General features of transmembrane beta barrels from a large database.

Large datasets contribute new insights to subjects formerly investigated by exemplars. We used coevolution data to create a large, high-quality database of transmembrane ß-barrels (TMBB). By applying simple feature detection on generated evolutionary contact maps, our method (IsItABarrel) achieves 95.88% balanced accuracy when discriminating among protein classes. Moreover, comparison with IsItABarrel revealed a high rate of false positives in previous TMBB algorithms. In addition to being more accurate than previous datasets, our database (available online) contains 1,938,936 bacterial TMBB proteins from 38 phyla, respectively, 17 and 2.2 times larger than the previous sets TMBB-DB and OMPdb. We anticipate that due to its quality and size, the database will serve as a useful resource where high-quality TMBB sequence data are required. We found that TMBBs can be divided into 11 types, three of which have not been previously reported. We find tremendous variance in proteome percentage among TMBB-containing organisms with some using 6.79% of their proteome for TMBBs and others using as little as 0.27% of their proteome. The distribution of the lengths of the TMBBs is suggestive of previously hypothesized duplication events. In addition, we find that the C-terminal ß-signal varies among different classes of bacteria though its consensus sequence is LGLGYRF. However, this ß-signal is only characteristic of prototypical TMBBs. The ten non-prototypical barrel types have other C-terminal motifs, and it remains to be determined if these alternative motifs facilitate TMBB insertion or perform any other signaling function.

Assessing Health Promotion Interventions: Limitations of Traditional Research Methods in Community-Based Studies.

Most low-income Americans fail to meet physical activity recommendations. Inactivity and poor diet contribute to obesity, a risk factor for multiple chronic diseases. Health promotion activities have the potential to improve health outcomes for low-income populations. Measuring the effectiveness of these activities, however, can be challenging in community settings. A "Biking for Health" study tested the impact of a bicycling intervention on overweight or obese low-income Latino and African American adults to reduce barriers to cycling and increase physical activity and fitness. A randomized controlled trial was conducted in Milwaukee, Wisconsin, in summer 2015. A 12-week bicycling intervention was implemented at two sites with low-income, overweight, or obese Latino and African American adults. We found that randomized controlled trial methodology was suboptimal for use in this small pilot study and that it negatively affected participation. More discussion is needed about the effectiveness of using traditional research methods in community settings to assess the effectiveness of health promotion interventions. Modifications or alternative methods may yield better results. The aim of this article is to discuss the effectiveness and feasibility of using traditional research methods to assess health promotion interventions in community-based settings.

Tricyclic and Tetracyclic Antidepressants for the Prevention of Frequent Episodic or Chronic Tension-Type Headache in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Tension-type headaches are a common source of pain and suffering. Our purpose was to assess the efficacy of tricyclic (TCA) and tetracyclic antidepressants in the prophylactic treatment of tension-type headache. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the ISI Web of Science, and clinical trial registries through 11 March 2017 for randomized controlled studies of TCA or tetracyclic antidepressants in the prevention of tension-type headache in adults. Data were pooled using a random effects approach. KEY RESULTS: Among 22 randomized controlled trials, eight included a placebo comparison and 19 compared at least two active treatments. Eight studies compared TCAs to placebo, four compared TCAs to selective serotonin reuptake inhibitors (SSRIs), and two trials compared TCAs to behavioral therapies. Two trials compared tetracyclics to placebo. Single trials compared TCAs to tetracyclics, buspirone, spinal manipulation, transcutaneous electrical stimulation, massage, and intra-oral orthotics. High-quality evidence suggests that TCAs were superior to placebo in reducing headache frequency (weighted mean differences (WMD): -4.8 headaches/month, 95% CI: -6.63 to -2.95) and number of analgesic medications consumed (WMD: -21.0 doses/month, 95% CI: -38.2 to -3.8). TCAs were more effective than SSRIs. Low-quality studies suggest that TCAs are superior to buspirone, but equivalent to behavioral therapy, spinal manipulation, intra-oral orthotics, and massage. Tetracyclics were no better than placebo for chronic tension-type headache. CONCLUSIONS: Tricyclic antidepressants are modestly effective in reducing chronic tension-type headache and are superior to buspirone. In limited studies, tetracyclics appear to be ineffective in the prophylactic treatment of chronic tension-type headache.

Biking for Health: Results of a Pilot Randomized Controlled Trial Examining the Impact of a Bicycling Intervention on Lower-Income Adults.

