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.

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.

Alpha-2 macroglobulin is genetically associated with Alzheimer disease.

Alpha-2-macroglobulin (alpha-2M; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region (exon 18) revealed that inheritance of the deletion (A2M-2) confers increased risk for AD (Mantel-Haenzel odds ratio=3.56, P=0.001). The sibship disequilibrium test (SDT) also revealed a significant association between A2M and AD (P=0.00009). These values were comparable to those obtained for the APOE-epsilon4 allele in the same sample, but in contrast to APOE-epsilon4, A2M-2 did not affect age of onset. The observed association of A2M with AD did not appear to account for the previously published linkage of AD to chromosome 12, which we were unable to confirm in this sample. A2M, LRP1 (encoding the alpha-2M receptor) and the genes for two other LRP ligands, APOE and APP (encoding the amyloid beta-protein precursor), have now all been genetically linked to AD, suggesting that these proteins may participate in a common neuropathogenic pathway leading to AD.

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.

Localization of inhibin/activin subunit mRNAs within the primate ovary.

In order to gain further understanding of the physiology of inhibin and activin in the primate, the expression of inhibin/activin subunit mRNAs in the monkey ovary was examined by in situ hybridization. Granulosa cells of small antral follicles were found to express mRNA for the beta B subunit, which decreased to undetectable levels in dominant follicles. In contrast, expression of alpha and beta A subunit mRNAs was detected in granulosa cells of dominant follicles and in corpora lutea, but not in small antral follicles. These results indicate that the expression of the beta A and beta B subunits is differentially regulated during the growth and development of ovarian follicles in the monkey.

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.

Developmental expression of Ca++/Mg++-dependent endonuclease activity in rat granulosa and luteal cells.

A Ca++/Mg++-sensitive endonuclease has been associated with programmed cell death in a variety of endocrine and non-endocrine dependent tissues. In view of the remarkable similarity of the process of the regression of the corpus luteum and other models of programmed cell death, we studied the occurrance of this endonuclease activity in granulosa cells at different developmental states and the corpus luteum. Our results show that while undifferentiated granulosa cells do not express this endonuclease activity, treatment with pregnant mares serum gonadotropin results in a rapid increase in endonuclease activity that is maintained following ovulation and luteinization of granulosa cells.

Expression of messenger ribonucleic acids that encode for 3 beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme throughout the luteal phase of the macaque menstrual cycle.

To study further the control of the primate corpus luteum, we obtained corpora lutea from cynomolgus macaques at defined stages of the luteal phase and examined steady state mRNA levels in these corpora lutea by Northern analysis for the two major enzymes involved in progesterone biosynthesis, cytochrome P450 cholesterol side-chain cleavage (P450SCC) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). mRNAs for both P450SCC and 3 beta HSD were maximal or near maximal shortly after ovulation and luteinization (days 3-5 of the luteal phase). mRNA for P450SCC exhibited a slight, but nonsignificant (P greater than 0.05) decline throughout the remainder of the luteal phase and was undetectable upon luteal regression. Steady state levels of 3 beta HSD mRNA were significantly lower (P less than 0.05) from corpora lutea removed during the midluteal phase (days 7-8 of the luteal phase) than those in newly formed corpora lutea and declined to 10% of early luteal phase values by days 13-15 of the luteal phase. 3 beta HSD mRNA levels fell to nondetectable values upon luteal regression. These results reveal a paradoxical relationship between the steroidogenic activity of the primate corpus luteum in vivo and the steady state levels of the mRNAs that encode for the major enzymes involved in progesterone biosynthesis. Unlike serum progesterone concentrations, which are very low immediately after ovulation and then rise during the midluteal phase, the steady stale levels of P450SCC mRNA and 3 beta HSD appeared to be maximal or near maximal shortly after ovulation and declined throughout the remainder of the luteal phase. These findings are consistent with the notion that luteal lifespan is set at the time of ovulation and luteinization, and the decline in luteal function may be due in part to decay of specialized luteal cell mRNAs with finite half-lives.

Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative.

OBJECTIVE: To assess interrater reliability and validity of NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer's disease (AD). DESIGN: A multisite reliability and validity study in which clinicians from each site diagnosed 60 case summaries yielding a preconsensus estimate of reliability and validity. A consensus conference was conducted for each disagreement, leading to a postconsensus estimate of validity. The criterion standard was a diagnosis of AD by autopsy. SETTING: Three academic medical centers. SUBJECTS: A convenience sample of 60 detailed case summaries, 40 with AD and 20 with other dementing disorders. MAIN OUTCOME MEASURES: The kappa coefficient, sensitivity, and specificity. RESULTS: The kappa coefficient for preconsensus agreement on a diagnosis of probable or possible AD vs non-AD was 0.51; the sensitivity of a diagnosis of probable or possible AD for a pathological diagnosis of AD was 0.81, and the specificity was 0.73. The postconsensus sensitivity was 0.83, and the specificity was 0.84. CONCLUSIONS: The results support the reliability and validity of NINCDS-ADRDA criteria and show that the consensus process may improve diagnostic accuracy. The cases are reviewed with a focus on the sources of diagnostic disagreements and errors and possible changes that might improve the accuracy of the criteria.

ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative.

