241 research outputs found
Mean sojourn time, overdiagnosis, and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening
This study aimed to assess the mean sojourn time (MST) of prostate cancer, to estimate the probability of overdiagnosis, and to predict the potential reduction in advanced stage disease due to screening with PSA. The MST of prostate cancer was derived from detection rates at PSA prevalence testing in 43 842 men, aged 50–69 years, as part of the ProtecT study, from the incidence of non-screen-detected cases obtained from the English population-based cancer registry database, and from PSA sensitivity obtained from the medical literature. The relative reduction in advanced stage disease was derived from the expected and observed incidences of advanced stage prostate cancer. The age-specific MST for men aged 50–59 and 60–69 years were 11.3 and 12.6 years, respectively. Overdiagnosis estimates increased with age; 10–31% of the PSA-detected cases were estimated to be overdiagnosed. An interscreening interval of 2 years was predicted to result in 37 and 63% reduction in advanced stage disease in men 65–69 and 50–54 years, respectively. If the overdiagnosed cases were excluded, the estimated reductions were 9 and 54%, respectively. Thus, the benefit of screening in reducing advanced stage disease is limited by overdiagnosis, which is greater in older men
Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2/3 and increasing MYL-9 expression
<p>Abstract</p> <p>Background</p> <p>Abnormal proliferation, apoptosis, migration and contraction of airway smooth muscle (ASM) cells in airway remodeling in asthma are basically excessive repair responses to a network of inflammatory mediators such as PDGF, but the mechanisms of such responses remain unclear. Nogo-B, a member of the reticulum family 4(RTN4), is known to play a key role in arteriogenesis and tissue repair. Further studies are needed to elucidate the role of Nogo-B in airway smooth muscle abnormalities.</p> <p>Methods</p> <p>A mouse model of chronic asthma was established by repeated OVA inhalation and subjected to Nogo-B expression analysis using immunohistochemistry and Western Blotting. Then, primary human bronchial smooth muscle cells (HBSMCs) were cultured <it>in vitro </it>and a siRNA interference was performed to knockdown the expression of Nogo-B in the cells. The effects of Nogo-B inhibition on PDGF-induced HBSMCs proliferation, migration and contraction were evaluated. Finally, a proteomic analysis was conducted to unveil the underlying mechanisms responsible for the function of Nogo-B.</p> <p>Results</p> <p>Total Nogo-B expression was approximately 3.08-fold lower in chronic asthmatic mice compared to naïve mice, which was obvious in the smooth muscle layer of the airways. Interference of Nogo-B expression by siRNA resulted nearly 96% reduction in mRNA in cultured HBSMCs. In addition, knockdown of Nogo-B using specific siRNA significantly decreased PDGF-induced migration of HBSMCs by 2.3-fold, and increased the cellular contraction by 16% compared to negative controls, but had limited effects on PDGF-induced proliferation. Furthermore, using proteomic analysis, we demonstrate that the expression of actin related protein 2/3 complex subunit 5 (ARPC 2/3) decreased and, myosin regulatory light chain 9 isoform a (MYL-9) increased after Nogo-B knockdown.</p> <p>Conclusions</p> <p>These data define a novel role for Nogo-B in airway remodeling in chronic asthma. Endogenous Nogo-B, which may exert its effects through ARPC 2/3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells.</p
The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition
ADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region
Molecular origin of enhanced proton conductivity in anhydrous ionic systems
YesIonic systems with enhanced proton conductivity are widely viewed as promising electrolytes in fuel cells and batteries. Nevertheless, a major challenge toward their commercial applications is determination of the factors controlling the fast proton hopping in anhydrous conditions. To address this issue, we have studied novel proton-conducting materials formed via a chemical reaction of lidocaine base with a series of acids characterized by a various number of proton-active sites. From ambient and high pressure experimental data, we have found that there are fundamental differences in the conducting properties of the examined salts. On the other hand, DFT calculations revealed that the internal proton hopping within the cation structure strongly affects the pathways of mobility of the charge carrier. These findings offer a fresh look on the Grotthuss-type mechanism in protic ionic glasses as well as provide new ideas for the design of anhydrous materials with exceptionally high proton conductivity
A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality
PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users
Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD
Assessment of serum catecholamine concentrations in patients with pheochromocytoma undergoing videolaparoscopic adrenalectomy
Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects
Synthesis of Tetranuclear Rhodium and Iridium Complexes Directed by 6-Mercaptopyridin-2-ol: Electrochemical Behavior, Chemical Oxidation, and Coordination Chemistry
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