Prevalence and correlates of alcohol dependence disorder among TB and HIV infected patients in Zambia.

OBJECTIVES: To determine the prevalence and correlates of alcohol dependence disorders in persons receiving treatment for HIV and Tuberculosis (TB) at 16 Primary Health Care centres (PHC) across Zambia. METHODS: 649 adult patients receiving treatment for HIV and/or TB at PHCs in Zambia (363 males, 286 females) were recruited between 1st December 2009 and 31st January 2010. Data on socio-demographic variables, clinical disease features (TB and HIV), and psychopathological status were collected. The Mini International Neuropsychiatric Interview (MINI) was used to diagnose alcohol dependence disorder. Correlates of alcohol dependence were analyzed for men only, due to low prevalence in women. Univariable and multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using general estimating equations to allow for within-PHC clustering. RESULTS: The prevalence of alcohol dependence was 27.2% (95%CI: 17.7-39.5%) for men and 3.9% (95%CI: 1.4-0.1%) for women. Factors associated with alcohol dependence disorder in men included being single, divorced or widowed compared with married (adjusted OR = 1.47, 95%CI: 1.00-2.14) and being unemployed (adjusted OR=1.30, 95%CI: 1.01-1.67). The highest prevalence of alcohol dependence was among HIV-test unknown TB patients (34.7%), and lowest was among HIV positive patients on treatment but without TB (14.1%), although the difference was not statistically significant (p=0.38). CONCLUSIONS: Male TB/HIV patients in this population have high prevalence of alcohol dependence disorder, and prevalence differs by HIV/TB status. Further work is needed to explore interventions to reduce harmful drinking in this population

Unlocking preservation bias in the amber insect fossil record through experimental decay.

Fossils entombed in amber are a unique resource for reconstructing forest ecosystems, and resolving relationships of modern taxa. Such fossils are famous for their perfect, life-like appearance. However, preservation quality is vast with many sites showing only cuticular preservation, or no fossils. The taphonomic processes that control this range are largely unknown; as such, we know little about potential bias in this important record. Here we employ actualistic experiments, using, fruit flies and modern tree resin to determine whether resin type, gut microbiota, and dehydration prior to entombment affects decay. We used solid phase microextraction gas chromatography-mass spectrometry (SPME GC-MS) to confirm distinct tree resin chemistry; gut microbiota of flies was modified using antibiotics and categorized though sequencing. Decay was assessed using phase contrast synchrotron tomography. Resin type demonstrates a significant control on decay rate. The composition of the gut microbiota was also influential, with minor changes in composition affecting decay rate. Dehydration prior to entombment, contrary to expectations, enhanced decay. Our analyses show that there is potential significant bias in the amber fossil record, especially between sites with different resin types where ecological completeness and preservational fidelity are likely affected

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+ T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+ T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.Wellcome Trust [108101/Z/15/Z]; Diabetes UK RD Lawrence fellowship (grant: 17/0005594)

Combined written and oral information prior to gastrointestinal endoscopy compared with oral information alone: a randomized trial

BACKGROUND: Little is known about how to most effectively deliver relevant information to patients scheduled for endoscopy. METHODS: To assess the effects of combined written and oral information, compared with oral information alone on the quality of information before endoscopy and the level of anxiety. We designed a prospective study in two Swiss teaching hospitals which enrolled consecutive patients scheduled for endoscopy over a three-month period. Patients were randomized either to receiving, along with the appointment notice, an explanatory leaflet about the upcoming examination, or to oral information delivered by each patient's doctor. Evaluation of quality of information was rated on scales between 0 (none received) and 5 (excellent). The analysis of outcome variables was performed on the basis of intention to treat-analysis. Multivariate analysis of predictors of information scores was performed by linear regression analysis. RESULTS: Of 718 eligible patients 577 (80%) returned their questionnaire. Patients who received written leaflets (N = 278) rated the quality of information they received higher than those informed verbally (N = 299), for all 8 quality-of-information items. Differences were significant regarding information about the risks of the procedure (3.24 versus 2.26, p < 0.001), how to prepare for the procedure (3.56 versus 3.23, p = 0.036), what to expect after the procedure (2.99 versus 2.59, p < 0.001), and the 8 quality-of-information items (3.35 versus 3.02, p = 0.002). The two groups reported similar levels of anxiety before procedure (p = 0.66), pain during procedure (p = 0.20), tolerability throughout the procedure (p = 0.76), problems after the procedure (p = 0.22), and overall rating of the procedure between poor and excellent (p = 0.82). CONCLUSION: Written information led to more favourable assessments of the quality of information and had no impact on patient anxiety nor on the overall assessment of the endoscopy. Because structured and comprehensive written information is perceived as beneficial by patients, gastroenterologists should clearly explain to their patients the risks, benefits and alternatives of endoscopic procedures. Trial registration: Current Controlled trial number: ISRCTN34382782

Symptom recognition and health care seeking among immigrants and native Swedish patients with heart failure

<p>Abstract</p> <p>Background</p> <p>It is not known what patient perceptions or beliefs lead to beneficial decisions or response patterns in symptom interpretation among heart failure (HF) patients, especially immigrants. The aim of this study was to explore and compare symptom recognition and health care seeking patterns among immigrants and native Swedes with HF.</p> <p>Methods</p> <p>The study used a qualitative design. Semi-structured interviews were conducted with 42 patients with HF, of whom 21 were consecutively selected immigrants and 21 were randomly selected Swedish patients. The interviews were analysed using content analysis.</p> <p>Results</p> <p>A majority of the immigrant patients sought health care for symptoms and signs, such as breathing difficulties, fatigue and swelling. Twice as many immigrants as Swedes were unaware of "what the illness experience entailed" and which symptoms indicated worsening of HF.</p> <p>Conclusion</p> <p>The symptoms that patients sought care for, were similar among immigrants and Swedes. However, when interpreting symptoms more immigrants were unaware of the connection between the symptoms/signs and their HF condition. More tailored educational interventions might improve recognition of worsening symptoms in immigrant patients with chronic heart failure.</p

Retention on Buprenorphine Is Associated with High Levels of Maximal Viral Suppression among HIV-Infected Opioid Dependent Released Prisoners

HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD).From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy. Maximum viral suppression (MVS), defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44) groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%), from Hartford (74.4% v 47.7%) and have higher mean global health quality of life indicator scores (54.18 v 51.40). MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1)], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1)] and negatively with being Black [AOR = 0.13 (0.03, 0.68)]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy

Asenapine effects in animal models of psychosis and cognitive function

Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, α-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties. The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone. Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01–0.3 mg/kg s.c.), Apo-PPI (0.001–0.3 mg/kg s.c.), DNMTP (0.01–0.1 mg/kg s.c.), and 5-CSR (0.003–0.3 mg/kg s.c.). Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents (P &lt; 0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03–0.3 mg/kg; and risperidone, 0.01–0.1 mg/kg) significantly impaired 5-CSR accuracy (P &lt; 0.05). Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone