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Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches., The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

Background Open fractures of the lower limb occur when a broken bone penetrates the skin and is exposed to the outside environment. These are life-changing injuries. The risk of deep infection may be as high as 27%. The type of dressing applied after surgical debridement could potentially reduce the risk of infection in the open-fracture wound. Objectives To assess the disability, rate of deep infection, quality of life and resource use in patients with severe open fracture of the lower limb treated with negative-pressure wound therapy (NPWT) versus standard wound management after the first surgical debridement of the wound. Design A pragmatic, multicentre randomised controlled trial. Setting Twenty-four specialist trauma hospitals in the UK Major Trauma Network. Participants A total of 460 patients aged ≥ 16 years with a severe open fracture of the lower limb were recruited from July 2012 through to December 2015. Patients were excluded if they presented more than 72 hours after their injury or were unable to complete questionnaires. Interventions Negative-pressure wound therapy (n = 226) where an ‘open-cell’ solid foam or gauze was placed over the surface of the wound and connected to a suction pump which created a partial vacuum over the dressing versus standard dressings not involving negative pressure (n = 234). Main outcome measures Disability Rating Index (DRI) – a score of 0 (no disability) to 100 (completely disabled) at 12 months was the primary outcome measure, with a minimal clinically important difference of 8 points. The secondary outcomes were deep infection, quality of life and resource use collected at 3, 6, 9 and 12 months post randomisaton. Results There was no evidence of a difference in the patients’ DRI at 12 months. The mean DRI in the NPWT group was 45.5 points [standard deviation (SD) 28.0 points] versus 42.4 points (SD 24.2 points) in the standard dressing group, giving a difference of –3.9 points (95% confidence interval –8.9 to 1.2 points) in favour of standard dressings (p = 0.132). There was no difference in HRQoL and no difference in the number of surgical site infections or other complications at any point in the 12 months after surgery. NPWT did not reduce the cost of treatment and it was associated with a low probability of cost-effectiveness. Limitations Owing to the emergency nature of the interventions, we anticipated that some patients who were randomised into the trial would subsequently be unable or unwilling to take part. Such post-randomisation withdrawal of patients could have posed a risk to the external validity of the trial. However, the great majority of these patients (85%) were found to be ineligible after randomisation. Therefore, we can be confident that the patients who took part were representative of the population with severe open fractures of the lower limb. Conclusions Contrary to the existing literature and current clinical guidelines, NPWT dressings do not provide a clinical or an economic benefit for patients with an open fracture of the lower limb. Future work Future work should investigate alternative strategies to reduce the incidence of infection and improve outcomes for patients with an open fracture of the lower limb. Two specific areas of potentially great benefit are (1) the use of topical antibiotic preparations in the open-fracture wound and (2) the role of orthopaedic implants with antimicrobial coatings when fixing the associated fracture. Trial registration Current Controlled Trials ISRCTN33756652 and UKCRN Portfolio ID 11783. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 73. See the NIHR Journals Library website for further project information.

Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEVWe identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.

Introduction The easily-imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia. Methods In a population-based study of 12,482 adults aged 50-73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993-1995) with incident all-cause dementia (1993-1995 to 2011-2013) and with etiologic subtype of dementia/mild cognitive impairment (2011-13). Results A total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.36–2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09–1.45) were associated with all-cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular-related, but not Alzheimer's disease–related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24–4.23). Discussion Exploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia.

© 2018 Elsevier B.V. Background and aims: The Ankle-Brachial index (ABI) is a well-accepted measure of peripheral artery disease (arterial stenosis and stiffness) and has been shown to be associated with cognitive function and disorders; however, these associations have not been examined in Hispanics/Latinos. Therefore, we sought to examine relationships between ABI and cognitive function among diverse middle-age and older Hispanics/Latinos. Methods: We used cross-sectional data on n = 7991 participants aged 45–74 years, without stroke or coronary heart disease, from the Hispanic Community Health Study/Study of Latinos. Our primary outcome, global cognition (GC), was a continuous composite score of four cognitive domains (verbal learning and memory, verbal fluency, executive function, and mental status). Secondary outcomes were the individual tests representing these domains. The ABI was analyzed continuously and categorically with standard clinical cut-points. We tested associations using generalized survey regression models incrementally adjusting for confounding factors. Age, sex, hypertension, diabetes, and dyslipidemia moderations were examined through interactions with the primary exposure. Results: In age, sex, and education adjusted models, continuous ABI had an inverse u-shape association with worse GC. We found similar associations with measures of verbal learning and memory, verbal fluency, executive function, but not with low mental status. The associations were attenuated, but not completely explained, by accounting for the confounders and not modified by age, sex, education, and vascular disease risks. Conclusions: In addition to being a robust indicator of arterial compromise, our study suggests that abnormal ABI readings may also be useful for early signaling of subtle cognitive deficits.

