Search

A 36-year-old man with schizophrenia, on two times per day clozapine, presented with a 2-year history of diffuse intermittent body pain.Per chart review—and on presentation—his physical examination had been consistently unremarkable, without point-tenderness elicited at any major muscle groups or focal neurological deficits. Workup for myopathy, neuropathy and supratherapeutic clozapine levels had similarly been unrevealing.Given that prior interventions had been unsuccessful in alleviating these symptoms, we queried whether clozapine might have been contributory. As a result, we adopted a previously described strategy of scheduling the bulk of patients’ medication during non-waking hours.At 1-month follow-up, the patient reported about a 50% improvement in his symptoms. At 6-month follow-up, this improvement in symptoms had been sustained.Our findings add to the limited anecdotal reports of this side effect whose true prevalence remains unknown. Timely recognition has the potential to promote adherence to therapy among patients in the maintenance phase.

Background: Intensive (ICU) care in many African countries, such as Uganda is comparatively underdeveloped and underprioritized, largely because of other pressing healthcare system needs. However, experiences like the COVID-19 pandemic, declines in infectious disease-associated mortality, and the ongoing epidemiologic transition make the current state of critical-care in the region important. But most countries in the region, including Uganda, do not collect ICU data, leaving published studies as one of few potential sources of robust data. Existing systematic reviews utilize this fact; however, these studies report their findings in aggregate, making country-specific conclusions impossible. As a result, aspects of critical care in several individual African countries remain unknown. Objective: To assess intensive care utilization in Uganda over time; specifically, we ascertain patient demographics and the most common reasons for ICU admission. Methods: We performed a systematic search of the following indexing databases: PuBMed, EMBASE, Google scholars, and African Journals Online prior to March 2020. To assess the gray literature, we searched the dissertation databases of the largest public universities in the country (Makerere & Mbarara University) for relevant papers. Inclusion criteria for studies were: (i) study conducted in Uganda at a facility with intensive care capacity, (ii) adult population; (iii) N>100 patients. Findings: A total of 10 papers, collectively reporting on 3519 adult patients and published between 2005 and 2018 met our study’s inclusion criteria. The median of the average age on admission was 35.50 [IQR: 26.11-43.4], with post-operative management as the most common reason for ICU admission. Median mortality was 37.50% [IQR: 28.5-40.5]. Conclusions: Our study provides evidence supporting previous anecdotal reports of a comparatively low median age of patients in Uganda’s ICUs. However, we also find that most ICU research is conducted at the national referral hospital, Mulago, in the country’s capital, Kampala. This second finding highlights a significant knowledge gap, as private ICUs (whose catchment population includes Uganda’s rapidly growing middle class), and other districts in the country are not represented. As a result, these results should be interpreted cautiously. Future research studies should attempt to include private hospitals and those outside Kampala. Systematic review registration: PROSPERO. Registration ID: CRD42020168940

INTRODUCTION Risk stratification has been proposed as a strategy to improve participation in colorectal cancer (CRC) screening, but evidence is lacking. We performed a randomized controlled trial of risk stratification using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool (CCRAT) on screening intent and completion. METHODS A total of 230 primary care patients eligible for first-time CRC screening were randomized to risk assessment via CCRAT or education control. Follow-up of screening intent and completion was performed by record review and phone at 6 and 12 months. We analyzed change in intent after intervention, time to screening, overall screening completion rates, and screening completion by CCRAT risk score tertile. RESULTS Of the patients, 61.7% of patients were aged

Descriptive and translational investigations into the human gut microbiome (GM) are rapidly expanding; however, studies are largely restricted to industrialized populations in the USA and Europe. Little is known about microbial variability and its implications for health and disease in other parts of the world. Populations in Africa are particularly underrepresented. What limited research has been performed has focused on a few subject domains, including the impact of long-term lifestyle and dietary factors on GM ecology, its maturation during infancy, and the interrelationships between the microbiome, infectious disease, and undernutrition. Recently, international consortia have laid the groundwork for large-scale genomics and microbiome studies on the continent, with a particular interest in the epidemiologic transition to noncommunicable disease. Here, we survey the current landscape of GM scholarship in Africa and propose actionable recommendations to improve research capacity and output.

Ras-dependent signaling is an important regulator of cell cycle progression, proliferation, senescence, and apoptosis. Several of the downstream effectors of Ras play dual roles in each of these processes. Under one set of conditions, they promote cell cycle progression and proliferation; yet, in a different paradigm, they drive cell cycle arrest and apoptosis. Furthermore, there is cross talk between certain downstream effectors of Ras including the PI3K-AKT and Raf-MEK-ERK pathways. Here we describe a series of experiments used to dissect the effect of different Ras-dependent signaling pathways on cell cycle progression, proliferation, senescence, and apoptosis. Furthermore, we highlight the importance of consistent growth conditions of cells in culture when studying Ras-dependent signaling as we show that the activation of downstream effectors of Ras changes with the confluency at which the cells are grown.

Ras-dependent signaling is an important regulator of cell cycle progression, proliferation, senescence, and apoptosis. Several of the downstream effectors of Ras play dual roles in each of these processes. Under one set of conditions, they promote cell cycle progression and proliferation; yet, in a different paradigm, they drive cell cycle arrest and apoptosis. Furthermore, there is cross talk between certain downstream effectors of Ras including the PI3K-AKT and Raf-MEK-ERK pathways. Here we describe a series of experiments used to dissect the effect of different Ras-dependent signaling pathways on cell cycle progression, proliferation, senescence, and apoptosis. Furthermore, we highlight the importance of consistent growth conditions of cells in culture when studying Ras-dependent signaling as we show that the activation of downstream effectors of Ras changes with the confluency at which the cells are grown.

Susan Reif,1 Rae Jean Proeschold-Bell,1,2 Jia Yao,1 Sara LeGrand,1,2 Anna Uehara,2 Edgar Asiimwe,2 Evelyn Byrd Quinlivan31Duke Center for Health Policy and Inequalities Research, 2Duke Global Health Institute, Duke University, Durham, NC, 3Center for Infectious Diseases, University of North Carolina Chapel Hill, Chapel Hill, NC, USABackground: Adherence with medication regimens for human immunodeficiency virus (HIV) is a life-saving behavior for people with HIV infection, yet adherence is challenging for many individuals with co-occurring substance use and/or mood disorders. Medication-taking self-efficacy, which is the confidence that one can take one's medication as prescribed, is associated with better adherence with HIV medication. However, little is known about the influence that other kinds of self-efficacy have on adherence with HIV medication, especially among HIV-infected individuals with co-occurring substance use and/or mood disorders. We sought to examine the relationship between adherence with HIV medication among substance users and three specific kinds of self-efficacy, ie, one's confidence that one can communicate with medical providers, get support, and manage one's mood. We further sought to examine whether symptoms of depression and anxiety moderate these relationships.Methods: Patients were recruited from three HIV clinics in the southeastern United States as part of an integrated study of treatment for HIV and substance use.Results: We interviewed 154 patients with HIV and substance use who reported taking HIV medications. Based on symptoms of depression and anxiety using the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale-Anxiety, 63% had probable depression and/or anxiety. Higher levels of self-efficacy in provider communication (β = 3.86, P < 0.01), getting needed support (β = 2.82, P < 0.01), and mood management (β = 2.29, P < 0.05) were related to better self-reported adherence with HIV medication among study participants with probable depression and/or anxiety. The three kinds of self-efficacy were not associated with medication adherence among participants with HIV and substance use only.Conclusion: In the search for mutable factors to improve medication adherence among individuals triply diagnosed with HIV, substance use, and mood disorders, these findings support previous research indicating the benefit of enhancing self-efficacy, and further point to three specific kinds of self-efficacy that may benefit medication adherence, ie, provider communication, getting support, and mood management.Keywords: human immunodeficiency virus, self-efficacy, substance use, depression, anxiety, interventions

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.