Barriers and facilitators of and strategies for successful community engagement in infectious disease clinical trials in low- and middle-income countries

Objectives: This is a protocol for a Cochrane Review (qualitative). The objectives are as follows:. 1. To identify and synthesise barriers and facilitators of successful community engagement in infectious disease clinical trials (e.g. HIV, tuberculosis, and malaria) in low- and middle-income countries; and. 2. To identify and synthesise strategies for engaging community stakeholders in infectious disease clinical trials in low- and middle-income countries. Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Biosynthesis of the protoberberine alkaloid jatrorrhizine

Feeding experiments with distant single or doubly labelled precursors show that the methylene dioxy group of berberine is opened in the formation of jatrorrhizine

¿Pasado, pisado? Las escuelas alemanas y una nueva proyección hacia la multiculturalidad

El presente trabajo analiza representativamente algunas escuelas alemanas de Argentina, el perfil de los alumnos, los objetivos de los profesores de alemán y la proyección de los directivos hacia una escuela multicultural, con la presentación de la actualidad de la enseñanza del idioma alemán, ¿como lengua extranjera en un mismo nivel con el idioma inglés? En la primera parte se presenta una breve reseña histórica de las olas inmigratorias de los germano-hablantes en la Argentina y la creación de escuelas para la enseñanza del alemán en los diferentes lugares de asentamiento. Luego de una escueta presentación de datos numéricos sobre la cantidad actual de escuelas alemanas del país, en la segunda parte se evalúa una encuesta realizada a alumnos de primero y quinto/sexto año de cuatro escuelas ubicadas en distintos puntos del país: el perfil de los alumnos, su interés tanto por el aprendizaje del idioma como por la cultura alemana. Un punto aparte encuesta a los alumnos del ciclo de especialización que realizaron el intercambio cultural con Alemania. Otro cuestionario evaluará las metas de los profesores de alemán, si son nativos o enviados por Alemania, así como una comparación de las horas cátedra delos idiomas inglés y alemán respectivamente. Asimismo los directivos contestan preguntas acerca del alumnado, del grado de multiculturalidad y de las propuestas actuales en pos de la preservación del idioma alemán. A partir de los resultados obtenidos se realiza el análisis de la actualidad del alemán y su futuro en las escuelas alemanas, el grado de multiculturalidad de las mismas y una comparación de las respuestas de los alumnos de los cuatro colegios analizados. Un apartado especial se dedica a las opiniones de los alumnos de quinto y sexto año tras su intercambio con alumnos alemanes.Fil: Späth, Brígida M. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina

A Novel Role for Stat1 in Phagosome Acidification and Natural Host Resistance to Intracellular Infection by Leishmania major

Intracellular parasites of the genus Leishmania generate severe diseases in humans, which are associated with a failure of the infected host to induce a protective interferon γ (IFNγ)-mediated immune response. We tested the role of the JAK/STAT1 signaling pathway in Leishmania pathogenesis by utilizing knockout mice lacking the signal transducer and activator of transcription 1 (Stat1) and derived macrophages. Unexpectedly, infection of Stat1-deficient macrophages in vitro with promastigotes from Leishmania major and attenuated LPG1 knockout mutants (lpg−) specifically lacking lipophosphoglycan (LPG) resulted in a twofold increased intracellular growth, which was independent of IFNγ and associated with a substantial increase in phagosomal pH. Phagosomes in Stat1−/− macrophages showed normal maturation as judged by the accumulation of the lysosomal marker protein rab7, and provided normal vATPase activity, but were defective in the anion conductive pathway required for full vesicular acidification. Our results suggest a role of acidic pH in the control of intracellular Leishmania growth early during infection and identify for the first time an unexpected role of Stat1 in natural anti-microbial resistance independent from its function as IFNγ-induced signal transducer. This novel Stat1 function may have important implications to studies of other pathogens, as the acidic phagolysosomal pH plays an important role in antigen processing and the uncoating process of many viruses

Microfluidic Evolution-On-A-Chip Reveals New Mutations that Cause Antibiotic Resistance

