Feasibility and Acceptability of a Program to Promote Positive Affect, Well-Being and Gender Empowerment in Black Women Living with HIV.

While programs and interventions intended to increase positive affect among people living with HIV (PLWH) and other chronic diseases have been associated with improved health outcomes, including decreased depression, programs have not been tailored specifically for Black women. We tailored a program designed to increase positive affect and to decrease depressive symptoms in PLWH to a group format for Black WLWH. We also added skills to increase gender empowerment. We then tested the acceptability and feasibility of this program with 8 Black WLWH. The program was acceptable and relatively feasible, as assessed by women's participation and feedback about program clarity and helpfulness, which women rated above 9 on a 10-point scale. A few women suggested that optimal delivery point for some skills taught would be shortly after HIV diagnosis. A proof-of-concept program intended to bolster positive emotions and gender empowerment and decrease depression can be tailored for Black WLWH and is relatively feasible and acceptable. A randomized controlled trial is needed to assess the preliminary efficacy of this program on positive affect, depression, and other health outcomes for WLWH.

Feasibility and Acceptability of an Online Positive Affect Intervention for Those Living with Comorbid HIV Depression.

Positive affect has unique beneficial effects on psychological and physical health, independent of the effects of negative affect. Interventions that explicitly target positive affect show promise for improving health outcomes in a number of chronic illnesses. In this article, we present pilot data on the acceptability and feasibility of an online intervention to increase positive affect in those living with comorbid human immunodeficiency virus (HIV) and depression. The intervention was rated both acceptable and feasible by participants. Six of nine participants completed the intervention and the subsequent follow-up assessment and a post-intervention phone call. We also present outcomes of planned comparisons of intervention effects on emotion, which indicate that positive affect increased significantly in the intervention group. Based upon results of the current study, future research should continue the development of positive affect interventions for people living with comorbid HIV and depression.

A Systematic Review of the Effects of Exercise Interventions on Body Composition in HIV+ Adults.

Over the years, physical activity and exercise have been used to positively impact the health and quality of life of persons infected with HIV and, more recently, has been associated with a spectrum of body composition changes. The aim of this review was to examine the effects of various exercise interventions on body composition in HIV positive adults, using a search strategy of randomized, controlled trials (RCTs). A systematic review was performed by five independent reviewers using a predetermined protocol adapted from previous research for assessing the articles for inclusion, the extracted data, and methodological quality. Eight RCTs involving 430 (26% female) HIV positive adults performing exercise a minimum of thrice weekly for at least six weeks were finally selected: Four were progressive resistance training (PRT) studies, three were aerobic training (AT) studies, and one involved yoga. In the PRT studies, there were significant increases in three anthropometric measures, namely, body mass, sum of skinfolds and sum of limb girths. In the AT studies, significant decreases were found in seven anthropometric measures, namely, body mass index, waist-hip ratio, body mass, triceps skinfold, waist circumference and sum of skinfolds. With yoga, the changes were non-significant. Exercise contributes to improved body composition and, when applied safely, appears to be beneficial for adults living with HIV/AIDS. However, these findings should be interpreted cautiously due to the relatively few RCTs published to date. Future studies would benefit from increased attention to sample size, female participants, participant follow-up, complete statistical analysis and intention-to-treat analysis.

Genetic determinants of neuroglobin transcription.

Neuroglobin (NGB) is a neuron-specific vertebrate globin shown to protect against hypoxia, ischemia, oxidative stress and the toxic effects of Amyloid-beta. Following on our and others' results highlighting the importance of NGB expression in disease, we searched for genetic determinants of its expression. We found that a microRNA expressed with the NGB transcript shows significant target enrichments in the angiogenesis pathway and the Alzheimer disease/presenilin pathway. Using reporter constructs we identified potential promoter/enhancer elements between the transcription start site and 1,142 bp upstream. Using 184 post-mortem temporal lobe samples we replicated the reported negative effect of age, and after genotyping tagging SNPs we found one (rs981471) showing a significant correlation with the gene's expression and another (rs8014408) showing an interaction with age, the rare C allele being correlated with higher expression and faster decline. The two SNPs are towards the 3' end of NGB within the same LD block, 52 Kb apart and modestly correlated (r (2) = 0.5). Next generation sequencing of the same 184 temporal lobe samples and 79 confirmed AD patients across the entire gene region (including >12 Kb on the 3' and 5' flank) revealed limited coding variation, suggesting purifying selection of NGB, but did not identify regulatory or disease associated rare variants. A dinucleotide repeat in intron 1 with extensive evidence of functionality showed interesting but inconclusive results, as it was not amenable to further molecular analysis.

Self-efficacy, imagery use, and adherence during injury rehabilitation.

Previous observational studies examining imagery, self-efficacy, and adherence during injury rehabilitation have been cross-sectional and thus have not provided a clear representation of what occurs over the course of the rehabilitation period. The objectives of this research were (1) to examine the temporal patterns of imagery, self-efficacy, and rehabilitation adherence during an 8-week rehabilitation program and (2) to identify the time-order relationships between imagery, self-efficacy, and adherence. The design of the study was prospective and observational. 90 injured people (n=57 males; n=33 females) aged 18-78 years attending an injury rehabilitation clinic participated. The main outcome measures were imagery (cognitive, motivational, and healing), self-efficacy (task and coping), and rehabilitation adherence (duration, quality, and frequency). Results indicated that task efficacy, imagery use, and adherence levels remained stable, while coping efficacy declined over time. During the course of rehabilitation, moderate to strong reciprocal relationships existed between self-efficacy and adherence to rehabilitation. Weak to moderate relationships were found between imagery use and rehabilitation adherence. The results of this study can be used to inform the development of interventions steeped in self-efficacy and imagery aimed at improving rehabilitation adherence and treatment outcome.

Alzheimer's risk variants in the clusterin gene are associated with alternative splicing.

Genetic variation in CLU encoding clusterin has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, but the underlying mechanisms remain unknown. Following earlier reports that tightly regulated CLU alternative transcripts have different functions, we tested CLU single nucleotide polymorphisms (SNPs) including those associated with AD for quantitative effects on individual alternative transcripts. In 190 temporal lobe samples without pathology we found that the risk allele of the AD associated SNP rs9331888 increases the relative abundance of transcript NM_203339 (P=4.3×10(-12)). Using an independent set of 115 AD and control samples, we replicated this result (p=0.0014) and further observed that multiple CLU transcripts are at higher levels in AD compared to controls. The AD SNP rs9331888 is located in the first exon of NM_203339 and therefore, it is a functional candidate for the observed effects. We tested this hypothesis by in vitro dual luciferase assays using SK-N-SH cells and mouse primary cortical neurons and found allelic effects on enhancer function, consistent with our results on post-mortem human brain. These results suggest a biological mechanism for the genetic association of CLU with AD risk and indicate that rs9331888 is one of the functional DNA variants underlying this association.

Intelligence and medial temporal lobe function in older adults: a functional MR imaging-based investigation.

BACKGROUND AND PURPOSE: The influence of general intelligence and formal education on functional MR imaging (fMRI) activation has not been thoroughly studied in older adults. Although these factors could be controlled for through study design, this approach makes sample selection more difficult and reduces power. This study was undertaken to examine our hypothesis that intelligence and education would impact medial temporal lobe (MTL) fMRI responses to an episodic memory task in healthy elderly subjects. MATERIALS AND METHODS: Thirty-six women and 38 men, 50-83 years of age (mean, 63.4 +/- 7.9 years), completed an auditory paired-associates paradigm in a 1.5T magnet. The amplitude and volume of fMRI activation for both the right and left MTLs and MTL subregions were correlated with the intelligence quotients (IQs) and educational levels by using Pearson correlation coefficient tests and regression analyses. RESULTS: The participants' mean estimated full scale IQ and verbal IQ scores were 110.4 +/- 7.6 (range, 92-123) and 108.9 +/- 8.7 (range, 88-123), respectively. The years of education showed a mean of 16.1 +/- 3.2 years (range, 8-25 years). The paradigm produced significant activation in the MTL and subregions. However, the volume and amplitude of activation were unrelated to either IQ or years of schooling in men and/or women. CONCLUSIONS: We found no evidence of an effect of IQ or education on either the volume or amplitude of fMRI activation, suggesting that these factors do not necessarily need to be incorporated into study design or considered when evaluating other group relationships with fMRI.

Past adult lead exposure is linked to neurodegeneration measured by brain MRI.

OBJECTIVE: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. METHODS: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. RESULTS: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. CONCLUSIONS: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

Modelling the glacial isostatic adjustment of the UK region.

The glacial isostatic adjustment of the UK region has been considered in a number of recent studies. We have revisited this problem in order to: (i) highlight some key issues with regard to limitations in the ice modelling approach adopted in these studies and (ii) consider the constraints provided from observations of crustal motion available via continuous global positioning system monitoring. With regard to the first aim, we have found that: (i) previous studies have significantly overestimated ice thicknesses in regions where trim line field constraints were adopted and (ii) the duration of the glaciation phase of the UK ice sheet is a critical aspect of the model and that discrepancies in this model component have led to inconsistent inferences of Earth model parameters. With regard to the second aim, we have found that predictions of horizontal velocities (relative to a chosen site) based on a UK ice model calibrated to fit the regional sea-level database capture the geometry of the signal well but only account for 10% of the magnitude (for a range of Earth models).

Analysis of large screening data sets via adaptively grown phylogenetic-like trees.

As the use of high-throughput screening systems becomes more routine in the drug discovery process, there is an increasing need for fast and reliable analysis of the massive amounts of the resulting data. At the forefront of the methods used is data reduction, often assisted by cluster analysis. Activity thresholds reduce the data set under investigation to manageable sizes while clustering enables the detection of natural groups in that reduced subset, thereby revealing families of compounds that exhibit increased activity toward a specific biological target. The above process, designed to handle primarily data sets of sizes much smaller than the ones currently produced by high-throughput screening systems, has become one of the main bottlenecks of the modern drug discovery process. In addition to being fragmented and heavily dependent on human experts, it also ignores all screening information related to compounds with activity less than the threshold chosen and thus, in the best case, can only hope to discover a subset of the knowledge available in the screening data sets. To address the deficiencies of the current screening data analysis process the authors have developed a new method that analyzes thoroughly large screening data sets. In this report we describe in detail this new approach and present its main differences with the methods currently in use. Further, we analyze a well-known, publicly available data set using the proposed method. Our experimental results show that the proposed method can improve significantly both the ease of extraction and amount of knowledge discovered from screening data sets.

The chimpanzee model of hepatitis C virus infections.

The chimpanzee (Pan troglodytes) is the only experimental animal susceptible to infection with hepatitis C virus (HCV). The chimpanzee model of HCV infection was instrumental in the initial studies on non-A, non-B hepatitis, including observations on the clinical course of infection, determination of the physical properties of the virus, and eventual cloning of the HCV nucleic acid. This review focuses on more recent aspects of the use of the chimpanzee in HCV research. The chimpanzee model has been critical for the analysis of early events in HCV infection because it represents a population for which samples are available from the time of exposure and all exposed animals are examined. For this reason, the chimpanzee represents a truly nonselected population. In contrast, human cohorts are often selected for disease status or antibody reactivity and typically include individuals that have been infected for decades. The chimpanzee model is essential to an improved understanding of the factors involved in viral clearance, analysis of the immune response to infection, and the development of vaccines. The development of infectious cDNA clones of HCV was dependent on the use of chimpanzees, and they will continue to be needed in the use of reverse genetics to evaluate critical sequences for viral replication. In addition, chimpanzees have been used in conjunction with DNA microarray technology to probe the entire spectrum of changes in liver gene expression during the course of HCV infection. The chimpanzee will continue to provide a critical aspect to the understanding of HCV disease and the development of therapeutic modalities.

Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection.

Hepatitis C virus (HCV) infections were evaluated in chimpanzees that had previously cleared HCV and were rechallenged. Animals that had previously cleared HCV infection rapidly cleared homologous and heterologous virus upon rechallenge, indicative of a strong protective immunity. In one animal, sterilizing immunity was observed with regard to viremia, although viral RNA was transiently detected in the liver. Accelerated viral clearance following rechallenge with HCV was observed in animals that had not been exposed to HCV for over 16 years, suggesting that long-lasting protective immunity may be possible. The ability of peripheral blood mononuclear cells (PBMC) to recognize HCV proteins was evaluated during the course of the rechallenge experiments. A very early and strong in vitro recall response to HCV nonstructural proteins appeared to be associated with viral clearance. In contrast, proliferative responses to HCV proteins were not observed in 4 persistently infected chimpanzees, and a weak proliferative response was observed in 1 of 2 animals during acute resolving infection. The results suggest that a strong T-cell proliferative response is induced upon rechallenge of chimpanzees with HCV and that this response is associated with rapid viral clearance. The antibody response to HCV proteins increased by over 1,000-fold in all animals following rechallenge as well. A more complete understanding of the role of the cellular immune response in the clearance of HCV and the nature of the protective immune response following viral clearance may aid in the generation of therapies and vaccines.

