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Evguenia Krastinova Remonie Seng Patrick Yeni Jean-Paul Viard Daniel Vittecoq Caroline Lascoux-Combe Erwan Fourn Golriz Pahlavan Jean Fran?ois Delfraissy Laurence Meyer for the ANRS PRIMO COPANA Cohorts 《PloS one》2013,8(8)
Objective
Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France.Methods
Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996–2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004–2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively.Results
ART initiation during PHI dramatically decreased from 91% of patients in 1996–99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm3 in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm3. Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions.Conclusion
HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients’ living conditions and physicians’ perceptions influence the decision to initiate treatment. 相似文献2.
Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity 下载免费PDF全文
George L. Sutphin Grant Backer Susan Sheehan Shannon Bean Caroline Corban Teresa Liu Marjolein J. Peters Joyce B. J. van Meurs Joanne M. Murabito Andrew D. Johnson Ron Korstanje the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium Gene Expression Working Group 《Aging cell》2017,16(4):672-682
We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity‐correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported. The five genes with the greatest impact on lifespan (>20% extension) encode the enzyme kynureninase (kynu‐1), a neuronal leucine‐rich repeat protein (iglr‐1), a tetraspanin (tsp‐3), a regulator of calcineurin (rcan‐1), and a voltage‐gated calcium channel subunit (unc‐36). Knockdown of each gene extended healthspan without impairing reproduction. kynu‐1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and Huntington's disease. Each gene displayed a distinct pattern of interaction with known aging pathways. In the context of published work, kynu‐1, tsp‐3, and rcan‐1 are of particular interest for immediate follow‐up. kynu‐1 is an understudied member of the kynurenine metabolic pathway with a mechanistically distinct impact on lifespan. Our data suggest that tsp‐3 is a novel modulator of hypoxic signaling and rcan‐1 is a context‐specific calcineurin regulator. Our results validate C. elegans as a comparative tool for prioritizing human candidate aging genes, confirm age‐associated gene expression data as valuable source of novel longevity determinants, and prioritize select genes for mechanistic follow‐up. 相似文献
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KC Lødrup Carlsen S Roll KH Carlsen P Mowinckel AH Wijga B Brunekreef M Torrent G Roberts SH Arshad I Kull U Krämer A von Berg E Eller A Høst C Kuehni B Spycher J Sunyer CM Chen A Reich A Asarnoj C Puig O Herbarth JM Mahachie John K Van Steen SN Willich U Wahn S Lau T Keil;GALEN WP . ‘Birth Cohorts’ working group 《PloS one》2012,7(8):e43214
Objective
To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years.Design
Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s.Exposure definition
Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life.Outcome definition
Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age.Data synthesis
Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.Results
We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.Conclusions
Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given. 相似文献
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