Antimicrobial Activity of the Quinoline Derivative HT61 against Staphylococcus aureus Biofilms.

Staphylococcus aureus biofilms are a significant problem in health care settings, partly due to the presence of a nondividing, antibiotic-tolerant subpopulation. Here we evaluated treatment of S. aureus UAMS-1 biofilms with HT61, a quinoline derivative shown to be effective against nondividing Staphylococcus spp. HT61 was effective at reducing biofilm viability and was associated with increased expression of cell wall stress and division proteins, confirming its potential as a treatment for S. aureus biofilm infections

Injury patterns of South African provincial cricket players over two seasons

Objective. To determine the incidence and nature of injury patternsin elite cricketers over two seasons.Methods. Physiotherapists and/or doctors working with 4 provincial teams completed a questionnaire for each cricketer who presented with an injury during the 2004 - 2005 (S1) and 2005 - 2006 (S2) cricket seasons. This was done to determine: (i) the anatomical site of injury; (ii) the month of injury during the season; (iii) the diagnosis using the OSCIS injury classification system; (iv) the mechanism of injury; (v) whether it was a recurrence of a previous injury; (vi) whether the injury had recurred again during the season; and (vii) biographical data.Results. The results showed that 180 injuries (S1 – 84; S2 – 96)were sustained. On average the teams spent 2 472 hours on matches, 4 148 on practices and 1 612 on fitness training during the two-season period. The injury prevalence was 8% per match, while the injury incidence was 30/10 000 hours of match, practice and training time, with the match incidence being 74 injuries/ 10 000 hours and the training incidence 15 injuries/10 000 hours. Bowling (29%), fielding and wicket-keeping (27%) and batting (19%) accounted for the majority of injuries. The occurrence of injuries was predominantly to the lower limbs (S1 – 45%; S2 – 42%),back and trunk (S1 – 19%; S2 – 19%), upper limbs (S1 – 19%; S2 – 22%), head and neck (S1 – 6%; S2 – 3%), and related to illnesses (S1 – 11%; S2 – 14%). The injuries occurred primarily during first-class matches (39%), limited-overs matches (22%), and practices (17%), and some were of gradual onset (20%). Acute injuries comprised 78% of injuries. The majority of injuries were first-time injuries (76%), with 11% and 14% recurrent injuries from the previous and current seasons, respectively. The major injuries during S1 were haematomas (19%), muscle strains(17%) and other trauma (14%), while during S2 the injuries were primarily muscle strains (16%), other trauma (20%), tendinopathy (16%) and acute sprains (15%). The primary mechanisms of injury occurred in the delivery stride when bowling (19%) and overbowling (7%), on impact by the ball when batting (11%), and on sliding to field the ball (6%).Conclusion. The results indicate a pattern of cause of injury, withthe fast bowler most likely to sustain an acute injury to the soft tissues of the lower limb while participating in matches and practices during the early part of the season

Volcanic Radiative Forcing From 1979 to 2015

Using volcanic sulfur dioxide emissions in an aerosol-climate model we derive a time-series of global-mean volcanic effective radiative forcing (ERF) from 1979 to 2015. For 2005-2015, we calculate a global multi-annual mean volcanic ERF of 0.08 W m 2 relative to the volcanically quiescent 1999-2002 period, due to a high frequency of small-to-moderate-magnitude explosive eruptions after 2004. For eruptions of large magnitude such as 1991 Mt. Pinatubo, our model-simulated volcanic ERF, which accounts for rapid adjustments including aerosol perturbations of clouds, is less negative than that reported in the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) that only accounted for stratospheric temperature adjustments. We find that, when rapid adjustments are considered, the relation between volcanic forcing and volcanic stratospheric optical depth (SAOD) is 13-21% weaker than reported in IPCC AR5 for large-magnitude eruptions. Further, our analysis of the recurrence frequency of eruptions reveals that sulfur-rich small-to-moderate-magnitude eruptions with column heights 10 km occur frequently, with periods of volcanic quiescence being statistically rare. Small-to-moderate-magnitude eruptions should therefore be included in climate model simulations, given the 50% chance of one or two eruptions to occur in any given year. Not all of these eruptions affect the stratospheric aerosol budget, but those that do increase the non-volcanic background SAOD by ~0.004 on average, contributing ~50% to the total SAOD in the absence of large-magnitude eruptions. This equates to a volcanic ERF of about 0.10 W m 2, which is about two-thirds of the ERF from ozone changes induced by ozone-depleting substances

