Comparative study of the epidemiology and aetiology of bloodstream infections in hospitalized adult patients in Tanzania, Malawi, and Thailand: the role of human immunodeficiency virus type 1 (HIV-1) infection.

Before 1995, the frequencies of mycobacterial and fungal bloodstream infections (BSI) in human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa and Southeast Asia were unknown. Therefore, a prospective survey of febrile (oral temperature >38 C or axillary temperature >37.5 C) adult patients who presented to sentinel teaching hospitals in Tanzania (1995), Thailand (1997), and Malawi (1997 dry season and 1998 wet season) was conducted. The objectives were to (i) determine the aetiology, prevalence, and clinical correlates of BSL and (ii) characterise the role played by HIV infection. After informed consent, a detailed history was recorded for each patient followed by physical examination. Next, blood was cultured for bacteria, mycobacteria, and fungi, and tested for HIV and malaria. Data were collected for 517 patients in Tanzania, 246 in Thailand, and 471 in Malawi. Respective BSI, HIV, and malaria parasitaemia rates were: Tanzania: 28%, 55%, 9.5% Thailand: 48%, 74%, 0 Malawi dry season: 30%, 74%, 4% Malawi wet season: 28%, 73%, 31%. The most frequently isolated bloodstream pathogens were Mycobacterium tuberculosis (MTB) and non-typhi Salmonella species (NTS) in Tanzania MTB and Cryptococcus neoformans in Thailand MTB and Streptococcus pneumoniae during Malawi dry season and MTB and NTS during Malawi wet season. In each country, HIV-infected patients were significantly more likely to acquire BSI all patients with mycobacteraemia were HIV-infected. The Malawi findings are the first description of seasonal variation in the occurrence of S. pneumoniae and NTS bacteraemias. Logistic regression models yielded predictors of BSI in Thailand (HIV infection, chronic diarrhoea, lymphadenopathy, or splenomegaly) and Malawi (HIV infection, chronic fever, oral candidiasis, or acute diarrhoea). In populations with high prevalence rates of HIV infection, MTB has become the foremost cause of documented BSI. Similar season- and country-specific surveys, performed periodically in HIV-endemic regions will provide data on the aetiology and predictors of BSI, and facilitate empirical therapy of febrile illnesses

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Excitatory and inhibitory responses in the brain to experimental pain: A systematic review of MR spectroscopy studies

Background The role of the brain in processing pain has been extensively investigated using various functional imaging techniques coupled with well controlled noxious stimuli. Studies applying experimental pain have also used proton magnetic resonance spectroscopy (1H-MRS). The advantage of MRS compared to other techniques is the capacity to non-invasively examine metabolites involved in neurotransmission of pain, including glutamate, γ-aminobutyric acid (GABA), glutamate + glutamine (Glx), and glutamine. Objective To systematically review MRS studies used in the context of studying experimental pain in healthy human participants. Data sources PubMed, Ovid Medline, and Embase databases were searched using pre-specified search terms. Eligibility criteria Studies investigating glutamate, GABA, Glx and/or glutamine in relation to experimental pain (e.g., heat) in healthy participants via MRS. Appraisal criteria Each study was evaluated with a modified quality criterion (used in previous imaging systematic reviews) as well as a risk of bias assessment. Results From 5275 studies, 14 met the selection criteria. Studies fell into two general categories, those examining changes in metabolites triggered by noxious stimulation or examining the relationship between sensitivity to pain and resting metabolite levels. In five (out of ten) studies, glutamate, Glx and/or glutamine increased significantly in response to experimental pain (compared to baseline) in three different brain areas. To date, there is no evidence to suggest Glx, glutamate or glutamine levels decrease, suggesting an overall effect in favour of increased excitation to pain. In addition to no changes, both increases and decreases were reported for levels of GABA+ (=GABA + macromolecules). A positive correlation between pain sensitivity and resting glutamate and Glx levels were reported across three studies (out of three). Further research is needed to examine the relationship of GABA+ and pain sensitivity. Limitations A major limitation of our review was a limited number of studies that used MRS to examine experimental pain. In light of this and major differences in study design, we did not attempt to aggregate results in a meta-analysis. As for the studies we reviewed, there was a limited number of brain areas were examined by studies included in our review. Moreover, the majority of studies included lacked an adequate control condition (i.e., non-noxious stimulation) or blinding, which represent a major source of potential bias. Conclusion MRS represents a promising tool to examine the brain in pain, functionally, and at rest with support for increased glutamate, glutamine and Glx levels in relation to pain. Implications Resting and functional MRS should be viewed as complementary to existing neuroimaging techniques, and serve to investigate the brain in pain.ISSN:1053-8119ISSN:1095-957

Characterization of Cryptococcus neoformans isolated from urban environmental sources in Goiânia, Goiás State, Brazil Caracterização de Cryptococcus neoformans isolados de fontes ambientais urbanas na cidade de Goiânia, estado de Goiás, Brasil

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis as the most frequent clinical presentation in immunocompromised patients, mainly in people infected by HIV. This fungus is an environmental encapsulated yeast, commonly found in soil enriched with avian droppings and plant material. A total of 290 samples of pigeon and the other avian droppings, soil, ornamental trees and vegetable material associated with Eucalyptus trees were collected to study environmental sources of Cryptococcus species in Goiânia, Goiás State. The determination of varieties, serotypes and the susceptibility in vitro to fluconazole, itraconazole and amphotericin B of C. neoformans isolates were performed. C. neoformans var. grubii (serotype A) was found in 20.3% (36/177) of pigeon dropping samples and in 14.3% (5/35) of samples of Eucalyptus. None of the environmental isolates of C. neoformans showed in vitro resistance to three antifungal agents. The knowledge of major route for human cryptococcal infection (inhalation of infectious particles from saprophytic sources) and a total of 60 C. neoformans isolates obtained from AIDS patients with cryptococcal meningitis between October 2001 and April 2002 justify the study of the habitats of these yeasts as probable sources of cryptococcosis in this city.<br>Cryptococcus neoformans é um fungo patogênico oportunista que causa meningoencefalite como a apresentação clínica mais importante em pacientes imunocomprometidos, principalmente, em pessoas infectadas pelo HIV. O agente é uma levedura encapsulada, comumente encontrada em solo enriquecido com excretas de aves e em resíduos de plantas. O total de 290 amostras de excretas de pombos e outras aves, de árvores ornamentais e materiais vegetais de Eucalyptus foram coletadas para estudar possíveis fontes ambientais de Cryptococcus spp, na cidade de Goiânia, Goiás. A determinação das variedades, sorotipos e suscetibilidade in vitro frente a fluconazol, itraconazol e anfotericina B dos isolados de C. neoformans foram realizadas. C. neoformans var. grubii (sorotipo A) foi a única isolada, ocorrendo em 36 (20.3%) das 177 amostras fecais de pombos e em 5 (14.3%) das 35 amostras de Eucalyptus. Nenhum dos isolados ambientais de C. neoformans mostrou resistência in vitro aos três antifúngicos avaliados. O conhecimento da principal via para infecção criptocócica humana, isto é inalação de partículas infecciosas de fontes saprofíticas e a ocorrência de 60 casos de criptococose em pacientes com AIDS, em Goiânia, entre outubro de 2001 e abril de 2002, justificam o estudo de habitats do agente como prováveis fontes de criptococose nesta cidade