Risk of mortality with a bloodstream infection is higher in the less severely ill at admission

RATIONALE: Health care-associated bloodstream infections are common in critically ill patients; however, investigators have had difficulty in quantifying the clinical impact of these infections given the high expected mortality among these patients. OBJECTIVE: To estimate the impact of health care-associated bloodstream infections on in-hospital mortality after adjusting for severity of illness at critical care admission. METHOD: A cohort of medical and surgical intensive care unit patients. MEASUREMENTS: Severity of illness at admission, bloodstream infection, and in-hospital mortality. MAIN RESULTS: Among the 2,783 adult patients, 269 developed unit-associated bloodstream infections. After adjusting for severity of illness, patients with a lower initial severity of illness who developed an infection had a greater than twofold higher risk for in-hospital mortality (hazard ratio [HR] = 2.42, 95% confidence interval [CI] 1.70, 3.44) when compared with patients without infection and with a similar initial severity of illness. In contrast, patients with a higher initial severity of illness who subsequently developed an infection did not have an increased risk for in-hospital mortality (HR = 0.96, 95%CI 0.76, 1.23) when compared with patients without infection but with a similar initial severity of illness. CONCLUSIONS: These results suggest that these infections in less ill patients have a higher attributable impact on subsequent mortality than in more severely ill patients. Focusing interventions to prevent bloodstream infections in less severely ill patients would be expected to have a greater benefit in terms of mortality reduction.     

A scoping review of time-use research in occupational therapy and occupational science

Background: Time use is a defining interest within occupational therapy and occupational science. This is evident through the range of contributions to the disciplinary knowledge base. Indeed it has been suggested that time-use methods are amongst the most established research techniques used to explore aspects of human occupation. However, the extent and nature of such activity in occupational therapy and occupational science has not been examined to date. Aim: This study sought to map the extent and nature of time-use research in occupational therapy and occupational science journals and the extent to which studies explored the relationship between time-use and health. Method: A scoping review method was used. Results: Sixty-one studies were included. Scandinavian countries contributed the largest number of studies (n = 16, 26%). While time-use diaries were used most frequently (n = 30, 49%) occupational therapists and occupational scientists have developed a range of data-collection instruments. Forty-nine studies (80%) focused on time-use in clinical or defined population sub-groups. Ten studies (16%) included an empirical examination of the relationship between time-use and health. Conclusion: Future research should examine time-use and health amongst well populations across the lifespan and in different parts of the world.     

Development of a new bisphenol A electrochemical sensor based on a cadmium(ii) porphyrin modified carbon paste electrode

In this study, the (5,10,15,20-tetrakis[(4-methoxyphenyl)]porphyrinato)cadmium(ii) complex ([Cd(TMPP)]) was successfully used as a modifier in a carbon paste electrode (CPE) and exploited for bisphenol A (BPA) detection. Analytical performance revealed two linear ranges from 0.0015–15 μM and 0.015–1.5 mM with a detection limit of 13.5 pM. The proposed method was implemented in water samples, which resulted in quantitative signals over the range 6.5–1000 μM with recoveries between 92.6 and 107.7% for tap water and between 96.6 to 106.0% for mineral water.

In this study, the (5,10,15,20-tetrakis[(4-methoxyphenyl)]porphyrinato)cadmium(ii) complex ([Cd(TMPP)]) was successfully used as a modifier in a carbon paste electrode (CPE) and exploited for bisphenol A (BPA) detection.     

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.     

A variation in the ghrelin gene increases weight and decreases insulin secretion in tall,obese children

Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.     

Objective discrimination between mandibular open/close excursion patterns: a clinical case report

The purpose of this clinical case report was to describe the kinematic variables of movement that best discriminated between asymmetrical and symmetrical mandibular excursion patterns in a patient with myogenic temporomandibular dysfunction. Two mandibular movements (deemed to be asymmetrical and symmetrical by both patient and physiotherapist) were each recorded six times on three occasions at six, twelve, and 15 weeks after commencement of an exercise programme. The mandibular movements were captured with a 12-camera Motion Analysis System (Motion Analysis Corp., Santa Rosa, CA) with kinematic variables expressed in six degrees-of-freedom. A two-way analysis of variance (ANOVA) for repeated measures was used to analyze the data. The asymmetrical pattern was characterized by increased axial rotation and decreased sagittal rotation but with no differences in translation values when compared to those of the symmetrical pattern. The results support the clinician's and patient's judgment regarding differences in quality of mandibular excursion patterns made over the course of time.     

UHRF1 regulation of the Keap1–Nrf2 pathway in pancreatic cancer contributes to oncogenesis

The cellular defence protein Nrf2 is a mediator of oncogenesis in pancreatic ductal adenocarcinoma (PDAC) and other cancers. However, the control of Nrf2 expression and activity in cancer is not fully understood. We previously reported the absence of Keap1, a pivotal regulator of Nrf2, in ～70% of PDAC cases. Here we describe a novel mechanism whereby the epigenetic regulator UHRF1 suppresses Keap1 protein levels. UHRF1 expression was observed in 20% (5 of 25) of benign pancreatic ducts compared to 86% (114 of 132) of pancreatic tumours, and an inverse relationship between UHRF1 and Keap1 levels in PDAC tumours (n = 124) was apparent (p = 0.002). We also provide evidence that UHRF1‐mediated regulation of the Nrf2 pathway contributes to the aggressive behaviour of PDAC. Depletion of UHRF1 from PDAC cells decreased growth and enhanced apoptosis and cell cycle arrest. UHRF1 depletion also led to reduced levels of Nrf2‐regulated downstream proteins and was accompanied by heightened oxidative stress, in the form of lower glutathione levels and increased reactive oxygen species. Concomitant depletion of Keap1 and UHRF1 restored Nrf2 levels and reversed cell cycle arrest and the increase in reactive oxygen species. Mechanistically, depletion of UHRF1 reduced global and tumour suppressor promoter methylation in pancreatic cancer cell lines, and KEAP1 gene promoter methylation was reduced in one of three cell lines examined. Thus, methylation of the KEAP1 gene promoter may contribute to the suppression of Keap1 protein levels by UHRF1, although our data suggest that additional mechanisms need to be explored. Finally, we demonstrate that K‐Ras drives UHRF1 expression, establishing a novel link between this oncogene and Nrf2‐mediated cellular protection. Since UHRF1 over‐expression occurs in other cancers, its ability to regulate the Keap1–Nrf2 pathway may be critically important to the malignant behaviour of these cancers. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.