Rural Friendship Bench: A qualitative study in Zaka district, Zimbabwe.

BACKGROUND: We piloted the Friendship Bench-an evidence-based, urban-area task sharing intervention for common mental disorders-in rural Zimbabwe. The intervention combines problem solving therapy with income generating activities. This study sought to understand the intervention's implementation in terms of acceptability, feasibility, and sustainability as well as local attitudes towards mental wellbeing in rural Zimbabwe. METHODS: Using four separate semi-structured interview guides, we conducted in-depth interviews (N = 32) with patients (n = 9), village health workers (n = 12), nurses (n = 6), and community leaders (n = 5). We analyzed our data using thematic analysis with a diverse coding team using an integrative deductive-inductive approach. RESULTS: Five themes emerged: 1) explanatory models for mental illness, 2) clinical workflow and emphasis on documentation, 3) positive feedback about the Friendship Bench, 4) accessibility, and 5) feasibility. CONCLUSION: In its current format, our intervention was acceptable but neither feasible nor sustainable. Sociocultural context is critical in the development of rural task sharing interventions for mental health. We thus recommend a robust pilot and adaptation phase when scaling task sharing interventions in rural sub-Saharan Africa to elevate community voices, leverage existing social structures, and embed interventions as deeply into communities as possible.

A review of bladder cancer in Sub-Saharan Africa: A different disease, with a distinct presentation, assessment, and treatment.

Background: Cancer of the bladder is the ninth leading cause of cancer in developed countries. It is the second most common urological malignancy. Transitional cell carcinoma (TCC) is the most common histological subtype in developed countries. In most of Africa, the most common type is squamous cell carcinoma (SCC). Cancer of bladder guidelines produced by the European Urological Association and the American Urological Association, including the tumor, node, and metastasis staging is focused on TCC of the bladder. Objectives: The purpose of the study is to review the pathogenesis, pathology, presentation, and management of cancer of the bladder in Africa and to use this information to propose a practical staging system for SCC. Methods: The study used the meta-analysis guideline provided by PRISMA using bladder cancer in Africa as the key search word. The study collected articles available on PubMed as of July 2017, Africa Online and Africa Index Medicus. PRISMA guidelines were used to screen for full-length hospital-based articles on cancer of the bladder in Africa. These articles were analyzed under four subcategories which were pathogenesis, pathology, clinical presentation, and management. The information extracted was pooled and used to propose a practical staging system for use in African settings. Results: The result of evaluation of 821 articles yielded 23 full-length papers on hospital-based studies of cancer of the bladder in Africa. Cancer of the bladder in most of Africa is still predominantly SCC (53%-69%). There has been a notable increase in TCC in Africa (9%-41%). The pathogenesis is mostly schistosoma-related SCC presents late with painful hematuria and necroturia (20%). SCC responds poorly to chemotherapy or radiotherapy. The main management of SCC is open surgery. This review allowed for a practical organ-based stage of SCC of the bladder that can be used in Africa. Conclusion: Bladder cancer in Africa presents differently from that in developed countries. Guidelines on cancer of the bladder may need to take account of this to improve bladder cancer management in Africa.