Association of a haplotype for tumor necrosis factor in siblings with late-onset Alzheimer disease: the NIMH Alzheimer Disease Genetics Initiative.

Tumor necrosis factor (TNF), a proinflammatory cytokine, may be involved in the pathogenesis of Alzheimer disease (AD) based on observations that senile plaques have been found to upregulate proinflammatory cytokines. Additionally, nonsteroidal anti-inflammatory drugs have been found to delay and prevent the onset of AD. A collaborative genome-wide scan for AD genes in 266 late-onset families implicated a 20 centimorgan region at chromosome 6p21.3 that includes the TNF gene. Three TNF polymorphisms, a -308 TNF promoter polymorphism, whose TNF2 allele is associated with autoimmune inflammatory diseases and strong transcriptional activity, the -238 TNF promoter polymorphism, and the microsatellite TNFa, whose 2 allele is associated with a high TNF secretion, were typed in 145 families consisting of 562 affected and unaffected siblings. These polymorphisms formed a haplotype, 2-1-2, respectively, that was significantly associated with AD (P = 0.005) using the sibling disequilibrium test. Singly, the TNFa2 allele was also significantly associated (P = 0.04) with AD in these 145 families. This TNF association with AD lends further support for an inflammatory process in the pathogenesis of AD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:823-830, 2000.

Genomic structure, expression pattern, and chromosomal localization of the human calsenilin gene: no association between an exonic polymorphism and Alzheimer's disease.

Calsenilin is a recently-identified member of the neuronal calcium sensor family. Like other members of this family, it is found in the brain and binds calcium. Calsenilin was discovered by virtue of its interaction with both presenilin-1 and -2, proteins that are involved in the etiology of Alzheimer's disease. Because calsenilin may play a role in Alzheimer's disease and other disease with alterations in calcium homeostasis, we characterized the human gene. The gene, which we localized to chromosome 2, extends over a region of at least 74 kb and includes nine exons. Interestingly, the ninth exon of calsenilin contains a highly polymorphic CA repeat, adjacent to the stop codon. In a study of Alzheimer patients and their unaffected siblings, there was no evidence of association of AD with any calsenilin allele. This CA repeat will be useful for linkage and linkage disequilibrium studies to determine whether calsenilin variants contribute to risk in other diseases.

What husbands in northern India know about reproductive health: correlates of knowledge about pregnancy and maternal and sexual health.

Women in India suffer from a high incidence of reproductive disease, disability and death. Very little work has been done on men, but a much higher incidence of sexual experience outside marriage and sexually transmitted diseases (STDs) among males than previously expected for this population is now being documented. In north India, women are dependent on their husbands and other family members for health-related decisions. Therefore, the behaviour, knowledge and attitudes of men are integral to the reproductive health status of couples there. This study explores knowledge about three distinct areas of reproductive health among 6549 married men in five districts of the northern state of Uttar Pradesh, India. Factors contributing to men's knowledge in the areas of fertility, maternal health and STDs were investigated. Results showed that very few men had basic knowledge in any of these areas. The likelihood of reporting knowledge was associated with a set of determinants that differed in their magnitude and effect across the areas of reproductive health explored. In particular, men's belief about the ability of an individual to prevent pregnancy demonstrated an independent association with men's knowledge. After controlling for factors such as age, parity and educational and economic status, men who believed it not possible to prevent a pregnancy were less likely to know when during the menstrual cycle women would become pregnant and certain facts about STDs, but they were more likely to be able to name two or more symptoms of serious maternal health conditions. Possible explanations for this trend are discussed.

Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees.

The putative envelope 2 (E2) gene of hepatitis C virus (HCV) contains a highly variable region referred to as hypervariable region 1 (HVR1). We hypothesized that this genetic variability is driven by immune selection pressure, rather than representing the accumulation of random mutations in a region with relatively little functional constraint. To test this hypothesis, we examined the E2 sequence of a human inoculum that was passaged through eight chimpanzees, which appear to have a replicative rate (opportunity for chance mutation) similar to that of humans. Acute-phase plasma samples from a human (the inoculum) and six of eight serially infected chimpanzees were studied. For each, 33 cloned cDNAs were examined by a combined heteroduplex-single-stranded conformational polymorphism assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns (clonotypes) for sequencing. The sequence diversity of HCV was significantly lower in the chimpanzees than in the humans, and during eight serial passages there was no change in the sequence of the majority clonotype from each animal examined. Similarly, the rates of protein sequence altering (nonsynonymous) substitution were lower in the chimpanzees than in the humans. These findings demonstrate that nonsynonymous mutations indicate selection pressure rather than being an incidental result of HCV replication.

Effects of iron loading on pathogenicity in hepatitis C virus-infected chimpanzees.

Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)-infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV-infected chimpanzees. Iron was supplemented in the diets of four HCV-infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV-infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Although various degrees of iron loading occurred in all chimpanzees, HCV-infected animals exhibited increased loading in comparison with uninfected animals. The effects of iron loading on HCV disease expression was determined by comparing disease parameters during an extended baseline period before iron loading with the period during iron loading and immediately following iron loading. Iron loading did not influence the viral load, but did exacerbate liver injury in HCV-infected chimpanzees, as evidenced by elevated ALT and histological changes. Because all chimpanzees on high iron diets experienced iron loading, but pathological effects were only observed in HCV-infected chimpanzees, HCV infection appears to increase the susceptibility of the liver to injury following iron loading. These results confirm and extend previous observations made in human populations and serve to further validate the chimpanzee model of chronic hepatitis C.

Viral persistence, antibody to E1 and E2, and hypervariable region 1 sequence stability in hepatitis C virus-inoculated chimpanzees.

The relationship of viral persistence, the immune response to hepatitis C virus (HCV) envelope proteins, and envelope sequence variability was examined in chimpanzees. Antibody reactivity to the HCV envelope proteins E1 or E2 was detected by enzyme-linked immunosorbent assay (ELISA) in more than 90% of a human serum panel. Although the ELISAs appeared to be sensitive indicators of HCV infection in human serum panels, the results of a cross-sectional study revealed that a low percentage of HCV-inoculated chimpanzees had detectable antibody to E1 (22%) and E2 (15%). Viral clearance, which was recognized in 28 (61%) of the chimpanzees, was not associated with an antibody response to E1 or E2. On the contrary, antibody to E2 was observed only in viremic chimpanzees. A longitudinal study of animals that cleared the viral infection or became chronically infected confirmed the low level of antibody to E1, E2, and the HVR-1. In 10 chronically infected animals, the sequence variation in the E2 hypervariable region (HVR-1) was minimal and did not coincide with antibody to E2 or to the HVR-1. In addition, low nucleotide and amino acid sequence variation was observed in the E1 and E2 regions from two chronically infected chimpanzees. These results suggest that mechanisms in addition to the emergence of HVR-1 antibody escape variants are involved in maintaining viral persistence. The significance of antibodies to E1 and E2 in the chimpanzee animal model is discussed.

Attention: neuropsychological predictor of competency in Alzheimer's disease.

This study was undertaken to examine the relationship between two different competencies, financial and medical decision making, and explore whether neuropsychological testing can identify a common underlying cognitive operation impaired in patients with AD. The objective was to examine the neuropsychological predictors of financial and medical decision-making competencies in patients with Alzheimer's disease (AD). Twenty individuals with mild to moderate AD and 20 control subjects matched for age and education were evaluated at a university medical center. All participants were administered a financial competency questionnaire, a competency test for medical decision making, and a set of standardized neuropsychological tests selected to reflect cognitive processes theoretically related to competency. In addition, an informant provided information regarding banking history for each participant. AD patients performed more poorly on all measures, including both measures of competency, which were highly related (R = .718, P < .001). Two tests, Trails A and Word List Recall, were significantly correlated with both competency measures, with Trails A predicting over 85% of the variance in competency scores. Trails A discriminated competent from not competent participants with an accuracy ranging from 77% to 82%. Measures of financial and medical decision-making competency were significantly correlated among patients with AD. One brief neuropsychological test of attention, Trails A, proved to be highly predictive of performance on both competency measures and useful in the discrimination of competent performance on these measures and by informant report.