Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.

Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize complex polysaccharides. Although vitamins and other nutrients are also essential for commensal fitness, much less is known about how commensal bacteria compete with each other or the host for these critical resources. Unlike in Escherichia coli, transport loci for vitamin B12 (cobalamin) and other corrinoids in human gut Bacteroides are replete with conserved genes encoding proteins whose functions are unknown. Here we report that one of these proteins, BtuG, is a surface-exposed lipoprotein that is essential for efficient B12 transport in B. thetaiotaomicron. BtuG binds B12 with femtomolar affinity and can remove B12 from intrinsic factor, a critical B12 transport protein in humans. Our studies suggest that Bacteroides use surface-exposed lipoproteins not only for capturing polysaccharides, but also to acquire key vitamins in the gut

The factors influencing car use in a cycle-friendly city: the case of Cambridge.

Encouraging people out of their cars and into other modes of transport, which has major advantages for health, the environment and urban development, has proved difficult. Greater understanding of the influences that lead people to use the car, particularly for shorter journeys, may help to achieve this. This paper examines the predictors of car use compared with the bicycle to explore how it may be possible to persuade more people to use the bicycle instead of the car. Multivariable logistic regression was used to examine the socio-demographic, transport and health-related correlates of mode choice for work, shopping and leisure trips in Cambridge, a city with high levels of cycling by UK standards. The key findings are that commuting distance and free workplace parking were strongly associated with use of the car for work trips, and car availability and lower levels of education were associated with car use for leisure, shopping and short-distanced commuting trips. The case of Cambridge shows that more policies could be adopted, particularly a reduction in free car parking, to increase cycling and reduce the use of the car, especially over short distances

Is Elective Vulvar Plastic Surgery Ever Warranted, and What Screening Should Be Conducted Preoperatively?

Introduction.  Elective vulvar plastic surgery was the topic of a heated discussion on the list-serve of the International Society for the Study of Women's Sexual Medicine. At the suggestion of a board member, it was determined that this discussion might of interest to journal readers in the form of a published controversy. Methods.  Six people with expertise and/or strong opinions in the area of vulvar health, several of whom had been involved in the earlier online discussion, were invited to submit evidence-based opinions on the topic. Main Outcome Measure.  To provide food for thought, discussion, and possible further research in a poorly discussed area of sexual medicine. Results.  Goodman believes that patients should make their own decisions. Bachmann further states that, while that is a woman's right, she should be counseled first, because variations in looks of the vulvar region are normal. Johnson furthers this thought, discussing the requirement for counseling before performing reinfibulation surgery on victims of female genital cutting. Fourcroy emphasizes the need to base surgical procedures on safety and efficacy in the long term, and not merely opportunity at the moment. Goldstein and Goldstein state that, based on the four principles of ethical practice of medicine, vulvar plastic surgery is not always ethical, but not always unethical. Sklar pursues this thought further, pointing out specific examples in regard to the principles of ethics. Conclusion.  Vulvar plastic surgery may be warranted only after counseling if it is still the patient's preference, provided that it is conducted in a safe manner and not solely for the purpose of performing surgery. Goodman MP, Bachmann G, Johnson C, Fourcroy JL, Goldstein A, Goldstein G, and Sklar S. Is elective vulvar plastic surgery ever warranted, and what screening should be done preoperatively? J Sex Med 2007;4:269–276.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72245/1/j.1743-6109.2007.00431.x.pd

Evidence For Gene-Smoking interactions For Hearing Loss and Deafness in Japanese american Families

BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. RESULTS: After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). CONCLUSIONS: to our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies

Web-Based Software for Managing Research

aeroCOMPASS is a software system, originally designed to aid in the management of wind tunnels at Langley Research Center, that could be adapted to provide similar aid to other enterprises in which research is performed in common laboratory facilities by users who may be geographically dispersed. Included in aeroCOMPASS is Web-interface software that provides a single, convenient portal to a set of project- and test-related software tools and other application programs. The heart of aeroCOMPASS is a user-oriented document-management software subsystem that enables geographically dispersed users to easily share and manage a variety of documents. A principle of "write once, read many" is implemented throughout aeroCOMPASS to eliminate the need for multiple entry of the same information. The Web framework of aeroCOMPASS provides links to client-side application programs that are fully integrated with databases and server-side application programs. Other subsystems of aeroCOMPASS include ones for reserving hardware, tracking of requests and feedback from users, generating interactive notes, administration of a customer-satisfaction questionnaire, managing execution of tests, managing archives of metadata about tests, planning tests, and providing online help and instruction for users

Enabling structural resilience of street-involved children and youth in Kenya: reintegration outcomes and the Flourishing Community model

IntroductionMillions of children and youth live on city streets across the globe, vulnerable to substance use, abuse, material and structural neglect. Structural resilience, the re-establishment of access to structural goods within a society such as housing, education, and healthcare following some interruption, provides an orientation for research and interventional efforts with street-involved children and youth (SICY). Further, a structural resilience framework supports organizing interactions between levels and sectors of a socio-ecology.MethodsFollowing the expressed interests of Kenyan SICY, and consistent with emerging policy interests at national and global levels, we assess reintegration trajectories of Kenyan SICY (n = 227) participating in a new program intervention and model. The intervention combines two coordinated, parallel programs – one focused on the rescue, rehabilitation, reintegration and resocialization of SICY, and the other focused on empowering families and communities to provide better care for children and youth who are reintegrating from life on the streets to the broader community. Data were collected and analyzed from multiple stages across SICY involvement with the intervention.ResultsWe found 79% of SICY participants reintegrated with the broader community, and 50% reintegrated with families of origin and returned to school. Twenty-five percent of participants reintegrated to a boarding school, polytechnical school, or began a business. Probability of reintegrating successfully was significantly improved among participants whose families participated in the family- and community-oriented program, who were younger, with less street-exposure, expressed more personal interests, and desired to reintegrate with family.DiscussionTo our knowledge, these are the first quantitative data published of successful reintegration of SICY to the broader, non-institutionalized community in any low- or middle-income country. Future research should (1) identify factors across socio-ecological levels and sectors contributing to health and developmental outcomes of reintegrated children and youth, (2) mechanisms to support SICY for whom the interventional strategy did not work, (3) methods to prevent street-migration by children and youth, and (4) system development to coordinate follow-up and relevant investment by institutions, organizations and community leaders to continue reintegration work

Common Data Elements for Traumatic Brain Injury: Recommendations From the Biospecimens and Biomarkers Working Group

Recent advances in genomics, proteomics, and biotechnology have provided unprecedented opportunities for translational research and personalized medicine. Human biospecimens and biofluids represent an important resource from which molecular data can be generated to detect and classify injury and to identify molecular mechanisms and therapeutic targets. To date, there has been considerable variability in biospecimen and biofluid collection, storage, and processing in traumatic brain injury (TBI) studies. To realize the full potential of this important resource, standardization and adoption of best practice guidelines are required to insure the quality and consistency of these specimens. The aim of the Biospecimens and Biomarkers Working Group was to provide recommendations for core data elements for TBI research and develop best practice guidelines to standardize the quality and accessibility of these specimens. Consensus recommendations were developed through interactions with focus groups and input from stakeholders participating in the interagency workshop on Standardization of Data Collection in TBI and Psychological Health held in Washington, DC, in March 2009. With the adoption of these standards and best practices, future investigators will be able to obtain data across multiple studies with reduced costs and effort and accelerate the progress of genomic, proteomic, and metabolomic research in TBI

Valvuloarterial Impedence, Strain, Exercise, and AS

Background - In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (LV-GLS) to treadmill stress echocardiography. Methods and Results - We studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age-sex predicted metabolic equivalents [%AGP-METs]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[LV-stroke volume index]) and LV-GLS(measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and LV-GLS were 0.46±0.1 cm2/m2, 4.5±0.9 mm Hg/mL per m2 and -16±4%, respectively; only 50% achieved >100% AGP-METs. Sixty-four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or HR 1.06), lower % AGP-METS (HR 1.16), higher Zva (HR 1.25) and lower LV-GLS (HR 1.12) were associated with higher longer-term mortality, while aortic valve replacement (HR 0.45) was associated with improved survival (all P<0.01). Sequential addition of ZVa and LV-GLS to clinical model (Society of Thoracic Surgeons score and %AGP-METs) increased the c-statistic from 0.65 to 0.69 and 0.75, respectively, both P<0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement. Conclusions - In asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography, LV-GLS and ZVa offer incremental prognostic value

Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial

BACKGROUND AND PURPOSE: FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. MATERIAL AND METHODS: Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion. RESULTS: 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. CONCLUSIONS: Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild