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Biofilm growth facilitates the interaction of uropathogenic Escherichia coli (UPEC) with the host environment. The extracellular polymeric substances (EPS) of UPEC biofilms are composed prominently of curli amyloid fiber and cellulose polysaccharide. When the organism is propagated as a colony biofilm on agar media, these macromolecules can generate pronounced macroscopic structures. Moreover, curli/cellulose associate tightly with Congo red, generating a characteristic pink-to-red staining pattern when the media is supplemented with this dye. Among different clinical isolates of UPEC, changes in the abundance of curli/cellulose can lead to diverse colony biofilm phenotypes on a strain-by-strain basis. Nevertheless, for any given isolate, these phenotypes are classically homogenous throughout the colony biofilm. Here, we report that a subset of clinical UPEC isolates display heterogenous 'peppermint' colony biofilms, with distinct pale and red subpopulations. Through isolation of these subpopulations and whole genome sequencing, we demonstrate various emergent mutations associated with the phenomenon, including within the gene encoding the outer membrane lipoprotein nlpI . Deletion of nlpI within independent strain-backgrounds increased biofilm rugosity, while its overexpression induced the peppermint phenotype. Upregulation of EPS-associated proteins and transcripts was likewise observed in the absence of nlpI . Overall, these results demonstrate that EPS elaboration in UPEC is impacted by nlpI . More broadly, this phenomenon of intra-strain colony biofilm heterogeneity may be leveraged as a tool to identify additional members within the broad collection of genes that regulate or otherwise affect biofilm formation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Co-author Maria Hadjifrangiskou currently works for Elsevier's Biofilm's editorial board. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07-1.55, P < 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5-7%, lowest risk quartile) to 41% (95%CI 33-49%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy., (© 2024. The Author(s).)

Opioid overdose and Opioid Use Disorder (OUD) statistics underscore an urgent need to significantly expand access to evidence-based OUD treatment. Office Based Opioid Treatment (OBOT) has proven effective for treating OUD. However, limited access to these treatments persists. Recognizing the need for significant investment in clinical, behavioral, and translational research, the Indiana State Department of Health and Indiana University embarked on a research initiative supported by the "Responding to the Addictions Crisis" Grand Challenge Program. This brief presents recommendations based on existing research and our own analyses of medical claims data in Indiana, where opioid misuse is high and treatment access is limited. The recommendations cover target providers, intervention focus, priority regions, and delivery methods., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cervical cancer (CC) is the most common cancer among women in Uganda, yet lifetime CC screening is as low as 5%. Training women who have screened for CC to engage in peer advocacy could increase uptake of CC screening in social networks. We conducted a randomized controlled trial of a peer-facilitated, manualized, 7-session group intervention to train women to engage in CC prevention advocacy. Forty women recently screened for CC (index participants) enrolled and were assigned to receive the intervention (n = 20) or wait-list control (n = 20). Each index was asked to recruit up to three female social network members (alters) who had not been screened for CC (n = 103 enrolled alters). All index and alter participants were assessed at baseline and month-6 follow-up. All but one (n = 39; 98%) index and 98 (95%) alter participants completed the month 6 assessment. In multivariate regression models controlling for baseline outcome measures and demographic covariates, intervention alters were more likely to have been screened for CC at month 6 [67% vs. 16%; adjusted OR (95% CI) = 12.13 (4.07, 36.16)], compared to control alters. Data also revealed significant increased engagement in CC prevention advocacy, among both index and alter participants in the intervention group at month 6, compared to the control group. The intervention was highly effective in increasing CC screening uptake among social network members, and engagement in CC prevention advocacy among not only intervention recipients, but also targets of advocacy, suggesting the potential for wide dissemination of CC knowledge.Trial Registration. NIH Clinical Trial Registry NCT04960748 ( clinicaltrials.gov )., (© 2023. The Author(s).)

Background: We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort., Methods: We analysed 454,712 UK Biobank participants with exome sequence and clinical data (data collected between March 2006 and June 2021). We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome. We calculated survival to cancer diagnosis (controlled for sex, death, recruitment centre, screening and prophylactic surgery)., Findings: Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1 , MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) than those without (13.0, 15.4 and 7.2). Penetrance to age 60 was also higher for carriers of a pathogenic MLH1 or MSH2 variant in those with a family history (30.9%, CI 18.1-49.3 and 38.3%, CI 21.5-61.8) versus those without (20.5% CI 9.6-40.5 and 8.3% CI 2.1-30.4), but not for MSH6 (6.5% CI 2.7-15.1 with family history versus 8.3%, CI 5.1-13.2). Relative risk increases were also observed both within and across conditions., Interpretation: Individuals with pathogenic cancer syndrome variants may be at a less elevated risk of cancer in the absence of a first-degree family history, so in the context of results return, family history should be considered when counselling patients on the risks and benefits of potential follow-up care., Funding: The current work is supported by the MRC (grant no MR/T00200X/1). The MRC had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Published by Elsevier Ltd.)

