Since establishment of Zimbabwe''s National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored.
Objective
To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART.
Methods
A retrospective review of abstracted patient records of adults ≥15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition.
Results
Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1–1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1–2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4–2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1–11.2).
Conclusions
Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention. 相似文献
Information obtained from the Internet often influences the treatment choices of patients with insomnia. This study explored patterns of online information seeking and utilization among patients with insomnia. A total of 1013 participants took part in an online survey about sleep health information between July 2012 and March 2013. Participants also completed the Insomnia Severity Index and the Dysfunctional Beliefs and Attitudes about Sleep Scale. The results showed that those seeking insomnia-related information resources frequently searched online, and the information found appeared to influence important health behaviors such as treatment decisions, taking medication and whether to seek professional care. Information of interest revolved around insomnia treatment options and symptomology. While no predictors for Internet use were identified, the Internet does represent an important health-care portal for insomnia patients and warrants further investigation as targeted e-health interventions become more prominent in the routine management of insomnia.
F1FO ATP synthases catalyze the synthesis of ATP from ADP and inorganic phosphate driven by ion motive forces across the membrane. A number of ATP synthases have been characterized to date. The one from the hyperthermophilic bacterium Aquifex aeolicus presents unique features, i.e. a putative heterodimeric stalk. To complement previous work on the native form of this enzyme, we produced it heterologously in Escherichia coli.
Methods
We designed an artificial operon combining the nine genes of A. aeolicus ATP synthase, which are split into four clusters in the A. aeolicus genome. We expressed the genes and purified the enzyme complex by affinity and size-exclusion chromatography. We characterized the complex by native gel electrophoresis, Western blot, and mass spectrometry. We studied its activity by enzymatic assays and we visualized its structure by single-particle electron microscopy.
Results
We show that the heterologously produced complex has the same enzymatic activity and the same structure as the native ATP synthase complex extracted from A. aeolicus cells. We used our expression system to confirm that A. aeolicus ATP synthase possesses a heterodimeric peripheral stalk unique among non-photosynthetic bacterial F1FO ATP synthases.
Conclusions
Our system now allows performing previously impossible structural and functional studies on A. aeolicus F1FO ATP synthase.
General significance
More broadly, our work provides a valuable platform to characterize many other membrane protein complexes with complicated stoichiometry, i.e. other respiratory complexes, the nuclear pore complex, or transporter systems. 相似文献
Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone.
Methods and Findings
In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5–14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms.IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19–0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03–1.08).
Conclusions
This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.
Guanylate cyclase (GC) catalyzes the formation of cGMP and it is only recently that such enzymes have been characterized in plants. One family of plant GCs contains the GC catalytic center encapsulated within the intracellular kinase domain of leucine rich repeat receptor like kinases such as the phytosulfokine and brassinosteroid receptors. In vitro studies show that both the kinase and GC domain have catalytic activity indicating that these kinase-GCs are examples of moonlighting proteins with dual catalytic function. The natural ligands for both receptors increase intracellular cGMP levels in isolated mesophyll protoplast assays suggesting that the GC activity is functionally relevant. cGMP production may have an autoregulatory role on receptor kinase activity and/or contribute to downstream cell expansion responses. We postulate that the receptors are members of a novel class of receptor kinases that contain functional moonlighting GC domains essential for complex signaling roles. 相似文献
Copper-deficient rat embryos are characterized by brain and heart anomalies, low superoxide dismutase activity, and high superoxide anion concentrations. One consequence of increased superoxide anions can be the formation of peroxynitrite, a strong biological oxidant. To investigate developmentally important features of copper deficiency, GD 8.5 mouse embryos from copper-adequate and copper-deficient dams were cultured in media that were adequate or deficient in copper. After 48 h, copper-deficient embryos exhibited brain and heart anomalies, and a high incidence of yolk sac vasculature abnormalities compared to controls. Immunohistochemistry of 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine for lipid and DNA damage, respectively, was similar between groups. In contrast, 3-nitrotyrosine, taken as a measure of protein nitration, was markedly higher in the neuroepithelium of the anterior neural tube of copper-deficient embryos than in controls. Repletion of copper-deficient media with copper, or supplementation with copper-zinc superoxide dismutase, Tiron, or glutathione peroxidase did not ameliorate the abnormal development, but did decrease 3-nitrotyrosine in neuroepithelium of copper-deficient embryos. These data support the concept that while copper deficiency compromises oxidant defense and increases protein nitration, additional mechanisms, e.g., altered nitric oxide metabolism may contribute to copper-deficiency-induced teratogenesis. 相似文献
Abstract Observations of the large earth bumblebee, Bombus terrestris (L.), in native vegetation were collated to determine the extent to which this exotic species has invaded Tasmanian native vegetation during the first 9 years after its introduction. The range of B. terrestris now encompasses all of Tasmania's major vegetation types, altitudes from sea level to 1260m a.s.L, and the entire breadth of annual precipitation in the state from more than 3200 mm to less than 600 mm. Observations of workers carrying pollen, together with the presence of large numbers of bumblebees at many localities across this range indicate that colonies are frequently established in native vegetation. Evidence that colonies are often successful was obtained from repeated observations of the species during more than 1 year at particular sites. Unequivocal evidence of colonies was obtained from six National Parks, including four of the five in the Tasmanian Wilderness World Heritage Area (WHA). Indeed, the species has been present in the WHA for at least as long as it has in the city of Hobart, where it was first recorded. In southwestern Tasmania, evidence of colonies was obtained up to 40km from gardens, 61 km from small towns and 93 km from large towns. Hence, contrary to previous suggestions, the species is established in the most remote parts of Tasmania and is not dependent on introduced garden plants. Given their strong record of invasion, it is likely that B. terrestris will form feral populations on the mainland of Australia and in many other parts of the world if introduced. Because of their likely negative impacts on native animals and plants, and potential to enhance seed production in weeds, the spread of bumblebees should be avoided. 相似文献
Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). The 2,6-difluorophenyl substitution was critical for potent inhibitory activity. A solid state structure of 21j, a close di-fluoro analogue, bound to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone. 相似文献