Is oxidative stress MYC’s Achilles heel?

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Postdialysis blood pressure rise predicts long-term outcomes in chronic hemodialysis patients: a four-year prospective observational cohort study

<p>Abstract</p> <p>Background</p> <p>The blood pressure (BP) of a proportion of chronic hemodialysis (HD) patients rises after HD. We investigated the influence of postdialysis BP rise on long-term outcomes.</p> <p>Methods</p> <p>A total of 115 prevalent HD patients were enrolled. Because of the fluctuating nature of predialysis and postdialysis BP, systolic BP (SBP) and diastolic BP before and after HD were recorded from 25 consecutive HD sessions during a 2-month period. Patients were followed for 4 years or until death or withdrawal.</p> <p>Results</p> <p>Kaplan-Meier estimates revealed that patients with average postdialysis SBP rise of more than 5 mmHg were at the highest risk of both cardiovascular and all-cause mortality as compared to those with an average postdialysis SBP change between -5 to 5 mmHg and those with an average postdialysis SBP drop of more than 5 mmHg. Furthermore, multivariate Cox regression analysis indicated that both postdialysis SBP rise of more than 5 mmHg (HR, 3.925 [95% CI, 1.410-10.846], <it>p </it>= 0.008) and high cardiothoracic (CT) ratio of more than 50% (HR, 7.560 [95% CI, 2.048-27.912], <it>p </it>= 0.002) independently predicted all-cause mortality. We also found that patients with an average postdialysis SBP rise were associated with subclinical volume overload, as evidenced by the significantly higher CT ratio (<it>p </it>= 0.008).</p> <p>Conclusions</p> <p>A postdialysis SBP rise in HD patients independently predicted 4-year cardiovascular and all-cause mortality. Considering postdialysis SBP rise was associated with higher CT ratio, intensive evaluation of cardiac and volume status should be performed in patients with postdialysis SBP rise.</p

Esophageal perforation in South of Sweden: Results of surgical treatment in 125 consecutive patients

<p>Abstract</p> <p>Background</p> <p>For many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients.</p> <p>Methods</p> <p>125 consecutive patients treated at the University Hospital of Lund from 1970 to 2006 were studied retrospectively. Prognostic factors were evaluated using the Cox proportional hazards model.</p> <p>Results</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome. Neck incision for cervical perforation (n = 8) and treatment with a covered stent with or without open drainage for a thoracic perforation (n = 6) had the lowest mortality. Esophageal resection (n = 8) had the highest mortality. A CAT scan or an oesophageal X-ray with oral contrast were the most efficient diagnostic tools. The preferred treatment strategy changed over the course of the study period, from a more aggressive surgical approach towards using covered stents to seal the perforation.</p> <p>Conclusion</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome in this study. Treatment strategies are changing as less traumatic options have become available. Sealing an esophageal perforation with a covered stent, in combination with open or closed drainage when necessary, is a promising treatment strategy.</p

Investigating post-stroke fatigue: An individual participant data meta-analysis

The prevalence of post-stroke fatigue differs widely across studies, and reasons for such divergence are unclear. We aimed to collate individual data on post-stroke fatigue from multiple studies to facilitate high-powered meta-analysis, thus increasing our understanding of this complex phenomenon.Methods: We conducted an Individual Participant Data (IPD) meta-analysis on post-stroke fatigue and its associated factors. The starting point was our 2016 systematic review and meta-analysis of post-stroke fatigue prevalence, which included 24 studies that used the Fatigue Severity Scale (FSS). Study authors were asked to provide anonymised raw data on the following pre-identified variables: (i) FSS score, (ii) age, (iii) sex, (iv) time post-stroke, (v) depressive symptoms, (vi) stroke severity, (vii) disability, and (viii) stroke type. Linear regression analyses with FSS total score as the dependent variable, clustered by study, were conducted.Results: We obtained data from 14 of the 24 studies, and 12 datasets were suitable for IPD meta-analysis (total n = 2102). Higher levels of fatigue were independently associated with female sex (coeff. = 2.13, 95% CI 0.44–3.82, p = 0.023), depressive symptoms (coeff. = 7.90, 95% CI 1.76–14.04, p = 0.021), longer time since stroke (coeff. = 10.38, 95% CI 4.35–16.41, p = 0.007) and greater disability (coeff. = 4.16, 95% CI 1.52–6.81, p = 0.010). While there was no linear association between fatigue and age, a cubic relationship was identified (p < 0.001), with fatigue peaks in mid-life and the oldest old.Conclusion: Use of IPD meta-analysis gave us the power to identify novel factors associated with fatigue, such as longer time since stroke, as well as a non-linear relationship with age

