[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: People with prehypertension (120-130/80-90 mmHg) are at increased risk of progressing to hypertension. Recommendations for prehypertension include engaging in regular physical activity. We aimed to assess feasibility and acceptability and collect preliminary outcome data on ChiRunning for people with elevated blood pressure. ChiRunning is a commercially available running program based on the mindful movements of Tai Chi, which is aimed at decreasing injury by both increasing body awareness and modifying running form. METHODS: We enrolled adults with elevated systolic (130-150 mmHg) or diastolic (80-100 mmHg) blood pressure in a 12-week pilot trial. Participants were randomized 2:1:1 to 8 weeks of: 1) intervention-a trainer-led ChiRunning group (n = 10); 2) active control-a trainer-led running group (n = 6); or 3) educational control-a self-directed running group (n = 6) and followed for 4 more weeks. The active control and educational control groups were combined for analysis. RESULTS: This study was feasible, meeting recruitment, retention and adherence goals, and acceptable to participants. Systolic and diastolic blood pressure did not change significantly over the study for either the ChiRunning or control groups. Changes in BMI over time were significantly different from zero in the ChiRunning group (p = 0.04) but not in the control group (slope for ChiRunning -0.05 [-0.1 to -0.002] vs. control -0.01 [-0.06 to 0.04], between slope difference, p = 0.22). Self-reported running-related injury (i.e. discomfort leading to a decrease in running) was similar between groups (ChiRunning, 4 [1.2 to 8.4] vs. control, 3 [0.7 to 7.1] injuries per 100 h of running, p = 0.72) although self-reported running-related discomfort (i.e. discomfort that does not lead to changes in running) trended higher in the ChiRunning group (ChiRunning, 10 [5.4 to 16.8] vs. control, 4 [1.5 to 9] reports of discomfort per 100 h of running, p = 0.06). CONCLUSION: ChiRunning appears to be a feasible and acceptable exercise program for people with elevated blood pressure. We did not find that ChiRunning had a significant impact on blood pressure or self reported injury, but did see a positive change in BMI over time. ChiRunning warrants further investigation in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01587183.
BMC Complementary and Alternative Medicine 12/2015; 15:368. DOI:10.1186/s12906-015-0895-x · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We used a stress and coping model to examine the association of dispositional mindfulness, defined as the tendency to intentionally bring non-judgmental attention and awareness to one's experience in the present moment, with psychological and physical health in adults with HIV. Data were collected at baseline of a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR). Four facets of mindfulness (acting with attention/awareness, non-judging of inner experience, observing, and describing) were examined as correlates of appraisal, positive and negative affect, coping, and indicators of psychological well-being and physical health. We found that mindfulness was inversely related to depression, stress appraisal, and negative affect, and positively related to positive affect. Mindfulness was also inversely related to escape/avoidance and self-blame forms of coping. Mediational analyses indicate that perceived stress and negative affect were the most consistent mediators of the association of mindfulness and psychological well-being. The findings from this paper contribute to a growing understanding of the potential adaptive role of mindfulness in people living with the stress of serious illness.
[Show abstract][Hide abstract] ABSTRACT: We evaluated changes in mindful eating as a potential mechanism underlying the effects of a mindfulness-based intervention for weight loss on eating of sweet foods and fasting glucose levels. We randomized 194 obese individuals (M age = 47.0 ± 12.7 years; BMI = 35.5 ± 3.6; 78 % women) to a 5.5-month diet-exercise program with or without mindfulness training. The mindfulness group, relative to the active control group, evidenced increases in mindful eating and maintenance of fasting glucose from baseline to 12-month assessment. Increases in mindful eating were associated with decreased eating of sweets and fasting glucose levels among mindfulness group participants, but this association was not statistically significant among active control group participants. Twelve-month increases in mindful eating partially mediated the effect of intervention arm on changes in fasting glucose levels from baseline to 12-month assessment. Increases in mindful eating may contribute to the effects of mindfulness-based weight loss interventions on eating of sweets and fasting glucose levels.
