clinical research with a comprehensive, concerted, international effort. This research will contribute to a better understanding of participant recruitment to RCTs, which could enhance efficiency and reduce the waste of resources in clinical research with a comprehensive, concerted, international effort. Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 11 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019. ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.An amendment to this paper has been published and can be accessed via the original article.In the context of a continuously increased delay of motherhood and of an increase of the incidence of premature ovarian failure, it is of the greatest interest to dispose of a predictive marker of the duration of the fertility window. Unfortunately, current available markers of women's fertility (hormonal rates or echography count of small follicles) have a poor predictive value of premature ovarian failure. In the last ten years, some studies have suggested that telomere length may be correlated with premature ovarian failure, but the results of these studies are contradictory.In accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this systematic review of the literature selected studies evaluating telomere length or telomerase activity in granulosa cells and/or in leukocytes as a premature ovarian failure marker.Five publications (252 premature ovarian failure patients) were included in this review of experimental evidence. Two of them studied telomerleucocytes as an early and reliable marker for the decline of ovarian function.Molecular chaperones and co-chaperones, which are part of the protein quality control machinery, have been shown to regulate distinct aspects of Alzheimer's Disease (AD) pathology in multiple ways. Notably, the co-chaperone STI1, which presents increased levels in AD, can protect mammalian neurons from amyloid-β toxicity in vitro and reduced STI1 levels worsen Aβ toxicity in C. elegans. However, whether increased STI1 levels can protect neurons in vivo remains unknown. We determined that overexpression of STI1 and/or Hsp90 protected C. https://www.selleckchem.com/products/on123300.html elegans expressing Aβ(3-42) against Aβ-mediated paralysis. Mammalian neurons were also protected by elevated levels of endogenous STI1 in vitro, and this effect was mainly due to extracellular STI1. Surprisingly, in the 5xFAD mouse model of AD, by overexpressing STI1, we find increased amyloid burden, which amplifies neurotoxicity and worsens spatial memory deficits in these mutants. Increased levels of STI1 disturbed the expression of Aβ-regulating enzymes (BACE1 and MMP-2), suggesting potential mechanisms by which amyloid burden is increased in mice. Notably, we observed that STI1 accumulates in dense-core AD plaques in both 5xFAD mice and human brain tissue. Our findings suggest that elevated levels of STI1 contribute to Aβ accumulation, and that STI1 is deposited in AD plaques in mice and humans. We conclude that despite the protective effects of STI1 in C. elegans and in mammalian cultured neurons, in vivo, the predominant effect of elevated STI1 is deleterious in AD. Arteriovenous (AV) hemodialysis access creation is recommended by international guidelines as the preferred method of hemodialysis access. However, most AV access sites will require revision to maintain patency. Although several treatment options exist, many have not been directly compared. We intend to compare the relative effectiveness of methods to maintain post-intervention primary patency of failing AV access. We will search EMBASE, MEDLINE, CENTRAL, trial registries, the grey literature, and ancestry and citation search from January 1977 to present, for randomized controlled trials comparing interventions to maintain primary patency of AV access. Two investigators will independently and blindly review all identified citations and extract data from included studies. The primary outcome is the primary patency 6 months after intervention. Secondary outcomes include immediate technical and functional success, reinterventions, patency, and mortality. Risk of bias, subgroup analyses, and sensitivity analyses are planned. There are a number of treatment modalities for the management of failing AV access. However, most modalities have only been directly compared with plain old balloon angioplasty, and currently synthesized evidence focuses on individual pairwise comparisons. In light of the lack of comprehensively synthesized evidence and clinical equipoise, our study intends to synthesize currently available evidence though it is unclear which treatment modality is most effective. PROSPERO ID CRD42020148224. PROSPERO ID CRD42020148224.