tbuckley/cabot-search huggingface dataset:
Use of antiretroviral therapy in households and risk of HIV acquisition in rural KwaZulu-Natal, South Africa, 2004–12: a prospective cohort study
Authors: Alain Vandormael, Marie-Louise Newell, Till Bärnighausen, Frank Tanser
Journal: The Lancet Global Health (2014)

Studies of HIV-serodiscordant couples in stable sexual relationships have provided convincing evidence that antiretroviral therapy can prevent the transmission of HIV. We aimed to quantify the preventive effect of a public-sector HIV treatment and care programme based in a community with poor knowledge and disclosure of HIV status, frequent migration, late marriage, and multiple partnerships. Specifically, we assessed whether an individual's hazard of HIV acquisition was associated with antiretroviral therapy coverage among household members of the opposite sex.In this prospective cohort study, we linked patients' records from a public-sector HIV treatment programme in rural KwaZulu-Natal, South Africa, with population-based HIV surveillance data collected between 2004 and 2012. We used information about coresidence to construct estimates of HIV prevalence and antiretroviral therapy coverage for each household. We then regressed the time to HIV seroconversion for 14,505 individuals, who were HIV-uninfected at baseline and individually followed up over time regarding their HIV status, on opposite-sex household antiretroviral therapy coverage, controlling for household HIV prevalence and a range of other potential confounders.2037 individual HIV seroconversions were recorded during 54,845 person-years of follow-up. For each increase of ten percentage points in opposite-sex household antiretroviral therapy coverage, the HIV acquisition hazard was reduced by 6% (95% CI 2–9), after controlling for other factors. This effect size translates into large reductions in HIV acquisition hazards when household antiretroviral therapy coverage is substantially increased. For example, an increase of 50 percentage points in household antiretroviral therapy coverage (eg, from 20% to 70%) reduced the hazard of HIV acquisition by 26% (95% CI 9–39).Our findings provide further evidence that antiretroviral therapy significantly reduces the risk of onward transmission of HIV in a real-world setting in sub-Saharan Africa. Awareness that antiretroviral therapy can prevent transmission to coresident sexual partners could be a powerful motivator for HIV testing and antiretroviral treatment uptake, retention, and adherence.Wellcome Trust and National Institute of Child Health and Human Development (US National Institutes of Health).
Pseudomonas aeruginosa and other related species
Authors: R. Wilson, R. B Dowling
Journal: Thorax (1998)

Pseudomonas aeruginosa was first obtained in pure culture by Gessard in 1882 from cutaneous wounds which had a blue green discolouration1 and is the major human pathogen from a large genus of strictly aerobic Gram-negative rods which are widely distributed in nature.2 The majority of P aeruginosa strains produce at least two pigments, a fluorescent yellow pigment and a blue pigment called pyocyanin, which together give the characteristic colour noted above when the bacterium is grown on agar.3 P aeruginosa is motile by means of a single flagellum and thrives in moist environments; it is extremely versatile biochemically and can grow in many habitats including soil, surface waters, plants and various foods such as vegetables eaten by man.2 4 In hospitals P aeruginosa can be found in sinks, respirators, humidifiers, etc, and is occasionally found on the hands of medical personnel.2 

P aeruginosa is an opportunistic pathogen which only causes disease in patients with impaired host defences. The patient’s defences may be generally weakened by debility or cancer, or there may be specific humeral or cellular defects. Neutropenic patients are especially susceptible to pseudomonas infection and to subsequent septicaemia. Alternatively, the body’s defences may be specifically breached as in corneal ulceration or skin burns, or artificially overcome as with assisted ventilation or by an indwelling urinary catheter.4 Patients with bronchiectasis are particularly prone to chronic infection, and delayed mucociliary clearance may be responsible.5 6 The use of broad spectrum antibiotics may kill commensal flora or more antibiotic-sensitive pathogenic species causing infection, and promote colonisation by the intrinsically resistant pseudomonas.7 P aeruginosa is particularly associated with progressive and ultimately fatal chronic respiratory infection in cystic fibrosis. Clues about the biological basis of this host-bacterial interaction which occurs almost inevitably are just being discovered. …
Oxaliplatin As Adjuvant Therapy for Colon Cancer: Updated Results of NSABP C-07 Trial, Including Survival and Subset Analyses
Authors: Greg Yothers, Michael J. O'Connell, Carmen J. Allegra, J. Philip Kuebler, Linda H. Colangelo, Nicholas J. Petrelli, Norman Wolmark
Journal: Journal of Clinical Oncology (2011)