Journal of Behavioral Medicine 11/2015; DOI:10.1007/s10865-015-9692-8 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.
We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.
Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).
It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission.
PLoS ONE 11/2015; 10(11):e0142638. DOI:10.1371/journal.pone.0142638 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gut microbes can profoundly modulate mucosal barrier-promoting Th17 cells in mammals. A salient feature of HIV/simian immunodeficiency virus (SIV) immunopathogenesis is the loss of Th17 cells, which has been linked to increased activity of the immunomodulatory enzyme, indoleamine 2,3-dioxygenase 1 (IDO 1). The role of gut microbes in this system remains unknown, and the SIV-infected rhesus macaque provides a well-described model for HIV-associated Th17 loss and mucosal immune disruption. We observed a specific depletion of gut-resident Lactobacillus during acute and chronic SIV infection of rhesus macaques, which was also seen in early HIV-infected humans. This depletion in rhesus macaques correlated with increased IDO1 activity and Th17 loss. Macaques supplemented with a Lactobacillus-containing probiotic exhibited decreased IDO1 activity during chronic SIV infection. We propose that Lactobacillus species inhibit mammalian IDO1 and thus may help to preserve Th17 cells during pathogenic SIV infection, providing support for Lactobacillus species as modulators of mucosal immune homeostasis.
[Show abstract][Hide abstract] ABSTRACT: T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.
Proceedings of the National Academy of Sciences 08/2015; 112(34):E4762-71. DOI:10.1073/pnas.1423228112 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obese individuals vary in their experience of food cravings and tendency to engage in reward-driven eating, both of which can be modulated by the neural reward system rather than physiological hunger. We examined two predictions in a sample of obese women: (1) whether opioidergic blockade reduced food-craving intensity, and (2) whether opioidergic blockade reduced an association between food-craving intensity and reward-driven eating, which is a trait-like index of three factors (lack of control over eating, lack of satiation, preoccupation with food).
Forty-four obese, pre-menopausal women completed the Reward-Based Eating Drive (RED) scale at study start and daily food-craving intensity on 5days on which they ingested either a pill-placebo (2days), a 25mg naltrexone dose (1day), or a standard 50mg naltrexone dose (2days).
Craving intensity was similar under naltrexone and placebo doses. The association between food-craving intensity and reward-driven eating significantly differed between placebo and 50mg naltrexone doses. Reward-driven eating and craving intensity were significantly positively associated under both placebo doses. As predicted, opioidergic blockade (for both doses 25mg and 50mg naltrexone) reduced the positive association between reward-driven eating and craving intensity to non-significance.
Opioidergic blockade did not reduce craving intensity; however, blockade reduced an association between trait-like reward-driven eating and daily food-craving intensity, and may help identify an important endophenotype within obesity.
Published by Elsevier Ltd.
[Show abstract][Hide abstract] ABSTRACT: Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the long-lived viral reservoir, but the low frequency of these cells makes this very challenging.
[Show abstract][Hide abstract] ABSTRACT: Introdução: As estratégias de prevenção da transmissão da infecção pelo vírus da imunodeficiência humana (HIV) em casais sorodiscordantes geralmente são voltadas para as pessoas HIV positivas, não havendo consenso sobre a abordagem das parcerias soronegativas.
Objetivo: Identificar e quantificar a ocorrência de comportamentos de risco em pessoas HIV negativas com parceria HIV positiva fixa.
Métodos: Examinamos a frequência com que os participantes de um estudo transversal relataram ter parceria HIV positiva no formulário padrão do serviço e/ou no questionário do estudo. Avaliamos comportamentos de risco e novos diagnósticos de infecção pelo HIV em pacientes “potencialmente sorodiscordantes” em comparação com os outros pacientes na população em geral. O diagnóstico de HIV foi realizado seguindo o algoritmo de testagem padrão. O teste BED EIA HIV-1 (Calypte Biomedical, Portland, OR; ODn cutoff=0,8) foi utilizado para classificar pessoas recentemente infectadas pelo HIV.
Resultados: Entre os 3.100 pacientes com nenhum teste reagente para HIV anterior, 490 (15,8%) relataram estar em um relacionamento fixo com uma pessoa HIV positiva. Esta proporção foi semelhante tanto para homens que fazem sexo com homens (HSH) como em heterossexuais. Menos da metade dos participantes reportou ter usado o preservativo durante o último ato sexual com o parceiro HIV positivo. Apenas um quarto dos homens heterossexuais e um terço dos HSH e mulheres reportaram o uso consistente de preservativos com seu parceiro no último ano. Os principais motivos para não usar preservativo com o parceiro fixo foram: “confia no parceiro” (31,7%), seguido de “não gosta” (15,1%) e “parceiro não aceita” (8,9%). Foram diagnosticadas novas infecções pelo HIV em 23% do grupo de pacientes potencialmente discordantes (versus 13% na população geral; p=0,01). Participantes com uso inconsistente de preservativos com parceiro fixo apresentaram uma chance 4 vezes maior de ter resultado positivo para HIV, quando comparados com aqueles que reportaram sempre usar preservativos com o parceiro fixo (OR=4,2; IC95% 2,3–7,5). Houve uma maior adesão à utilização de preservativos com parcerias casuais no último ato sexual, variando de 58,5% (homens heterossexuais) a 75% (HSH e mulheres).
Conclusão: Parcerias sorodiscordantes fixas, com elevado risco de transmissão do HIV, podem ser identificadas no momento da testagem e do aconselhamento. O acesso a essa população é fundamental para a implantação de estratégias de prevenção em localidades com alta incidência de HIV.
X Congresso da Sociedade Brasileira de DST - VI Congresso Brasileiro de AIDS, São Paulo, SP, Brazil; 05/2015
[Show abstract][Hide abstract] ABSTRACT: CD8+ T cells are important for HIV-1 virus control, but are also a major contributing factor that drives HIV-1 virus sequence evolution. Although HIV-1 cytotoxic T cell (CTL) escape mutations are a common aspect during HIV-1 infection, less is known about the importance of T cell pressure in reversing HIV-1 virus back to a consensus sequences. In this study we aimed to assess the frequency with which reversion of transmitted mutations in T cell epitopes were associated with T cell responses to the mutation. This study included 14 HIV-1 transmission pairs consisting of a 'source' (virus-donor) and a 'recipient' (newly infected individual). Non-consensus B sequence amino acids (mutations) in T cell epitopes in HIV-1 gag regions p17, p24, p2 and p7 were identified in each pair and transmission of mutations to the recipient was verified with population viral sequencing. Longitudinal analyses of the recipient's viral sequence were used to identify whether reversion of mutations back to the consensus B sequence occurred. Autologous 12-mer peptides overlapping by 11 were synthesized, representing the sequence region surrounding each reversion and longitudinal analysis of T cell responses to source-derived mutated and reverted epitopes were assessed. We demonstrated that mutations in the source were frequently transmitted to the new host and on an average 17 percent of mutated epitopes reverted to consensus sequence in the recipient. T cell responses to these mutated epitopes were detected in 7 of the 14 recipients in whom reversion occurred. Overall, these findings indicate that transmitted non-consensus B epitopes are frequently immunogenic in HLA-mismatched recipients and new T cell pressures to T cell escape mutations following transmission play a significant role in maintaining consensus HIV-1 sequences.
PLoS ONE 04/2015; 10(4):e0120787. DOI:10.1371/journal.pone.0120787 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background context:
Primary care clinicians need to identify candidates for early interventions to prevent patients with acute pain from developing chronic pain.
