Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt

Prediction of Obesity in Children at 5 years: A Cohort Study

Objective To examine determinants of moderate and severe obesity in children at 5 years of age. Methodology A prospective cohort of mothers were enrolled at first antenatal visit, and interviewed shortly after delivery, at 6 months and 5 years. Detailed health, psychological and social questionnaires were completed at each phase by mothers, and child health questionnaires at 6 months and 5 years. At 5 years 4062 children were assessed physically, the Peabody Picture Vocabulary Test administered and mothers completed a modified Child Behaviour Checklist. Moderate obesity was defined as BMI between 85th and 94th percentiles inclusively, and severe obesity as a BMI greater than the 94th percentile. Results Independent predictors of severe obesity at 5 years were birthweight, female gender, maternal BMI and paternal BMI. Moderate obesity at 5 years was predicted by birthweight, paternal BMI and sleeplessness at 6 months, while small for gestational age (SGA) status and feeding problems at 6 months were protective factors for moderate obesity. Obesity was not associated with problems of language comprehension or behaviour. Conclusions Findings of this study suggest that biological rather than psychosocial factors are the major determinants of obesity at 5 years

Secure and scalable deduplication of horizontally partitioned health data for privacy-preserving distributed statistical computation

Background Techniques have been developed to compute statistics on distributed datasets without revealing private information except the statistical results. However, duplicate records in a distributed dataset may lead to incorrect statistical results. Therefore, to increase the accuracy of the statistical analysis of a distributed dataset, secure deduplication is an important preprocessing step. Methods We designed a secure protocol for the deduplication of horizontally partitioned datasets with deterministic record linkage algorithms. We provided a formal security analysis of the protocol in the presence of semi-honest adversaries. The protocol was implemented and deployed across three microbiology laboratories located in Norway, and we ran experiments on the datasets in which the number of records for each laboratory varied. Experiments were also performed on simulated microbiology datasets and data custodians connected through a local area network. Results The security analysis demonstrated that the protocol protects the privacy of individuals and data custodians under a semi-honest adversarial model. More precisely, the protocol remains secure with the collusion of up to N − 2 corrupt data custodians. The total runtime for the protocol scales linearly with the addition of data custodians and records. One million simulated records distributed across 20 data custodians were deduplicated within 45 s. The experimental results showed that the protocol is more efficient and scalable than previous protocols for the same problem. Conclusions The proposed deduplication protocol is efficient and scalable for practical uses while protecting the privacy of patients and data custodians

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Ambulatory assessment of psychophysiological stress among police officers: A proof-of-concept study.

Occupational stress has been widely recognized as a global challenge and has received increased attention by the academic community. Ambulatory Assessment methodologies, combining psychophysiological measures of stress, offer a promising avenue for future prevention and/or rehabilitation stress research. Considering that policing is well known for being a particularly stressful occupation, Emergency Responders Officers (EROs) stress levels were investigated. Particularly, this study analyzed: (i) physiological stress data obtained during shifts and compared these data with baseline levels (days off), as well as (ii) with normative values for healthy populations; (iii) stress symptoms differences from beginning to end of shift; (iv) stress events and events intensity and (v) the acceptability and feasibility of this proof-of-concept study in a highly stressful occupation. A Geo-location event system was used to help retrospective accounts of psychological stress, combined with electrocardiogram (ECG) data and mobile self-reports, that include stress symptoms, event types and event intensity. Results suggest that EROs experience high levels of stress (both on-duty and off duty) when compared to healthy populations. Stress symptoms increase from the beginning to end of the shift. However, the mean events intensity was very low. It can be concluded that stress may not always be diagnosed when using merely self-reports. These findings highlight the importance of combining both self-report and physiological stress measures in occupational health contexts. Finally, results confirm the acceptability and feasibility of the multi-method used. Key implications for policy makers and applied practitioners in the area of occupational health and future research directions are discussed

Ischemia and reperfusion of the soleus muscle of rats with pentoxifylline

BACKGROUND: Reperfusion of the skeletal muscle worsens existing lesions during ischemia, since the production of reactive oxygen species, associated with intense participation of neutrophils, increases the inflammatory reaction that induces tissue changes. OBJECTIVE: To evaluate the morphological and immunohistochemical changes of the skeletal (soleus) muscle of rats submitted to ischemia and reperfusion with pentoxifylline. METHODS: Sixty rats were submitted to ischemia of the pelvic limb for 6 hours induced by clamping the left common iliac artery. After ischemia, group A animals (n = 30) were observed for 4 hours and group B animals (n = 30) for 24 hours. Six animals constituted the sham group. Pentoxifylline was applied only in the reperfusion period A2 (n = 10) and B2 (n = 10), and in ischemia and reperfusion periods in A3 (n = 10) and B3 (n = 10). The soleus muscle was evaluated by histological (fiber disruption, leukocyte infiltrate, necrosis) and immunohistochemical (apoptosis through caspase-3 expression) analysis. The non-parametric tests Kruskal-Wallis and Mann-Whitney (p < 0.05) were applied. RESULTS: The changes were more intense in group B1, with fiber disruption mean scores of 2.16±0.14; neutrophilic infiltrate of 2.05±0.10; and caspase-3 expression in the perivascular area of 4.30±0.79; and less intense in group A3, with means of 0.76±0.16; 0.92±0.10; 0.67±0,15, respectively (p < 0.05). Caspase-3 was more expressive in group B1 in the perivascular area, with mean of 4.30±0.79 when compared with group B1 in the perinuclear area, with mean of 0.91±0.32 (p < 0.05) CONCLUSIONS: The lesions were more intense when observation time was longer after reperfusion, and pentoxifylline attenuated these lesions, above all when used in the beginning of ischemia and reperfusion phases.CONTEXTO: A reperfusão de músculo esquelético piora as lesões já presentes no período de isquemia, pois a produção de espécies reativas de oxigênio, associadas à intensa participação de neutrófilos, amplia a reação inflamatória que induz alterações teciduais. OBJETIVO: Avaliar as alterações morfológicas e imuno-histoquímicas de músculo esquelético (sóleo) de ratos submetidos a isquemia e reperfusão com pentoxifilina. MÉTODOS: Sessenta ratos foram submetidos a isquemia do membro pélvico, por 6 horas, pelo clampeamento da artéria ilíaca comum esquerda. Após isquemia, os animais do grupo A (n = 30) foram observados por 4 horas, e os do grupo B (n = 30), por 24 horas. Seis animais constituíram o grupo simulado. Administrou-se pentoxifilina apenas no período de reperfusão em A2 (n = 10) e B2 (n = 10) e nos períodos de isquemia e reperfusão em A3 (n = 10) e B3 (n = 10). O músculo sóleo foi avaliado por análise histológica (dissociação de fibras, infiltrado leucocitário, necrose) e imuno-histoquímica (apoptose pela expressão da caspase-3). Foram aplicados os testes não-paramétricos de Kruskal-Wallis e Mann-Whitney (p < 0,05). RESULTADOS: As alterações foram mais intensas no grupo B1, com médias de escore da dissociação de fibras musculares de 2,16 ± 0,14, infiltrado neutrofílico de 2,05 ± 0,10 e expressão da caspase-3 na área perivascular de 4,30 ± 0,79; e menos intensas no grupo A3, com respectivas médias de 0,76 ± 0,16, 0,92 ± 0,10 e 0,67 ± 0,15 (p < 0,05). A caspase-3 mostrou-se mais expressiva no grupo B1 na área perivascular, com média de 4,30 ± 0,79, em comparação com o grupo B1 na área perinuclear, com média de 0,91 ± 0,32 (p < 0,05). CONCLUSÕES: As lesões são mais intensas quando o tempo de observação é maior após a reperfusão, e a pentoxifilina atenua essas lesões, sobretudo quando usada no início das fases de isquemia e de reperfusão.SBACVUniversidade Federal de Mato Grosso do Sul Hospital UniversitárioUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUFMSUNIFESP-EPM Departamento de PatologiaUFMS Departamento de Clínica CirúrgicaUFMS Hospital Universitário Comissão de Residência MédicaUNIFESP, EPM, Depto. de PatologiaSciEL

Exploring the relationship between experiential avoidance, coping functions and the recency and frequency of self-harm

This study investigated the relationship between experiential avoidance, coping and the recency and frequency of self-harm, in a community sample (N = 1332, aged 16–69 years). Participants completed online, self-report measures assessing self-harm, momentary affect, experiential avoidance and coping in response to a recent stressor. Participants who had self-harmed reported significantly higher levels of experiential avoidance and avoidance coping, as well as lower levels of approach, reappraisal and emotional regulation coping, than those with no self-harm history. Moreover, more recent self-harm was associated with lower endorsement of approach, reappraisal and emotion regulation coping, and also higher levels of both avoidance coping and experiential avoidance. Higher experiential avoidance and avoidance coping also predicted increased lifetime frequency of self-harm. Conversely, increased approach and reappraisal coping were associated with a decreased likelihood of high frequency self-harm. Although some of the effects were small, particularly in relation to lifetime frequency of self-harm, overall our results suggest that experiential avoidance tendency may be an important psychological factor underpinning self-harm, regardless of suicidal intent (e.g. including mixed intent, suicidal intent, ambivalence), which is not accounted for in existing models of self-harm

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Female Burying Beetles Benefit from Male Desertion: Sexual Conflict and Counter-Adaptation over Parental Investment

Sexual conflict drives the coevolution of sexually antagonistic traits, such that an adaptation in one sex selects an opposing coevolutionary response from the other. Although many adaptations and counteradaptations have been identified in sexual conflict over mating interactions, few are known for sexual conflict over parental investment. Here we investigate a possible coevolutionary sequence triggered by mate desertion in the burying beetle Nicrophorus vespilloides, where males commonly leave before their offspring reach independence. Rather than suffer fitness costs as a consequence, our data suggest that females rely on the male's absence to recoup some of the costs of larval care, presumably because they are then free to feed themselves on the carcass employed for breeding. Consequently, forcing males to stay until the larvae disperse reduces components of female fitness to a greater extent than caring for young singlehandedly. Therefore we suggest that females may have co-evolved to anticipate desertion by their partners so that they now benefit from the male's absence