The National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial demonstrated that the addition of oxaliplatin to fluorouracil plus leucovorin (FULV) improved disease-free survival (DFS) in patients with stage II or III colon cancer. This analysis is the first publication of overall survival (OS) for the NSABP C-07 study. We updated DFS and examined both end points in clinically relevant patient subsets.
The TNFR family members OX40 and CD27 link viral virulence to protective T cell vaccines in mice
Authors: Shahram Salek-Ardakani, Rachel Flynn, Ramon Arens, Hideo Yagita, Geoffrey L. Smith, Jannie Borst, Stephen P. Schoenberger, Michael Croft
Journal: Journal of Clinical Investigation (2010)

Induction of CD8+ T cell immunity is a key characteristic of an effective vaccine. For safety reasons, human vaccination strategies largely use attenuated nonreplicating or weakly replicating poxvirus-based vectors, but these often elicit poor CD8+ T cell immunity and might not result in optimal protection. Recent studies have suggested that virulence is directly linked to immunogenicity, but the molecular mechanisms underlying optimal CD8+ T cell responses remain to be defined. Here, using natural and recombinant vaccinia virus (VACV) strains, we have shown in mice that VACV strains of differing virulence induce distinct levels of T cell memory because of the differential use of TNF receptor (TNFR) family costimulatory receptors. With strongly replicating (i.e., virulent) VACV, the TNFR family costimulatory receptors OX40 (also known as CD134) and CD27 were engaged and promoted the generation of high numbers of memory CD8+ T cells, which protected against a lethal virus challenge in the absence of other mechanisms, including antibody and help from CD4+ T cells. In contrast, weakly replicating (i.e., low-virulence) VACV strains were poor at eliciting protective CD8+ T cell memory, as only the Ig family costimulatory receptor CD28 was engaged, and not OX40 or CD27. Our results suggest that the virulence of a virus dictates costimulatory receptor usage to determine the level of protective CD8+ T cell immunity.
Broadly neutralizing antibodies abrogate established hepatitis C virus infection
Authors: Ype P. de Jong, Marcus Dorner, Michiel C. Mommersteeg, Jing W. Xiao, Alejandro B. Balazs, Justin B. Robbins, Benjamin Y. Winer, Sherif Gerges, Kevin Vega, Rachael N. Labitt, Bridget M. Donovan, Erick Giang, Anuradha Krishnan, Luis Chiriboga, Michael R. Charlton, Dennis R. Burton, David Baltimore, Mansun Law, Charles M. Rice, Alexander Ploss
Journal: Science Translational Medicine (2014)

HCV-specific neutralizing antibodies protect humanized mice from challenge and suppress established infections.
PREVALENCE OF PAIN AND QUALITY OF LIFE IN HIGH-PERFORMANCE ATHLETES
Authors: L Martins, J Paiva, A Freitas, L Miguel, A Andrade, FAltermann Neto, A Bacha, L Dalenogare, WV Menezes, A Silva, MA Bolze, F Maia
Journal: British Journal of Sports Medicine (2014)

