The Neonatal Microbiome and Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating disorder that affects approximately 10% of premature infants. Its mortality remains high (15-30%), and its cause remains unknown. About 80% of cases occur within 35 days of birth among hospitalized newborns of low birth weight. Probiotics diminish the incidence and severity of NEC, and NEC does not occur antepartum. NEC affects a readily identifiable at-risk group, has a tightly defined interval before its onset, occurs in an organ system that is intimately associated with a microbial population in flux, has a plausible association with the intestinal microbiota, and cohorts at risk have rarely been studied in large numbers, or prospectively. This disorder, therefore, provides a unique opportunity to explore the role of the human enteric microbiome in a devastating disease. Moreover, NEC epidemiology and age-incidence present an ability to enroll and study cohorts that are highly likely to provide valuable pathophysiologic and microbiologic insights.

In this project, we will identify and quantify the microbial components of stool and its products before and at the onset of NEC. In doing so, we will test the overarching hypothesis that NEC is a direct or indirect consequence of the enteric biomass, its products, or both. We will use multicenter cohorts of premature infants at high risk of developing NEC, extend our research on this disease currently sponsored by the Washington University Institute of Clinical and Translational Sciences, and continue our longstanding collaborations with the Genome Center at Washington University and the Washington University Digestive Diseases Research Core Center (Informatics Core). The Aims of this proposal are to (1) conduct a case cohort study in which we compare clinical data and biological specimens from cases and well-matched controls; (2) determine if the kind and density of intestinal biomass, its gene content, and transcriptional activity are associated with, and potential determinants of, NEC; and (3) determine if host risk alleles for intestinal inflammation play a role in the development of NEC. These efforts will be accomplished using subjects from three collaborating neonatal intensive care units (NICUs), focusing on the critical, instructive, and understudied pre-NEC stage of illness, and formulating a data repository that will be a resource for investigators worldwide who wish to focus their efforts on NEC, its precipitants, and its prevention and cure.
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The Effects of High Concentrations of Ionic Liquid on GB1 Protein Structure and Dynamics Probed by High-Resolution Magic-Angle-Spinning NMR Spectroscopy

Ionic liquids have great potential in biological applications and biocatalysis, as some ionic liquids can stabilize proteins and enhance enzyme activity, while others have the opposite effect. However, on the molecular level, probing ionic liquid interactions with proteins, especially in solutions containing high concentrations of ionic liquids, has been challenging. In the present work the 13C, 15N-enriched GB1 model protein was used to demonstrate applicability of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy to investigate ionic liquid–protein interactions. Effect of an ionic liquid (1-butyl-3- methylimidazolium bromide, [C4-mim]Br) on GB1was studied over a wide range of the ionic liquid concentrations (0.6–3.5 M, which corresponds to 10–60% v/v). Interactions between GB1 and [C4-mim]Br were observed from changes in the chemical shifts of the protein backbone as well as the changes in 15N ps-ns dynamics and rotational correlation times. Site-specific interactions between the protein and [C4-mim]Br were assigned using 3D methods under HR-MAS conditions. Thus, HR-MAS NMR is a viable tool that could aid in elucidation of molecular mechanisms of ionic liquid–protein interactions

Barriers and proposed solutions to at-home colorectal cancer screening tests in medically underserved health centers across three US regions to inform a randomized trial.

INTRODUCTION: At-home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population-based outreach approaches, we conducted qualitative research on current processes and barriers to at-home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. METHODS: We conducted 53 semi-structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT-DNA (i.e., Cologuard) workflows, referral for a follow-up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub-themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. RESULTS: Each sites process for stool-based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. CONCLUSION: Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs

Recruitment and retention of participants in a pragmatic randomized intervention trial at three community health clinics: Results and lessons learned

Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge. Methods: Be Fit, Be Well was a pragmatic randomized weight loss and hypertension management trial of patients attending one of three community health centers in Boston, Massachusetts. Participants were asked to complete follow-up assessments every 6-months for two years. We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention. We also identify baseline participant characteristics associated with retention status. Retention strategies included financial incentives, contact between assessment visits, building relationships with health center primary care providers (PCPs) and staff, and putting participant convenience first. Results: Active refusal rates were low with 130 of 2,631 patients refusing participation (4.9%). Of 474 eligible persons completing telephone screening, 365 (77.0%) completed their baseline visit and were randomized into the study. The study population was predominantly non-Hispanic Black (71.2%), female (68.5%) and reported annual household income of less than $35,000 (70.1%). Recruitment strategies included use of passive approval of potential participants by PCPs, use of part-time staff, and outsourcing calls to a call center. A total of 314 (86.0%) people completed the 24-month visit. Retention levels varied across study visits and intervention condition. Most participants completed three or more visits (69.6%), with 205 (56.2%) completing all four. At 24-months, lower retention was observed for males and the intervention condition. Retention strategies included building strong relationships with clinic staff, flexibility in overcoming participant barriers through use of taxi vouchers, night and weekend appointments, and keeping participants engaged via newsletters and social gatherings. Conclusion: We were able to retain 86.0% of participants at 24-months. Recruitment and retention of high percentages of racial/ethnic minorities and lower income samples is possible with planning, coordination with a trusted community setting and staff (e.g. community health centers and RAs), adaptability and building strong relationships. Trial registration Clinicaltrials.gov Identifier: NCT0066181

