Development of the Prevent for Work questionnaire (P4Wq) for assessment of musculoskeletal risk in the workplace: part 1-literature review and domains selection

Objective This study aims to define appropriate domains and items for the development of a self-administered questionnaire to assess the risk of developing work-related musculoskeletal disorder (WMSD) and the risk of its progression to chronicity. Design Literature review and survey study. Setting and participants A literature review and a two-round interview with 15 experts in musculoskeletal pain were performed to identify the available domains for WMSD assessment. Interventions and outcome To ensure quality, only validated questionnaires were included for the Delphi process. A three-round Delphi method, with three round steps, was used to select the most pertinent and relevant domains and items. Results Nine questionnaires were identified through the expert discussion and literature review, comprising 38 candidate domains and 504 items. In the first round of the Delphi group, 17 domains reached more than 70% agreement and were selected. In the second round, 10 domains were rejected, while 11 were selected to complete the pool of domains. In the third and final round, 89 items belonging to 28 domains were defined as significant to develop a WMSDs risk assessment questionnaire. Conclusions No specific risk assessment questionnaires for WMSDs were identified from the literature. WMSD risk of presence and chronicity can be defined by an assessment tool based on the biopsychosocial model and the fear-avoidance components of chronic pain. The present study provides the formulation and operationalisation of the constructs in domains and items needed for developing and validating the questionnaire

2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care: Endorsed by the American Heart Assocation, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d\u27intervention.

Although historically the intra-aortic balloon pump has been the only mechanical circulatory support device available to clinicians, a number of new devices have become commercially available and have entered clinical practice. These include axial flow pumps, such as Impella(®); left atrial to femoral artery bypass pumps, specifically the TandemHeart; and new devices for institution of extracorporeal membrane oxygenation. These devices differ significantly in their hemodynamic effects, insertion, monitoring, and clinical applicability. This document reviews the physiologic impact on the circulation of these devices and their use in specific clinical situations. These situations include patients undergoing high-risk percutaneous coronary intervention, those presenting with cardiogenic shock, and acute decompensated heart failure. Specialized uses for right-sided support and in pediatric populations are discussed and the clinical utility of mechanical circulatory support devices is reviewed, as are the American College of Cardiology/American Heart Association clinical practice guidelines

2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care: Endorsed by the American Heart Assocation, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d\u27intervention.

Although historically the intra-aortic balloon pump has been the only mechanical circulatory support device available to clinicians, a number of new devices have become commercially available and have entered clinical practice. These include axial flow pumps, such as Impella(®); left atrial to femoral artery bypass pumps, specifically the TandemHeart; and new devices for institution of extracorporeal membrane oxygenation. These devices differ significantly in their hemodynamic effects, insertion, monitoring, and clinical applicability. This document reviews the physiologic impact on the circulation of these devices and their use in specific clinical situations. These situations include patients undergoing high-risk percutaneous coronary intervention, those presenting with cardiogenic shock, and acute decompensated heart failure. Specialized uses for right-sided support and in pediatric populations are discussed and the clinical utility of mechanical circulatory support devices is reviewed, as are the American College of Cardiology/American Heart Association clinical practice guidelines

Evaluation of flow after transcatheter aortic valve replacement in patients with low-flow aortic stenosis : a secondary analysis of the PARTNER randomized clinical trial