RésuméContexte: Le cancer de la vessie est la neuvième cause de cancer dans les pays développés. C'est le deuxième plus fréquent urologique malignité. Le carcinome à cellules transitionnelles (TCC) est le sous-type histologique le plus commun dans les pays développés. Dans la majeure partie de l'Afrique, le plus le type commun est le carcinome épidermoïde (SCC). Lignes directrices sur le cancer de la vessie produites par l'Association européenne d'urologie et American Urological Association, y compris la tumeur, le nœud, et la mise en scène de la métastase est axée sur le TCC de la vessie. Objectifs: Le Le but de l'étude est d'examiner la pathogenèse, la pathologie, la présentation et la gestion du cancer de la vessie en Afrique et d'utiliser cette information pour proposer un système de mise en scène pratique pour SCC. Méthodes: L'étude a utilisé la ligne de méta-analyse fournie par PRISMA en utilisant le cancer de la vessie en Afrique comme le mot clé de recherche. L'étude a recueilli des articles disponibles sur PubMed à partir de juillet 2017, Africa Online et Africa Index Medicus. Les directives PRISMA ont été utilisées pour dépister des articles hospitaliers complets sur le cancer de la vessie en Afrique. Ces articles ont été analysés sous quatre sous-catégories qui étaient la pathogenèse, la pathologie, la présentation clinique et la gestion. le les informations extraites ont été regroupées et utilisées pour proposer un système de mise en scène pratique à utiliser dans les contextes africains. Résultats: Le résultat de l'évaluation sur 821 articles, 23 articles complets ont été publiés sur les études hospitalières sur le cancer de la vessie en Afrique. Cancer de la vessie dans la plupart des L'Afrique est toujours principalement SCC (53% -69%). Il y a eu une augmentation notable du TCC en Afrique (9% -41%). La pathogenèse est principalement la SCC liée au schistosome se manifeste tardivement par une hématurie douloureuse et une nécroturie (20%). SCC répond faiblement à la chimiothérapie ou la radiothérapie. La gestion principale de SCC est la chirurgie ouverte. Cette revue a permis un stade pratique de la CEC de la vessie qui peut être utilisé. en Afrique. CONCLUSION: Le cancer de la vessie en Afrique présente différemment de celui des pays développés. Lignes directrices sur le cancer de la vessie Il faudra peut-être en tenir compte pour améliorer la gestion du cancer de la vessie en Afrique.

MR enterography under the age of 10 years: a single institutional experience.

BACKGROUND: MR enterography (MRE) plays a major role in the imaging of pediatric patients with inflammatory bowel disease (IBD) but can be challenging to perform in young children. OBJECTIVE: To review our institutional experience regarding the performance of MRE in children younger than 10 years of age, including the use of general anesthesia (GA). MATERIALS AND METHODS: Institutional review board approval was obtained. Radiology and anesthesia records were searched to identify MRE exams in children younger than 10 years old between June 2009 and May 2013. The following information was documented: demographics, indications for MRE, use of GA, imaging diagnoses, and documented GA-related side effects or adverse events. Imaging was reviewed to document study length, quality and progression of oral contrast material. RESULTS: One hundred six children (59 boys [56%]) younger than 10 years old underwent 119 MRE examinations (age range: 1 month to 9 years, 11 months). Common indications for MRE included known IBD (42%) and suspected IBD (38%). One hundred ten (92%) examinations were performed under GA. Mean exam length was 52 ± 13 min for GA patients with a range of 31--113 min. Median time under GA was 155 min. Oral contrast material reached the terminal ileum in 31%. Side effects/adverse events associated with GA were uncommon and minor, including transient nausea in 13 children (11%) and emesis in 9 (8%). CONCLUSION: Diagnostic-quality MRE can be performed successfully in young children. The majority of MRE exams were performed under GA, with only occasional minor side effects/adverse events.

A map of the PPARα transcription regulatory network for primary human hepatocytes.

Nuclear receptor activation in liver leads to coordinated alteration of the expression of multiple gene products with attendant phenotypic changes of hepatocytes. Peroxisome proliferators including endogenous fatty acids, environmental chemicals, and drugs induce a multi-enzyme metabolic response that affects lipid and fatty acid processing. We studied the signaling network for the peroxisome proliferator-associated receptor alpha (PPARα) in primary human hepatocytes using the selective PPARα ligand, GW7647. We measured gene expression over multiple concentrations and times and conducted ChIP-seq studies at 2 and 24h to assess genomic binding of PPARα. Over all treatments there were 192 genes differentially expressed. Of these only 51% showed evidence of PPARα binding-either directly at PPARα response elements or via alternative mechanisms. Almost half of regulated genes had no PPARα binding. We then developed two novel bioinformatics methods to visualize the dose-dependent activation of both the transcription factor circuitry for PPARα and the downstream metabolic network in relation to functional annotation categories. Available databases identified several key transcription factors involved with the non-genomic targets after GW7647 treatment, including SP1, STAT1, ETS1, ERα, and HNF4α. The linkage from PPARα binding through gene expression likely requires intermediate protein kinases to activate these transcription factors. We found enrichment of functional annotation categories for organic acid metabolism and cell lipid metabolism among the differentially expressed genes. Lipid transport processes showed enrichment at the highest concentration of GW7647 (10 µM). While our strategy for mapping transcriptional networks is evolving, these approaches are necessary in moving from toxicogenomic methods that derive signatures of activity to methods that establish pathway structure, showing the coordination of the activated nuclear receptor with other signaling pathways.

Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic.

OBJECTIVES: To describe initial registration characteristics of adult and paediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 and December 2010. METHODS: Routine data on patient with TB category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB only, TB/HIV co-infected patients not on ART and TB/HIV co-infected patients on ART using chi-square tests. Trends over time illustrate strengths and weaknesses of integrated service provision. RESULTS: Among 10 143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear-positive pulmonary TB (PTB) was highest among HIV-negative patients with TB (34.9%); extra-pulmonary TB (EPTB) was lowest among TB only (16.2%). Among 338 children <15 years, EPTB and smear-positive PTB were more common among TB-only patients. Time trends showed significant increases in the proportion of adults with smear-positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co-infected patients still delay ART initiation. CONCLUSIONS: HIV ascertainment and ART uptake among co-infected patients are successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow-up care. Improved TB diagnostics and screening efforts, especially for paediatric patients, may help improve quality care for co-infected patients. These results may aid efforts to prioritise TB and HIV prevention, education and treatment campaigns for specific populations.

The relative merits of the tetO2 and tetO7 promoter systems for the functional analysis of heterologous genes in yeast and a compilation of essential yeast genes with tetO2 promoter substitutions.

We have generated a collection of yeast strains, each of which has an essential yeast gene under the control of the tetracycline-responsive, tetO, promoter. Screens using first-generation promoter-swap strains uncovered the non-specific responsiveness of the tetO7 promoter to a known human transcription factor (hIRF-1). Non-specific regulation was not observed with the tetO2 promoter. Reporter assays have been used to demonstrate this phenomenon. Subsequent efforts to generate a collection of tetracycline-regulatable strains have focused on the tetO2 promoter. These strains are available to the yeast community and can be used for functional genomics studies.

Transcriptome analysis of recombinant protein secretion by Aspergillus nidulans and the unfolded-protein response in vivo.

Filamentous fungi have a high capacity for producing large amounts of secreted proteins, a property that has been exploited for commercial production of recombinant proteins. However, the secretory pathway, which is key to the production of extracellular proteins, is rather poorly characterized in filamentous fungi compared to yeast. We report the effects of recombinant protein secretion on gene expression levels in Aspergillus nidulans by directly comparing a bovine chymosin-producing strain with its parental wild-type strain in continuous culture by using expressed sequence tag microarrays. This approach demonstrated more subtle and specific changes in gene expression than those observed when mimicking the effects of protein overproduction by using a secretion blocker. The impact of overexpressing a secreted recombinant protein more closely resembles the unfolded-protein response in vivo.

Scaling up HIV/AIDS and joint HIV-TB services in Malawi.

Two country-wide surveys were undertaken to assess progress in scaling up human immunodeficiency virus/ acquired immune-deficiency syndrome (HIV/AIDS) and HIV-tuberculosis (TB) services in the public health sector in Malawi between 2002 and 2003. In 2003, 118 sites were performing counselling and HIV testing compared with 70 in 2002. There were 215 269 HIV tests carried out in 2003 compared with 149 540 in 2002, the largest increases being in pregnant women (from 5059 to 26791), patients with TB (from 2130 to 3983) and patients/clients attending health facilities (from 35 407 to 79 584). In 2003, 3703 patients with AIDS were started on antiretroviral therapy compared with 1220 patients in 2002.

Combining transcriptome data with genomic and cDNA sequence alignments to make confident functional assignments for Aspergillus nidulans genes.

