The Value of Removing Daily Obstacles via Everyday Problem-Solving Theory: Developing an Applied Novel Procedure to Increase Self-Efficacy for Exercise

The objective of the study was to develop a novel procedure to increase self-efficacy for exercise. Gains in one’s ability to resolve day-to-day obstacles for entering an exercise routine were expected to cause an increase in self-efficacy for exercise. Fifty-five sedentary participants (did not exercise regularly for at least 4 months prior to the study) who expressed an intention to exercise in the near future were selected for the study. Participants were randomly assigned to one of three conditions: (1) an Experimental Group in which they received a problem-solving training session to learn new strategies for solving day-to-day obstacles that interfere with exercise, (2) a Control Group with Problem-Solving Training which received a problem-solving training session focused on a typical day-to-day problem unrelated to exercise, or (3) a Control Group which did not receive any problem-solving training. Assessment of obstacles to exercise and perceived self-efficacy for exercise were conducted at baseline; perceived self-efficacy for exercise was reassessed post-intervention (1 week later). No differences in perceived challenges posed by obstacles to exercise or self-efficacy for exercise were observed across groups at baseline. The Experimental Group reported greater improvement in self-efficacy for exercise compared to the Control Group with Training and the Control Group. Results of this study suggest that a novel procedure that focuses on removing obstacles to intended planned fitness activities is effective in increasing self-efficacy to engage in exercise among sedentary adults. Implications of these findings for use in applied settings and treatment studies are discussed

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.

ObjectivesTo examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.DesignOpen-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study.MethodsHIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.ResultsAll eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046).ConclusionSBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy

Unbiased molecular analysis of T cell receptor expression using template-switch achored RT-PCR

A detailed knowledge of the principles that guide clonal selection within the memory and effector T cell pools is essential to further our understanding of the factors that influence effective T cell-mediated immunity and has direct implications for the rational design of vaccines and immunotherapies. This unit provides methods for the unbiased quantification and characterization of all expressed T cell receptor (TCR) gene products within any defined T cell population. The approach is based on a template-switch anchored reverse transcription–polymerase chain reaction (RT-PCR) and is optimized for the analysis of antigen-specific T cells isolated directly ex vivo

A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

The clonal composition of human CD4+CD25+Foxp3+ cells determined by a comprehensive DNA-based multiplex PCR for TCRB gene rearrangements

The characterization of the T-cell receptor (TCR) repertoire of CD4+ regulatory T cells (TR) have been limited due to the RNA degradation that results following permeabilization and fixation as routinely used for intracellular staining of Foxp3. In the present study the clonal composition of human umbilical cord blood (UCB) and adult peripheral blood mononuclear cells (PBMC) CD4+ TR and non-TR was characterized by a DNA-based multiplex PCR which allowed for the consistent clonotypic characterization of cells that have undergone fixation and permeabilization. To validate this method, CD8+ T cells from two HLA A*0201 individuals were sorted and compared clonotypically based upon their ability either to secrete interferon-γ in response to a CMV pp65 epitope or to bind to the corresponding pMHC I tetramer. In the UCB and PBMCs clonotypes shared between the CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− was observed in all 3 UCB and in one adult PBMCs, suggesting that naïve and memory CD4+ TR can share the same clonotypes as CD4+ non-TR in humans

Viral population estimation using pyrosequencing

The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well as for vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used for quantifying this diversity by ultra-deep sequencing of virus samples. We present computational methods for the analysis of such sequence data and apply these techniques to pyrosequencing data obtained from HIV populations within patients harboring drug resistant virus strains. Our main result is the estimation of the population structure of the sample from the pyrosequencing reads. This inference is based on a statistical approach to error correction, followed by a combinatorial algorithm for constructing a minimal set of haplotypes that explain the data. Using this set of explaining haplotypes, we apply a statistical model to infer the frequencies of the haplotypes in the population via an EM algorithm. We demonstrate that pyrosequencing reads allow for effective population reconstruction by extensive simulations and by comparison to 165 sequences obtained directly from clonal sequencing of four independent, diverse HIV populations. Thus, pyrosequencing can be used for cost-effective estimation of the structure of virus populations, promising new insights into viral evolutionary dynamics and disease control strategies.Comment: 23 pages, 13 figure

Contrast-enhanced imaging in the biological and functional assessment of breast cancer

Contrast-enhanced MRI and ultrasound have emerged as additional imaging modalities in the management of breast cancer. This thesis examines the role these modalities currently play in the surgical management of breast cancer. Ways in which MRI may contribute to staging, diagnosis, treatment and prognosis are investigated. It was demonstrated that small additional enhancing foci on MRI, away from the primary tumour, represent in-situ or invasive cancer foci. Although their resection may result in extended wide local excisions or even unnecessary mastectomies, it was demonstrated that MRI findings do not currently influence the amount of tissue removed during breast conservation surgery. Volumetric analysis of breast MRI was proposed as an accurate objective assessment of the extent of surgery required for a particular tumour. Breast MRI was shown to be useful in the assessment of extent of residual disease during primary medical therapy but not in the detection of axillary lymph node metastases. In the second section of this thesis, the clinical application of pre-operative MRI in providing prognostic as well as diagnostic information was evaluated. Contrast- enhancement with both MRI and ultrasound is believed to depend on tumour angiogenesis but only a weak correlation was demonstrated between contrast- enhancement intensity and tumour angiogenesis. The detection of angiogenesis was applied to Doppler ultrasound using a novel microbubble ultrasound contrast agent (Levovist). Within a multicentre prospective study, Doppler ultrasound was shown to be a powerful discriminator of malignancy in suspected local recurrence. A strong correlation was found between MRI and histological assessment of tumour size but there was no correlation between enhancement intensity and other pathological prognostic variables. This thesis has shown that breast MRI is useful in pre-operative planning of surgery and provides diagnostic as well as limited prognostic information. Future proposed studies to determine the effect of MRI on patient management and patient outcome in breast cancer are considered

The Tug between Private and Public Power Online

Professor Zittrain\u27s article describes, in his characteristically vivid and engaging way, one of the most consequential tugs of war of the internet age: the battle over the rules for what can and cannot be said online. The legal centerpiece of Zittrain\u27s story is the Skokie case from the late 1970s, which held that Nazis had a First Amendment right to march in a Chicago suburb with a large population of Holocaust survivors.1 Zittrain calls the case a near-perfect encapsulation of mainstream late twentieth century characterization of the right to free speech in America. 2 And he\u27s right-there is perhaps no more iconic decision in the First Amendment canon.3 It is considered by many to be one of the truly great victories for the First Amendment. 4 And the Skokie case matters to the tug of war over online speech because the ethos of American civil libertarianism that reached apogee in the 1960s and 70s political and legal establishments in turn infused the mainstream use of the Internet. 5 No other case so neatly encapsulates the spirit of the early internet era