Genome analysis of a highly virulent serotype 1 strain of streptococcus pneumoniae from West Africa

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content

Exploration of bacterial community classes in major human habitats

BACKGROUND: Determining bacterial abundance variation is the first step in understanding bacterial similarity between individuals. Categorization of bacterial communities into groups or community classes is the subsequent step in describing microbial distribution based on abundance patterns. Here, we present an analysis of the groupings of bacterial communities in stool, nasal, skin, vaginal and oral habitats in a healthy cohort of 236 subjects from the Human Microbiome Project. RESULTS: We identify distinct community group patterns in the anterior nares, four skin sites, and vagina at the genus level. We also confirm three enterotypes previously identified in stools. We identify two clusters with low silhouette values in most oral sites, in which bacterial communities are more homogeneous. Subjects sharing a community class in one habitat do not necessarily share a community class in another, except in the three vaginal sites and the symmetric habitats of the left and right retroauricular creases. Demographic factors, including gender, age, and ethnicity, significantly influence community composition in several habitats. Community classes in the vagina, retroauricular crease and stool are stable over approximately 200 days. CONCLUSION: The community composition, association of demographic factors with community classes, and demonstration of community stability deepen our understanding of the variability and dynamics of human microbiomes. This also has significant implications for experimental designs that seek microbial correlations with clinical phenotypes

Deformation of Small Compressed Droplets

We investigate the elastic properties of small droplets under compression. The compression of a bubble by two parallel plates is solved exactly and it is shown that a lowest-order expansion of the solution reduces to a form similar to that obtained by Morse and Witten. Other systems are studied numerically and results for configurations involving between 2 and 20 compressing planes are presented. It is found that the response to compression depends on the number of planes. The shear modulus is also calculated for common lattices and the stability crossover between f.c.c.\ and b.c.c.\ is discussed.Comment: RevTeX with psfig-included figures and a galley macr

Effect of telehealth on glycaemic control: analysis of patients with type 2 diabetes in the Whole Systems Demonstrator cluster randomised trial

Background: The Whole Systems Demonstrator was a large, pragmatic, cluster randomised trial that compared telehealth with usual care among 3,230 patients with long-term conditions in three areas of England. Telehealth involved the regular transmission of physiological information such as blood glucose to health professionals working remotely. We examined whether telehealth led to changes in glycosylated haemoglobin (HbA1c) among the subset of patients with type 2 diabetes. Methods: The general practice electronic medical record was used as the source of information on HbA1c. Effects on HbA1c were assessed using a repeated measures model that included all HbA1c readings recorded during the 12-month trial period, and adjusted for differences in HbA1c readings recorded before recruitment. Secondary analysis averaged multiple HbA1c readings recorded for each individual during the trial period. Results: 513 of the 3,230 participants were identified as having type 2 diabetes and thus were included in the study. Telehealth was associated with lower HbA1c than usual care during the trial period (difference 0.21% or 2.3 mmol/mol, 95% CI, 0.04% to 0.38%, p = 0.013). Among the 457 patients in the secondary analysis, mean HbA1c showed little change for controls following recruitment, but fell for intervention patients from 8.38% to 8.15% (68 to 66 mmol/mol). A higher proportion of intervention patients than controls had HbA1c below the 7.5% (58 mmol/mol) threshold that was targeted by general practices (30.4% vs. 38.0%). This difference, however, did not quite reach statistical significance (adjusted odds ratio 1.63, 95% CI, 0.99 to 2.68, p = 0.053). Conclusions: Telehealth modestly improved glycaemic control in patients with type 2 diabetes over 12 months. The scale of the improvements is consistent with previous meta-analyses, but was relatively modest and seems unlikely to produce significant patient benefit

Improving Characterization of Understudied Human Microbiomes Using Targeted Phylogenetics.

Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective.IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies

Adequacy of Diabetes Care for Older U.S. Rural Adults: A Cross-sectional Population Based Study Using 2009 BRFSS Data

Background: In the U.S. diabetes prevalence estimates for adults ≥ 65 years exceed 20%. Rural communities have higher proportions of older individuals and health disparities associated with rural residency place rural communities at risk for a higher burden from diabetes. This study examined the adequacy of care received by older rural adults for their diabetes to determine if older rural adults differed in the receipt of adequate diabetes care when compared to their non-rural counterparts. Methods: Cross-sectional data from the 2009 Behavioral Risk Factor Surveillance Survey were examined using bivariate and multivariate analytical techniques. Results: Logistic regression analysis revealed that older rural adults with diabetes were more likely to receive less than adequate care when compared to their non-rural counterparts (OR = 1.465, 95% CI: 1.454-1.475). Older rural adults receiving less than adequate care for their diabetes were more likely to be: male, non-Caucasian, less educated, unmarried, economically poorer, inactive, a smoker. They were also more likely to: have deferred medical care because of cost, not have a personal health care provider, and not have had a routine medical check-up within the last 12 months. Conclusion: There are gaps between what is recommended for diabetes management and the management that older individuals receive. Older adults with diabetes living in rural communities are at greater risk for less than adequate care when compared to their non-rural counterparts. These results suggest the need to develop strategies to improve diabetes care for older adults with diabetes and to target those at highest risk

The influence of tumor regression, solar elastosis, and patient age on pathologists\u27 interpretation of melanocytic skin lesions.

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists\u27 interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist\u27s characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists\u27 clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward a less severe diagnosis when patients were70 years of age, or by the presence of tumor regression or solar elastosis (58.5%, 71.0%, and 57.0%, respectively). Generally, pathologists with dermatopathology board certification and/or a high caseload of MSLs were more likely to be influenced, whereas those with more years\u27 experience interpreting MSL were less likely to be influenced. Our findings indicate that the interpretation of MSLs is influenced by patient age, tumor regression, and solar elastosis; such influence is associated with dermatopathology training and higher caseload, consistent with expertise and an appreciation of lesion complexity

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Comparing Cutaneous Research Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease Results

Importance Disease burden data helps guide research prioritization. Objective To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project. Design Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. Setting The United States NIAMS database and GBD 2010 skin condition disability data. Main Outcome(s) and Measure(s) Relationship of NIAMS grant database topic funding with percent total GBD 2010 DALY and DALY rank for 15 skin conditions. Results During fiscal year 2013, 1,443 NIAMS grants were issued at a total value of $424 million. Of these grants, 17.7% covered skin topics. Of the total skin disease funding, 82% (91 grants) were categorized as “general cutaneous research.” Psoriasis, leprosy, and “other skin and subcutaneous diseases” (ie; immunobullous disorders, vitiligo, and hidradenitis suppurativa) were over-represented when funding was compared with disability. Conversely, cellulitis, decubitus ulcer, urticaria, acne vulgaris, viral skin diseases, fungal skin diseases, scabies, and melanoma were under-represented. Conditions for which disability and funding appeared well-matched were dermatitis, squamous and basal cell carcinoma, pruritus, bacterial skin diseases, and alopecia areata. Conclusions and Relevance Degree of representation in NIAMS is partly correlated with DALY metrics. Grant funding was well-matched with disability metrics for five of the 15 studied skin diseases, while two skin diseases were over-represented and seven were under-represented. Global burden estimates provide increasingly transparent and important information for investigating and prioritizing national research funding allocations