Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients

Perceptions of Cardiovascular Health in Underserved Communities

Introduction: Cardiovascular disease is the leading cause of deaths and illnesses in US adults, and the prevalence is disproportionately high in underserved populations. In this study, we assessed respondents' understanding of context-specific differences in knowledge and perceptions of disease, risk, and prevention in 6 underserved communities, with the longer-term goal of developing appropriate interventions. Methods: Thirty-nine small-group sessions and 14 interviews yielded data from 318 adults. Each site's researchers coded, analyzed, and extracted key themes from local data. Investigators from all sites synthesized results and identified common themes and differences. Results: Themes clustered in 3 areas (barriers to cardiovascular health, constraints related to multiple roles, and suggestions for effective communications and programs). Barriers spanned individual, social and cultural, and environmental levels; women in particular cited multiple roles (eg, competing demands, lack of self-care). Programmatic suggestions included the following: personal, interactive, social context; information in language that people use; activities built around cultural values and interests; and community orientation. In addition, respondents preferred health-related information from trusted groups (eg, AARP), health care providers (but with noticeable differences of opinion), family and friends, and printed materials. Conclusion: Interventions to decrease barriers to cardiovascular health are needed; these strategies should include family and community context, small groups, interactive methods, culturally sensitive materials, and trusted information sources. New-immigrant communities need culturally and linguistically tailored education before receiving more substantive interventions

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission

The membrane-localized protein kinase MAP4K4/TOT3 regulates thermomorphogenesis

Plants respond to mild warm temperature conditions by increased elongation growth of organs to enhance cooling capacity, in a process called thermomorphogenesis. To this date, the regulation of thermomorphogenesis has been exclusively shown to intersect with light signalling pathway. To identify regulators of thermomorphogenesis that are conserved in flowering plants, we map changes in protein phosphorylation in both dicots and monocots exposed to warm temperature. We identify MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE KINASE4 (MAP4K4)/TARGET OF TEMPERATURE3 (TOT3) as a regulator of thermomorphogenesis that impinges on brassinosteroid signalling in Arabidopsis thaliana. In addition, we show that TOT3 plays a role in thermal response in wheat, a monocot crop. Altogether, the conserved thermal regulation by TOT3 expands our knowledge of thermomorphogenesis beyond the well-studied pathways and can contribute to ensuring food security under a changing climate

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches

Perceptions of Cardiovascular Health in Underserved Communities

Introduction: Cardiovascular disease is the leading cause of deaths and illnesses in US adults, and the prevalence is disproportionately high in underserved populations. In this study, we assessed respondents' understanding of context-specific differences in knowledge and perceptions of disease, risk, and prevention in 6 underserved communities, with the longer-term goal of developing appropriate interventions. Methods: Thirty-nine small-group sessions and 14 interviews yielded data from 318 adults. Each site's researchers coded, analyzed, and extracted key themes from local data. Investigators from all sites synthesized results and identified common themes and differences. Results: Themes clustered in 3 areas (barriers to cardiovascular health, constraints related to multiple roles, and suggestions for effective communications and programs). Barriers spanned individual, social and cultural, and environmental levels; women in particular cited multiple roles (eg, competing demands, lack of self-care). Programmatic suggestions included the following: personal, interactive, social context; information in language that people use; activities built around cultural values and interests; and community orientation. In addition, respondents preferred health-related information from trusted groups (eg, AARP), health care providers (but with noticeable differences of opinion), family and friends, and printed materials. Conclusion: Interventions to decrease barriers to cardiovascular health are needed; these strategies should include family and community context, small groups, interactive methods, culturally sensitive materials, and trusted information sources. New-immigrant communities need culturally and linguistically tailored education before receiving more substantive interventions