1,721,155 research outputs found
Access barriers to antiretroviral therapy (ART) in Zimbabwe: a case study of Chivhu Hospital
No full textIncludes abstract.Includes bibliographical references.Access to healthcare is one of the basic social goods which ensures that individuals lead healthy and long lives. There is an increased need towards ensuring access to health care for all, which has led to the question of how access is defined. Access in this study is defined as the degree of fit between the health care system and patients. It involves an interaction between the system and patients in a way which removes access barriers to care. A comprehensive framework was used to measure access in this study. The framework allows for a systematic approach to the concept of access and measures access in three dimensions namely affordability, availability and acceptability. Using this framework, the study looked into the factors affecting access to antiretroviral therapy (ART) by patients at Chivhu Hospital in Zimbabwe. Chivhu was chosen because it has a mixed population of urban and rural patients which represents the typical Zimbabwean population. A cross sectional study design was adopted for this study
Friedreich's ataxia protein: Phylogenetic evidence for mitochondrial dysfunction
No full textFriedreich's ataxia is the most common inherited spinocerebellar ataxia. A decade of linkage and physical mapping studies have culminated in the identification of the Friedreich's ataxia gene. The presence of homologues in purple bacterial genomes, but not in other bacteria, allows us to infer a mitochondrial location for frataxin (Friedreich's ataxia protein) on the basis of bacterial phylogeny. Frataxin possesses a non-globular N-terminus domain providing a candidate mitochondrial targeting peptide. Clues to the function of frataxin are provided by the mitochondrial location, a clinically similar ataxia with vitamin E deficiency, and certain neuropathies with mitochondrial DNA instability caused by mutations in nuclear genes
Prevalence and incidence of renal dysfunction in patients initiating Antiretroviral Therapy at a Primary Health Care Centre in Gugulethu, Cape Town : a cohort study
No full textIncludes bibliographical references.Tenofovir disoproxil fumarate (TDF) is used worldwide for the treatment of HIV-1 infection. Tenofovir has been found to be associated with declines in renal function and chronic kidney disease in HIV-infected patients. There are limited data on how soon after antiretroviral therapy (ART) initiation any loss of renal function can be detected. We studied a cohort of HIV-infected adults initiating TDF-containing ART regimens at the Hannan Crusaid Antiretroviral Treatment Centre in Gugulethu. The centre provides ART to the residents of the Gugulethu and Nyanga districts situated on the outskirts of Cape Town. We described the prevalence and incidence of renal dysfunction in this cohort, the patterns of change in their renal function in the first 12 months on therapy and factors associated with renal dysfunction. We also examined the diagnostic value of early serum creatinine tests in identifying incident renal dysfunction after 12 months
Substitutions to initial anteretroviral therapy due to toxicity or contraindication among children in South Africa
No full textIncludes bibliographical references.According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) South Africa 2010 Country Progress report, 81% of South African children in need of antiretroviral therapy (ART) were receiving treatment which is a 20% increment in treatment access from 2008 to 2009. With increase in access to treatment, understanding drug tolerability, safety and durability is important especially among children whose drug options are limited due to few drugs being available in suitable formulations and the need for refrigeration of some drugs. While there are many paediatric studies on ART durability in the developed world, data from the developing world are limited. There is therefore a need to understand the drug-specific probability of and reasons for drug stops or changes among children initiated on ART in South Africa. This knowledge could help in optimisation of use of firstline ART in order to maximise time on first-line therapy and thereby maintain simplicity of programs (program-level benefit) and save alternative drugs for situations of toxicity and virological failure (individual benefit)
A qualitative study assessing the general health problems of street-based female sex workers in Cape Town