Down-Regulation of MiR-127 Facilitates Hepatocyte Proliferation during Rat Liver Regeneration

Liver regeneration (LR) after partial hepatectomy (PH) involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells

People and Things on the Move: Domestic Material Culture, Poverty and Mobility in Victorian London

© 2016, The Author(s). The development of what Mayne and Lawrence (Urban History 26: 325–48, 1999) termed “ethnographic” approaches to studying nineteenth-century households and urban communities has gathered momentum in recent years. As such research agendas have taken hold and been applied to new contexts, so critiques, methodological developments, and new intellectual and theoretical currents, have provided opportunities to enhance and develop approaches. This article contributes to this on-going process. Drawing upon household archaeological research on Limehouse, a poor neighborhood in Victorian London, and inspired by the theoretical insights provided by the “new mobilities paradigm,” it aims to place “mobility” as a central and enabling intellectual framework for understanding the relationships between people, place, and poverty. Poor communities in nineteenth-century cities were undeniably mobile and transient. Historians and archaeologists have often regarded this mobility as an obstacle to studying everyday life in such contexts. However, examining temporal routines and geographical movements across a variety of time frames and geographical scales, this article argues that mobility is actually key to understanding urban life and an important mechanism for interpreting the fragmented material and documentary traces left by poor households in the nineteenth-century metropolis.We are grateful to the UK’s Arts and Humanities Research Council who funded the research upon which this paper is based (Grant Reference AH/E002285/1): ‘Living in Victorian London: Towards a Material History of Everyday Domestic Life in the Nineteenth-Century Metropolis

Evaluating the impact of MEDLINE filters on evidence retrieval: study protocol

<p>Abstract</p> <p>Background</p> <p>Rather than searching the entire MEDLINE database, clinicians can perform searches on a filtered set of articles where relevant information is more likely to be found. Members of our team previously developed two types of MEDLINE filters. The 'methods' filters help identify clinical research of high methodological merit. The 'content' filters help identify articles in the discipline of renal medicine. We will now test the utility of these filters for physician MEDLINE searching.</p> <p>Hypothesis</p> <p>When a physician searches MEDLINE, we hypothesize the use of filters will increase the number of relevant articles retrieved (increase 'recall,' also called sensitivity) and decrease the number of non-relevant articles retrieved (increase 'precision,' also called positive predictive value), compared to the performance of a physician's search unaided by filters.</p> <p>Methods</p> <p>We will survey a random sample of 100 nephrologists in Canada to obtain the MEDLINE search that they would first perform themselves for a focused clinical question. Each question we provide to a nephrologist will be based on the topic of a recently published, well-conducted systematic review. We will examine the performance of a physician's unaided MEDLINE search. We will then apply a total of eight filter combinations to the search (filters used in isolation or in combination). We will calculate the recall and precision of each search. The filter combinations that most improve on unaided physician searches will be identified and characterized.</p> <p>Discussion</p> <p>If these filters improve search performance, physicians will be able to search MEDLINE for renal evidence more effectively, in less time, and with less frustration. Additionally, our methodology can be used as a proof of concept for the evaluation of search filters in other disciplines.</p

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700