Microfluidic devices can mimic naturally occurring microenvironments and create microbial population heterogeneities ranging from planktonic cells to biofilm states. The exposure of such populations to spatially organized stress gradients can promote their adaptation into complex phenotypes, which are otherwise difficult to achieve with conventional experimental setups. Here a microfluidic chip that employs precise chemical gradients in consecutive microcompartments to perform microbial adaptive laboratory evolution (ALE), a key tool to study evolution in fundamental and applied contexts is described. In the chip developed here, microbial cells can be exposed to a defined profile of stressors such as antibiotics. By modulating this profile, stress adaptation in the chip through resistance or persistence can be specifically controlled. Importantly, chip‐based ALE leads to the discovery of previously unknown mutations in Escherichia coli that confer resistance to nalidixic acid. The microfluidic device presented here can enhance the occurrence of mutations employing defined micro‐environmental conditions to generate data to better understand the parameters that influence the mechanisms of antibiotic resistance

Between empathy and anger: healthcare workers’ perspectives on patient disengagement from antiretroviral treatment in Khayelitsha, South Africa - a qualitative study

Background & objectives: The benefits of long-term adherence to antiretroviral therapy (ART) are countered by interruptions in care or disengagement from care. Healthcare workers (HCWs) play an important role in patient engagement and negative or authoritarian attitudes can drive patients to disengage. However, little is known about HCWs’ perspectives on disengagement. We explored HCWs’ perspectives on ART disengagement in Khayelitsha, a peri-urban area in South Africa with a high HIV burden. Method: Semi-structured interviews were conducted with 30 HCWs in a primary care HIV clinic to explore their perspectives of patients who disengage from ART. HCWs interviewed included clinical (doctors and nurses) and support staff (counsellors, social workers, data clerks, security guards, and occupational therapists). The interview guide asked HCWs about their experience working with patients who interrupt treatment and return to care. Transcripts were audio-recorded, transcribed, and analysed using an inductive thematic analysis approach. Results: Most participants were knowledgeable about the complexities of disengagement and barriers to sustaining engagement with ART, raising their concerns that disengagement poses a significant public health problem. Participants expressed empathy for patients who interrupted treatment, particularly when the challenges that led to their disengagement were considered reasonable by the HCWs. However, many also expressed feelings of anger and frustration towards these patients, partly because they reported an increase in workload as a result. Some staff, mainly those taking chronic medication themselves, perceived patients who disengage from ART as not taking adequate responsibility for their own health. Conclusion: Lifelong engagement with HIV care is influenced by many factors including disclosure, family support, and HCW interactions. Findings from this study show that HCWs had contradictory feelings towards disengaged patients, experiencing both empathy and anger. Understanding this could contribute to the development of more nuanced interventions to support staff and encourage true person-centred care, to improve patient outcomes

(E)-3-Propoxymethyl­idene-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one monohydrate

The title compound, C15H16N2O2·H2O, was synthesized via the alkyl­ation of 3-hydroxy­methyl­idene-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one with n-propyl iodide in the presence of sodium hydroxide. The organic mol­ecule and the water mol­ecule both lie on a crystallographic mirror plane. In the crystal structure, inter­molecular O—H⋯O and O—H⋯N hydrogen bonds link the components into extended chains along [100]

Automatic segmentation of the left ventricle cavity and myocardium in MRI data

A novel approach for the automatic segmentation has been developed to extract the epi-cardium and endo-cardium boundaries of the left ventricle (lv) of the heart. The developed segmentation scheme takes multi-slice and multi-phase magnetic resonance (MR) images of the heart, transversing the short-axis length from the base to the apex. Each image is taken at one instance in the heart's phase. The images are segmented using a diffusion-based filter followed by an unsupervised clustering technique and the resulting labels are checked to locate the (lv) cavity. From cardiac anatomy, the closest pool of blood to the lv cavity is the right ventricle cavity. The wall between these two blood-pools (interventricular septum) is measured to give an approximate thickness for the myocardium. This value is used when a radial search is performed on a gradient image to find appropriate robust segments of the epi-cardium boundary. The robust edge segments are then joined using a normal spline curve. Experimental results are presented with very encouraging qualitative and quantitative results and a comparison is made against the state-of-the art level-sets method