OBJECTIVE: To explore the impact of apoE-4 on Alzheimer's disease (AD) and its age at onset. DESIGN: A genetic linkage study using affected relative pairs, predominantly siblings. SETTING: Three academic medical centers ascertained subjects from memory disorder clinics, nursing homes, and the local community. SUBJECTS: 310 families including 679 subjects with AD by NINCDS/ADRDA and/or Khachaturian criteria and 231 unaffected subjects. OUTCOME MEASURE: ApoE genotype. ANALYTIC METHODS: Association, affected pedigree member, sibling pair, and lod score analyses. RESULTS: ApoE-4 was strongly associated with AD in this sample (allele frequency = 0.46 vs. 0.14 in controls, p < 0.000001). Results of lod score, affected pedigree member analysis, and sib-pair analysis also supported apoE-4 as a risk factor for AD. When the sample was stratified on family mean age at onset, the risk conferred by apoE-4 was most marked in the 61 to 65 age group. Individuals with two copies of apoE-4 had a significantly lower age at onset than those with one or no copies (66.4 vs. 72.0, p < 0.001), but individuals with one copy did not differ from those with none. Within families, the individual with the earliest age at onset had, on average, significantly more apoE-4 alleles (p < 0.0001) than the individual with the latest onset. DISCUSSION: This work supports previous reports of an association between apoE-4 and the development of AD and demonstrates that apoE-4 exerts its maximal effect before age 70. These findings have important implications for the potential use of apoE genotyping for diagnosis and prediction of disease. They also underscore the need to identify additional genetic factors involved in AD with onset beyond age 70 years.

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.

Predicting performance on the Mini-Mental State Examination. Use of age- and education-specific equations.

Inclusion of a mental status examination in research and clinical screening instruments lengthens the protocol, thereby adding to the difficulty of using instruments addressing all relevant issues under study without taxing participants. The purpose of the present study was to evaluate the possibility of substituting a subset of items from the widely used Mini-Mental State Examination (MMSE) for the entire examination in order to reduce the time needed to screen for cognitive status. Study data came from a health study of 783 community-dwelling, white females, 65 years of age and over, selected randomly from a 20-census-tract area of northeast Baltimore. Results indicate that seven MMSE items can be used to reliably predict total MMSE scores. Because of an age X education interaction in the prediction of total MMSE scores, four age X education-specific predictive equations were developed. These four equations are most useful for predicting continuous MMSE scores rather than for categorizing individuals according to impaired versus unimpaired status. A short form of the MMSE and four age X education-specific scoring equations are presented and their potential utility discussed.

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.

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.

Memory complaint, memory performance, and psychiatric diagnosis: a community study.

This study examined the prevalence of memory complaint and poor memory performance on brief screening measures within a community sample of 810 adults. All individuals received an extensive household interview and a clinical psychiatric evaluation. Overall, 22% indicated that they currently had trouble with their memory. This percentage increased with age, rising to 43% for those 65 to 74 years old, 51% for those 75 to 84 years old, and 88% for those 85 years of age and older; the percentage indicating memory problems decreased with educational attainment. The prevalence of poor memory performance was 11%, also increasing with less education and increased age, rising to 26% for those 65 to 74 years old and to 40% for those older then 75. Those who complained of memory trouble were twice as likely to show poor memory performance (29%) compared with those who did not complain (15%). Multivariate analysis found age, emotional distress, and physical illness to be independent predictors of memory complaint; age, functional disability, education, and physical illnesses proved to be independently associated with poor memory performance. A higher prevalence of complaints of memory trouble was found not only for those with affective disorders, as might be expected, but also among those with schizophrenic, cognitive, anxiety, and adjustment disorders. However, only individuals with cognitive disorders showed a higher prevalence of poor memory performance.

Development and validation of a Structured Telephone Interview for Dementia Assessment (STIDA): the NIMH Genetics Initiative.

As part of the NIMH Genetics Initiative Alzheimer's Disease (AD) Study Group, a brief structured telephone interview to distinguish individuals with normal cognitive functioning from those with changes in cognition and daily functioning suggestive of early AD was developed. The Structured Telephone Interview for Dementia Assessment (STIDA), yields a dementia score between 0 and 81 (higher scores indicating greater impairment). Subscales corresponding to the subscales of the Clinical Dementia Rating Scale (CDR) can be derived. The STIDA performed well as a screening instrument for mildly demented individuals. When a score of 10 or more (based on informant interview and subject testing) was used to identify mildly impaired individuals, the STIDA had a sensitivity of .93 and a specificity of .92 for a clinician-derived CDR of 0.5 or more. The STIDA was also capable of accurately assessing the level of dementia. STIDA-derived CDR ratings agreed with clinician-derived CDR scores in 23 of 28 cases, corresponding to an unweighted kappa of.71 and a weighted kappa of.81. A much-abbreviated short STIDA that could be administered directly to the subject was able to detect possible impairment with a sensitivity of .93 and a specificity of.77. These results suggest that the short STIDA provides a sensitive and fairly specific telephone screen for dementia, and that the full STIDA, consisting of an interview with a knowledgeable informant and subject testing, approximates the success of a face-to-face clinical interview, and provides reliable and valid screening and staging of dementia over the telephone.

Reliability of proxy response on mental health indices for aged, community-dwelling women.

The correspondence between respondent and proxy response was evaluated on 4 mental health measures (Affect Balance Scale, Center for Epidemiological Studies Depression Scale, Mental Status Questionnaire, and Mini-Mental State Examination) with a sample of 538 respondent-proxy pairs. Results indicated that respondent and proxy responses were strongly associated, particularly for the cognitive measures. This association was found even for respondents classified as depressed or cognitively impaired. Although there was evidence of proxy bias, with proxies underrating affective status and overrating cognitive status, the magnitude of the bias proved small for all scales but the Mental Status Questionnaire. Examination of response comparability by proxy characteristics showed that choice of proxy affected agreement and bias. Implications of these findings for survey research are discussed.

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.

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.