Problem opioid use and opioid-related drug overdoses remain a major public health concern despite attempts to reduce and monitor opioid prescriptions and increase access to office-based opioid treatment. Current provider-focused interventions are implemented at the federal, state, regional, and local levels but have not slowed the epidemic. Certain targeted interventions aimed at opioid prescribers rely on populations defined along geographic, political, or administrative boundaries; however, those boundaries may not align well with actual provider-patient communities or with the geographic distribution of high-risk opioid use. Instead of relying exclusively on commonly used geographic and administrative boundaries, we suggest augmenting existing strategies with a social network-based approach to identify communities (or clusters) of providers that prescribe to the same set of patients as another mechanism for targeting certain interventions. To test this approach, we analyze 1 year of prescription data from a commercially insured population in the state of Indiana. The composition of inferred clusters is compared to Indiana's Public Health Preparedness Districts (PHPDs). We find that in some cases the correspondence between provider networks and PHPDs is very high, while in other cases the overlap is low. This has implications for whether an intervention is reaching its intended provider targets efficiently and effectively. Assessing the best intervention targeting strategy for a particular outcome could facilitate more effective interventions to tackle the ongoing opioid use epidemic., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions., Methods: Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within 2 years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer., Results: A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase = 2.12 [1.86-2.41] P = 3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739-0.796]). Prostate cancer incidence was 8.1% (6.7-9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was <1%., Conclusions: This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care., (© 2022. The Author(s).)

Introduction: Innovative strategies are needed to disseminate HIV prevention messages across communities efficiently, as well as reduce HIV stigma while promoting HIV prevention. This randomized controlled trial will evaluate the efficacy of a social network-based group intervention, Game Changers, which trains persons living with HIV (PLWH) to encourage members of their social network to use HIV protective behaviors METHODS: PLWH in HIV care for at least 1 year will be randomly assigned to receive the 8-session group advocacy training intervention or no-intervention control group. Each enrolled PLWH (index participant) will be asked to recruit up to four social network members (alter participant). Assessments will be administered at baseline and months 6, 12, and 18 to both index and alter participants. The primary outcomes are HIV testing and condom use among alter participants; secondary outcomes are engagement in HIV prevention advocacy and internalized HIV stigma among index participants. Repeated-measures multivariable regression analyses will be conducted to compare outcomes between the intervention and control arms, in addition to a cost-effectiveness evaluation., Discussion: This social network-based approach to HIV prevention is particularly timely in the era of biomedical interventions, which require widespread penetration of effective HIV prevention and care messaging into communities. Positioning PLWH as central to the solution for controlling (vs. causing) the HIV epidemic has the potential to reduce HIV stigma and improve prevention outcomes at the individual and network levels., Trial Registration: ClinicalTrials.gov NIH Clinical Trial Registry NCT05098015. Registered on October 18, 2021., (© 2022. The Author(s).)