No full textIncludes bibliographical references.Generally, sex workers are a socially marginalized group with poor physical health. Within the hierarchy of sex workers, street-based sex workers are at the bottom. Street-based sex workers face different kinds of work experiences and exposure, with varying degrees of health problems. Their health problems are more severe and worse than the other classes of sex workers. Street-based sex workers are subjected to considerable risks of physical abuse, beatings and rape. These impact greatly on their health. This study explored the general health problems of street-based female sex workers. The study was carried out in Cape Town among street-based female sex workers aged 18 years and above. It was cross-sectional, conducted over a period of six months using fifteen (15) in-depth interviews and four (4) focus group discussions. The respondents were non-randomly recruited through the Embrace Dignity Project, whose activities involved sex workers. The study discovered that condom use was inconsistent as a result of financial incentives, condom breakage, violence, rape and non-payment from clients when insisting on condom use. But some respondents were not using condoms at all. The majority of respondents reported stigmatization and discrimination by community members and the police. Most of the respondents do not go for routine and other medical checks. Some respondents were not satisfied with health care provision due to discrimination by providers and long waiting times. Notwithstanding, respondents reported a long list of health problems including: flu, cough, HIV/AIDS, TB, headache, vaginal discharge, itchy vagina, sleeplessness, high blood pressure, fever, heart problems, diarrhoea, sweating at night, arthritis, diabetes, alcoholic problems, bad breath, sore throat, and mouth rash. Physical and psychological problems were also mentioned. Most respondents rated their health status as bad. The illegality of sex work in South Africa pushes sex workers to practice the trade in obscure places making them very vulnerable. Street-based female sex workers have numerous general health problems, but with limited access to health services. The law does not also help the course of street-based female sex workers. There is an urgent need to partially criminalize sex work. Reorientation and education of sex workers and providers is also required. All these will help promote the welfare of sex workers
Friedreich's ataxia protein: Phylogenetic evidence for mitochondrial dysfunction
No full textFriedreich's ataxia is the most common inherited spinocerebellar ataxia. A decade of linkage and physical mapping studies have culminated in the identification of the Friedreich's ataxia gene. The presence of homologues in purple bacterial genomes, but not in other bacteria, allows us to infer a mitochondrial location for frataxin (Friedreich's ataxia protein) on the basis of bacterial phylogeny. Frataxin possesses a non-globular N-terminus domain providing a candidate mitochondrial targeting peptide. Clues to the function of frataxin are provided by the mitochondrial location, a clinically similar ataxia with vitamin E deficiency, and certain neuropathies with mitochondrial DNA instability caused by mutations in nuclear genes
Automatically extracting functionally equivalent proteins from SwissProt
Full text linkBackground: There is a frequent need to obtain sets of functionally equivalent homologous proteins (FEPs) from different species. While it is usually the case that orthology implies functional equivalence, this is not always true; therefore datasets of orthologous proteins are not appropriate. The information relevant to extracting FEPs is contained in databanks such as UniProtKB/SwissProt and a manual analysis of these data allow FEPs to be extracted on a one-off basis. However there has been no resource allowing the easy, automatic extraction of groups of FEPs - for example, all instances of protein C.We have developed FOSTA, an automatically generated database of FEPs annotated as having the same function in UniProtKB/SwissProt which can be used for large-scale analysis. The method builds a candidate list of homologues and filters out functionally diverged proteins on the basis of functional annotations using a simple text mining approach.Results: Large scale evaluation of our FEP extraction method is difficult as there is no gold-standard dataset against which the method can be benchmarked. However, a manual analysis of five protein families confirmed a high level of performance. A more extensive comparison with two manually verified functional equivalence datasets also demonstrated very good performance.Conclusion: In summary, FOSTA provides an automated analysis of annotations in UniProtKB/SwissProt to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/SwissProt functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/SwissProt annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/SwissProt format, which would facilitate text-mining of UniProtKB/ SwissProt
Identification of an ortholog of the eukaryotic RNA polymerase III subunit RPC34 in Crenarchaeota and Thaumarchaeota suggests specialization of RNA polymerases for coding and non-coding RNAs in Archaea.
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80405.pdf (Publisher’s version ) (Open Access)One of the hallmarks of eukaryotic information processing is the co-existence of 3 distinct, multi-subunit RNA polymerase complexes that are dedicated to the transcription of specific classes of coding or non-coding RNAs. Archaea encode only one RNA polymerase that resembles the eukaryotic RNA polymerase II with respect to the subunit composition. Here we identify archaeal orthologs of the eukaryotic RNA polymerase III subunit RPC34. Genome context analysis supports a function of this archaeal protein in the transcription of non-coding RNAs. These findings suggest that functional separation of RNA polymerases for protein-coding genes and non-coding RNAs might predate the origin of the Eukaryotes
Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements
No full textAbstract Background In eukaryotes, RNA interference (RNAi) is a major mechanism of defense against viruses and transposable elements as well of regulating translation of endogenous mRNAs. The RNAi systems recognize the target RNA molecules via small guide RNAs that are completely or partially complementary to a region of the target. Key components of the RNAi systems are proteins of the Argonaute-PIWI family some of which function as slicers, the nucleases that cleave the target RNA that is base-paired to a guide RNA. Numerous prokaryotes possess the CRISPR-associated system (CASS) of defense against phages and plasmids that is, in part, mechanistically analogous but not homologous to eukaryotic RNAi systems. Many prokaryotes also encode homologs of Argonaute-PIWI proteins but their functions remain unknown. Results We present a detailed analysis of Argonaute-PIWI protein sequences and the genomic neighborhoods of the respective genes in prokaryotes. Whereas eukaryotic Ago/PIWI proteins always contain PAZ (oligonucleotide binding) and PIWI (active or inactivated nuclease) domains, the prokaryotic Argonaute homologs (pAgos) fall into two major groups in which the PAZ domain is either present or absent. The monophyly of each group is supported by a phylogenetic analysis of the conserved PIWI-domains. Almost all pAgos that lack a PAZ domain appear to be inactivated, and the respective genes are associated with a variety of predicted nucleases in putative operons. An additional, uncharacterized domain that is fused to various nucleases appears to be a unique signature of operons encoding the short (lacking PAZ) pAgo form. By contrast, almost all PAZ-domain containing pAgos are predicted to be active nucleases. Some proteins of this group (e.g., that from Aquifex aeolicus) have been experimentally shown to possess nuclease activity, and are not typically associated with genes for other (putative) nucleases. Given these observations, the apparent extensive horizontal transfer of pAgo genes, and their common, statistically significant over-representation in genomic neighborhoods enriched in genes encoding proteins involved in the defense against phages and/or plasmids, we hypothesize that pAgos are key components of a novel class of defense systems. The PAZ-domain containing pAgos are predicted to directly destroy virus or plasmid nucleic acids via their nuclease activity, whereas the apparently inactivated, PAZ-lacking pAgos could be structural subunits of protein complexes that contain, as active moieties, the putative nucleases that we predict to be co-expressed with these pAgos. All these nucleases are predicted to be DNA endonucleases, so it seems most probable that the putative novel phage/plasmid-defense system targets phage DNA rather than mRNAs. Given that in eukaryotic RNAi systems, the PAZ domain binds a guide RNA and positions it on the complementary region of the target, we further speculate that pAgos function on a similar principle (the guide being either DNA or RNA), and that the uncharacterized domain found in putative operons with the short forms of pAgos is a functional substitute for the PAZ domain. Conclusion The hypothesis that pAgos are key components of a novel prokaryotic immune system that employs guide RNA or DNA molecules to degrade nucleic acids of invading mobile elements implies a functional analogy with the prokaryotic CASS and a direct evolutionary connection with eukaryotic RNAi. The predictions of the hypothesis including both the activities of pAgos and those of the associated endonucleases are readily amenable to experimental tests. Reviewers This article was reviewed by Daniel Haft, Martijn Huynen, and Chris Ponting.</p
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