Anti-retroviral treatment outcomes among older adults in Zomba district, Malawi

Background

There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes.

Methods

A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan–Meier survival plots and Cox proportional hazards regression models.

Results

There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419) were more likely to be male (P<0.0001) and located in rural areas (P = 0.003) than those aged 25–49. Crude survival estimates among those aged 50–59 were not statistically different from those aged 25–49 (P = 0.925). However, survival among those aged 60 and older (N = 345) was worse (P = 0.019) than among those 25–59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50–59 did not differ significantly from those aged 25–49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998) but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032) for those aged 60 and older compared to those aged 25–49.

Conclusions

Treatment outcomes of those aged 50–59 are similar to those aged 25–49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services.     

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: role of insulin and C-peptide

Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.     

Impact of dry mouth conditions on oral health-related quality of life in older people

Objective: The aim of the present study was to evaluate the impact of dry mouth conditions on oral health‐related quality of life in frail old people, residents at community care centers. Further, reliability and validity of a visual analogue scale (VAS) for dry mouth symptoms were determined within the study cohort. Background: In old people functional, social and psychological impacts of oral conditions are associated with an overall sense of well being and general health. Subjective dry mouth and reduced saliva flow are common disorders in old people caused by disease and medication. Thus, dry mouth conditions may be determinants for compromised oral health‐related quality of life in old people. Method: In total, 50 old people living at service homes for the old people were asked to answer questionnaires on subjective dry mouth (VAS) and Oral Health Impact Profile (OHIP14) for oral health‐related quality of life. Saliva flow was estimated by absorbing saliva into a pre‐weighed cotton roll. Results: The final study cohort comprised 41 old people (aged 83–91 years). Significant associations were identified between both objective and subjective dry mouth and overall or specific aspects of oral health‐related quality of life. Conclusion: Dry mouth (objective and subjective) is significantly associated with oral health‐related quality of life strengthening the value of monitoring dry mouth conditions in the care of frail old people.     

Complete nucleotide sequence of polyomavirus SA12

The Polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded DNA. Polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. We report the complete nucleotide sequence of simian agent 12 (SA12), whose natural host is thought to be Papio ursinus, the chacma baboon. The 5,230-bp genome has a genetic organization typical of polyomaviruses. Sequences encoding large T antigen, small t antigen, agnoprotein, and the viral capsid proteins VP1, VP2, and VP3 are present in the expected locations. We show that, like its close relative simian virus 40 (SV40), SA12 expresses microRNAs that are encoded by the late DNA strand overlapping the 3' end of large T antigen coding sequences. Based on sequence comparisons, SA12 is most closely related to BK virus (BKV), a human polyomavirus. We have developed a real-time PCR test that distinguishes SA12 from BKV and the other closely related polyomaviruses JC virus and SV40. The close relationship between SA12 and BKV raises the possibility that these viruses circulate between human and baboon hosts.     

Ethics guidelines for research with the recently dead

The objective of the multidisciplinary expert Consensus Panel on Research with the Recently Dead (CPRRD) was to craft ethics guidelines for research with the recently dead. The CPRRD recommends that research with the recently dead: (i) receive scientific and ethical review and oversight; (ii) involve the community of potential research subjects; (iii) be coordinated with organ procurement organizations; (iv) not conflict with organ donation or required autopsy; (v) use procedures respectful of the dead; (vi) be restricted to one procedure per day; (vii) preferably be authorized by first-person consent, though both general advance research directives and surrogate consent are acceptable; (viii) protect confidentiality; (ix) not impose costs on subjects' estates or next of kin and not involve payment; (x) clearly explain ultimate disposition of the body.     

Biofluid 1H NMR-based metabonomic techniques in nutrition research - metabolic effects of dietary isoflavones in humans

A metabonomic approach to nutrition research may provide an insight into in vivo mechanisms of action following nutritional intervention. This approach was applied to investigate changes in the (1)H NMR spectral profile of urine collected from controlled dietary intervention studies conducted in premenopausal women before and following soy or miso consumption. The aim of the study was to identify the biochemical effects of a diet rich in soy isoflavones, phytochemicals which are receiving significant attention because of their potential importance to human health and wide bioactivity in vitro. By applying various chemometric techniques to the data the biochemical effects of conjugated and unconjugated isoflavones were determined. The biochemical changes observed suggest that soy isoflavone ingestion had significant effects on several metabolic pathways associated with osmolyte fluctuation and energy metabolism. These biochemical changes were more significant following ingestion of the unconjugated soy isoflavone (miso) diet suggesting that the chemical composition of the isoflavones present in soy-based foods may have an effect on their biological efficacy in vivo. This study describes a novel application for (1)H NMR analysis by determining subtle differences in biochemical profiles following dietary intervention and providing further insight into the mechanisms of action of phytochemicals in vivo.     

Multilocus and interaction-based genome scan for alcoholism risk factors in Caucasian Americans: the COGA study

In this paper, we applied the nonparametric linkage regression approach to the Caucasian genome scan data from the Collaborative Study on the Genetics of Alcoholism to search for regions of the genome that exhibit evidence for linkage to putative alcoholism-predisposing genes. The multipoint single-locus model identified four regions of the genome with LOD scores greater than one. These regions were on 7p near D7S1790 (LOD = 1.31), two regions on 7q near D7S1870 (LOD = 1.15) and D7S1799 (LOD = 1.13) and 21q near D21S1440 and D21S1446 (LOD = 1.78). Jointly modeling these loci provided stronger evidence for linkage in each of these regions (LOD = 1.58 on 7q11, LOD = 1.61 on 11q23, and LOD = 1.95 on 21q22). The evidence for linkage tended to increase among pedigrees with earlier mean age of onset at 8q23 (p = 0.0016), 14q21 (p = 0.0079), and 18p12 (p = 0.0021) and with later mean age of onset at 4q35 (p = 0.0067) and 9p22 (p = 0.0008).     

Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12

Carotid intimal medial thickness (IMT) is a heritable quantitative measure of atherosclerosis. A genomewide linkage analysis was conducted to localize a quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingham Heart Study Offspring cohort. B-mode carotid ultrasonography was used to define mean IMT of the carotid artery segments. Multipoint variance-component linkage analysis was performed. Evidence for significant linkage to internal carotid artery (ICA) IMT (two-point log odds [LOD] score 4.1, multipoint LOD score 3.4) was found 161 cM from the tip of the short arm of chromosome 12; these results were confirmed using the GENEHUNTER package (multipoint LOD score 4.3). No LOD scores >2.0 were observed for common carotid artery (CCA) IMT. Association analysis of a single-nucleotide-polymorphism variant of SCARB1 (minor allele frequency 0.13), a gene in close proximity to the region of peak linkage, revealed a protective association of the missense variant allele in exon 1 of SCARB1, with decreased ICA IMT compared with subjects homozygous for the common allele. Although the exon 1 variant contributed 2% to overall variation in ICA IMT, there was no significant change in the peak LOD score after adjustment in the linkage analyses. These data provide substantial evidence for a QTL on chromosome 12 influencing ICA IMT and for association of a rare variant of SCARB1, or a nearby locus, with ICA IMT. Because this rare SCARB1 variant does not account for our observed linkage, further investigations are warranted to identify additional candidate-gene variants on chromosome 12 predisposing to atherosclerosis phenotypes and clinical vascular disease.     

Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study

Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; -1131T>C, -3A>G, 56C>G IVS3+ 476G>A, and 1259T>C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C>G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population. SNP analyses revealed that the -1131T>C and 56C>G SNPs were significantly associated with higher plasma TG concentrations in both men and women. For RLP and lipoprotein subclasses, we observed gender-specific association for the -1131T>C and 56C>G SNPs. Female carriers of the -1131C allele had higher RLP concentrations, whereas in males, significant associations for RLPs were observed for the 56G allele. Moreover, haplotype analyses confirmed these findings and revealed that the 22122 and 11211 haplotypes exhibited different associations with HDL cholesterol concentrations. In women, the -1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03-3.34; P = 0.04), in agreement with the association of this SNP with higher RLPs.     

Proteomic analysis of recurrent joint inflammation in juvenile idiopathic arthritis

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the joint, were identified. Synovial fluids from children with single-event knee joint inflammation were then compared with a group with recurrent knee disease. Nine synovial specific proteins were significantly differentially expressed in the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and T-cell receptor alpha-region have been identified among this protein cluster. Putative biomarkers, overexpressed in the joint and differentially expressed in children with recurrent joint inflammation, have been identified. These proteins may play a significant role determining the pathological state within the chronically inflamed joint and influence disease progression in JIA. This is the first study of the synovial proteome in children.