We conducted a 2-year prospective cohort study of risk factors for the progression to chronic pain and developed and internally validated a clinical decision rule (CDR) that stratifies patients into low-, medium-, and high-risk groups for chronic pain.
This is a prospective cohort study in primary care.
Patients with acute low back pain (LBP, ≤30 days duration) were included.
Outcome measures were self-reported perceived nonrecovery and chronic pain.
Patients were surveyed at baseline, 6 months, and 2 years. We conducted bivariate and multivariate regression analyses of demographic, clinical, and psychosocial variables for chronic pain outcomes, developed a CDR, and assessed its performance by calculating the bootstrapped areas under the receiver-operating characteristic curve (AUC) and likelihood ratios.
Six hundred five patients enrolled: 13% had chronic pain at 6 months and 19% at 2 years. An eight-item CDR was most parsimonious for classifying patients into three risk levels. Bootstrapped AUC was 0.76 (0.70-0.82) for the 6-month CDR. Each 10-point score increase (60-point range) was associated with an odds ratio of 11.1 (10.8-11.4) for developing chronic pain. Using a less than 5% probability of chronic pain as the cutoff for low risk and a greater than 40% probability for high risk, likelihood ratios were 0.26 (0.14-0.48) and 4.4 (3.0-6.3) for these groups, respectively.
A CDR was developed that may help primary care clinicians classify patients with strictly defined acute LBP into low-, moderate-, and high-risk groups for developing chronic pain and performed acceptably in 1,000 bootstrapped replications. Validation in a separate sample is needed.
The spine journal: official journal of the North American Spine Society 03/2015; 15(7). DOI:10.1016/j.spinee.2015.03.003 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
The stability of the HIV-1 reservoir and the contribution of cellular proliferation to the maintenance of the reservoir during treatment are uncertain. Therefore, we conducted a longitudinal analysis of HIV-1 in T-cell subsets in different tissue compartments from subjects on effective antiretroviral therapy (ART).
Using single-proviral sequencing, we isolated intracellular HIV-1 genomes derived from defined subsets of CD4+ T-cells from peripheral blood, gut-associated lymphoid tissue and lymph node tissue, from eight virally suppressed subjects on long-term ART at two time points, separated by 7-9 months.
DNA integrant frequencies were stable over time (<4-fold difference) and were highest in memory T-cells. Phylogenetic analyses showed that subjects treated during chronic infection contained viral populations with up to 73% identical sequence expansions, only three of which were observed in pre-therapy specimens. At both times points, such clonally expanded populations were found predominantly in effector memory T-cells from peripheral blood and lymph node tissue.
Memory T-cells maintained a relatively constant HIV-1 DNA integrant pool that was genetically stable during long-term effective ART. These integrants appear to be maintained by cellular proliferation and longevity of infected cells rather than by ongoing viral replication.
The Journal of Infectious Diseases 02/2015; 212(4). DOI:10.1093/infdis/jiv092 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To investigate the changes in running biomechanics after training in Form-Focused running using ChiRunning vs. Not-Form focused training and Self-Directed training in untrained individuals.Design: Pilot study - Randomized controlled trial. Setting: Research Institution with Tertiary Care Medical Center. Participants: Seventeen subjects (9 males, 8 females) with pre-hypertension. METHODS: Twenty-two participants were randomized to three study arms but 17 completed the study. The study arms were: 1) group-based Form-Focused running using ChiRunning (enrolled, n =10; completed, n=7); 2) group-based conventional running (enrolled, n =6; completed, n=4); 3) self-directed training with educational materials (enrolled, n =6; completed, n=6). The training schedule was prescribed for 8 weeks with 4 weeks of follow-up. All subjects completed overground running motion analyses before and after training. OUTCOMES: Ankle, knee, hip joint peak moments and powers; Average vertical loading rate (AVLR), impact peak, cadence, stride length, strike index, and stride reach. Paired T-tests were used to compare differences with-in groups over-time. RESULTS: Form-Focused group reduced their Stride Reach (P = .047) after the training but not the other groups. Form-Focused group showed a close to significant reduction in knee adduction moment (P = .051) and a reduction in the peak ankle eversion moment (P = .027). Self-Directed group showed an increase in the running speed, (P =.056) and increases in ankle and knee joint powers and moments. CONCLUSIONS: There are differences in the changes in running biomechanics between individuals trained in running form that emphazies mid-foot strike, higher cadence, and shorter stride compared to those not trained in the thise technique. These differences may be associated with reduced lower extremity stress in individuals trained in this running form but future studies are needed to confirm these findings in larger samples.
