The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Using formative research to develop the healthy eating component of the CHANGE! school-based curriculum intervention

Background: Childhood obesity is a significant public health concern. Many intervention studies have attempted to combat childhood obesity, often in the absence of formative or preparatory work. This study describes the healthy eating component of the formative phase of the Children’s Health Activity and Nutrition: Get Educated! (CHANGE!) project. The aim of the present study was to gather qualitative focus group and interview data regarding healthy eating particularly in relation to enabling and influencing factors, barriers and knowledge in children and adults (parents and teachers) from schools within the CHANGE! programme to provide populationspecific evidence to inform the subsequent intervention design. Methods: Semi-structured focus group interviews were conducted with children, parents and teachers across 11 primary schools in the Wigan borough of North West England. Sixty children (N = 24 boys), 33 parents (N = 4 male) and 10 teachers (N = 4 male) participated in the study. Interview questions were structured around the PRECEDE phases of the PRECEDE-PROCEED model. Interviews were transcribed verbatim and analysed using the pen-profiling technique. Results: The pen-profiles revealed that children’s knowledge of healthy eating was generally good, specifically many children were aware that fruit and vegetable consumption was ‘healthy’ (N = 46). Adults’ knowledge was also good, including restricting fatty foods, promoting fruit and vegetable intake, and maintaining a balanced diet. The important role parents play in children’s eating behaviours and food intake was evident. The emerging themes relating to barriers to healthy eating showed that external drivers such as advertising, the preferred sensory experience of “unhealthy” foods, and food being used as a reward may play a role in preventing healthy eating. Conclusions: Data suggest that; knowledge related to diet composition was not a barrier per se to healthy eating, and education showing how to translate knowledge into behavior or action is required. The key themes that emerged through the focus groups and pen-profiling data analysis technique will be used to inform and tailor the healthy eating component of the CHANGE! intervention study. Trial registration: Current Controlled Trials ISRCTN03863885 Keywords: Nutrition, Childhood obesity, Pen-profiles, Health, School

Recent Salmon Declines: A Result of Lost Feeding Opportunities Due to Bad Timing?

As the timing of spring productivity blooms in near-shore areas advances due to warming trends in global climate, the selection pressures on out-migrating salmon smolts are shifting. Species and stocks that leave natal streams earlier may be favoured over later-migrating fish. The low post-release survival of hatchery fish during recent years may be in part due to static release times that do not take the timing of plankton blooms into account. This study examined the effects of release time on the migratory behaviour and survival of wild and hatchery-reared coho salmon (Oncorhynchus kisutch) using acoustic and coded-wire telemetry. Plankton monitoring and near-shore seining were also conducted to determine which habitat and food sources were favoured. Acoustic tags (n = 140) and coded-wire tags (n = 266,692) were implanted into coho salmon smolts at the Seymour and Quinsam Rivers, in British Columbia, Canada. Differences between wild and hatchery fish, and early and late releases were examined during the entire lifecycle. Physiological sampling was also carried out on 30 fish from each release group. The smolt-to-adult survival of coho salmon released during periods of high marine productivity was 1.5- to 3-fold greater than those released both before and after, and the fish's degree of smoltification affected their downstream migration time and duration of stay in the estuary. Therefore, hatchery managers should consider having smolts fully developed and ready for release during the peak of the near-shore plankton blooms. Monitoring chlorophyll a levels and water temperature early in the spring could provide a forecast of the timing of these blooms, giving hatcheries time to adjust their release schedule

Colorectal cancer screening, perceived discrimination, and low-income and trust in doctors: a survey of minority patients

<p>Abstract</p> <p>Background</p> <p>Completion of colorectal cancer (CRC) screening testing is lower among low-income and minority groups than the population as a whole. Given the multiple cancer screening health disparities known to exist within the U.S., this study investigated the relationship between perceived discrimination, trust in most doctors, and completion of Fecal Occult Blood Testing (FOBT) among a low-income, minority primary care population in an urban setting.</p> <p>Methods</p> <p>We recruited a convenience sample of adults over age 40 (n = 282) from a federally qualified community health center (70% African American). Participants completed a survey which included measures of trust in most doctors, perceived discrimination, demographics and report of cancer screening.</p> <p>Results</p> <p>Participants reported high levels of trust in most doctors, regardless of sex, race, education or income. High trust was associated with low perceived discrimination (p < 0.01). The trend was for older participants to express more trust (p = 0.09) and less perceived discrimination (p < 0.01). Neither trust nor discrimination was associated with race or education. Trust was higher among participants over 50 who were up-to-date on FOBT screening vs. those who were not (31 vs. 29 (median), p < 0.05 by T-test). Among those over 50, up-to-date FOBT screening was nearly associated with high trust (p < 0.06; 95% CI 0.99, 1.28) and low perceived discrimination (p < 0.01; 95% CI 0.76, 0.96). Nevertheless, in multivariate-modeling, age and income explained FOBT completion better than race, trust and discrimination.</p> <p>Conclusion</p> <p>Perceived discrimination was related to income, but not race, suggesting that discrimination is not unique to minorities, but common to those in poverty. Since trust in most doctors trended toward being related to age, FOBT screening could be negatively influenced by low trust and perceived discrimination in health care settings. A failure to address these issues in middle-aged, low income individuals could exacerbate future disparities in CRC screening.</p

Integrated Assessment of Heavy Metal Contamination in Sediments from a Coastal Industrial Basin, NE China

The purpose of this study is to investigate the current status of metal pollution of the sediments from urban-stream, estuary and Jinzhou Bay of the coastal industrial city, NE China. Forty surface sediment samples from river, estuary and bay and one sediment core from Jinzhou bay were collected and analyzed for heavy metal concentrations of Cu, Zn, Pb, Cd, Ni and Mn. The data reveals that there was a remarkable change in the contents of heavy metals among the sampling sediments, and all the mean values of heavy metal concentration were higher than the national guideline values of marine sediment quality of China (GB 18668-2002). This is one of the most polluted of the world’s impacted coastal systems. Both the correlation analyses and geostatistical analyses showed that Cu, Zn, Pb and Cd have a very similar spatial pattern and come from the industrial activities, and the concentration of Mn mainly caused by natural factors. The estuary is the most polluted area with extremely high potential ecological risk; however the contamination decreased with distance seaward of the river estuary. This study clearly highlights the urgent need to make great efforts to control the industrial emission and the exceptionally severe heavy metal pollution in the coastal area, and the immediate measures should be carried out to minimize the rate of contamination, and extent of future pollution problems

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.