Whole genome sequencing of several filamentous ascomycetes is complete or in progress; these species, such as Aspergillus nidulans, are relatives of Saccharomyces cerevisiae. However, their genomes are much larger and their gene structure more complex, with genes often containing multiple introns. Automated annotation programs can quickly identify open reading frames for hypothetical genes, many of which will be conserved across large evolutionary distances, but further information is required to confirm functional assignments. We describe a comparative and functional genomics approach using sequence alignments and gene expression data to predict the function of Aspergillus nidulans genes. By highlighting examples of discrepancies between the automated genome annotation and cDNA or EST sequencing, we demonstrate that the greater complexity of gene structure in filamentous fungi demands independent data on gene expression and the gene sequence be used to make confident functional assignments.

Counselling, HIV testing and adjunctive cotrimoxazole for TB patients in Malawi: from research to routine implementation.

SETTING: Fifteen hospitals in Malawi that offer voluntary counselling and testing (VCT) for the human immunodeficiency virus (HIV) for tuberculosis (TB) patients and cotrimoxazole (CTX) for patients found to be HIV-positive. OBJECTIVES: 1) To describe the process of developing a national TB-HIV plan, conducting a country-wide situational assessment, and producing national guidelines on VCT and CTX for TB patients, and 2) to assess the implementation of VCT and CTX for TB patients registered between July and September 2003. DESIGN: A descriptive study. RESULTS: The 3-year HIV-TB plan was finalised in 2002. Between January and March 2003, an assessment was carried out of HIV/AIDS and joint HIV-TB services in Malawi and a decision made to support 15 hospitals in implementing VCT and CTX for TB patients. Between April and June 2003, national guidelines on VCT and CTX were developed through a consultative process, and treatment units were prepared for implementation. Between July and September 2003, 2397 TB patients were registered, and 1404 (59%) accepted VCT; 956 (68%) were HIV-positive, of whom 927 (97%) started CTX. Deficiencies in the registration process and in patient understanding about VCT and CTX were identified. CONCLUSION: The results show that it is feasible to routinely implement VCT and CTX for TB patients.

Comparative genomic hybridization provides new insights into the molecular taxonomy of the Saccharomyces sensu stricto complex.

The science of taxonomy is constantly improving as new techniques are developed. Current practice is to construct phylogenetic trees based on the analysis of the DNA sequence of single genes, or parts of single genes. However, this approach has recently been brought into question as several tree topologies may be produced for the same clade when the sequences for various different genes are used. The availability of complete genome sequences for several organisms has seen the adoption of microarray technology to construct molecular phylogenies of bacteria, based on all of the genes. Similar techniques have been used to reveal the relationships between different strains of the yeast Saccharomyces cerevisiae. We have exploited microarray technology to construct a molecular phylogeny for the Saccharomyces sensu stricto complex of yeast species, which is based on all of the protein-encoding genes revealed by the complete genome sequence of the paradigmatic species, S. cerevisiae. We also analyze different strains of S. cerevisiae itself, as well as the putative species S. boulardii. We show that in addition to the phylogeny produced, we can identify and analyze individual ORF traits and interpret the results to give a detailed explanation of evolutionary events underlying the phylogeny.

Use of expressed sequence tag analysis and cDNA microarrays of the filamentous fungus Aspergillus nidulans.

The use of microarrays in the analysis of gene expression is becoming widespread for many organisms, including yeast. However, although the genomes of a number of filamentous fungi have been fully or partially sequenced, microarray analysis is still in its infancy in these organisms. Here, we describe the construction and validation of microarrays for the fungus Aspergillus nidulans using PCR products from a 4092 EST conidial germination library. An experiment was designed to validate these arrays by monitoring the expression profiles of known genes following the addition of 1% (w/v) glucose to wild-type A. nidulans cultures grown to mid-exponential phase in Vogel's minimal medium with ethanol as the sole carbon source. The profiles of genes showing statistically significant differential expression following the glucose up-shift are presented and an assessment of the quality and reproducibility of the A. nidulans arrays discussed.