[Show abstract][Hide abstract] ABSTRACT: The eradication of HIV necessitates elimination of the HIV latent reservoir. Identifying host determinants governing latency and reservoir size in the setting of antiretroviral therapy (ART) is an important step in developing strategies to cure HIV infection. We sought to determine the impact of cell-intrinsic immunity on the HIV latent reservoir.
We investigated the relevance of a comprehensive panel of established anti-HIV-1 host restriction factors to multiple established virologic and immunologic measures of viral persistence in HIV-1-infected, ART-suppressed individuals.
We measured the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell-associated HIV-1 RNA, levels of total pol and 2-long terminal repeat (2-LTR) circle HIV-1 DNA and immunophenotypes of CD4 T cells in 72 HIV-1-infected individuals on suppressive ART (23 individuals initiated ART less than 1 year postinfection, and 49 individuals initiated ART greater than 1 year post-infection). Correlations were analysed using nonparametric tests.
The enhanced expression of a few select host restriction factors, p21, schlafen 11 and PAF1, was strongly associated with reduced CD4 T-cell associated HIV RNA during ART (P < 0.001). In addition, our data suggested that ART perturbs the regulatory relationship between CD4 T-cell activation and restriction factor expression. Lastly, cell-intrinsic immune responses were significantly enhanced in individuals who initiated ART during early versus chronic infection and may contribute to the reduced reservoir size observed in these individuals.
Intrinsic immune responses modulate HIV persistence during suppressive ART and may be manipulated to enhance the efficacy of ART and promote viral eradication through reversal of latency in vivo.
AIDS (London, England) 01/2015; 29(4). DOI:10.1097/QAD.0000000000000572 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The 9-item STarT-Back screening tool was developed in primary care patients with low back pain (LBP) to identify those at greatest risk for chronic pain and requiring targeted treatment. We conducted a secondary data analysis study to examine the performance of comparable questionnaire items in a sample of primary care patients with well-defined acute LBP.Methods
In a prospective cohort study, 605 primary care patients with LBP of less than 30 days answered a questionnaire with 6 items identical and 3 items analogous to the 9-item STarT-Back. Participants were followed up at 6 months and 2 years. STarT-Back rules were applied to classify participant's risk of chronic LBP, and the performance of the screening items in predicting outcomes was assessed using likelihood ratios.ResultsThe proportion of patients with chronic pain at follow-up was considerably lower (6 months: 22%; 2 years: 25%) than in the STarT-Back validation cohort (40%) of patients with pain of any duration. The probability of developing chronic pain given a high-risk designation by items similar to the STarT-Back increased the pre-test probability to 31% and 35%. Likelihood ratios were close to 1.ConclusionsA risk classification schema using the recommended cut-off scores with items similar to the STarT-Back in a primary care population with strictly defined acute LBP had limited ability to identify persons who progressed to chronic pain. The results suggest caution when applying the STarT-Back in patients with acute LBP and a need to consider a modification of its cut-offs.
European journal of pain (London, England) 12/2014; 19(3). DOI:10.1002/ejp.615 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1) in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.
PLoS ONE 10/2014; 9(10):e110731. DOI:10.1371/journal.pone.0110731 · 3.23 Impact Factor