Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Endotoxins are ubiquitously present in the environment and constitute a significant component of ambient air. These substances have been shown to modulate the allergic response, however a consensus has yet to be reached whether they attenuate or exacerbate asthmatic responses. The current investigation examined whether reducing the concentration of lipopolysaccharide (LPS) in a house dust extract (HDE) containing high concentrations of both cockroach allergens <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and LPS would attenuate asthma-like pulmonary inflammation.</p> <p>Methods</p> <p>Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured.</p> <p>Results</p> <p>Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge. <it>Conclusion: </it>These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.</p

Peripheral vasoconstriction influences thenar oxygen saturation as measured by near-infrared spectroscopy

Purpose: Near-infrared spectroscopy has been used as a noninvasive monitoring tool for tissue oxygen saturation (StO2) in acutely ill patients. This study aimed to investigate whether local vasoconstriction induced by body surface cooling significantly influences thenar StO2 as measured by InSpectra model 650. Methods: Eight healthy individuals (age 26 ± 6 years) participated in the study. Using a cooling blanket, we aimed to cool the entire body surface to induce vasoconstriction in the skin without any changes in central temperature. Thenar StO2 was noninvasively measured during a 3-min vascular occlusion test using InSpectra model 650 with a 15-mm probe. Measurements were analyzed for resting StO2 values, rate of StO2 desaturation (RdecStO2, %/min), and rate of StO2 recovery (RincStO2, %/s) before, during, and after skin cooling. Measurements also included heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), capillary refill time (CRT), forearm-to-fingertip skintemperature gradient (Tskin-diff), perfusion index (PI), and tissue hemoglobin index (THI). Results: In all subjects MAP, CO, SV, and core temperature did not change during the procedure. Skin cooling resulted in a significant decrease in StO2 from 82% (80-87) to 72% (70-77) (P\0.05) and in RincStO2 from 3.0%/s (2.8-3.3) to 1.7%/s (1.1-2.0) (P\0.05). Similar changes in CRT, Tskin-diff, and PI were also observed: from 2.5 s (2.0-3.0) to 8.5 s (7.2-11.0) (P\0.05), from 1.0 (-1.6-1.8) to 3.1 (P\0.05), and from 10.0% (9.1-11.7) to 2.5

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

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed

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

Regulatory and Activated T Cells in Human Schistosoma haematobium Infections

Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens. Data from experimental models suggest that immunity is also influenced by regulatory T cells (Treg), but as yet studies on Treg in human schistosome infections are limited

Prions in Milk from Ewes Incubating Natural Scrapie

Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species

Current influences and approaches to promote future physical activity in 11–13 year olds: a focus group study

BACKGROUND: Many children and adolescents are failing to meet current physical activity (PA) guidelines and consequently not achieving the benefits associated with regular participation in PA, with girls consistently less active than boys. In order to design interventions to increase physical activity in adolescents it is important to understand their perceptions of and preferences for physical activity. METHODS: One hundred eighty participants, mean (SD) age 12.1 (0.5) years, completed the Physical Activity Questionnaire for Children (PAQ-C) and had height and weight measured. This information was used to select a subsample of participants (n64; mean (SD) age 12.3 (0.4) years; 39 females; 25 males; 25 % overweight/obese) to take part in focus group discussions. Participants were grouped based on PAQ-C responses into ‘low-active’ and ‘highly-active’ groups, so that those with similar existing levels of PA were in the same focus group. A semi-structured discussion guide was employed to explore the key influences on current PA participation and to actively seek ideas on how best to promote future PA in this population. In total, nine focus groups (mixed-gender) were conducted within the school setting. All focus groups were audio recorded, transcribed verbatim and analysed thematically. RESULTS: A number of themes emerged in relation to influences on current PA including friendship and peers, family and other people, the consequences of not taking part in PA, changing priorities, and cost and access to resources. With regards to the future provision of PA, participants favoured opportunities to try new activities, increased provision of school-based activities which can be undertaken with friends and activities which incorporated the use of technology and encouragement through rewards and incentives. Gender differences were apparent in relation to the types of activities participants preferred taking part in. Differences were also observed between ‘low-active’ and ‘highly-active’ groups in relation to barriers to current participation in PA. CONCLUSIONS: This study has highlighted a number of influences on current and future participation in PA, which differed based on gender and existing PA levels, for example, maximising the potential of the school day and including technology and incentives. These components can inform targeted interventions to increase PA in low active adolescents

Identification of an Intracellular Site of Prion Conversion

Prion diseases are fatal, neurodegenerative disorders in humans and animals and are characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPC), denoted PrPSc, which represents the major component of infectious scrapie prions. Characterization of the mechanism of conversion of PrPC into PrPSc and identification of the intracellular site where it occurs are among the most important questions in prion biology. Despite numerous efforts, both of these questions remain unsolved. We have quantitatively analyzed the distribution of PrPC and PrPSc and measured PrPSc levels in different infected neuronal cell lines in which protein trafficking has been selectively impaired. Our data exclude roles for both early and late endosomes and identify the endosomal recycling compartment as the likely site of prion conversion. These findings represent a fundamental step towards understanding the cellular mechanism of prion conversion and will allow the development of new therapeutic approaches for prion diseases