INTRODUCTION: This pilot study tested the efficacy of a bicycling intervention targeting inactive, low-income, overweight adults on reducing perceived barriers to bicycling, increasing physical activity, and improving health. METHODS: A nonblinded 2-site randomized controlled trial was conducted in Milwaukee, Wisconsin, in summer 2015. Participants included members from 1 largely Latino community and a second primarily African American neighborhood. A certified bicycling instructor led a 12-week bicycling intervention. Outcome measures including biking-related attitudes, self-reported physical activity, fitness as measured by the 6-minute step test, and biometric data were collected at baseline, 12 weeks, and 20 weeks. RESULTS: Thirty-eight participants completed the study. Barriers to bicycling declined significantly among intervention group participants at 12 weeks with some declines persisting to 20 weeks. Bicycling for leisure or non work transportation increased significantly more in the intervention than control group from baseline to 12 weeks but this difference attenuated by 20 weeks. Both groups increased their fitness between baseline and 12 weeks, with a trend towards greater gains in the bicycling intervention group. No significant change in biometric measurements was seen at either 12 weeks or 20 weeks. CONCLUSION: Despite the small study size, this bicycling intervention decreased perceived barriers to bicycling and increased bicycling activity in low-income minority participants. These findings support a larger-scale study to measure fitness and health changes from bicycling interventions.

Diabetes and hypertension prevalence in homeless adults in the United States: a systematic review and meta-analysis.

We estimated hypertension and diabetes prevalence among US homeless adults compared with the general population, and investigated prevalence trends. We systematically searched 5 databases for published studies (1980-2014) that included hypertension or diabetes prevalence for US homeless adults, pooled disease prevalence, and explored heterogeneity sources. We used the National Health Interview Survey for comparison. We included data from 97366 homeless adults. The pooled prevalence of self-reported hypertension was 27.0% (95% confidence interval=23.8%, 29.9%; n=43 studies) and of diabetes was 8.0% (95% confidence interval=6.8%, 9.2%; n=39 studies). We found no difference in hypertension or diabetes prevalence between the homeless and general population. Additional health care and housing resources are needed to meet the significant, growing burden of chronic disease in the homeless population.

Structural Relationships to Efficacy for Prazole-Derived Antivirals.

Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the ß-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by increasing flexibility. Further, the formation of a novel secondary Tsg101 adduct for several of the tested compounds and the commercial drug lansoprazole. The secondary adduct involved the loss of the 4-pyridyl substituent to form an irreversible species, with implications for increasing the half-life of the active species or its specificity toward Tsg101 UEV. It is also determined that sulfide derivatives display effective viral inhibition, presumably through cellular sulfoxidation, allowing for delayed conversion within the cellular environment, and identify SARS-COV-2 as a target of prazole inhibition. These results open multiple avenues for the design of prazole derivatives for antiviral applications.

Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas.

PURPOSE: Cytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting their clinical potential despite potent antitumor effects. We previously engineered cytokines that bind and anchor to tumor collagen following intratumoral injection, and sought to test their safety and biomarker activity in spontaneous canine soft-tissue sarcomas (STS). EXPERIMENTAL DESIGN: Collagen-binding cytokines were canine-ized to minimize immunogenicity and were used in a rapid dose-escalation study in healthy beagles to identify a maximum tolerated dose. Ten client-owned pet dogs with STS were then enrolled into trial, receiving cytokines at different intervals prior to surgical tumor excision. Tumor tissue was analyzed through IHC and NanoString RNA profiling for dynamic changes within treated tumors. Archived, untreated STS samples were analyzed in parallel as controls. RESULTS: Intratumorally administered collagen-binding IL2 and IL12 were well tolerated by STS-bearing dogs, with only Grade 1/2 adverse events observed (mild fever, thrombocytopenia, neutropenia). IHC revealed enhanced T-cell infiltrates, corroborated by an enhancement in gene expression associated with cytotoxic immune function. We found concordant increases in expression of counter-regulatory genes that we hypothesize would contribute to a transient antitumor effect, and confirmed in mouse models that combination therapy to inhibit this counter-regulation can improve responses to cytokine therapy. CONCLUSIONS: These results support the safety and activity of intratumorally delivered, collagen-anchoring cytokines for inflammatory polarization of the canine STS tumor microenvironment. We are further evaluating the efficacy of this approach in additional canine cancers, including oral malignant melanoma.

Factors Associated with Cigarette Smoking in Homeless Adults: Findings From an Outpatient Counseling Clinic.

BACKGROUND: Those who are homeless are 4 times more likely to smoke cigarettes than the general population in the United States. Though research has investigated smoking risk factors among homeless individuals, further investigation is needed to understand factors that can be addressed by smoking cessation programs. This study seeks to understand characteristics associated with cigarette use in clients of the counseling clinic at a Midwest homeless shelter, including whether homeless individuals who smoke demonstrate lower self-efficacy, greater social isolation, poorer perception of therapy, and greater levels of chronic homelessness than nonsmokers. METHODS: From 2014 through 2019, clients of the counseling clinic were invited to contribute to a data bank. Logistic regression was performed to determine predictors of smoking status. RESULTS: No association was identified between smoking status and self-efficacy, social isolation, perception of therapy, or chronic homelessness. Compared to those without a high school degree, odds of being a smoker were 95% lower for those with a high school degree or equivalent and 93% lower for those with more than a high school education. Those with 3 or more episodes of prior substance abuse treatment were more likely to be smokers. CONCLUSION: This study demonstrates that cigarette use among the homeless population is associated with low education level and prior substance abuse treatment. Smoking cessation programs would benefit from tailoring information to the education level of their audience. Further study could determine whether use of other substances may contribute to cigarette use in the homeless population and how this may be addressed by smoking cessation programs.

When to stop screening: a review of breast, gynecologic, and colorectal cancer screening in women over age 65.

Because age alone is not an indicator of health, there is no clear consensus among the various cancer screening guidelines on when to stop cancer screening. For breast, cervical, and colorectal cancer, there are recommended screening tests, while, for other gynecologic cancers, there are not. When discussing with older women patients when to stop cancer screening, we encourage practitioners to review the goals of the screening test, assess the health and functional status of the patient, and discuss her values and health goals. To facilitate this discussion, we review proposed frameworks for determining when to screen older patients for cancer. We also review the concepts of "well" and "frail" older adults. Finally, we review the current screening recommendations for breast, gynecological, and colorectal cancers, and the reasoning behind them, from the United States Preventative Screening Task Force, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the American Geriatric Society.

Comparison of Attitudes of Wisconsin Health Care Providers and Pharmacists Toward Vaccine Administration and Perceived Barriers.

OBJECTIVE: To measure the attitudes of pharmacists and other health care providers towards vaccine administration, overall acceptance of pharmacists as immunization providers, and perceived immunization barriers in Wisconsin. METHODS: The authors conducted a cross-sectional study utilizing an online survey to assess the attitudes of pharmacists and other health care providers toward their role as immunization providers and perceived barriers to providing immunizations. The survey was distributed between November 2018 and February 2019. RESULTS: Two hundred thirty-six pharmacists and 51 other health care providers completed the survey. Of the pharmacists who responded, 203 (86%) provided immunizations. Most respondents (97.9% of pharmacists and 90.2% of other health care providers) see vaccinations as a shared professional responsibility. Both pharmacists (82.6%) and other health care providers (79.6%) believe pharmacists have adequate training to administer vaccines to patients. Immunizing pharmacists identified 2 primary barriers to providing immunizations: patients refusing vaccines for financial reasons (55%) and patients not having insurance coverage for vaccines received in a pharmacy (55%). In contrast, the primary barrier identified by non-immunizing pharmacists is other responsibilities taking precedence over vaccinating (75%). Other health care providers identified determining whether their patients' insurance will reimburse for a vaccine (52%) as their primary barrier toward providing immunizations. CONCLUSION: These surveys provide a baseline measure of the attitudes of Wisconsin pharmacists and other health care providers toward immunization provision and offer opportunities for comparison. Our findings highlight barriers, such as insurance coverage for immunizations, that may prevent pharmacists from increasing vaccination rates in Wisconsin.

Immunizations at Wisconsin Pharmacies: Results of a statewide vaccine registry analysis and pharmacist survey.

BACKGROUND: There is currently limited data in the United States on the proportion of immunization doses given at pharmacies outside the influenza vaccine. This study aims to obtain baseline information on the percentage of vaccine doses administered at pharmacies in Wisconsin and to understand the immunization barriers for Wisconsin pharmacists, to inform interventions to increase immunization access at pharmacies. METHODS: Aggregated data from the Wisconsin Immunization Registry (WIR) was obtained for all vaccines administered at pharmacies to patients over the age of six from July 2017 through June 2018. In addition, a survey on attitudes towards and barriers to vaccination was sent to 2000 Wisconsin pharmacists with 236 respondents yielding a 12% response rate. RESULTS: WIR data demonstrates that zoster and influenza vaccines have the highest proportion of doses administered at pharmacies (39% and 20%, respectively). Human papillomavirus (HPV) vaccines have the lowest proportion of doses at 0.2%. Pharmacy survey shows that 86% provide immunizations. Most stock influenza vaccines (84%), whereas much fewer stock HPV vaccines (21%). The greatest immunization barriers for the pharmacy respondents include billing and reimbursement challenges and competing demands for staff. CONCLUSIONS: Despite the barriers, community pharmacies have significant potential to address vaccination gaps. Physicians, patients, and legislative bodies are generally well-accepting of pharmacists as immunizers. Pharmacists, in order to be fully utilized as immunizers, must engage in active communication with patients and be willing to collaborate with physicians. Legislative policy and health insurance reimbursement reforms are also necessary to facilitate further pharmacist participation in immunization.

Implementation of a primary care physician-led Cavity Clinic using silver diamine fluoride.

OBJECTIVES: Early childhood caries (ECC) disproportionately affects lower socioeconomic status households. In this article, we describe a novel intervention utilizing physician-applied silver diamine fluoride (SDF) in a primary care "Cavity Clinic." METHODS: Building on literature review and expert consultation, Cavity Clinic using SDF for children without dentists was implemented in a family medicine residency setting. Process outcomes were evaluated through chart review and structured field notes. RESULTS: From December 2017 to December 2018, 30 patients have been treated. Their average age is 5.5 years (2-9), 82 percent are African American, and all are insured by Medicaid. Most have severe ECC. Thirty-eight percent have successfully established dental homes through participation. CONCLUSIONS: It is feasible and acceptable for physicians to treat ECC with SDF in a primary care setting. Partnership with an on-site hygienist is helpful but physician-only sessions were still beneficial. This strategy holds potential for addressing the epidemic of ECC.

Continuity in Community Medicine Training: Is It Time to Rethink the Block Rotation?

BACKGROUND AND OBJECTIVES: Family medicine residency training emphasizes the importance of community medicine. Recent scholarship has helped to identify important elements of community partnerships, including bidirectionality and continuity. Given the importance of continuity in family medicine and community partnerships, this study explores the relationship between continuity in community medicine curricula, partnership quality, and residents' community medicine competency. METHODS: Survey questions were included in the 2015-2016 Council of Academic Family Medicine Educational Research Alliance (CERA) Family Medicine Program Director survey that probed community medicine curricular structures, partnership quality, and outgoing resident competency in community medicine. Multivariate logistic regression was used to test the impact of continuity on the outcomes of partnership quality and residents' community medicine competency. RESULTS: Respondents represented 227 of 461 family medicine programs (49%). Block rotation, used in 150 (66%) programs, was the approach most commonly used to deliver community medicine curriculum. Eighty-five (45%) programs self-reported high quality partnerships and about one-third described outgoing residents as highly proficient in community medicine competencies. Program-level continuity in community partnerships was significantly correlated to high quality partnerships (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.79-6.89, P<0.001) and educational outcomes (OR 2.85, 95% CI 1.38-5.89, P=0.005), while resident-level continuity was not. CONCLUSIONS: Our findings support the importance of continuity to the quality of family medicine residency community partnerships as well as resident education in community medicine. Further research is needed to understand the importance of continuity at the program level versus individual resident level.

A Multielement Community Medicine Curriculum for the Family Medicine Clerkship.

INTRODUCTION: Many medical schools provide opportunities for students to learn about health disparities, social determinants of health, and the role physicians play in promoting health equity. The family medicine clerkship exposes medical students to these topics to help them understand the health status of patients. A multielement curriculum was incorporated into the core family medicine clerkship to provide the full medical school class exposure to community medicine and was updated in 2014 to increase the emphasis on clinical correlation of community medicine concepts. METHODS: This curriculum consists of a community medicine orientation, a community-based experience, a didactic session, and a reflection paper. The orientation serves as an introduction to the course, and the community-based experience provides hands-on understanding of community medicine. The didactic session encompasses a half-day session of preparatory work, team-based exercises, an interactive lecture, individual reflection, and a seminar-style discussion. Students share their experience with the curriculum in their reflection papers. RESULTS: Since 2014, 286 have students completed the updated curriculum, and reactions have been highly favorable. Most students have agreed or strongly agreed that the sessions met the learning objectives. Student preparation was demonstrated by individual quiz scores (average: 87%, n = 93). Learning and behavior change were evaluated using structured rubric scoring of reflection papers (average: 94%, n = 67). DISCUSSION: Overall, this community medicine curriculum includes a variety of learning experiences for medical students to gain knowledge, attitudes, and skills that are applicable to care in all specialties and may be easily adapted to use in other settings.

Improving Access to Vision Care for People Who are Homeless through Eyeglasses Recycling.

Visual impairment disproportionately affects the health and function of people who are homeless. A common and correctable cause of visual impairment is refractive error. However, eyeglasses remain an unmet need for the poor and underinsured. This report describes eyeglasses recycling and vision screening to reduce the burden of correctable visual impairment.