AB Purpose: This study described participant adherence to wearing the accelerometer and accelerometer performance in a cohort study of adults. Methods: From 2008 to 2011, 16,415 US Hispanic/Latino adults age 18-74 yr enrolled in the Hispanic Community Health Study/Study of Latinos. Immediately after the baseline visit, participants wore an Actical accelerometer for 1 wk. This study explored correlates of accelerometer participation and adherence, defined as wearing it for at least three of a possible six days for >=10 h[middle dot]d-1. Accelerometer performance was assessed by exploring the number of different values of accelerometer counts per minute for each participant. Results: Overall, 92.3% (n = 15,153) had at least 1 d with accelerometer data and 77.7% (n = 12,750) were adherent. Both accelerometer participation and adherence were higher among participants who were married or partnered, reported a higher household income, were first-generation immigrants, or reported lower sitting time. Participation was also higher among those with no stair limitations. Adherence was higher among participants who were male, older, employed or retired, not US born, preferred Spanish over English, reported higher work activity or lower recreational activity, and with a lower body mass index. Among the sample that met the adherence definition, the maximum recorded count per minute was 12,000, and there were a total of 5846 different counts per minute. On average, participants had 112.5 different counts per minute over 6 d (median, 106; interquartile range, 91-122). The number of different counts per minute was higher among men, younger ages, normal weight, and those with higher accelerometer-assessed physical activity. Conclusion: Several correlates differed between accelerometer participation and adherence. These characteristics could be targeted in future studies to improve accelerometer wear. The performance of the accelerometer provided insight into creating a more accurate nonwear algorithm.

OBJECTIVE Hispanics/Latinos have the highest risks for metabolic syndrome (MetS) in the U.S. and are also at increased risk for Alzheimer disease. In this study, we examined associations among neurocognitive function, MetS, and inflammation among diverse middle-aged and older Hispanics/Latinos. RESEARCH DESIGN AND METHODS Cross-sectional data (2008–2011) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analyzed to examine associations between neurocognition and MetS among diverse Hispanics/Latinos (N = 9,136; aged 45–74 years). RESULTS MetS status was associated with lower global neurocognition, mental status, verbal learning and memory, verbal fluency, and executive function. Age significantly modified the associations between MetS and learning and memory measures. Significant associations between MetS and neurocognition were observed among middle-aged Hispanics/Latinos, and all associations remained robust to additional covariates adjustment. CONCLUSIONS We found that MetS was associated with lower neurocognitive function, particularly in midlife. Our findings support and extend current hypotheses that midlife may be a particularly vulnerable developmental period for unhealthy neurocognitive aging.

Seven national 2020 Strategic Impact Goals for cardiovascular health (Life's Simple 7 [LS7]) estimates for major ethnic/racial groups are available, but not for diverse Hispanics/Latinos. Herein, we describe and examine LS7 profiles of diverse Hispanic/Latino groups.HCHS/SOL (analytic n = 15,825; ages 18-74 years) data were used to estimate LS7 metrics. LS7 metrics were operationalized as Ideal, Intermediate, or Poor and indexed as an additive score. We calculated Hispanic/Latino group and sex-specific prevalence estimates for LS7 metrics and used survey-based regression models to examine (1) associations between LS7 scores and pertinent sociocultural characteristics and (2) relationships between LS7 scores and coronary heart disease, and stroke and transient ischemic attacks prevalence.Few HCHS/SOL participants met all 7 Ideal LS7 criteria (1%), and a similarly small proportion did not meet any Ideal LS7 criteria (1.1%). We found significant variability in LS7 distributions between men and women and across HCHS/SOL Hispanic/Latino heritages. We also found a substantial sex-adjusted age gradient in LS7 cardiovascular health (ie, ≥4 Ideal LS7s). Finally, higher Ideal LS7 scores were associated with decreased odds of both coronary heart disease and self-reported stroke/transient ischemic attack; these associations persisted after model covariate adjustments.Hispanic/Latino LS7s compared favorably with existing national estimates; however, we found areas for improvement. Several Hispanic/Latino LS7 strengths and weaknesses varied by sex and heritage, providing important information to guide targeted health promotion efforts toward achieving 2020 goals.

