Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.

BackgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.MethodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.ResultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.ConclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors

COLOUR IN FASHION: EFFECTS ON PERSONALITY

Colours have much impact on users – either positively or negatively – when they are used for fashion objects. This paper is purposed to identify major ways in which fashion designers in tertiary institutions within Kumasi metropolis use colours for their fashion objects and the effects of the colours on their clients. Qualitative research approach was employed for this research. Specifically, the descriptive research method was adopted for the study. One hundred and fifty (150) respondents with fashion design and textiles background from three public tertiary institutions offering fashion design and textiles as programme of study in the Kumasi metropolis of Ashanti region, were purposively sampled for the study. Identification, beautification and communication, constituting 92.0%, 84.7% and 84.7% respectively of the 150 respondents, ranked as the top three purposes for which people use colours in fashion goods. Interior decoration, communication, designing textiles and enhancement of the aesthetic appeal of clothes, representing 100%, 92.7%, 92.7% and 92.7% respectively were found to be the highest positive impact of colour in fashion. In the study, 85.3% of the respondents stated that some colours cause people to have low self-esteem while 62.0% of them said some colours cause people to feel lazy. It is recommended that people should select colours wisely to enhance their images.  Article visualizations

Barriers to recruiting primary care practices for implementation research during COVID-19: A qualitative study of practice coaches from the Stop Unhealthy (STUN) Alcohol Use Now trial

Background: The COVID-19 pandemic has brought widespread change to health care practice and research. With heightened stress in the general population, increased unhealthy alcohol use, and added pressures on primary care practices, comes the need to better understand how we can continue practice-based research and address public health priorities amid the ongoing pandemic. The current study considers barriers and facilitators to conducting such research, especially during the COVID-19 pandemic, within the context of recruiting practices for the STop UNhealthy (STUN) Alcohol Use Now trial. The STUN trial uses practice facilitation to implement screening and interventions for unhealthy alcohol use in primary care practices across the state of North Carolina. Methods: Semistructured interviews were conducted with a purposive sample of 15 practice coaches to discuss their recruitment experiences before and after recruitment was paused due to the pandemic. An inductive thematic analysis was used to identify themes and subthemes. Results: Pandemic-related barriers, including challenges in staffing, finances, and new COVID-19-related workflows, were most prominent. Competing priorities, such as quality improvement measures, North Carolina's implementation of Medicaid managed care, and organizational structures hampered recruitment efforts. Coaches also described barriers specific to the project and to the topic of alcohol. Several facilitators were identified, including the rising importance of behavioral health due to the pandemic, as well as existing relationships between practice coaches and practices. Conclusions: Difficulty managing competing priorities and obstacles within existing practice infrastructure inhibit the ability to participate in practice-based research and implementation of evidence-based practices. Lessons learned from this trial may inform strategies to recruit practices into research and to gain buy-in from practices in adopting evidence-based practices more generally. Plain Language Summary What is known: Unhealthy alcohol use is a significant public health issue, which has been exacerbated during the COVID-19 pandemic. Screening and brief intervention for unhealthy alcohol use is an evidence-based practice shown to help reduce drinking-related behaviors, yet it remains rare in practice. What this study adds: Using a qualitative approach, we identify barriers and facilitators to recruiting primary care practices into a funded trial that uses practice facilitation to address unhealthy alcohol use. We identify general insights as well as those specific to the COVID-19 pandemic. Barriers are primarily related to competing priorities, incentives, and lack of infrastructure. Facilitators are related to framing of the project and the anticipated level and type of resources needed to address unhealthy alcohol use especially as the pandemic wanes. Implications: Our findings provide information on barriers and facilitators to recruiting primary care practices for behavioral health projects and to implementing these activities. Using our findings, we provide a discussion of suggestions for conducting these types of projects in the future which may be of interest to researchers, practice managers, and providers

