ABSTRACT
Benefits of a Mediterranean diet for cognition have been suggested, but epidemiologic studies have been relatively small and of limited duration. To prospectively assess the association between long-term adherence to a Mediterranean dietary pattern and self-reported subjective cognitive function (SCF). Prospective observational study. The Health Professionals' Follow-up Study, a prospective cohort of 51,529 men, 40-75 years of age when enrolled in 1986, of whom 27,842 were included in the primary analysis. Mediterranean diet (MD) score, computed from the mean of five food frequency questionnaires, assessed every 4 years from 1986 to 2002. Self-reported SCF assessed by a 6-item questionnaire in 2008 and 2012, and validated by association with genetic variants in apolipoprotein-4. Using the average of 2008 and 2012 SCF scores, 38.0% of men were considered to have moderate memory scores and 7.3% were considered to have poor scores. In a multivariate model, compared with men having a MD score in the lowest quintile, those in the highest quintile had a 36% lower odds of a poor SCF score (odds ratio 0.64, 95% CI 0.55-0.75; P, trend < 0.001) and a 24% lower odds of a moderate SCF score (OR 0.76, 95% CI 0.70-0.83; P, trend < 0.001). Both remote and more recent diet contributed to this relation. Associations were only slightly weaker using baseline dietary data and a lag of 22 years. Long-term adherence to the Mediterranean diet pattern was strongly related to lower subjective cognitive function. These findings provide further evidence that a healthy dietary pattern may prevent or delay cognitive decline.
Subject(s)
Alzheimer Disease/epidemiology , Cognition Disorders/epidemiology , Cognition , Dementia/epidemiology , Diet, Mediterranean , Patient Compliance , Adult , Aged , Follow-Up Studies , Humans , Life Style , Male , Middle Aged , Neuropsychological Tests , Prospective Studies , Surveys and Questionnaires , United States/epidemiologyABSTRACT
Viruses and other pathogens can diverge in their evolved host-use strategies because of exposure to different host types and conflicts between within-host reproduction and between-host survival. Most host-pathogen studies have emphasized the role of intrahost reproduction in the evolution of pathogen virulence, whereas the role of extra-host survival has received less attention. Here, we examine the evolution of free-living virion survival in RNA virus populations differing in their histories of host use. To do so, we used lineages of vesicular stomatitis virus (VSV) that were experimentally evolved in laboratory tissue culture for 100 generations on cancer-derived cells, noncancerous cells, or alternating passages of the two host types. We observed that free-living survival improved when VSV populations specialized on human epithelial carcinoma (HeLa) cells, whereas this trait was not associated with selection on noncancer cells or combinations of the cell types. We attributed this finding to shorter-lived HeLa monolayers and/or rapid cell-to-cell spread of viruses on HeLa cells in tissue culture, both of which could select for enhanced virus stability between host-cell replenishment. We also showed evidence that increases in virion survival were associated with decreases in virulence, which suggests a trade-off between survival and virulence for the VSV populations on one cell type. Our results shed new light on the causes and consequences of "sit and wait" infection strategies in RNA viruses.
Subject(s)
Evolution, Molecular , Host-Pathogen Interactions , Vesiculovirus/genetics , Cell Line, Tumor , Directed Molecular Evolution , HeLa Cells , Humans , Madin Darby Canine Kidney Cells , Vesiculovirus/pathogenicity , Vesiculovirus/physiology , VirulenceABSTRACT
BACKGROUND: Transmission of drug susceptible and drug resistant TB occurs in health care facilities, and community and households settings, particularly in highly prevalent TB and HIV areas. There is a paucity of data regarding factors that may affect TB transmission risk in household settings. We evaluated air exchange and the impact of natural ventilation on estimated TB transmission risk in traditional Zulu homes in rural South Africa. METHODS: We utilized a carbon dioxide decay technique to measure ventilation in air changes per hour (ACH). We evaluated predominant home types to determine factors affecting ACH and used the Wells-Riley equation to estimate TB transmission risk. RESULTS: Two hundred eighteen ventilation measurements were taken in 24 traditional homes. All had low ventilation at baseline when windows were closed (mean ACH = 3, SD = 3.0), with estimated TB transmission risk of 55.4% over a ten hour period of exposure to an infectious TB patient. There was significant improvement with opening windows and door, reaching a mean ACH of 20 (SD = 13.1, p < 0.0001) resulting in significant decrease in estimated TB transmission risk to 9.6% (p < 0.0001). Multivariate analysis identified factors predicting ACH, including ventilation conditions (windows/doors open) and window to volume ratio. Expanding ventilation increased the odds of achieving ≥12 ACH by 60-fold. CONCLUSIONS: There is high estimated risk of TB transmission in traditional homes of infectious TB patients in rural South Africa. Improving natural ventilation may decrease household TB transmission risk and, combined with other strategies, may enhance TB control efforts.
