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Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b-/- mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptortarget genes in Atp7b-/- mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to assess the impact of thrombus aspiration on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI). Background The clinical effect of routine intracoronary thrombus aspiration before primary PCI in patients with ST-segment elevation myocardial infarction is uncertain. Methods We undertook an observational cohort study of 10,929 ST-segment elevation myocardial infarction patients from January 2005 to July 2011 at 8 centers across London, United Kingdom. Patients’ details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society PCI dataset. Primary outcome was all-cause mortality at a median follow-up of 3.0 years (interquartile range: 1.2 to 4.6 years). Results In our cohort, 3,572 patients (32.7%) underwent thrombus aspiration during primary PCI. Patients who had thrombus aspiration were younger, had lower rates of previous myocardial infarction but were more likely to have poor left ventricular function. Procedural success rates were higher (90.9% vs. 89.2%; p = 0.005) and in-hospital major adverse cardiac event rates were lower (4.4% vs. 5.5%; p = 0.012) in patients undergoing thrombus aspiration. However, Kaplan-Meier analysis demonstrated no significant difference in mortality rates between patients with and without thrombus aspiration (14.8% aspiration vs. 15.3% PCI only; p = 0.737) during the follow-up period. After multivariate Cox analysis (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.65 to 1.23) and the addition of propensity matching (HR: 0.85 95% CI: 0.60 to 1.20) thrombus aspiration was still not associated with decreased mortality. Conclusions In this cohort of nearly 11,000 patients, routine thrombus aspiration was not associated with a reduction in long-term mortality in patients undergoing primary PCI, although procedural success and in-hospital major adverse cardiac event rates were improved. [ABSTRACT FROM AUTHOR]

Total parenteral nutrition (TPN) provides all nutrition intravenously. Although TPN therapy has grown enormously, it causes significant complications, including gut and hepatic dysfunction. Current models use animal tethering which is unlike ambulatory human TPN delivery and is cost prohibitive. We hypothesize that using ultramobile infusion pumps, TPN can be delivered cost-effectively, resulting in classical gut and hepatic injury, and we thus aim to establish a new model system. Neonatal pigs (n = 8) were implanted with jugular vein and duodenal catheters. Animals were fitted in dual-pocket jackets. An ultramobile ambulatory pump was placed in one pocket and connected to the jugular vein or duodenal catheter. Isocaloric TPN or swine formula was placed in the other pocket. Rigorous Wifi-based video and scheduled monitoring was performed. After 14 days, the animals were euthanized. The mean (±SD) daily weight gain (in grams) for enteral-fed control (EN) vs TPN animals was 102.4 ± 10.8 and 91.03 ± 12.1 respectively ( P < .05). Total parenteral nutrition resulted in significant conjugated bilirubin elevation and hepatomegaly. Mean (±SD) serum conjugated bilirubin (in μmol/L) was 1.5 ± 0.7 for EN and 6.3 ± 2.8 for TPN ( P < .05). Marked gut atrophy was noted with TPN. The mean (±SD) gut weight as a percent of body weight was 4.30 ± 0.26 for EN and 2.62 ± 0.48 for TPN ( P < .05). Surgical sites healed well. All animals remained completely mobile. We thus established that TPN can be successfully delivered using ultramobile pumps and believe that this remains the first such description of an ambulatory piglet TPN model system. In addition to cholestasis and gut atrophy, classical TPN-induced injury was documented. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to measure employees’ attitude toward distributed leadership (DL) practices and investigate the challenges involved in implementing DL practices in Indian organizations. Design/methodology/approach – This study is conducted within an exploratory research framework. The data were collected from 180 young middle-level executives from a diverse group of industry sectors belonging to private and multinational organization located in northern part of India. Unstructured (personal interviews and focus group interviews) and structured interview schedule (questionnaire) were administered to measure employees’ attitude and challenges of implementation. Findings – The qualitative and quantitative analytic strategies were adopted to analyze the data. Results of exploratory factors analysis showed the existence of five underlying dimensions about the significance of DL practices, namely, self-initiatives, improved functioning, achieving organizational goals, accountability and mutual respect. Furthermore, results showed the importance of contextual factors in implementing DL practices namely horizontal structure, professionalism, work commitment and power sharing. Also, the attitudinal dimensions were found to be positively correlated with the dimensions of implementing DL practices in Indian work context. Research limitations/implications – This study strengthens the importance of measuring employees’ attitudes that can be a good predictor of implementing best practices in organizations. The major limitation of this study is of the small sample size and has been limited to young managers. Originality/value – This is an original paper based on the empirical data from Indian managers. No study is conducted on the concept of distributing leadership in Indian work context on a similar or related theme. [ABSTRACT FROM AUTHOR]

Aims Myocardial revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) carries the risk of serious complications. Observational data suggest that outcomes may be improved by experienced operators, but there are few studies that have analysed the relationship between mortality and primary operator grade. The aim of this study was to investigate the effect of operator grade (trainee vs. consultant) upon outcomes of revascularization procedures. Methods and results This was an observational study at a tertiary cardiology centre with accredited training programmes, between 2003 and 2011. A total of 22 697 consecutive patients undergoing either CABG or PCI were included. Associations between operator grade and mortality were assessed by hazard ratios, estimated by Cox regression analyses; 6689 patients underwent CABG, whereas 16 008 underwent PCI. Trainees performed 1968 (29.4%) CABG procedures and 8502 (53.1%) PCI procedures. The proportion of procedures performed by trainees declined over time for both CABG (30.2% in 2003 vs. 26.0% in 2010) and for PCI (58.1% in 2003 vs. 44.5% in 2010). In the unadjusted Cox analysis, consultant operator grade was associated with an increased 5-year mortality after both CABG [HR: 1.26 (95% CI: 1.07–1.47)] and PCI procedures [HR: 1.34 (95% CI: 1.22–1.47)] compared with a trainee operator. However, following multiple adjustment, consultant grade was no longer associated with mortality after either procedure [CABG: HR: 1.02 (95% CI: 0.87–1.20), PCI: HR: 1.08 (95% CI: 0.98–1.20)]. Conclusion There was no observed detrimental effect on patient outcomes arising from procedures undertaken by trainees working in a structured training environment compared with consultants. [ABSTRACT FROM PUBLISHER]