The effect of environmental oxidative stress on airway inflammation

Asthma is an inflammatory respiratory condition with significant associated morbidity and mortality that is increasing in prevalence. Air pollution is an important factor in both the development of asthma and in asthma exacerbations. Oxidative stress as a result of exposure to air pollution and underlying genetic polymorphisms that may play a role in susceptibility to this oxidative stress are the subject of current investigation

Exploration of the effects of classroom humidity levels on teachers’ respiratory symptoms

Previous studies indicate that teachers have higher asthma prevalence than other non-industrial worker groups. Schools frequently have trouble maintaining indoor relative humidity (RH) within the optimum range (30-50%) for reducing allergens and irritants. However, the potential relationship between classroom humidity and teachers’ health has not been explored. Thus, we examined the relationship between classroom humidity levels and respiratory symptoms among North Carolina teachers

Environmental determinants of allergy and asthma in early life

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR.ConclusionUsing a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88)

Airway purinergic responses in healthy, atopic nonasthmatic, and atopic asthmatic subjects exposed to ozone

Ozone exposure triggers airway inflammatory responses that may be influenced by biologically active purine metabolites

Muon-spin relaxation investigation of magnetic bistability in a crystalline organic radical compound

We present the results of a muon-spin relaxation ($\mu^{+}$SR) investigation of the crystalline organic radical compound 4-(2-benzimidazolyl)-1,2,3,5-dithiadiazolyl (HbimDTDA), in which we demonstrate the hysteretic magnetic switching of the system that takes place at $T = 274 \pm 11\,\mathrm{K}$ caused by a structural phase transition. Muon-site analysis using electronic structure calculations suggests a range of candidate muon stopping sites. The sites are numerous and similar in energy but, significantly, differ between the two structural phases of the material. Despite the difference in the sites, the muon remains a faithful probe of the transition, revealing a dynamically-fluctuating magnetically disordered state in the low-temperature structural phase. In contrast, in the high temperature phase the relaxation is caused by static nuclear moments, with rapid electronic dynamics being motionally narrowed from the muon spectra

IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers

Asthma with neutrophil predominance is challenging to treat with corticosteroids. Novel treatment options for asthma include those that target innate immune activity. Recent literature has indicated a significant role for IL-1β in both acute and chronic neutrophilic asthma

ORMIR_XCT: A Python package for high resolution peripheral quantitative computed tomography image processing

High resolution peripheral quantitative computed tomography (HR-pQCT) is an imaging technique capable of imaging trabecular bone in-vivo. HR-pQCT has a wide range of applications, primarily focused on bone to improve our understanding of musculoskeletal diseases, assess epidemiological associations, and evaluate the effects of pharmaceutical interventions. Processing HR-pQCT images has largely been supported using the scanner manufacturer scripting language (Image Processing Language, IPL, Scanco Medical). However, by expanding image processing workflows outside of the scanner manufacturer software environment, users have the flexibility to apply more advanced mathematical techniques and leverage modern software packages to improve image processing. The ORMIR_XCT Python package was developed to reimplement some existing IPL workflows and provide an open and reproducible package allowing for the development of advanced HR-pQCT data processing workflows

Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.

OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model