Importance: During the pandemic, access to medical care unrelated to COVID-19 was limited because of concerns about viral spread and corresponding policies. It is critical to assess how these conditions affected modes of pain treatment, given the addiction risks of prescription opioids., Objective: To assess the trends in opioid prescription and nonpharmacologic therapy (ie, physical therapy and complementary medicine) for pain management during the COVID-19 pandemic in 2020 compared with the patterns in 2019., Design, Setting, and Participants: This retrospective, cross-sectional study used weekly claims data from 24 million US patients in a nationwide commercial insurance database (Optum's deidentified Clinformatics Data Mart Database) from January 1, 2019, to September 31, 2020. Among patients with diagnoses of limb, extremity, or joint pain, back pain, and neck pain for each week, patterns of treatment use were identified and evaluated. Data analysis was performed from April 1, 2021, to September 31, 2021., Main Outcomes and Measures: The main outcomes of interest were weekly rates of opioid prescriptions, the strength and duration of related opioid prescriptions, and the use of nonpharmacologic therapy. Transition rates between different treatment options before the outbreak and during the early months of the pandemic were also assessed., Results: A total of 21 430 339 patients (mean [SD] age, 48.6 [24.0] years; 10 960 507 [51.1%] female; 909 061 [4.2%] Asian, 1 688 690 [7.9%] Black, 2 276 075 [10.6%] Hispanic, 11 192 789 [52.2%] White, and 5 363 724 [25.0%] unknown) were enrolled during the first 3 quarters in 2019 and 20 759 788 (mean [SD] age, 47.0 [23.8] years; 10 695 690 [51.5%] female; 798 037 [3.8%] Asian; 1 508 023 [7.3%] Black, 1 976 248 [9.5%] Hispanic, 10 059 597 [48.5%] White, and 6 417 883 [30.9%] unknown) in the first 3 quarters of 2020. During the COVID-19 pandemic, the proportion of patients receiving a pain diagnosis was smaller than that for the same period in 2019 (mean difference, -15.9%; 95% CI, -16.1% to -15.8%). Patients with pain were more likely to receive opioids (mean difference, 3.5%; 95% CI, 3.3%-3.7%) and less likely to receive nonpharmacologic therapy (mean difference, -6.0%; 95% CI, -6.3% to -5.8%), and opioid prescriptions were longer and more potent during the early pandemic in 2020 relative to 2019 (mean difference, 1.07 days; 95% CI, 1.02-1.17 days; mean difference, 0.96 morphine milligram equivalents; 95% CI, 0.76-1.20). Analysis of individuals' transitions between treatment options for pain found that patients were more likely to transition out of nonpharmacologic therapy, replacing it with opioid prescriptions for pain management during the COVID-19 pandemic than in the year before., Conclusions and Relevance: Nonpharmacologic therapy is a benign treatment for pain often recommended instead of opioid therapy. The decrease in nonpharmacologic therapy and increase in opioid prescription during the COVID-19 pandemic found in this cross-sectional study, especially given longer days of prescription and more potent doses, may exacerbate the US opioid epidemic. These findings suggest that it is imperative to investigate the implications of limited medical access on treatment substitution, which may increase patient risk, and implement policies and guidelines to prevent those substitutions.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition., Competing Interests: The authors have declared that no competing interests exist.

Objective: Despite the efficacy of pre-exposure prophylaxis (PrEP) in reducing the risk of HIV infection, uptake remains low among many who are most vulnerable to HIV, such as Black and Latinx women. Interventions that target social networks to encourage at-risk women to initiate PrEP are underused., Design: This study used an egocentric network design and sampled Black/African American and Latinx women at risk of HIV as well as people from their social networks (N = 211) in a small, western city., Methods: Multivariable generalized linear mixed effects regression models investigated individual-level and network-level characteristics associated with likely future PrEP use., Results: PrEP awareness was low, but once informed, 36% considered themselves likely to take it in the future. Perceived risk of HIV, perceived barriers to HIV testing, and participation in a 12-step program increased odds of anticipated PrEP use. A higher proportion of friends in one's network decreased odds of future PrEP use, whereas a higher proportion of network members who tested regularly for HIV increased odds of future PrEP use. A marginally significant interaction was detected between proportion of friends in one's network and proportion of the network perceived to test for HIV regularly (ie, testing norms). When HIV testing norms were low, a higher proportion of friends in the network decreased odds of likely PrEP use. However, this effect was reversed in contexts with strong testing norms., Conclusion: Women who are interested in PrEP may be embedded within social and normative contexts that can foster or inhibit PrEP uptake., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking., Aim: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD., Methods: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis., Results: The median [IQR] diagnosis sub-intervals were: (a) patient = 2.1 months [0.9-5.1]; (b) GP = 0.3 months [0.0-0.9]; (c) secondary care = 1.1 months [0.5-2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1-15.0]) than ulcerative colitis (3.3 months [1.9-7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course., Conclusion: Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course., (© 2020 John Wiley & Sons Ltd.)

Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD., Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). We tested observational and MR-based associations between GORD and four adiposity measures [body mass index (BMI), waist-hip ratio (WHR), a metabolically favourable higher body-fat percentage and waist circumference], smoking status, smoking frequency and caffeine consumption., Results: Observationally, all adiposity measures were associated with higher odds of GORD. Ever and current smoking were associated with higher odds of GORD. Coffee consumption was associated with lower odds of GORD but, among coffee drinkers, more caffeinated-coffee consumption was associated with higher odds of GORD. Using MR, we provide strong evidence that higher WHR and higher WHR adjusted for BMI lead to GORD. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded. This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference., Conclusions: These results provide strong evidence that a higher waist-hip ratio leads to GORD. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see "Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli : The Status of the Field and New Clinical Opportunities" [1]., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier Inc.)