Serologic Screening for Genital Herpes: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Genital herpes simplex virus (HSV) infection is a prevalent sexually transmitted infection. Vertical transmission of HSV can lead to fetal morbidity and mortality. Objective: To assess the evidence on serologic screening and preventive interventions for genital HSV infection in asymptomatic adults and adolescents to support the US Preventive Services Task Force for an updated recommendation statement. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through March 31, 2016. Surveillance for new evidence in targeted publications was conducted through October 31, 2016. Study Selection: English-language randomized clinical trials (RCTs) comparing screening with no screening in persons without past or current symptoms of genital herpes; studies evaluating accuracy and harms of serologic screening tests for HSV-2; RCTs assessing preventive interventions in asymptomatic persons seropositive for HSV-2. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; pooled sensitivities and specificities of screening tests using a hierarchical summary receiver operating characteristic curve analysis when at least 3 similar studies were available. Main Outcomes and Measures: Accuracy of screening tests, benefits of screening, harms of screening, reduction in genital herpes outbreaks. Results: A total of 17 studies (n = 9736 participants; range, 24-3290) in 19 publications were included. No RCTs compared screening with no screening. Most studies of the accuracy of screening tests were from populations with high HSV-2 prevalence (greater than 40% based on Western blot). Pooled estimates of sensitivity and specificity of the most commonly used test at the manufacturer's cutpoint were 99% (95% CI, 97%-100%) and 81% (95% CI, 68%-90%), respectively (10 studies; n = 6537). At higher cutpoints, pooled estimates were 95% (95% CI, 91%-97%) and 89% (95% CI, 82%-93%), respectively (7 studies; n = 5516). Use of this test at the manufacturer's cutpoint in a population of 100 000 with a prevalence of HSV-2 of 16% (the seroprevalence in US adults with unknown symptom status) would result in 15 840 true-positive results and 15 960 false-positive results (positive predictive value, 50%). Serologic screening for genital herpes was associated with psychosocial harms, including distress and anxiety related to positive test results. Four RCTs compared preventive medications with placebo, 2 in nonpregnant asymptomatic adults who were HSV-2 seropositive and 2 in HSV-2-serodiscordant couples. Results in both populations were heterogeneous and inconsistent. Conclusions and Relevance: Serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from RCTs does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit

Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine

Implementation and Quality Improvement of a Screening and Counseling Program for Unhealthy Alcohol Use in an Academic General Internal Medicine Practice

Unhealthy alcohol use is the third leading cause of preventable death in the United States (U.S.). The U.S. Preventive Services Task Force recommends screening for unhealthy alcohol use but little is known about how best to do so. We used quality improvement techniques to implement a systematic approach to screening and counseling primary care patients for unhealthy alcohol use. Components included use of validated screening and assessment instruments; an evidence-based 2-visit counseling intervention using motivational interviewing techniques for those with risky drinking behaviors who did not have an alcohol use disorder (AUD); shared decision making about treatment options for those with an AUD; support materials for providers and patients; and training in motivational interviewing for faculty and residents. Over the course of one year, we screened 52% (N=5,352) of our clinic’s patients and identified 294 with positive screens. Of those 294, appropriate screening-related assessments and interventions were documented for 168 and 72 patients, respectively. Although we successfully implemented a systematic screening program and structured processes of care, ongoing quality improvement efforts are needed to screen the rest of our patients and to improve the consistency with which we provide and document appropriate interventions

Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Many adverse health outcomes are associated with obstructive sleep apnea (OSA). Objective: To review primary care-relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016. Study Selection: English-language randomized clinical trials (RCTs); studies evaluating accuracy of screening questionnaires or prediction tools, diagnostic accuracy of portable monitors, or association between apnea-hypopnea index (AHI) and health outcomes among community-based participants. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles. When multiple similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Sensitivity, specificity, area under the curve (AUC), AHI, Epworth Sleepiness Scale (ESS) scores, blood pressure, mortality, cardiovascular events, motor vehicle crashes, quality of life, and harms. Results: A total of 110 studies were included (N = 46 188). No RCTs compared screening with no screening. In 2 studies (n = 702), the screening accuracy of the multivariable apnea prediction score followed by home portable monitor testing for detecting severe OSA syndrome (AHI ≥30 and ESS score >10) was AUC 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively, but the studies oversampled high-risk participants and those with OSA and OSA syndrome. No studies prospectively evaluated screening tools to report calibration or clinical utility for improving health outcomes. Meta-analysis found that continuous positive airway pressure (CPAP) compared with sham was significantly associated with reduction of AHI (weighted mean difference [WMD], -33.8 [95% CI, -42.0 to -25.6]; 13 trials, 543 participants), excessive sleepiness assessed by ESS score (WMD, -2.0 [95% CI, -2.6 to -1.4]; 22 trials, 2721 participants), diurnal systolic blood pressure (WMD, -2.4 points [95% CI, -3.9 to -0.9]; 15 trials, 1190 participants), and diurnal diastolic blood pressure (WMD, -1.3 points [95% CI, -2.2 to -0.4]; 15 trials, 1190 participants). CPAP was associated with modest improvement in sleep-related quality of life (Cohen d, 0.28 [95% CI, 0.14 to 0.42]; 13 trials, 2325 participants). Mandibular advancement devices (MADs) and weight loss programs were also associated with reduced AHI and excessive sleepiness. Common adverse effects of CPAP and MADs included oral or nasal dryness, irritation, and pain, among others. In cohort studies, there was a consistent association between AHI and all-cause mortality. Conclusions and Relevance: There is uncertainty about the accuracy or clinical utility of all potential screening tools. Multiple treatments for OSA reduce AHI, ESS scores, and blood pressure. Trials of CPAP and other treatments have not established whether treatment reduces mortality or improves most other health outcomes, except for modest improvement in sleep-related quality of life