Background On study of athletes, science has been devoted focusing on athletic performance. However, more recently, researchers have been concerned with other aspects that transcend obtaining results such as the health and well being of high-performance athletes. Objective To investigate the occurrence of pain and associated factors and its relation to the quality of life in elite athletes of various sports. Design An observational, cross-sectional and analytical study. Setting Level of competition: International, World and Olympic. Participants The study population was composed of 86 high-performance athletes: 13 of judo, 42 of swimming, 22 of parachuting, and 9 of volleyball. Risk factor assessment The risk factors were: training aspects (sports practice time in years, number of training hours accumulated per week) and complementary training (stretching, resistance exercises and functional training). The evaluation was made by self-reported questionnaires. The occurrence of pain was assessed as a risk factor for quality of life. Main outcome measurements The prevalence of pain (primary outcome) was estimated by self-reported questionnaire referring to anatomical region that occurred. Quality of life (secondary outcome) was investigated using the WHOQOL-Brief. Results Sports practice time and gender were not associated with the occurrence of pain. Multiple logistic regression analysis showed that sport (Figure 1) and age were associated with the outcome (P&lt;.05). Pain was associated with lower quality of life in domains physical, psychological and environmental. Figure 1 Prevalence of pain according to sport. . Conclusions The occurrence of pain can affect the amount of training supported by the athlete, resulting in decreased performance. Therefore it is imperative the monitoring for reducing pain in elite athletes. These are highly demanded both psychologically and physically; that's why it is equally important that they also be assisted to improve their perceived quality of life.
T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing
Authors: Qi Zhou, Irene C. Schneider, Inan Edes, Annemarie Honegger, Patricia Bach, Kurt Schönfeld, Axel Schambach, Winfried S. Wels, Sabrina Kneissl, Wolfgang Uckert, Christian J. Buchholz
Journal: Blood (2012)
Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells
Authors: Stephen McCartney, William Vermi, Susan Gilfillan, Marina Cella, Theresa L. Murphy, Robert D. Schreiber, Kenneth M. Murphy, Marco Colonna
Journal: The Journal of Experimental Medicine (2009)

The double-stranded RNA (dsRNA) analogue poly(I:C) is a promising adjuvant for cancer vaccines because it activates both dendritic cells (DCs) and natural killer (NK) cells, concurrently promoting adaptive and innate anticancer responses. Poly(I:C) acts through two dsRNA sensors, Toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein-5 (MDA5). Here, we investigated the relative contributions of MDA5 and TLR3 to poly(I:C)-mediated NK cell activation using MDA5−/−, TLR3−/−, and MDA5−/−TLR3−/− mice. MDA5 was crucial for NK cell activation, whereas TLR3 had a minor impact most evident in the absence of MDA5. MDA5 and TLR3 activated NK cells indirectly through accessory cells and induced the distinct stimulatory cytokines interferon-α and interleukin-12, respectively. To identify the relevant accessory cells in vivo, we generated bone marrow chimeras between either wild-type (WT) and MDA5−/− or WT and TLR3−/− mice. Interestingly, multiple accessory cells were implicated, with MDA5 acting primarily in stromal cells and TLR3 predominantly in hematopoietic cells. Furthermore, poly(I:C)-mediated NK cell activation was not notably impaired in mice lacking CD8α DCs, providing further evidence that poly(I:C) acts through diverse accessory cells rather than solely through DCs. These results demonstrate distinct yet complementary roles for MDA5 and TLR3 in poly(I:C)-mediated NK cell activation.
Role of Soluble Vascular Endothelial Growth Factor Receptor-1 in the Vitreous in Proliferative Diabetic Retinopathy
Authors: Nozomu Matsunaga, Yuichi Chikaraishi, Hiroshi Izuta, Nahoko Ogata, Masamitsu Shimazawa, Miyo Matsumura, Hideaki Hara
Journal: Ophthalmology (2008)
Impaired regulatory capacities of B lymphocytes in systemic lupus erytematosus
Authors: J.-O. Pers, S. Lemoine, A. Morva, A. Saraux, C. Jamin, P. Youinou
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> B lymphocytes have the capacity to modulate autoimmune and inflammatory responses. In mice, activation of dendritic cells (DCs) and Th1 differentiation of T lymphocytes are repressed by a B cell dependent regulation. The aim of our study was to further analyse the regulatory properties of human B cells in systemic lupus erythematosus (SLE). <h3>Materials and methods</h3> B cells purified from the peripheral blood (PB) of four SLE patients and six healthy controls (HCs) were stimulated through CD40 and TLR9. They were co-cultured with either autologous DCs that were preliminary differentiated from PB monocytes with GM-CSF plus IL-4 and then with LPS plus interferon γ, or with autologous T cells stained with CFSE and stimulated with anti-CD3 and anti-CD28 antibodies. All analyses were performed by flow cytometry. Variations of HLA-DR, CD80 and CD86 expressions and of IL-12 production by the DCs were used to examine the B cell effects on DCs. The modulation of CFSE fluorescence was evaluated to determine the B cell effect on the T cell proliferative response. <h3>Results</h3> When cultured alone, differentiated DCs from HCs and SLE patients strongly expressed HLA-DR, CD80 and CD86, and produced high level of IL-12. In the presence of autologous B cells, densities of HLA-DR, CD80 and CD86 were decreased, while the production of IL-12 was downregulated in HC co-cultures, but not in SLE co-cultures. T lymphocytes from HCs and SLE patients proliferated following anti-CD3 and anti-CD28 stimulation. In the presence of autologous B cells, the proliferative response was inhibited in HC co-cultures, but unaffected in SLE co-cultures. <h3>Conclusions</h3> First, we demonstrate that human B cells can regulate DC differentiation. This is partially impaired in SLE since IL-12 production is not suppressed with SLE B cells. Second, human B cells can also control the proliferation of T cells. This capacity is defective in patients with SLE, since their B cells do not prevent T cell proliferation. This data raises the issue as to how overcome each deficiency in order to recover efficient regulatory B cell functions.
Atopic Diseases, Allergic Sensitization, and Exposure to Traffic-related Air Pollution in Children
Authors: Verena Morgenstern, Anne Zutavern, Josef Cyrys, Inken Brockow, Sibylle Koletzko, Ursula Krämer, Heidrun Behrendt, Olf Herbarth, Andrea von Berg, Carl Peter Bauer, H.-Erich Wichmann, Joachim Heinrich
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent.To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life.We studied 2,860 children at the age of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM(2.5)), PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants.Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM(2.5) absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no association was found for allergic sensitization.This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.
The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling
Authors: Hang-Zi Chen, Qing-Feng Liu, Li Li, Wei-Jia Wang, Lu-Ming Yao, Meng Yang, Bo Liu, Wei Chen, Yan-Yan Zhan, Ming-Qing Zhang, Jian-Chun Cai, Zhong-hui Zheng, Sheng-Cai Lin, Bo-An Li, Qiao Wu
Journal: Gut (2011)