Importance: Low-flow (LF) severe aortic stenosis (AS) is an independent predictor of mortality in patients undergoing aortic valve replacement (AVR). Little is known about improvement in flow after AVR and its effects on survival. Objective: To determine whether higher flow (left-ventricular stroke volume index [LVSVI]) after transcatheter AVR (TAVR) would indicate better clinical outcomes in this at-risk population. Design, Setting, and Participants: A substudy analysis of data from the Placement of Aortic Transcatheter Valves (PARTNER) randomized clinical trial and continued-access registry was conducted. A total of 984 participants with evaluable echocardiograms and baseline LF AS (LVSVI =35 mL/m2) were included. The trial was conducted at 26 sites in the United States and Canada. Patients were stratified after TAVR into tertiles by discharge LVSVI status (severe low flow [SLF], moderate low flow [MLF], and normal flow [(NF]). The present study was conducted from May 11, 2007, to January 9, 2012, with data analysis performed from April 25, 2014, to January 21, 2016. Main Outcomes and Measures: The primary end point was all-cause mortality at 1 year. Results: Baseline characteristics of 984 patients with LF AS included mean (SD) age, 84 (7) years; 582 (59.1%) men; mean Society of Thoracic Surgeons (STS) score, 11.4% (4.0%); and mean LVSVI, 27.6 (5.0) mL/m2. The discharge LVSVI values by group were SLF, 23.1 (3.5) mL/m2; MLF, 31.7 (2.2) mL/m2; and NF, 43.1 (7.0). All-cause mortality at 1 year was SLF, 26.5%; MLF, 20.1%; and NF, 19.6% (P¿=¿.045). Mean LVSVI normalized by 6 months in the MLF (35.9 [9.3] mL/m2) and NF (38.8 [11.1] mL/m2) groups, but remained low in the SLF group at 6 months and 1 year (31.4 [8.4] and 33.0 [8.3] mL/m2], respectively) (P¿<¿.001 for all groups). Reported as multivariate hazard ratio, mortality at 1 year was higher in the SLF group compared with the other groups (1.61; 95% CI, 1.17-2.23; P¿=¿.004). In addition to SLF, sex (1.59; 95% CI, 1.18-2.13; P¿=¿.002), presence of atrial fibrillation (1.41; 95% CI, 1.06-1.87; P¿=¿.02), STS score (1.03; 95% CI, 1.01-1.06; P¿=¿.02), presence of moderate or severe mitral regurgitation at discharge (1.65; 95% CI, 1.21-2.26; P¿=¿.001), pre-TAVR mean transvalvular gradient (0.98; 95% CI, 0.97-0.99; P¿=¿.004), and effective orifice area index (1.87; 95% CI, 1.09-3.19; P¿=¿.02) were independent predictors of 1-year mortality.CONCLUSIONS AND RELEVANCE: Severe LF at discharge is associated with an increased risk of mortality following TAVR in patients with severe AS and preexisting LF. The identification of remedial causes of persistent LF after TAVR may represent an opportunity to improve the outcome of these patients

Divergent transcriptional activities determine limb identity

Limbs develop using a common genetic programme despite widely differing morphologies. This programme is modulated by limb-restricted regulators such as hindlimb (HL) transcription factors Pitx1 and Tbx4 and the forelimb (FL) Tbx5. Both Tbx factors have been implicated in limb patterning and growth, but their relative activities and underlying mechanisms remain unclear. In this paper, we show that Tbx4 and Tbx5 harbour conserved and divergent transcriptional regulatory domains that account for their roles in limb development. In particular, both factors share an activator domain and the ability to stimulate limb growth. However, we find that Tbx4 is the primary effector of HL identity for both skeletal and muscle development; this activity relies on a repressor domain that is inactivated by a human TBX4 small-patella syndrome mutation. We propose that limb identity is largely achieved by default in FL, whereas a specific repressor activity unique to Tbx4 determines HL identity

Receptors for Hyaluronic Acid and Poliovirus: A Combinatorial Role in Glioma Invasion?

Background: CD44 has long been associated with glioma invasion while, more recently, CD155 has been implicated in playing a similar role. Notably, these two receptors have been shown closely positioned on monocytes. Methods and Findings: In this study, an up-regulation of CD44 and CD155 was demonstrated in established and earlypassage cultures of glioblastoma. Total internal reflected fluorescence (TIRF) microscopy revealed close proximity of CD44 and CD155. CD44 antibody blocking and gene silencing (via siRNA) resulted in greater inhibition of invasion than that for CD155. Combined interference resulted in 86 % inhibition of invasion, although in these investigations no obvious evidence of synergy between CD44 and CD155 in curbing invasion was shown. Both siRNA-CD44 and siRNA-CD155 treated cells lacked processes and were rounder, while live cell imaging showed reduced motility rate compared to wild type cells. Adhesion assay demonstrated that wild type cells adhered most efficiently to laminin, whereas siRNA-treated cells (p,0.0001 for both CD44 and CD155 expression) showed decreased adhesion on several ECMs investigated. BrdU assay showed a higher proliferation of siRNA-CD44 and siRNA-CD155 cells, inversely correlated with reduced invasion. Confocal microscopy revealed overlapping of CD155 and integrins (b1, avb1 and avb3) on glioblastoma cell processes whereas siRNAtransfected cells showed consequent reduction in integrin expression with no specific staining patterns. Reduced expression of Rho GTPases, Cdc42, Rac1/2/3, RhoA and RhoB, was seen in siRNA-CD44 and siRNA-CD155 cells. In contrast t

Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles.

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI