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- Do Duy, Cuong
(author)
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Antiretroviral therapy among HIV-infected persons in northeastern Vietnam : impact of peer support on virologic failure and mortality in a cluster randomized controlled trial
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Background: Wide access to antiretroviral therapy (ART) has substantially improved the prognosis of patients living with HIV/AIDS (PLHIV). However, in resource-limited countries, sustaining ART programs to prevent drug resistance and treatment failure and to maximize the existing human resources is still challenging. In 2010, Vietnam had 254,000 PLHIV and 52,000 people accessed ART. Viral load (VL) testing has not been routinely performed for monitoring treatment failures due to the high cost and the necessity of advanced laboratory equipment. Peer support has been proven to improve quality of life, reduce stigma and to improve adherence to treatment. However, there is little known about the impact of peer adherence support on ART outcomes. The overall aim of this study was to assess the impact of peer support on virologic and immunologic treatment outcomes and mortality among HIV-infected patients by monitoring routinely a simple- and low- cost VL in a cluster randomized controlled trial in Quang Ninh, Vietnam. The primary outcome was virologic failure rate between intervention and control group. Methods: A total of 640 HIV-infected patients recruited from 59 clusters (communes) were randomized into either intervention or control group. Both groups received first-line ART regimens according to the National Treatment Guidelines and were followed up for 24 months. Viral load (ExaVirTM Load) and CD4 counts were measured every 6 months. Patients in the intervention group received enhanced adherence support by 14 peer supporters. Survival analyses with Kaplan-Meier curve and Cox proportional hazard model were used to identify survival rate and risk factors for deaths. Causes of death were assessed through medical records and verbal autopsy questionnaire. Cluster longitudinal and survival analyses with intention-to-treat were used to study time to virologic failure and CD4 trends and to compare between the intervention and control groups. At baseline, we monitored the spread of infection and prevalence of transmitted drug resistance mutations (TDRMs) by analyzing 63 1000bp pol-gene sequences generated from 63 treatment-naïve HIV-1 CRF01_AE patients. Through the cohort, we determined the feasibility, sensitivity and specificity of ExaVir Load in 605 HIV treatment-naïve patients and compared the correlation and agreement of 60 samples between Roche Cobas TaqMan® VL and ExaVir Load. Results: After 24 months of follow-up, 78% of the patients remained in the study, mortality rate was 11% (6.4/100 person-years), cumulative virologic failure rate (VL >1,000 copies/ml) was 7.2% and the median CD4 increase was 286 cells/μl. There were no significant differences between intervention and control groups in virologic failure rates (VL >1,000 copies/ml) [6.9% vs 7.5%, respectively, RR 0.93; (95%CI: 0.13-6.54), p=0.94], in the time to virologic failure [HR 1.0; (95%CI 0.5-1.7), p=0.94], in CD4 trends [Coeff. (95%CI: 0.2(-0.6;-0.9), p=0.69] and in mortality (Log-rank p=0.79). Risk factors for virologic failure were ART-non-naïve status [aHR 6.9;(95%CI 3.2-14.6); p<0.01]; baseline VL >100,000 copies/ml [aHR 2.3;(95%CI 1.2-4.3); p<0.05] and incomplete adherence (self-reported missing more than one dose during 24 months) [aHR 3.1;(95%CI 1.1-8.9); p<0.05]. From the cohort of 605 ART-treatment naïve patients, we found the virologic suppression rate (VL <200 copies/ml) after 24 months was 64% (intention-to-treat) and 94% among patients assessed with VL (on-treatment). Tuberculosis (TB) was the most common cause of death (40%). Risk factors for AIDS-related death were age >35 years, clinical stage 3 or 4, body mass index (BMI) <18 kg/m2, CD4 count <100/μl, haemoglobin level <100 g/l, and plasma VL >100,000 copies/ml. The TDRMs including Y181C, L210W, L74I and V75M were found in 4/63 patients (6.3%). Phylogenetic analysis for calculating the time of the most recent common ancestor (tMRCA) was shown in two distinct groups: the small group (n=3) had tMRCA in year 1997.5 and the larger group had tMRCA in 1989.8. The ExaVir Load and the Roche Cobas TaqMan showed a strong correlation (r2 =0.97), high agreement (log difference =0.34; 95% CI -0.35;1.03), high sensitivity (98%) and high specificity (100%). Conclusions: Enhanced adherence intervention by peer support had no impact on virologic failure and CD4 trends as well as on mortality after 24 months of ART initiation. Early deaths occurred among patients presented late to ART and majority of deaths were attributable to TB. Baseline VL >100,000 copies/ml was a predictive factor for virologic failure, CD4 changes and mortality. Transmitted drug resistance rate should be monitored regularly and prospectively in Vietnam. Using ExaVir Load is feasible to monitor efficacy of ART programs in resource-limited settings.
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| 2. |
- Willander, M., et al.
(author)
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Potentiometric Biosensors Based on Metal Oxide Nanostructures
- 2017
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In: Reference Module in Chemistry, Molecular Sciences and Chemical Engineering. - : Elsevier. - 9780124095472
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Book chapter (peer-reviewed)abstract
- Numerous potentiometric biosensors are fabricated via biocatalytic and bioaffinity-based biosensing mechanisms. Only few of them are useful and applicable to the biomedical application and analysis. The most of those sensing schemes are mainly related to the protein metabolism especially urea and creatinine. The emergence of nanoscience and nanotechnology in the biomedical applications has provided the solid platform for the development of sensitive and selective potentiometric biosensors as new generation analytical devices. Therefore, among the nanomaterials, metal oxides are of prime importance for the potentiometric analytical devices due to generation of strong potential signals and excellent biocompatibility with the proteins such as enzymes, antibodies, DNA, and biological cells. This book chapter is dedicated to the recent advancement in the development of potentiometric biosensors such as urea, uric acid, glucose, and cholesterol due to nanoscience from fundamental to advanced configuration approach of devices.
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- Jin, Shao-Bo, et al.
(author)
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CRM1 and Ran are present but a NES-CRM1-RanGTP complex is not required in Balbiani ring mRNP particles from the gene to the cytoplasm
- 2004
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In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 117, s. 1553-1566
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Journal article (peer-reviewed)abstract
- Messenger RNA is formed from precursors known as pre-mRNA. Theseprecursors associate with proteins to form pre-mRNA-protein(pre-mRNP) complexes. Processing machines cap, splice and polyadenylatethe pre-mRNP and in this way build the mRNP. These processingmachines also affect the export of the mRNP complexes from thenucleus to the cytoplasm. Export to the cytoplasm takes placethrough a structure in the nuclear membrane called the nuclearpore complex (NPC). Export involves adapter proteins in themRNP and receptor proteins that bind to the adapter proteinsand to components of the NPC. We show that the export receptorchromosomal region maintenance protein 1 (CRM1), belonging toa family of proteins known as importin-ß-like proteins,binds to gene-specific Balbiani ring (BR) pre-mRNP while transcriptiontakes place. We also show that the GTPase known as Ran bindsto BR pre-mRNP, and that it binds mainly in the interchromatin.However, we also show using leptomycin B treatment that a NES-CRM1-RanGTPcomplex is not essential for export, even though both CRM1 andRan accompany the BR mRNP through the NPC. Our results thereforesuggest that several export receptors associate with BR mRNPand that these receptors have redundant functions in the nuclearexport of BR mRNP.
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- Lagesson, Annelie, 1986-
(author)
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Fish on drugs : behaviour modifying contaminants in aquatic ecosystems
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Contamination of surface waters is a worldwide problem. One group of emerging contaminants that reach aquatic ecosystems via sewage treatment plant effluents and agricultural run-offs is pharmaceuticals. Impacts of pharmaceuticals on the behaviour of aquatic organisms can have important ecological and evolutionary consequences because behaviour is directly linked to fitness. The aim of my doctoral thesis was to increase our understanding of the fate and effects of behaviour modifying drugs in aquatic ecosystems.While studying an aquatic ecosystem spiked with pharmaceuticals, I found that the benthic species at the bottom of the food chain were the main receivers (highest bioaccumulation factor; BAF) while fish at the top of the food web had the lowest uptake of the studied drugs. Interestingly, the BAF of the anxiolytic pharmaceutical oxazepam, increased in fish (perch; Perca fluviatilis) over the study period, suggesting that this drug can be transferred between trophic levels in food webs. To assess whether oxazepam could affect growth and survival in perch, I exposed perch populations to oxazepam for 2-months in a replicated pond experiment. In this study, I tested the hypothesis that oxazepam exposed perch would grow faster but also suffer from increased predation. Oxazepam has been shown previously to induce ‘anti-anxiety’ behaviours that improve foraging but may also make individuals more exposed to predators. In contrast, I found no statistically significant increase in growth and mortality in the exposed perch. However, the study revealed that the natural predator of perch (pike; Esox lucius) became less effective at catching prey when exposed to oxazepam. This exposure effect on predation efficiency likely contributed to the absence of predation effects in the exposed ponds. In two following laboratory studies I investigated effects of behaviour modifying drugs (oxazepam and a growth hormone, 17β-trenbolone) in combination with additional stressors (temperature and predator cues). Drug and temperature interactions were found for 17β-trenbolone, where water temperature interacted with treatment to induce changes in predator escape behaviour, boldness, and exploration in mosquitofish (Gambusia holbrooki). However, in the other study, we found that oxazepam, temperature, and predator cue all affected perch ‘anti-anxiety’ behaviours, but independently.I conclude that pharmaceuticals can alter ecologically important behaviours in fish, and that at least some, can accumulate in aquatic food webs. It seems that in situ effects of behaviour modifying drugs in aquatic ecosystems depend on both species-specific responses and abiotic interactions. As such, it is far from straightforward to predict net ecosystem effects based on experiments conducted using single species and static conditions. Future studies should assess the effects of pharmaceuticals in aquatic ecosystems under more complex conditions for us to gain a better understanding of what consequences behaviour modifying drugs have in the environment.
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