Study objectives To evaluate the association between sleep duration and neurocognitive function in a representative sample of middle-aged to older Hispanic/Latino adults in the US. We tested the hypothesis that sleep duration has a nonlinear, inverted U-shaped association with neurocognitive function. Methods We performed a cross-sectional analysis from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants ages 45-74 years (n = 8,676). HCHS/SOL is a community-based cohort from four US urban areas sampled using a probability design from 2008-2011. Self-reported sleep duration was calculated as a weighted average of the difference between habitual wake and bedtimes assessed by separate questions for weekdays and weekends. Neurocognitive function was measured with standardized scores for Word (Phonemic) Fluency (WF), Brief-Spanish English Verbal learning test (B-SEVLT), and Digit Symbol Substitution (DSS) tests. Results The mean age was 56.5 years; 55% were women; and 40.4% had less than high school education. Average sleep duration was 7.8 ± 1.7 hours. There was an inverted U-shaped association with sleep duration and WF, B-SEVLT sum, and the DSS, with no association with B-SEVLT delayed-recall. Participants with intermediate sleep duration had the best neurocognitive function, while long sleepers had worse neurocognitive function adjusting for demographic, behavioral, and medical factors, daytime sleepiness, and use of sleep medications. Conclusions Sleep duration had curvilinear inverted U-shaped associations with neurocognitive function, with worse scores among participants with longer sleep duration. These findings may provide a framework to further examine sleep duration in the prevention and treatment of neurocognitive disorders.

The study assessed whether overall perceived ethnic discrimination and four unique discrimination types were associated with binge drinking in participants from the Hispanic Community Health Study/Study of Latinos who also completed the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n = 5,313). In unadjusted analyses that were weighted for sampling strategy and design, each unit increase in discrimination type was associated with a 12-63% increase in odds of binge drinking; however, after adjusting for important demographic variables including age, sex, heritage group, language, and duration of U.S. residence, there was no longer an association between discrimination and binge drinking. Further research still needs to identify the salient factors that contribute to increased risk for binge drinking among Hispanics/Latinos.

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for one year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.

Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1–69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a ≥5% prevalence across centres.Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities. Pseudomonas was associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with a Pseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del.In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects.

Importance Regular ocular care is critical to early detection and prevention of eye disease and associated morbidity and mortality; however, there have been relatively few studies of ocular health care utilization among Hispanics/Latinos of diverse backgrounds. Objective To examine factors associated with ocular health care utilization among Cuban, Central American, and South American Hispanics/Latinos in a cohort study. Design, Setting, and Participants An ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) evaluating ocular health, knowledge, risk factors, and health care use was conducted with 1235 HCHS/SOL participants (aged ≥40 years) at the Miami, Florida, study site. Data were collected from October 17, 2011, to September 30, 2013, and analyses were conducted from May 28, 2014, to March 18, 2015. Descriptive and multivariable logistic regression analyses were performed for 3 ocular health care outcomes. Regression models were built sequentially with variables conceptually grouped according to Andersen’s Behavioral Model of Health Services Use. Main Outcomes and Measures Ever having an eye examination, having an eye examination performed within the past 2 years, and difficulty obtaining needed eye care in the past year. Results Of the 1235 participants, 478 were men and 757 were women, and they had a mean (SD) age of 53.6 (8.1) years. Those who never had insurance were less likely to have had an eye examination (with data reported as odds ratios [95% CIs]) ever, 0.19 (0.07-0.53) and in the past 2 years, 0.22 (0.15-0.33) and were more likely to have had difficulty obtaining needed eye care in the past year (3.72 [1.75-7.93]). Those with less than excellent or good self-rated eyesight were less likely to ever have had an eye examination (0.26 [0.12-0.56]) and more likely to have had difficulty obtaining care (3.00 [1.48-6.11]). Men were less likely to ever have had an eye examination (0.31 [0.18-0.53]). Older (55-64 years) Hispanics/Latinos (3.04 [1.47-6.31]) and those with a high school degree or general educational development certification (2.06 [1.02-4.13]) or higher levels of education (4.20 [2.12-8.30]) were more likely to ever have had an eye examination. Finally, those living in the United States for more than 15 years (0.42 [0.21-0.82]) were less likely to have had difficulty obtaining care. Conclusions and Relevance Our findings suggest that increasing insurance coverage, decreasing the costs of care, and increasing the availability of care for Hispanics/Latinos with poor self-rated eyesight are relevant issues to address to improve ocular health care use among Hispanics/Latinos of diverse backgrounds.