<h3>Aims</h3> Wnt signalling is involved in cellular homeostasis and development. Dysregulation of the Wnt signalling pathway has been linked to colorectal cancer. The orphan nuclear receptor TR3 plays important roles in proliferation and apoptosis. In this study, we investigated how TR3 suppresses intestinal tumorigenesis by regulating Wnt signalling. <h3>Methods</h3> Intestinal polyps were quantified in <i>Apc<sup>min/+</sup></i>, <i>Apc<sup>min/+</sup>/TR3<sup>−/−</sup></i> and <i>Apc<sup>min/+</sup>/villin-TR3</i> mice. Wnt signalling activity was evaluated by assessing β-galactosidase activity in a BAT-Gal reporter strain. The TR3 agonist cytosporone B was used to evaluate the role of TR3 in intestinal tumorigenesis. Crosstalk between TR3 and β-catenin/TCF4 was analysed by molecular methods in colorectal cancer cells. The phosphorylation of TR3 by glycogen synthase kinase (GSK) 3β and the correlation between GSK3β activity and TR3 phosphorylation were evaluated in clinical samples and colorectal cancer cells. <h3>Results</h3> TR3 was found to significantly suppress Wnt signalling activity and the proliferation of intestinal epithelial cells. <i>Apc<sup>min/+</sup>/TR3<sup>−/−</sup></i> mice developed more intestinal polyps than <i>Apc<sup>min/+</sup>/TR3<sup>+/+</sup></i> mice, whereas either transgenic overexpression of TR3 in the intestine or treatment with cytosporone B in <i>Apc<sup>min/+</sup></i> mice significantly decreased intestinal tumour number. Mechanistically, TR3 disrupted the association of β-catenin and TCF4 on chromatin and facilitated the recruitment of transcriptional co-repressors to the promoters of Wnt signalling target genes. However, TR3 was phosphorylated by GSK3β in most clinical colorectal cancers, which attenuated the inhibitory activity of TR3 towards Wnt signalling. <h3>Conclusions</h3> TR3 is a negative regulator of Wnt signalling and thus significantly suppresses intestinal tumorigenesis in <i>Apc<sup>min/+</sup></i> mice. This inhibitory effect of TR3 may be paradoxically overcome through phosphorylation by GSK3β in clinical colorectal cancers.
Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi
Authors: Ola Snøve, John J Rossi
Journal: Genome biology (2006)

