The diagnostic value of endoscopy and Helicobacter pylori tests for peptic ulcer patients in late post-treatment setting

BACKGROUND: Guidelines for management of peptic ulcer patients after the treatment are largely directed to detection of H. pylori infection using only non-invasive tests. We compared the diagnostic value of non-invasive and endoscopy based H. pylori tests in a late post-treatment setting. METHODS: Altogether 34 patients with dyspeptic complaints were referred for gastroscopy 5 years after the treatment of peptic ulcer using a one-week triple therapy scheme. The endoscopic and histologic findings were evaluated according to the Sydney classification. Bacteriological, PCR and cytological investigations and (13)C-UBT tests were performed. RESULTS: Seventeen patients were defined H. pylori positive by (13)C-UBT test, PCR and histological examination. On endoscopy, peptic ulcer persisted in 4 H. pylori positive cases. Among the 6 cases with erosions of the gastric mucosa, only two patients were H. pylori positive. Mucosal atrophy and intestinal metaplasia were revealed both in the H. pylori positive and H. pylori negative cases. Bacteriological examination revealed three clarithromycin resistant H. pylori strains. Cytology failed to prove validity for diagnosing H. pylori in a post-treatment setting. CONCLUSIONS: In a late post-treatment setting, patients with dyspepsia should not be monitored only by non-invasive investigation methods; it is also justified to use the classical histological evaluation of H. pylori colonisation, PCR and bacteriology as they have shown good concordance with (13)C-UBT. Moreover, endoscopy and histological investigation of a gastric biopsy have proved to be the methods with an additional diagnostic value, providing the physician with information about inflammatory, atrophic and metaplastic lesions of the stomach in dyspeptic H. pylori positive and negative patients. Bacteriological methods are suggested for detecting the putative antimicrobial resistance of H. pylori, aimed at successful eradication of infection in persistent peptic ulcer cases

Harmonic Allocation of Authorship Credit: Source-Level Correction of Bibliometric Bias Assures Accurate Publication and Citation Analysis

Authorship credit for multi-authored scientific publications is routinely allocated either by issuing full publication credit repeatedly to all coauthors, or by dividing one credit equally among all coauthors. The ensuing inflationary and equalizing biases distort derived bibliometric measures of merit by systematically benefiting secondary authors at the expense of primary authors. Here I show how harmonic counting, which allocates credit according to authorship rank and the number of coauthors, provides simultaneous source-level correction for both biases as well as accommodating further decoding of byline information. I also demonstrate large and erratic effects of counting bias on the original h-index, and show how the harmonic version of the h-index provides unbiased bibliometric ranking of scientific merit while retaining the original's essential simplicity, transparency and intended fairness. Harmonic decoding of byline information resolves the conundrum of authorship credit allocation by providing a simple recipe for source-level correction of inflationary and equalizing bias. Harmonic counting could also offer unrivalled accuracy in automated assessments of scientific productivity, impact and achievement

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

BACKGROUND: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. METHODS/DESIGN: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. SETTING: NHS stroke services. PARTICIPANTS: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. PRIMARY OUTCOME: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. SECONDARY OUTCOMES: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. SAMPLE SIZE: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. DISCUSSION: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013

Mycobacterium tuberculosis WhiB3 Maintains Redox Homeostasis by Regulating Virulence Lipid Anabolism to Modulate Macrophage Response

The metabolic events associated with maintaining redox homeostasis in Mycobacterium tuberculosis (Mtb) during infection are poorly understood. Here, we discovered a novel redox switching mechanism by which Mtb WhiB3 under defined oxidizing and reducing conditions differentially modulates the assimilation of propionate into the complex virulence polyketides polyacyltrehaloses (PAT), sulfolipids (SL-1), phthiocerol dimycocerosates (PDIM), and the storage lipid triacylglycerol (TAG) that is under control of the DosR/S/T dormancy system. We developed an in vivo radio-labeling technique and demonstrated for the first time the lipid profile changes of Mtb residing in macrophages, and identified WhiB3 as a physiological regulator of virulence lipid anabolism. Importantly, MtbΔwhiB3 shows enhanced growth on medium containing toxic levels of propionate, thereby implicating WhiB3 in detoxifying excess propionate. Strikingly, the accumulation of reducing equivalents in MtbΔwhiB3 isolated from macrophages suggests that WhiB3 maintains intracellular redox homeostasis upon infection, and that intrabacterial lipid anabolism functions as a reductant sink. MtbΔwhiB3 infected macrophages produce higher levels of pro- and anti-inflammatory cytokines, indicating that WhiB3-mediated regulation of lipids is required for controlling the innate immune response. Lastly, WhiB3 binds to pks2 and pks3 promoter DNA independent of the presence or redox state of its [4Fe-4S] cluster. Interestingly, reduction of the apo-WhiB3 Cys thiols abolished DNA binding, whereas oxidation stimulated DNA binding. These results confirmed that WhiB3 DNA binding is reversibly regulated by a thiol-disulfide redox switch. These results introduce a new paradigmatic mechanism that describes how WhiB3 facilitates metabolic switching to fatty acids by regulating Mtb lipid anabolism in response to oxido-reductive stress associated with infection, for maintaining redox balance. The link between the WhiB3 virulence pathway and DosR/S/T signaling pathway conceptually advances our understanding of the metabolic adaptation and redox-based signaling events exploited by Mtb to maintain long-term persistence

Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

<p>Abstract</p> <p>Objective</p> <p>Sympathetic stimulation leads to a change in electrical skin impedance. So far it is unclear whether this effect can be used to measure the effects of anaesthetics during general anaesthesia. The aim of this prospective study is to determine the electrical skin impedance during induction of anaesthesia for coronary artery bypass surgery with fentanyl and etomidate.</p> <p>Methods</p> <p>The electrical skin impedance was measured with the help of an electro-sympathicograph (ESG). In 47 patients scheduled for elective cardiac surgery, anaesthesia was induced with intravenous fentanyl 10 μg/kg and etomidate 0.3 mg/kg. During induction, the ESG (Electrosympathicograph), BIS (Bispectral IndeX), BP (arterial blood pressure) and HR (heart rate) values of each patient were recorded every 20 seconds. The observation period from administration of fentanyl to intubation for surgery lasted 4 min.</p> <p>Results</p> <p>The ESG recorded significant changes in the electrical skin impedance after administration of fentanyl and etomidate(p < 0.05). During induction of anaesthesia, significant changes of BIS, HR and blood pressure were observed as well (p < 0.05).</p> <p>Conclusions</p> <p>The electrical skin impedance measurement may be used to monitor the effects of anesthetics during general anaesthesia.</p

Effect of Angiogenesis Inhibitor Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor which has been used in conjunction with other anti-cancer agents in the treatment of patients with many cancers. It remains controversial whether bevacizumab can prolong survival in cancer patients. This meta-analysis was therefore performed to evaluate effect of bevacizumab on survival in cancer patients. PubMed, EMBASE, and Web of Science databases were searched for English-language studies of randomized controlled trials comparing bevacizumab with control therapy published through February 8, 2012. Progression-free survival, overall survival, and one-year survival rate were analyzed using random- or fixed-effects model. Thirty one assessable randomized controlled trials were identified. A significant improvement in progression-free survival in cancer patients was attributable to bevacizumab compared with control therapy (hazard ratio, 0.72; 95% confidence interval, 0.68 to 0.76; p<0.001). Overall survival was also significantly longer in patients were treated with bevacizumab (hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.91; p<0.001). The significant benefit in one-year survival rate was further seen in cancer patients receiving bevacizumab (odds ratio, 1.30; 95% confidence interval, 1.20 to 1.41; p<0.001). Current evidences showed that bevacizumab prolong progression-free survival and overall survival, and increase one-year survival rate in cancer patients as compared with control therapy

Acute kidney injury biomarkers: renal angina and the need for a renal troponin I

Acute kidney injury (AKI) in hospitalized patients is independently associated with increased morbidity and mortality in pediatric and adult populations. Continued reliance on serum creatinine and urine output to diagnose AKI has resulted in our inability to provide successful therapeutic and supportive interventions to prevent and mitigate AKI and its effects. Research efforts over the last decade have focused on the discovery and validation of novel urinary biomarkers to detect AKI prior to a change in kidney function and to aid in the differential diagnosis of AKI. The aim of this article is to review the AKI biomarker literature with a focus on the context in which they should serve to add to the clinical context facing physicians caring for patients with, or at-risk for, AKI. The optimal and appropriate utilization of AKI biomarkers will only be realized by understanding their characteristics and placing reasonable expectations on their performance in the clinical arena

Influence of Primary Care Physician Availability and Socioeconomic Deprivation on Breast Cancer from 1988 to 2008: A Spatio-Temporal Analysis

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States. It is unclear how county-level primary care physician (PCP) availability and socioeconomic deprivation affect the spatial and temporal variation of breast cancer incidence and mortality.We used the 1988-2008 public-use county-based data from nine Surveillance, Epidemiology, and End Results (SEER) programs to analyze the temporal and spatial disparity of PCP availability and socioeconomic deprivation on early-stage incidence, advanced-stage incidence and breast cancer mortality. The spatio-temporal analysis was implemented by a novel structural additive modeling approach.Greater PCP availability was significantly associated with higher early-stage incidence, advanced-stage incidence and mortality during the entire study period while socioeconomic deprivation was significantly negatively associated with early-stage incidence, advanced-stage incidence, and mortality up to 1992. However, the observed influence of PCP availability and socioeconomic deprivation varied by county.We showed important associations of PCP availability and socioeconomic deprivation with the three breast cancer indicators. However, the effect of these associations varied over time and across counties. The association of PCP availability and socioeconomic deprivation was stronger in selected counties