Water Cycle Changes

This chapter assesses multiple lines of evidence to evaluate past, present and future changes in the global water cycle. It complements material in Chapters 2, 3 and 4 on observed and projected changes in the water cycle, and Chapters 10 and 11 on regional climate change and extreme events. The assessment includes the physical basis for water cycle changes, observed changes in the water cycle and attribution of their causes, future projections and related key uncertainties, and the potential for abrupt change. Paleoclimate evidence, observations, reanalyses and global and regional model simulations are considered. The assessment shows widespread, nonuniform human-caused alterations of the water cycle, which have been obscured by a competition between different drivers across the 20th century and that will be increasingly dominated by greenhouse gas forcing at the global scale

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Insight regarding transfusion practices in Hematopoietic Stem cell Transplantation (HSCT) are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated. Red blood cell transfusion can be life-saving, however, liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit. A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality. The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospective randomized study of transfusion is required to gain insight and knowledge on best transfusion practices in this high risk population.</p> <p>Methods</p> <p>This report describes the design and methodological issues of a randomized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation. This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinicaltrials.gov NCT01237639.</p> <p>Results</p> <p>In 3 Canadian centres, 100 patients undergoing Hematopoietic Stem Cell Transplantation will be randomized to either a restrictive (target hemoglobin of 70-90 g/L) or liberal (target hemoglobin of 90-110 g/L) red cell transfusion strategy, based daily hemoglobin values up to 100 days post-transplant. The study will stratify participants by centre and type of transplant. The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1) Transfusion Requirements, 2) Transplant Related Mortality, 3) Maximum grade of acute Graft versus Host Disease, 4) Veno-occlusive Disease, 5) Serious Infections, 6) Bearman Toxicity Score, 7) Bleeding, 8) Quality of Life, 9) Number of Hospitalizations and 10) Number of Intensive Care Unit (ICU) Admissions.</p> <p>Conclusion</p> <p>Upon completion, this pilot trial will provide preliminary insight into red cell transfusion practice and its influence in hematopoietic stem cell transplant outcomes. The results of this trial will inform the conduct of a larger study.</p

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

© 2017 The Authors Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases

The global-scale impacts of climate change on water resources and flooding under new climate and socio-economic scenarios

This paper presents a preliminary assessment of the relative effects of rate of climate change (four Representative Concentration Pathways - RCPs), assumed future population (five Shared Socio-economic Pathways - SSPs), and pattern of climate change (19 CMIP5 climate models) on regional and global exposure to water resources stress and river flooding. Uncertainty in projected future impacts of climate change on exposure to water stress and river flooding is dominated by uncertainty in the projected spatial and seasonal pattern of change in climate. There is little clear difference in impact between RCP2.6, RCP4.5 and RCP6.0 in 2050, and between RCP4.5 and RCP6.0 in 2080. Impacts under RCP8.5 are greater than under the other RCPs in 2050 and 2080. For a given RCP, there is a difference in the absolute numbers of people exposed to increased water resources stress or increased river flood frequency between the five SSPs. With the ‘middle-of-the-road’ SSP2, climate change by 2050 would increase exposure to water resources stress for between approximately 920 and 3400 million people under the highest RCP, and increase exposure to river flood risk for between 100 and 580 million people. Under RCP2.6, exposure to increased water scarcity would be reduced in 2050 by 22-24%, compared to impacts under the RCP8.5, and exposure to increased flood frequency would be reduced by around 16%. The implications of climate change for actual future losses and adaptation depend not only on the numbers of people exposed to changes in risk, but also on the qualitative characteristics of future worlds as described in the different SSPs. The difference in ‘actual’ impact between SSPs will therefore be greater than the differences in numbers of people exposed to impact

Congenital diaphragmatic hernia and retinoids: searching for an etiology

Congenital diaphragmatic hernia (CDH) is a major life-threatening cause of respiratory failure in the newborn. Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the epidemiology and pathophysiology of human CDH, the metabolism of retinoids and the implications of retinoids in the development of the diaphragm and lung. Finally, we describe the existing evidence of a disruption of the retinoid-signaling pathway in CDH