.</p> <p>Methods</p> <p>To assess the safety and efficacy of <it>P. ostreatus </it>in patients with HIV and ART-induced hyperlipidemia, a single-arm, open-label, proof-of-concept study of 8 weeks' duration with a target enrollment of 20 subjects was conducted. Study patients with ART-induced elevated non-HDL cholesterol levels (> 160 mg/dL) were enrolled. Participants received packets of freeze-dried <it>P. ostreatus </it>(15 gm/day) to be administered orally for the 8 week trial period. Lipid levels were drawn every two weeks to assess efficacy. Safety assessments included self-reported incidence of muscle aches and measurement of liver and muscle enzymes. Mean within-person change in lipid levels were estimated using generalized estimating equations to account for repeated observations on individuals. A 30 mg/dL decrease in non-HDL cholesterol was deemed clinically significant.</p> <p>Results</p> <p>126 patients were screened to enroll 25, of which 20 completed the 8-week study. The mean age was 46.4 years (36-60). Patients had a mean 13.7 yrs of HIV infection. Mean non-HDL cholesterol was 204.5 mg/dL at day 0 and 200.2 mg/dL at day 56 (mean within-person change = -1.70; 95% confidence interval (CI) = -17.4, 14.0). HDL cholesterol levels increased from 37.8 mg/dL at day 0 to 40.4 mg/dL on day 56 (mean within-person change = 2.6; 95% CI = -0.1, 5.2). Triglycerides dropped from 336.4 mg/dL on day 0 to 273.4 mg/dL on day 56 (mean within-person change = -63.0; 95% CI = -120.9, -5.1). Only 3 individuals achieved a sustained clinically significant (30 mg/dL) decline in non-HDL cholesterol after 8 weeks of therapy. There were no adverse experiences reported other than patients' distaste for the preparation. Liver function tests and muscle enzymes were not affected by the 8 weeks of treatment.</p> <p>Conclusions</p> <p><it>Pleurotus ostreatus </it>as administered in this experiment did not lower non-HDL cholesterol in HIV patients with ART-induced hypercholesterolemia. Small changes in HDL and triglycerides were not of a clinical magnitude to warrant further study.</p> <p>Trial Registration</p> <p>clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00069524">NCT00069524</a></p

Feasibility of offering nicotine replacement therapy as a relapse prevention treatment in routine smoking cessation services

Background: National Health Service stop smoking services (NHS SSS) in the UK offer cost- effective smoking cessation services. Despite high abstinence rates after acute cessation treatment, the majority of clients have relapsed by one year. Several interventions have been identified, from trial data, as effective in preventing relapse to smoking. This study investigated uptake, feasibility and acceptability of offering nicotine replacement therapy (NRT) as a relapse prevention intervention (RPI) in NHS SSS. Methods: Eligible smokers who had successfully completed acute cessation treatment using NRT at Nottingham City NHS SSS between April 2010 and January 2011 were offered the RPI and the rate of uptake was monitored. Consenting individuals completed a baseline questionnaire, providing demographic and smoking behaviour data. The RPI consisted of using NRT for a further 12 weeks after initial cessation-orientated treatment had ended. At a six-month review, self-reported smoking status was assessed via telephone. Anonymised demographic data on NHS SSS users who did not agree to participate in the study were retrieved from NHS SSS records and used to determine the presence of any socio-demographic differences between individuals who agreed to participate in the study and those who did not. Semi-structured telephone interviews were conducted with a selection of participants; these were audio-recorded, transcribed and analysed to identify participants’ views on the RPI. Results: Of 493 stop smoking service clients who were assessed, 260 were eligible for and offered the RPI and 115 (44%, CI 38%- 50%) accepted. Individuals who accepted NRT were significantly more likely to be older (p < 0.001) and to pay for their prescriptions (p < 0.001). Quitters who had never worked or were unemployed were significantly less likely to accept the offer of relapse prevention compared to those in routine and manual occupations (55% reduction in odds, p = 0.026). Interview findings revealed that clients who accepted extended NRT felt the longer duration of pharmacological and psychological support were both valuable in helping them to remain abstinent. Conclusion: In routine smoking cessation service care, it is feasible to offer clients extended courses of NRT as a RPI. The RPI was acceptable to them as almost half of the eligible clients offered this treatment accepted it. Keywords: Smoking relapse prevention, Nicotine replacement therapy, Feasibility study, Smoking cessation servic

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

The relationships between golf and health:A scoping review

OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping review. DATA SOURCES: Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts. REVIEW METHODS: A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated

Brain arteriolosclerosis

Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer’s disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g. hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that include consideration of comorbid diseases, B-ASC is independently associated with impairments in global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability

A conceptual framework for invasion in microbial communities

There is a growing interest in controlling-promoting or avoiding-the invasion of microbial communities by new community members. Resource availability and community structure have been reported as determinants of invasion success. However, most invasion studies do not adhere to a coherent and consistent terminology nor always include rigorous interpretations of the processes behind invasion. Therefore, we suggest that a consistent set of definitions and a rigorous conceptual framework are needed. We define invasion in a microbial community as the establishment of an alien microbial type in a resident community and argue how simple criteria to define aliens, residents, and alien establishment can be applied for a wide variety of communities. In addition, we suggest an adoption of the community ecology framework advanced by Vellend (2010) to clarify potential determinants of invasion. This framework identifies four fundamental processes that control community dynamics: dispersal, selection, drift and diversification. While selection has received ample attention in microbial community invasion research, the three other processes are often overlooked. Here, we elaborate on the relevance of all four processes and conclude that invasion experiments should be designed to elucidate the role of dispersal, drift and diversification, in order to obtain a complete picture of invasion as a community process

The coral core microbiome identifies rare bacterial taxa as ubiquitous endosymbionts

© 2015 International Society for Microbial Ecology All rights reserved. Despite being one of the simplest metazoans, corals harbor some of the most highly diverse and abundant microbial communities. Differentiating core, symbiotic bacteria from this diverse hostassociated consortium is essential for characterizing the functional contributions of bacteria but has not been possible yet. Here we characterize the coral core microbiome and demonstrate clear phylogenetic and functional divisions between the micro-scale, niche habitats within the coral host. In doing so, we discover seven distinct bacterial phylotypes that are universal to the core microbiome of coral species, separated by thousands of kilometres of oceans. The two most abundant phylotypes are co-localized specifically with the corals' endosymbiotic algae and symbiont-containing host cells. These bacterial symbioses likely facilitate the success of the dinoflagellate endosymbiosis with corals in diverse environmental regimes