Does perception equal reality? Weight misperception in relation to weight-related attitudes and behaviors among overweight and obese US adults

<p>Abstract</p> <p>Background</p> <p>Weight misperception might preclude the adoption of healthful weight-related attitudes and behaviors among overweight and obese individuals, yet limited research exists in this area. We examined associations between weight misperception and several weight-related attitudes and behaviors among a nationally representative sample of overweight and obese US adults.</p> <p>Methods</p> <p>Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used. Analyses included non-pregnant, overweight and obese (measured body mass index ≥ 25) adults aged 20 and older. Weight misperception was identified among those who reported themselves as "underweight" or "about the right weight". Outcome variables and sample sizes were: weight-loss attitudes/behaviors (wanting to weigh less and having tried to lose weight; n = 4,784); dietary intake (total energy intake; n = 4,894); and physical activity (meets 2008 US physical activity recommendations, insufficiently active, and sedentary; n = 5,401). Multivariable regression models were stratified by gender and race/ethnicity. Analyses were conducted in 2009-2010.</p> <p>Results</p> <p>These overweight/obese men and women who misperceived their weight were 71% (RR 0.29, 95% CI 0.25-0.34) and 65% (RR 0.35, 95% CI 0.29-0.42) less likely to report that they want to lose weight and 60% (RR 0.40, 95% CI 0.30-0.52) and 56% (RR 0.44, 95% CI 0.32-0.59) less likely to have tried to lose weight within the past year, respectively, compared to those who accurately perceived themselves as overweight. Blacks were particularly less likely to have tried to lose weight. Weight misperception was not a significant predictor of total energy intake among most subgroups, but was associated with lower total energy intake among Hispanic women (change -252.72, 95% CI -433.25, -72.18). Men who misperceived their weight were less likely (RR 0.68, 95% CI 0.52-0.89) to be insufficiently active (the strongest results were among Black men) and women who misperceived their weight were less likely (RR 0.74, 95% CI 0.54, 1.00, <it>p </it>= 0.047) to meet activity recommendations compared to being sedentary.</p> <p>Conclusion</p> <p>Overall, weight misperception among overweight and obese adults was associated with less likelihood of interest in or attempts at weight loss and less physical activity. These associations varied by gender and race/ethnicity. This study highlights the importance of focusing on inaccurate weight perceptions in targeted weight loss efforts.</p

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426)

Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations

The Study on Stress, Spirituality, and Health (SSSH): Psychometric Evaluation and Initial Validation of the SSSH Baseline Spirituality Survey

This paper describes the development and initial psychometric testing of the baseline Spirituality Survey (SS-1) from the Study on Stress, Spirituality, and Health (SSSH) which contained a mixture of items selected from validated existing scales and new items generated to measure important constructs not captured by existing instruments. The purpose was to establish the validity of new and existing measures in our racially/ethnically diverse sample. Psychometric properties of the SS-1 were evaluated using standard psychometric analyses in 4,634 SSSH participants. Predictive validity of SS-1 scales was assessed in relation to the physical and mental health component scores from the Short-Form 12 Health Survey (SF-12). Scales exhibited adequate to strong psychometric properties and demonstrated construct and predictive validity. Overall, the correlational findings provide solid evidence that the SS-1 scales are associated with a wide range of relevant R/S attitudes, mental health, and to a lesser degree physical health

Ten Years In: Implementing Strategic Approaches to Cyberspace

This book represents a look beyond theories and analogies to examine the challenges of strategy implementation. In the essays that follow, practitioners who are building cyberspace forces at-scale join scholars who study power and force in this new domain to collectively offer a unique perspective on the evolution and future of cyber strategy and operations.https://digital-commons.usnwc.edu/usnwc-newport-papers/1044/thumbnail.jp