Subject(s)
Housing/standards , Tuberculosis/prevention & control , Ventilation/methods , Air Movements , Analysis of Variance , Humans , Multivariate Analysis , Risk , Risk Factors , South Africa/epidemiology , Temperature , Tuberculosis/epidemiology , Tuberculosis/transmissionABSTRACT
OBJECTIVE: To evaluate the prospective association of long-term intake of vegetables and fruits with late-life subjective cognitive function (SCF). METHODS: Among 27,842 men with a mean age of 51 years in 1986, we used multinomial logistic regression to examine the relation of vegetable and fruit consumption to future SCF. Average dietary intake was calculated from 5 repeated food frequency questionnaires collected every 4 years until 2002. SCF score was assessed twice (2008 and 2012) using a 6-item questionnaire; validity was supported by strong associations with APO ε4 genotype. We categorized the average of the 2 scores as good, moderate, and poor SCF. RESULTS: Higher intakes of total vegetables, total fruits, and fruit juice were each significantly associated with lower odds of moderate or poor SCF after controlling for major nondietary factors and total energy intake. The association with total fruit intake was weaker after further adjusting for major dietary factors. In this model, the multivariate odds ratios (95% confidence intervals) for vegetable intake (top vs bottom quintile) were 0.83 (0.76-0.92), p trend <0.001 for moderate SCF and 0.66 (0.55-0.80), p trend <0.001 for poor SCF. For orange juice, compared to <1 serving/mo of intake, daily consumption was associated with a substantially lower odds of poor SCF (0.53 [0.43-0.67], p trend <0.001). Higher consumption of vegetables and fruits 18 to 22 years before SCF assessment was associated with lower odds of poor SCF independent of more proximal intake. CONCLUSION: Our findings support a long-term beneficial role of vegetable, fruit, and orange juice consumption on SCF.
Subject(s)
Cognition Disorders/epidemiology , Cognition/physiology , Fruit , Vegetables , Adult , Aged , Humans , Longitudinal Studies , Male , Middle Aged , Neuropsychological Tests , Odds Ratio , Surveys and Questionnaires , United States/epidemiologyABSTRACT
BACKGROUND: Recurrent tuberculosis (TB) following TB treatment completion in HIV-infected individuals remains a major public health burden. We assessed the role of various risk factors in mediating the development of recurrent TB and subsequent resistance to antiretroviral therapy and anti-TB drugs. PATIENTS AND METHODS: We analyzed secondary demographic, clinical, and laboratory data from medical records of five HIV-infected TB patients enrolled between 2009 and 2014 in a prospective observational study investigating TB recurrence. Paired clinical isolates of Myco-bacterium tuberculosis were typed by IS6110 restriction fragment length polymorphism analysis to determine the mechanism of TB recurrence. Plasma samples were genotyped to determine acquisition of HIV drug resistance mutations on antiretroviral treatment (ART). RESULTS: All five patients were HIV-coinfected, with a previous history of TB infection and prior exposure to anti-TB treatment, and residual lung damage, and demonstrated poor treatment adherence - significant risk factors linked to the development of recurrent TB disease. Furthermore, three of the five patients had multiple episodes of drug-susceptible TB infection with subsequent drug-resistant TB infection. Genotyping of the initial and recurrent M. tuberculosis isolates demonstrated three cases of recurrent TB because of relapse and two because of reinfection. All five patients had no mutations at ART initiation; however, by the end of the study follow-up, all patients developed dual class resistance. CONCLUSION: This series demonstrates the complexity of recurrent TB in HIV coinfection. We highlight the challenges of managing coinfected patients and the increased propensity for the development of drug resistance. We report on the role of various risk factors mediating the development of resistance and subsequent clinical impact. This report underscores the need for structural clinical and adherence interventions for the management of complex treatment and dosing.
ABSTRACT
Life-history theory predicts that traits for survival and reproduction cannot be simultaneously maximized in evolving populations. For this reason, in obligate parasites such as infectious viruses, selection for improved between-host survival during transmission may lead to evolution of decreased within-host reproduction. We tested this idea using experimental evolution of RNA virus populations, passaged under differing transmission times in the laboratory. A single ancestral genotype of vesicular stomatitis virus (VSV), a negative-sense RNA Rhabdovirus, was used to found multiple virus lineages evolved in either ordinary 24-h cell-culture passage, or in delayed passages of 48 h. After 30 passages (120 generations of viral evolution), we observed that delayed transmission selected for improved extracellular survival, which traded-off with lowered viral fecundity (slower exponential population growth and smaller mean plaque size). To further examine the confirmed evolutionary trade-off, we obtained consensus whole-genome sequences of evolved virus populations, to infer phenotype-genotype associations. Results implied that increased virus survival did not occur via convergence; rather, improved virion stability was gained via independent mutations in various VSV structural proteins. Our study suggests that RNA viruses can evolve different molecular solutions for enhanced survival despite their limited genetic architecture, but suffer generalized reproductive trade-offs that limit overall fitness gains.
Subject(s)
Evolution, Molecular , Selection, Genetic , Vesicular stomatitis Indiana virus/genetics , Animals , Cell Line , Cricetinae , Genetic Fitness , Genome, Viral , Host Specificity , Vesicular stomatitis Indiana virus/pathogenicity , Virulence/geneticsABSTRACT
PURPOSE: - Little is understood about the self-described barriers that recently released HIV-infected prisoners face when accessing healthcare and adhering to medications. The purpose of this paper is to elucidate these barriers from the perspective of released prisoners themselves. DESIGN/METHODOLOGY/APPROACH: - A qualitative assessment using 30 semi-structured interviews explored individuals' self-reported acute stressors and barriers to health-seeking during community re-integration for recidivist prisoners. Leventhal's Self-Regulation Model of Illness (SRMI) is applied to examine both structural and psychological barriers. FINDINGS: - The SRMI explains that individuals have both cognitive and emotional processing elements to their illness representations, which mediate coping strategies. Cognitive representations of HIV that mediated treatment discontinuation included beliefs that HIV was stigmatizing, a death sentence, or had no physiological consequences. Negative emotional states of hopelessness and anger were either acute or chronic responses that impaired individuals' motivation to seek care post-release. Individuals expressed feelings of mistrust, fatalism and denial as coping strategies in response to their illness, which reduced likelihood to seek HIV care. ORIGINALITY/VALUE: - Interventions for HIV-infected individuals transitioning to the community must incorporate structural and psychological components. Structural support includes housing assistance, employment and health insurance, and linkage to mental health, substance abuse and HIV care. Psychological support includes training to enhance agency with medication self-administration and HIV education to correct false beliefs and reduce distress. Additionally, healthcare workers should be specifically trained to establish trust with these vulnerable populations.
ABSTRACT
BACKGROUND: This paper examines how family and social relations facilitate and inhibit adherence to antiretroviraltherapy (ART) for people living with HIV (PLH) who have underlying substance use disorders and are transitioningto the community post-incarceration. METHODS: Combining the methods of inductive close reading and constantcomparison, we analyzed the data from 30 semi-structured interviews of PLH who had recently transitioned to thecommunity within the previous 90 days. RESULTS: Three central themes were anticipated as important socialrelationships post-release: self-reported family, friends and clinicians. Among these, four sub-themes (social isolation, 'double jeopardy', search for belonging, and trust and respect) emerged, highlighting how they impacted ART adherence. Post-release, participants returned to resource-poor communities where they experienced socialisolation. ART adherence was enabled by having a purpose in life, which correlated with having robust family support structures. Many former prisoners felt that a chasm between them and their families existed, both because of HIV stigma and their addiction problems. In this context, relationships with untrustworthy friends from their druguse networks led to relapse of drug use and risky behaviors, jeopardizing participants' ART adherence and persistence. To avoid the double jeopardy, defined as seeking friends for support but who were also the ones who contributed to drug relapse, participants searched for new social anchors, which often included their healthcare providers who represented trusted and respected persons in their life. CONCLUSIONS: While some former prisonersperceived doctors as uncaring and their relationships asymmetrical, positive relationships with these providers,when respect and trust was mutual, reinforced the participants' sense of belonging to what they called 'the world that don't do drugs' and motivated them to adhere to ART.
ABSTRACT
BACKGROUND: The challenge of early tuberculosis (TB) infection among rural patients accessing highly active antiretroviral therapy (HAART) in a resource-limited setting with high HIV and TB burden has not been fully quantified. METHODS: This is a retrospective study nested within a prospective study of 969 patients consecutively initiated onto HAART at the CAPRISA AIDS Treatment programme in rural KwaZulu-Natal between January 2007 and December 2010. Patients were screened for clinical symptoms consistent with TB using a standardized checklist, and routine clinical investigations that included sputum microscopy and chest x-ray diagnosis. RESULTS: Of 969 HIV-infected patients initiated on HAART, 173 [17.9%; 95% confidence interval (CI): 15.5 to 20.4] had active TB at HAART initiation. TB incidence rates were 3-fold higher in the first 3 months (early incident TB) after HAART initiation [11.5/100 person-years (py); 95% CI: 7.1 to 17.5] compared with 4-24 months (late incident TB) post-HAART initiation (3.2/100 py; 95% CI: 2.2 to 4.5; incidence rate ratio: 3.6; 95% CI: 2.0 to 6.4; P < 0.001). Immune status of patients at HAART initiation did not impact TB incidence rates in patients with CD4 counts of <50 (5.3/100) and >200 (4.9/100 py; P = 0.81) cells per cubic millimeter. CD4 count gains achieved 12 months post-HAART initiation were significantly different in patients with early incident TB versus late incident TB; P = 0.03. CONCLUSIONS: Rural HIV treatment programmes in TB-endemic settings experience high rates of TB irrespective of immunologic status of patients at HAART initiation, or duration on HAART.