Clinical significance of HIV-1 coreceptor usage

The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis

Data Availability: The full datasets can be obtained from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) as GSE94438 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94438) and GSE89403 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89403). These details are also provided in the Methods. Additional data on PET-CT scores accompany the revised document as S1 Table (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278295#pone.0278295.s001).The authors acknowledge the Centre for High Performance Computing (CHPC), South Africa, for providing computational resources to this research project.Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13–18 months, 742 at 7–12 months and 5,131 detected 1–6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1–6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.SM, EM, GT and GW were supported by the South African Tuberculosis Bioinformatics Initiative (SATBBI), a Strategic Health Innovation Partnership grant from the South African Medical Research Council (https://www.samrc.ac.za/) and South African Department of Science and Innovation (https://www.dst.gov.za/); no grant number. STM received funding from the EDCTP2 program (Grant Number CDF1576) supported by the European Union (http://www.edctp.org/projects-2/#). GW received funding from the South African National Research Foundation (SARChI TB Biomarkers #86535) and the South African Medical Research Council (https://www.samrc.ac.za/). SHEK, TJS and GW received funding from the Bill and Melinda Gates Foundation (Grant Numbers OPP37772 & OPP1055806), (https://www.gatesfoundation.org/) GW received funding from the Bill and Melinda Gates Foundation (Grant Number OPP51919) (https://www.gatesfoundation.org/) through the Catalysis Foundation for Health (https://catalysisfoundation.org/) AGL is supported by the NRF-CSUR (Grant Number CSUR60502163639) and by the Centre for Tuberculosis Research from the South African Medical Research Council (https://www.samrc.ac.za/). JAS is supported by a Clinician Scientist Fellowship (Grant Number MR/R007942/1) jointly funded by the UK Medical Research Council (MRC; https://www.ukri.org/about-us/mrc/) and the UK Department for International Development [DFID; replaced by Foreign, Commonwealth & Development Office (FCDO); https://www.gov.uk/government/organisations/foreign-commonwealth-development-office] under the MRC/DFID Concordat agreement

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Ethnicity, belonging and identity among the Eastern Gurage of Ethiopia

In this paper, I will analyse a case of ethnic transformation in post-1991 Ethiopia based on an ethnographic study of the Eastern Gurage. The case represents an ethnic setting where the conventional conceptualization of ethnicity in terms of a notion of origin undermines the diversities expressed in various forms of category and boundary formations. The ethnic setting does not also fall into, but combines, the commonplace dichotomization of primordialist versus constructivist notion of ethnicity. Not only by taking Barth’s (1969) formalist anthropological conception of ethnicity as boundary formation, but also suggesting my own analytical distinction, I will attempt to account for the various forms of ethnicities particularly those based on clanship, locality, Islam and state’s categorization. In this regard, I have introduced a distinction between the concepts of identity and belonging in order to explain the different forms of social and political classifications, ideologies and power relationships that are often treated as implying a single phenomenon, i.e. identity formation