Short hairpin RNAs can provide stable gene silencing via RNA interference. Recent studies have shown toxicity in vivo that appears to be related to saturation of the endogenous microRNA pathway. Will these findings limit the therapeutic use of such hairpins?
Assisted reproductive technologies are an integrated part of national strategies addressing demographic and reproductive challenges
Authors: S. Ziebe, P. Devroey
Journal: Human Reproduction Update (2008)

The decline in the total fertility rate in the latter half of the 20th century in many European countries is becoming increasingly important in determining the demographic composition of Europe and its individual member states. This review focuses on discussion surrounding how assisted reproductive technology (ART) can impact declining fertility rates.This article summarizes key aspects of presentations given at the 'State of the ART 2007-ART and Society' meeting held in Lyon, France, in June 2007. For each topic, searches were conducted in MEDLINE and other databases and the results, alongside unpublished data and personal opinion, were presented to the Workshop Group. Individual subjects were discussed and any disagreements or omissions resolved.Although reduced fertility rates will have an impact on total population number, it is the change in the age structure of the population that is likely to be the most challenging factor faced by the European Union (EU). With evidence suggesting that an ageing population threatens future standards of living and social cohesion, managing demographic change through integrated policy response has become an important component of EU legislation. However, current measures fail to tackle the contribution that ART may play in alleviating falling fertility rates. Indeed, ART can have an important impact on economic and demographic factors, and should be incorporated into a population policy mix. Current barriers to ART include legislative restriction across different EU countries, limited availability to ART and current perception of ART in society.The inclusion of ART as part of a population policy mix in Europe is justified but must involve better communication among ART professionals, politicians and the general public.
Proteoglycans in granulomatous lung diseases
Authors: ES Bensadoun, AK Burke, JC Hogg, CR Roberts
Journal: European Respiratory Journal (1997)

In nongranulomatous fibrotic lung conditions, we have recently shown that early collagen synthesis by myofibroblasts occurs in an extracellular matrix rich in the proteoglycan versican. We hypothesized that versican is associated with the process of collagen synthesis resulting from chronic inflammation. In this study, we examined the localization of proteoglycans and collagen in the granulomatous lung conditions, sarcoidosis, extrinsic allergic alveolitis (EAA) and tuberculosis (TB). Tissue from individuals with sarcoidosis (n=6), EAA (n=4) and TB (n=2) was examined for glycosaminoglycans and collagen using histochemistry, and for versican, decorin, biglycan, hyaluronan, type I procollagen and alpha-smooth muscle actin using immunohistochemistry. The results showed that in sarcoidosis, EAA and TB, the rim of connective tissue surrounding granulomas contained glycosaminoglycans and collagen, and that glycosaminoglycan staining corresponded to localization of versican. Versican-rich zones contained myofibroblasts that stained intracellularly for type I procollagen. Hyaluronan was found diffusely throughout the matrix. Decorin was localized intracellularly in the epithelioid cells of granulomas and some myofibroblasts. We conclude that the deposition of versican is specific to the early remodelling process in both granulomatous and nongranulomatous lung diseases. In both forms of lung fibrosis, regardless of the nature of the driving inflammatory process, collagen synthesis takes place in a versican-rich provisional matrix. These results suggest that versican may influence the progression of the repair process following many different types of lung injury.