Antigen Sensitization Influences Organophosphorus Pesticide–Induced Airway Hyperreactivity

BackgroundRecent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, we have demonstrated that environmentally relevant concentrations of OPs induce airway hyperreactivity in guinea pigs.ObjectivesSensitization to allergen is a significant contributing factor in asthma, and we have shown that sensitization changes virus-induced airway hyperreactivity from an eosinophil-independent mechanism to one mediated by eosinophils. Here, we determine whether sensitization similarly influences OP-induced airway hyperreactivity.MethodsNonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously with the OP parathion (0.001-1.0 mg/kg). Twenty-four hours later, animals were anesthetized and ventilated, and bronchoconstriction was measured in response to either vagal stimulation or intravenous acetylcholine. Inflammatory cells and acetylcholinesterase activity were assessed in tissues collected immediately after physiologic measurements.ResultsOvalbumin sensitization decreased the threshold dose for parathion-induced airway hyperreactivity and exacerbated parathion effects on vagally induced bronchoconstriction. Pretreatment with antibody to interleukin (IL)-5 prevented parathion-induced hyperreactivity in sensitized but not in nonsensitized guinea pigs. Parathion did not increase the number of eosinophils in airways or the number of eosinophils associated with airway nerves nor did it alter eosinophil activation as assessed by major basic protein deposition.ConclusionsAntigen sensitization increases vulnerability to parathion-induced airway hyperreactivity and changes the mechanism to one that is dependent on IL-5. Because sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children), these findings have significant implications for OP risk assessment, intervention, and treatment strategies

Sensitivity and specificity of lung cancer screening using chest low-dose computed tomography

Lung cancer screening programmes using chest X-ray and sputum cytology are routinely performed in Japan; however, the efficacy is insufficient. Screening using low-dose computed tomography (CT) is a more effective approach and has the potential to detect the disease more accurately. A total of 7183 low-dose CT screening tests for 4689 participants and 36 085 chest X-ray screening tests for 13 381 participants were conducted between August 1998 and May 2002. Sensitivity and specificity of lung cancer screening were calculated by both the detection method and the incidence method by linkage of the screening database and the Cancer Registry database. The preclinical detectable phase was assumed to be 1 year. Sensitivity and specificity by the detection method were 88.9 and 92.6% for low-dose CT and 78.3 and 97.0% for chest X-ray, respectively. Sensitivity of low-dose CT by the incidence method was 79.5%, whereas that of chest X-ray was 86.5%. Lung cancer screening using low-dose CT resulted in higher sensitivity and lower specificity than traditional screening according to the detection method. However, sensitivity by the incidence method was not as high as this. These findings demonstrate the potential for overdiagnosis in CT screening-detected cases

The effect of temperature, gradient and load carriage on oxygen consumption, posture and gait characteristics

Purpose The purpose of this experiment was to evaluate the effect of load carriage in a range of temperatures to establish the interaction between cold exposure, the magnitude of change from unloaded to loaded walking and gradient. Methods Eleven participants (19-27 years) provided written informed consent before performing six randomly ordered walking trials in six temperatures (20°C, 10°C, 5°C, 0°C, -5°C and -10°C). Trials involved two unloaded walking bouts before and after loaded walking (18.2 kg) at 4 km.hr⁻¹, on 0% and 10% gradients in 4 minute bouts. Results The change in absolute oxygen consumption (V̇O₂) from the first unloaded bout to loaded walking was similar across all six temperatures. When repeating the second unloaded bout, V̇O₂ at both -5°C and-10°C was greater compared to the first. At -10°C, V̇O₂ was increased from 1.60 ± 0.30 L.min⁻¹ to 1.89 ± 0.51 L.min⁻¹. Regardless of temperature, gradient had a greater effect on V̇O₂ and heart rate (HR) than backpack load. HR was unaffected by temperature. Stride length (SL) decreased with decreasing temperature but trunk forward lean was greater during cold exposure. Conclusion Decreased ambient temperature did not influence the magnitude of change in V̇O₂ from unloaded to loaded walking. However, in cold temperatures, V̇O₂ was significantly higher than in warm conditions. The increased V̇O₂ in colder temperatures at the same exercise intensity is predicted to ultimately lead to earlier onset of fatigue and cessation of exercise. These results highlight the need to consider both appropriate clothing and fitness during cold exposure

Genetic Diversity among Enterococcus faecalis

Enterococcus faecalis, a ubiquitous member of mammalian gastrointestinal flora, is a leading cause of nosocomial infections and a growing public health concern. The enterococci responsible for these infections are often resistant to multiple antibiotics and have become notorious for their ability to acquire and disseminate antibiotic resistances. In the current study, we examined genetic relationships among 106 strains of E. faecalis isolated over the past 100 years, including strains identified for their diversity and used historically for serotyping, strains that have been adapted for laboratory use, and isolates from previously described E. faecalis infection outbreaks. This collection also includes isolates first characterized as having novel plasmids, virulence traits, antibiotic resistances, and pathogenicity island (PAI) components. We evaluated variation in factors contributing to pathogenicity, including toxin production, antibiotic resistance, polymorphism in the capsule (cps) operon, pathogenicity island (PAI) gene content, and other accessory factors. This information was correlated with multi-locus sequence typing (MLST) data, which was used to define genetic lineages. Our findings show that virulence and antibiotic resistance traits can be found within many diverse lineages of E. faecalis. However, lineages have emerged that have caused infection outbreaks globally, in which several new antibiotic resistances have entered the species, and in which virulence traits have converged. Comparing genomic hybridization profiles, using a microarray, of strains identified by MLST as spanning the diversity of the species, allowed us to identify the core E. faecalis genome as consisting of an estimated 2057 unique genes

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

Road ahead to respiratory health: experts chart future research directions.

Respiratory illnesses are a huge and rising burden to health-care systems and societies worldwide. Research is crucial to tackle the enormous problem of chest diseases. However the vast number of research questions and available research approaches often creates confusion and risks dilution of resources by spreading them too diffusely. Clear research directions will help to use research funds efficiently to provide treatment advances that benefit patient care. This paper presents the visions of leading experts on future research directions, focusing on what should rather than what is going to be done. These opinions provide a guide for new investigators and a platform for intellectual debates through which coordinated research efforts can help progress towards respiratory health