The continuing HIV pandemic calls for broad, multi-sectoral responses that foster community control of local prevention and care services, with the goal of leveraging high quality treatment as a means of reducing HIV incidence. Service system improvements require stakeholder input from across the care continuum to identify gaps and to inform strategic plans that improve HIV service integration and delivery. System dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and about ways to achieve sustainable system-level improvements. Via an intensive group model building process with a task force of community stakeholders with diverse roles and responsibilities for HIV service implementation, delivery and surveillance, we designed and validated a multi-module system dynamics model of the HIV care continuum, in relation to local prevention and care service capacities. Multiple sources of data were used to calibrate the model for a three-county catchment area of central Connecticut. We feature a core module of the model for the purpose of illustrating its utility in understanding the dynamics of treatment as prevention at the community level. We also describe the methods used to validate the model and support its underlying assumptions to improve confidence in its use by stakeholders for systems understanding and decision making. The model's generalizability and implications of using it for future community-driven strategic planning and implementation efforts are discussed., Competing Interests: The authors have declared that no competing interests exist.

Objective: To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition., Data Sources/study Setting: The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis., Study Design: We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition., Data Collection Methods: Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period., Principal Findings: The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition., Conclusions: Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance., (© Health Research and Educational Trust.)

Objective: Many national HIV guidelines recommend that health care providers encourage patients to identify a treatment partner from their social network to support antiretroviral therapy adherence. This study examined associations of patient and treatment partner characteristics with patient viral suppression in Botswana., Design: One hundred thirty-one patients [67 (51.1%) virally suppressed and 64 (48.9%) not suppressed] and their treatment partners were recruited for cross-sectional interviews from one HIV clinic., Methods: Participants completed surveys assessing social network, sociodemographic, and psychosocial characteristics. Open-ended questions explored treatment partner relationship quality., Results: Multivariate logistic regressions indicated a higher likelihood of viral suppression among patients who reported greater average emotional closeness to their network members [odds ratio (95% confidence interval) = 3.8 (1.3 to 11.5), P = 0.02] and whose treatment partners were spouses/partners [odds ratio (95% confidence interval) = 2.6 (1.0 to 6.7), P = 0.04]. Qualitative analyses indicated that treatment partners of suppressed patients provided both medical and nonmedical support, whereas treatment partners of unsuppressed patients focused mainly on adherence reminders and appointment accompaniment. Treatment partners, especially of unsuppressed patients, requested ongoing training and counseling skills., Conclusions: Additional research is needed to further explore effective characteristics of treatment partners to inform HIV treatment guidelines. Standard training for treatment partners could include medical-related information and counseling education.

Background and Setting: Black men who have sex with men (BMSM) in the United States have disproportionately high HIV infection rates. Social networks have been shown to influence HIV risk behavior; however, little is known about whether they affect the risk of HIV seroconversion. This study uses data from the BROTHERS (HPTN 061) study to test whether contextual factors related to social networks are associated with HIV seroconversion among BMSM., Methods: We analyzed data from the BROTHERS study (2009-2011), which examined a multicomponent intervention for BMSM in 6 US cities. We ran a series of Cox regression analyses to examine associations between time-dependent measures of network support (personal/emotional, financial, medical, and social participation) and time to HIV seroconversion. We ran unadjusted models followed by models adjusted for participant age at enrollment and study location., Results: A total of 1000 BMSM tested HIV negative at baseline and were followed at 6- and 12-month study visits. Twenty-eight men tested HIV positive. In adjusted hazard ratio models, study participants who remained HIV negative had higher proportions of social network members who provided personal/emotional {0.92 [95% confidence interval (CI): 0.85 to 0.99]}, medical [0.92 (95% CI: 0.85 to 0.99)], or social participation [0.91 (95% CI: 0.86 to 0.97)] support., Conclusion: Findings suggest that the increased presence of social network support can be protective against HIV acquisition. Future research should explore the processes that link social network support with sexual and other transmission risk behaviors as a basis to inform HIV prevention efforts.

This study aimed to determine prevalence of Ralstonia spp. in cystic fibrosis patients, look for any evidence of cross infection and to describe clinical outcomes for patients infected by Ralstonia spp. Prevalence of Ralstonia spp. was calculated annually from 2008 to 2016. Pulsed-field gel electrophoresis was performed on ⩾1 sample from patients with an isolation of Ralstonia spp. between 2008 and 2016. A prospective, longitudinal observational study of adult patients was performed with 12 months follow-up from recruitment. Prevalence of Ralstonia spp. rose from 0·6% in 2008 to 2·4% in 2016. In total 12 out of 14 (86%) patients with ⩾1 isolation of Ralstonia spp. developed chronic infection. A pair and a group of three unrelated patients with epidemiological connections shared strains of Ralstonia mannitolilytica. Lung function of Ralstonia spp. infected patients was moderately to severely impaired. Prevalence of Ralstonia spp. is low but increasing. The risk of a patient developing chronic Ralstonia spp. infection following first acquisition is high and cross-infection may be possible. Whether Ralstonia spp. infection causes increased pulmonary exacerbation frequency and lung function decline needs to be evaluated in larger prospective studies.

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is commonly initiated by ectopic beats originating from a small myocardial sleeve extending over the pulmonary veins. Pulmonary vein isolation therapy attempts to isolate the pulmonary veins from the left atrium by ablating tissue, commonly by using radiofrequency ablation. During this procedure, the cardiologist records electrical activity using a lasso catheter, and the activation pattern recorded is used as a guide toward which regions to ablate. However, poor contact between electrode and tissue can lead to important regions of electrical activity not being recorded in clinic. We reproduce these signals through the use of a phenomenological model of the cardiac action potential on a cylinder, which we fit to post-AF atrial cells, and model the bipolar electrodes of the lasso catheter by an approximation of the surface potential. The resulting activation pattern is validated by direct comparison with those of clinical recordings. A potential application of the model is to reconstruct the missing electrical activity, minimizing the impact of the information loss on the clinical procedure, and we present results to demonstrate this.

A fundamental feature of community-based participatory research (CBPR) is sharing findings with community members and engaging community partners in the dissemination process. To be truly collaborative, dissemination should involve community members in a two-way dialogue about new research findings. Yet little literature describes how to engage communities in dialogue about research findings, especially with historically marginalized communities where mistrust of researchers may exist because of past or present social injustices. Through a series of interactive community presentations on findings from a longitudinal study, we developed a process for community dissemination that involved several overlapping phases: planning, outreach, content development, interactive presentations, and follow-up. Through this process, we built on existing and new community relationships. Following each interactive presentation, the research team debriefed and reviewed notes to identify lessons learned from the process. Key themes included the importance of creating a flexible dissemination plan, tailoring presentations to each community group, establishing a point person to serve as a community liaison, and continuing dialogue with community members after the presentations. Core strategies for developing trust during dissemination included engaging community members at every step, reserving ample time for discussion during presentations, building rapport by sharing personal experiences, being receptive to and learning from criticism, and implementing input from community members. This process led to a deeper understanding of research findings and ensured that results reached community members who were invested in them.

Background: Hyperkalaemia is a common potentially fatal complication of chronic kidney disease (CKD). It may manifest as electrocardiogram (ECG) changes, the earliest of which is T-wave 'tenting'. However, this occurs in less than half of episodes of hyperkalaemia. The aim of this study was to determine what other clinical features relate to the probability of T-wave tenting; and if there is a longer-term survival difference between patients who develop tenting and those who do not., Method: One hundred and forty-five patients with end-stage renal disease who had standard 12-lead ECG and concurrent serum potassium measurement were enrolled. The presence of tenting and the ratio of the amplitude of the tallest precordial T-wave and R-wave were determined (T:R)., Results: Tenting was as common in normal range serum potassium as hyperkalaemia (33 versus 31%) and less common than in left ventricular hypertrophy (44%). T:R was less sensitive (24 versus 33%) but more specific (85 versus 67%) than tenting at correctly identifying hyperkalaemia ≥ 6.0 mmol/L. Tenting became less common with increasing age. Dialysis patients were more likely to show increased T:R that pre-dialysis Stage 5 CKD. Elevated T:R was not associated with worse cardiovascular outcome but was associated with increased risk of sudden death over a mean follow-up of 3.8 years (hazard ratio = 8.3, P = 0.021)., Conclusions: The reason for the variability in T-wave changes is not clear. The ratio of precordial T-wave to R-wave amplitude is a more specific measure than tenting but both are poorly sensitive at detecting hyperkalaemia. The greater risk for sudden death may represent a susceptibility to cardiac arrhythmia during repolarization.

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Young's) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Young's modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Young's modulus of elasticity.