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51.

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Patients and Methods

Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c).

Results

A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P = .003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c.

Conclusion

Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations.  相似文献   
52.
ABSTRACT

The aim of the study was to assess the use of different positioning systems and sampling frequencies to measure spatial-positioning variables in team sports. Articles were selected when the sampling frequency was detailed. 2,194 articles were identified and 59 works were selected for the systematic review. The sampling frequency used to measure tactical behaviour differed considerably among studies. For Global Navigation Satellite System, the sampling frequency ranged from 5- to 15 Hz for raw data, the most commonly used sampling frequency being 5 Hz. For Optic-based tracking systems, the sampling frequency ranged from 10- to 30 Hz. For Local Position System, the sampling frequency ranged from 45- to 100 Hz, the most commonly used sampling frequency being 42 Hz and 57.7 Hz. There is no common criterion in the sampling frequency used to measure each tactical variable. Further studies should investigate the impact of the sampling frequency on the measurement of the tactical variables.  相似文献   
53.
Abstract

Background: Opioid overdose deaths constitute a public health crisis in the United States. Strategies for reducing opioid-related harm are underutilized due in part to clinicians’ low knowledge about harm reduction theory and limited preparedness to prescribe naloxone. Educational interventions are needed to improve knowledge and attitudes about, and preparedness to address, opioid overdoses among medical students. Methods: Informed by the Department of Veterans Affairs’ Overdose Education and Naloxone Distribution (OEND) program and narrative medicine, we developed and led a mandatory workshop on harm reduction for clerkship medical students. Using validated scales, we assessed students’ knowledge and attitudes about, and preparedness to address, opioid overdoses before the workshop and 6 weeks after. Results: Of 75 participating students from February through December 2017, 55 (73%) completed pre-workshop and 38 (51%) completed both pre- and post-workshop surveys. At baseline, 40 (73%) encountered patients with perceived at-risk opioid use in the previous 6 weeks, but only 11 (20%) recalled their teams prescribing naloxone for overdose prevention. Among those completing both surveys, knowledge about and preparedness to prevent overdose showed large improvement (Cohen’s d?=?0.85, P?<?.001; Cohen’s d?=?1.24, P?<?.001, respectively) and attitudes showed moderate improvement (Cohen’s d?=?0.32, P = .04). Discussion: Educational interventions grounded in harm reduction theory can increase students’ knowledge and attitudes about, and preparedness to address, opioid overdoses.  相似文献   
54.
ABSTRACT

Purpose

The aim of the present study was to assess the association between levels of physical activity (PA) and the presence of cataracts in people aged 15–69 years residing in Spain.  相似文献   
55.
Electrocatalytic generation of H2 is challenging in neutral pH water, where high catalytic currents for the hydrogen evolution reaction (HER) are particularly sensitive to the proton source and solution characteristics. A tris(hydroxymethyl)aminomethane (TRIS) solution at pH 7 with a [2Fe-2S]-metallopolymer electrocatalyst gave catalytic current densities around two orders of magnitude greater than either a more conventional sodium phosphate solution or a potassium chloride (KCl) electrolyte solution. For a planar polycrystalline Pt disk electrode, a TRIS solution at pH 7 increased the catalytic current densities for H2 generation by 50 mA/cm2 at current densities over 100 mA/cm2 compared to a sodium phosphate solution. As a special feature of this study, TRIS is acting not only as the primary source of protons and the buffer of the pH, but the protonated TRIS ([TRIS-H]+) is also the sole cation of the electrolyte. A species that is simultaneously the proton source, buffer, and sole electrolyte is termed a protic buffer electrolyte (PBE). The structure–activity relationships of the TRIS PBE that increase the HER rate of the metallopolymer and platinum catalysts are discussed. These results suggest that appropriately designed PBEs can improve HER rates of any homogeneous or heterogeneous electrocatalyst system. General guidelines for selecting a PBE to improve the catalytic current density of HER systems are offered.

Molecular hydrogen (H2), a clean-burning and energy-dense fuel source, has been widely discussed as an attractive way to store intermittent energy from solar and wind through water electrolysis (1, 2). Current commercial electrolyzers can be separated into two categories based on their operating pH. The first are acidic polymer electrolyte membrane electrolyzers that work best with rare and expensive platinum-based electrocatalysts for the hydrogen evolution reaction (HER) (3). The second are strongly alkaline electrolyzers that suffer from caustic basic reaction conditions (4). Neutral pH conditions with inexpensive catalysts composed of Earth-abundant elements are a target for practical solar-to-hydrogen fuel devices due to lower cost and fewer safety concerns (5), but achieving fast rates with mild overpotentials under neutral conditions remains a challenge (612). In the pH range from 5 to 9, the electrocatalytic activity of platinum (Pt) itself does not conform to the expected thermodynamic potential shift with pH dependence of −59 mV/pH (13). This is due to the low concentration of the hydronium ion in this pH range and a transition to water as the primary reactant, which has a higher thermodynamic requirement for hydrogen evolution (13). Studies of electrocatalysts using buffers to maintain the pH in this range and ionic salts such as potassium chloride (KCl) to provide ionic strength to ensure high solution conductivity have shown that the buffer can aid the HER activity, presumably by acting as a proton donor (6, 1418). To extend the scope of water-soluble electrocatalysts, biopolymers and bioinspired metallopolymer catalysts have also been studied (7, 12, 1726). Bren and coworkers recently reported particularly enlightening studies of the effects of buffer pKa and structure on the mechanism of the hydrogen evolution reaction for cobalt minienzymes (17, 18).We recently reported a new metallopolymer catalyst system built around a customized [2Fe-2S] catalyst site with a bridging aryldithiolato ligand which exhibits remarkable catalytic activity, air stability, and chemical stability (21). The electrocatalytic mechanism of the [2Fe-2S] catalysts with aryldithiolato ligands is known from previous studies and these catalysts operate at rates of 105 s−1 and faster (2730). The readily synthesized and water-soluble metallopolymer composed of tertiary amine side-chain groups, PDMAEMA-g-[2Fe-2S] (Fig. 1), approached the current density of Pt operating in neutral water under the same conditions and matched the Faradaic yield (97 ± 3%) (21). Although the detailed structural and mechanistic causality of these profound improvements for these metallopolymer electrocatalysts remain subjects of study, the nature of this molecular system is ideal for studying solution effects on the HER reaction at neutral pH for complexes that are normally insoluble in water. In the course of characterizing these electrocatalysts, solutions containing tris(hydroxymethyl)aminomethane (TRIS) at pH 7 were discovered to be exceptionally advantageous to the catalytic rate. In contrast to the few previous studies of TRIS buffer with electrocatalysts (14, 15, 18), we utilized TRIS at a high concentration. At pH 7, TRIS is sufficiently in the cationic protonated form that additional electrolyte such as KCl is not needed for conductance. This important distinction from conventional studies allows TRIS to simultaneously play the roles of pH buffer, proton source, and sole electrolyte. There is precedence in employing buffers in a manner in which they are the sole electrolyte (7, 3134). Referring to such species simply as a “buffer” or as an “electrolyte” is inadequate in representing the three functions including proton source. For the purposes of this paper we term a species that serves all three functions a protic buffer electrolyte (PBE). In the following discussion, a TRIS PBE solution is one in which [TRIS-H]+Cl is the sole electrolyte and the cation is a proton source, and a sodium phosphate PBE solution is one in which Na+[H2PO4] is the sole electrolyte and the anion is a proton source.Open in a separate windowFig. 1.(A) Depiction of the 2e electrocatalytic HER with POEGMA-g-[2Fe-2S] and/or PDMAEMA-g-[2Fe-2S] metallopolymers using TRIS or sodium phosphate protic buffer electrolytes at pH 7. (B) Image of POEGMA-g-[2Fe-2S] with MW = 14,216 grown in silico. The [2Fe-2S] active site is in the center of the polymer, blue represents the polymer backbone, and the rest are the oligo(ethylene glycol) side chains. See SI Appendix for the details of modeling and a larger image.One of the key unanswered questions for these new catalyst systems is whether the metallopolymer composition (i.e., amine side-chain groups) or the PBEs are more important to afford this outstanding catalytic activity. Herein we study the effects of PBEs by comparing the HER performances of a standard platinum catalyst and a [2Fe-2S] metallopolymer catalyst in TRIS PBE solutions, sodium phosphate PBE solutions, and a KCl electrolyte solution without a PBE. For this study, nonionic water-soluble metallopolymers were used, which were made using oligo(ethylene glycol) side-chain groups on the polymer to avoid the possibility of contributing effects of the protonated amino groups of PDMAEMA-g-[2Fe-2S] referred to earlier. The metallopolymer catalyst used in this work is designated as POEGMA-g-[2Fe-2S] (Fig. 1). We previously reported that this water-soluble metallopolymer was largely inactive for H2 electrocatalysis at neutral pH in phosphate buffer (22). The current findings suggest that the use of electrolytes composed of inexpensive cationic organic proton donors can be readily applied to any homogeneous or heterogeneous electrocatalyst system as a facile means to enhance HER activity.  相似文献   
56.
Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.

Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.

Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.  相似文献   

57.
Consensus has yet to be reached about the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ), which is a treatment sequela of several antiresorptive therapies and other pharmaceutical interventions. Several epidemiologic studies have identified periodontal disease (PD) as a risk factor for this outcome. Thus, the objective of this systematic review and meta-analysis was to investigate this association and its magnitude. A systematic search in MEDLINE via PubMed, Scopus and ISI Web of Science, and a meta-analysis were undertaken. Observational studies that gathered information regarding prefixed definitions for both outcomes were selected, and the relevant information was then extracted, and their risk of bias was evaluated using the Newcastle-Ottawa Scale. The protocol of the study was registered on PROSPERO (CRD42019125646). The initial search yielded 757 eligible records, of which 12 were deemed adequate for inclusion (5 cohort studies and 7 case-control studies). On a random-effects meta-analysis, the risk of PD in MRONJ-affected sites compared with at-risk non-affected patients was significantly greater, with a risk ratio of 2.75 (95% CI: 1.67-4.52). Nonetheless, from a pooled analysis of three standardized periodontal measures (ie plaque index, clinical attachment loss and probing depth) no significant results were obtained. MRONJ appears to be associated with an increase in prevalence of PD. The direction of this association, and the factors influencing it must be investigated using further prospective data, and likewise, the possibility for using periodontal therapy as a prevention strategy must be looked into. Periodontal screening needs to be made an indispensable requisite for clinicians in order to establish a correct multidisciplinary approach in MRONJ.  相似文献   
58.
Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.

Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.

Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.  相似文献   

59.

Background

Liver transplantation from donors after either controlled or uncontrolled cardiac death (DCD) is associated with considerable rates of primary nonfunction (PNF) and ischemic cholangiopathy (IC). Normothermic regional perfusion (NRP) could significantly reduce such rates.

Methods

Retrospective study to analyze short-term (mortality, PNF, vascular complications) and long-term (IC, survival) complications in 11 liver transplants from controlled DCDs using NRP with extracorporeal membrane oxygenation (ECMO) (group 1). They were compared with 51 patients transplanted with grafts from donors after brain death (DBD) (group 2). Mean recipient age, sex, and Model for End-stage Liver Disease (MELD) score were not significantly different.

Results

In group 1, mean functional warm ischemia time was 15.8 (range, 7–40) minutes and 94.1 (range, 20–150) minutes on NRP. The ischemic damage was minimal, as shown by the slight alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rises in the donor serum after 1 hour on NRP and similar rises 24 hours after transplantation in both groups. No patient had IC or acute renal failure. No significant difference was found between the groups for vascular or biliary complications. One group 1 patient had PNF (9.1%), resulting in death. Overall retransplantation and in-hospital death rates were 8.1% and 4.8%, respectively, with no significant difference between groups. Estimated mean survival was 24.6 (95% confidence interval [CI], 20.2–29.1) months in group 1 and 32.3 (95% CI, 30.4–34.2) months in group 2 (not a statistically significant difference).

Conclusion

In our experience, liver transplants from controlled DCDs using NRP with ECMO is associated with a low risk of PNF and IC, with short- and long-term results comparable to those in DBD transplants.  相似文献   
60.

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Methods and results

In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.

Conclusion

SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.  相似文献   
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