A clean fuel cookstove is associated with improved lung function: Effect modification by age and secondhand tobacco smoke exposure.

Household air pollution (HAP) secondary to the burning of solid fuels is a major risk factor for the development of COPD. Our study seeks to examine the impact of a clean cookstove, liquid petroleum gas (LPG), on respiratory outcomes. Women (n = 200) from neighboring Indian communities, one cooking with LPG and one with biomass, were enrolled. Spirometry was performed. Relationships between primary cooking fuel and spirometry measures, as raw values, Global Lung Initiative (GLI) percent predicted (pp), and GLI z-scores, were examined using linear regression. Effect modification by age was explored. Women were young (average age 33.3 years), with low education (median 5.0 years), and the majority had multiple sources of air pollution exposures. Overall, the lung function in both groups was poor [FEV1 z-score median -2.05, IQR (-2.64, -1.41). Biomass was associated with lower FEV1/FVC (raw values -7.0, p = 0.04; GLI pp -7.62, p = 0.05, and z-score -0.86, p = 0.05) and FEF25-75 (GLI pp -25.78, p = 0.05, z-score -1.24, p = 0.05), after adjusting for confounders. Increasing impairment in lung function with age was found among biomass users (p-interaction = 0.01). In conclusion, use of a clean fuel cookstove may improve lung function. These findings have broad implications for research and public policy.

Effects of AR Display Context Switching and Focal Distance Switching on Human Performance.

In augmented reality (AR) environments, information is often distributed between real world and virtual contexts, and often appears at different distances from the user. Therefore, to integrate the information, users must repeatedly switch context and refocus the eyes. To focus at different distances, the user's eyes must accommodate, which when done repeatedly can cause eyestrain and degrade task performance. An experiment was conducted that examined switching context and focal distance between a real and an AR environment, using a text-based visual search task and a monocular optical see-through AR display. Both context switching and focal distance switching resulted in significantly reduced performance. In addition, repeatedly performing the task caused visual fatigue to steadily increase. Performance was particularly poor for virtual text presented at optical infinity, and for target letters that participants tried to read before their eyes had completely accommodated to a new focal distance. The results show that context switching and focal distance switching are important AR user interface design issues.

The enabling effect of food assistance in improving adherence and/or treatment completion for antiretroviral therapy and tuberculosis treatment: a literature review.

Socioeconomic costs of HIV and TB and the difficulty of maintaining optimal treatment are well documented. Social protection measures such as food assistance may be required to offset some of the treatment related costs as well as to ensure food security and maintain good health of the affected individual and household. Programmes have started placing greater emphasis on treatment adherence and are looking for proven interventions that can optimize it. This paper looks at the effect of food assistance for enabling treatment adherence and reviews studies that used food assistance to promote adherence. Eight of ten studies found that provision of food can improve adherence and/or treatment completion for HIV care and treatment, ART and TB-DOTS. This indicates that food provision is not only a biological, but also a behavioural intervention, and underscores that unresolved food insecurity can be an impediment to treatment adherence and consequently to good treatment outcomes.

A comparison of the inflammatory and proteolytic effects of dung biomass and cigarette smoke exposure in the lung.

RATIONALE: Biomass is the energy source for cooking and heating for billions of people worldwide. Despite their prevalent use and their potential impact on global health, the effects of these fuels on lung biology and function remain poorly understood. METHODS: We exposed human small airway epithelial cells and C57BL/6 mice to dung biomass smoke or cigarette smoke to compare how these exposures impacted lung signaling and inflammatory and proteolytic responses that have been linked with disease pathogenesis. RESULTS: The in vitro exposure and siRNA studies demonstrated that biomass and cigarette smoke activated ERK to up regulate IL-8 and MMP-1 expression in human airway epithelial cells. In contrast to cigarette smoke, biomass also activated p38 and JNK within these lung cells and lowered the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Similarly, in the lungs of mice, both biomass and cigarette smoke exposure increased macrophages, activated ERK and p38 and up regulated MMP-9 and MMP-12 expression. The main differences seen in the exposure studies was that mice exposed to biomass exhibited more perivascular inflammation and had higher G-CSF and GM-CSF lavage fluid levels than mice exposed identically to cigarette smoke. CONCLUSION: Biomass activates similar pathogenic processes seen in cigarette smoke exposure that are known to result in the disruption of lung structure. These findings provide biological evidence that public health interventions are needed to address the harm associated with the use of this fuel source.

Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) and can be difficult to treat. The class Ic antiarrhythmic drug flecainide blocks RyR2 channels and prevents CPVT in mice and humans. It is not known whether other class I antiarrhythmic drugs also block RyR2 channels and to what extent RyR2 channel inhibition contributes to antiarrhythmic efficacy in CPVT. METHODS AND RESULTS: We first measured the effect of all class I antiarrhythmic drugs marketed in the United States (quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, and propafenone) on single RyR2 channels incorporated into lipid bilayers. Only flecainide and propafenone inhibited RyR2 channels, with the S-enantiomer of propafenone having a significantly lower potency than R-propafenone or flecainide. In Casq2(-/-) myocytes, the propafenone enantiomers and flecainide significantly reduced arrhythmogenic Ca(2+) waves at clinically relevant concentrations, whereas Na(+) channel inhibitors without RyR2 blocking properties did not. In Casq2(-/-) mice, 5 mg/kg R-propafenone or 20 mg/kg S-propafenone prevented exercise-induced CPVT, whereas procainamide (20 mg/kg) or lidocaine (20 mg/kg) were ineffective (n=5 to 9 mice, P<0.05). QRS duration was not significantly different, indicating a similar degree of Na(+) channel inhibition. Clinically, propafenone (900 mg/d) prevented ICD shocks in a 22-year-old CPVT patient who had been refractory to maximal standard drug therapy and bilateral stellate ganglionectomy. CONCLUSIONS: RyR2 cardiac Ca(2+) release channel inhibition appears to determine efficacy of class I drugs for the prevention of CPVT in Casq2(-/-) mice. Propafenone may be an alternative to flecainide for CPVT patients symptomatic on ß-blockers.

Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma.

Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation. Transgenic (TG) and wild-type (WT) mice were immunized and challenged with ovalbumin. Forty-eight hours after the ovalbumin challenge, airway hyperresponsiveness (AHR) was measured, and inflammatory cell infiltration was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue. Baseline levels of inflammation were similar in the TG and WT groups of mice, and pulmonary eosinophilia was established in both groups by sensitization and challenge with ovalbumin. There was a significant reduction in AHR in sensitized and challenged trangenics compared with WT controls. Although total BALF cell counts were similar in both groups, the lymphocyte number in the lavage of the TG group was significantly diminished compared with the WT group (0.25 +/- 0.08 vs. 0.89 +/- 0.53; P = 0.0032). In addition, the draining lymphocytes were found to be larger in the TG animals compared with the WT mice. Equal numbers of macrophages, eosinophils, and neutrophils were seen in both groups. IL-13 levels were found to be lower in the sensitized TG compared with the WT mice. These results demonstrate an inverse relationship between human MMP-9 and AHR and suggest that MMP-9 expression alters leukocyte extravasation by reducing lymphocyte accumulation in the walls of asthmatic airways.

Blockade of receptor for advanced glycation end product attenuates pulmonary reperfusion injury in mice.

OBJECTIVE: The receptor for advanced glycation end products (RAGE) is expressed at high levels in the lung, particularly in type 1 alveolar cells, and has been shown to amplify injury triggered by acute stress. Previous studies suggest serum concentrations of soluble RAGE increase during pulmonary reperfusion injury after transplantation. RAGE blockade has been shown to suppress hepatic and cardiac ischemia and reperfusion injury in mice. Thus we tested the hypothesis that RAGE mediates tissue-injury mechanisms in ischemia and reperfusion injury in the lung. METHODS: C57BL/6 mice were subjected to 30 minutes of pulmonary ischemia by clamping the left hilum, followed by 60 minutes of reperfusion. Lung function was assessed by means of blood gas analysis, and capillary leak was assessed by injecting fluorescein isothiocyanate-labeled albumin and comparing fluorescence in bronchial lavage fluid with that in serum. Histologic analysis of the lung was performed by a pathologist naive to the experimental conditions. RESULTS: In animals subjected to RAGE blockade, significant increases in Po(2) (108 vs 73 mm Hg, P = .0094) and more than 3-fold decrease in capillary leak Relative Fluorescent Units (RFU, 6.12 vs 1.75; P = .001) were observed. Histologic examination revealed significant injury reduction in soluble RAGE-treated animals versus control animals. RAGE knockout mice exhibited a protected phenotype when exposed to pulmonary ischemia and reperfusion. Additionally, interleukin 8 production and nuclear factor kappaB activation were increased in control mice. CONCLUSION: Abrogation of RAGE signaling attenuates pulmonary ischemia and reperfusion injury. This study suggests that RAGE might play a central role in pulmonary reperfusion injury and in transplantation and that blockade of RAGE might offer a potential target to abrogate pulmonary reperfusion injury in clinical transplantation.

Is it open or is it closed? Thrombosis of a St. Jude's tricuspid valve prosthesis.

A 49-year-old woman with mitral and tricuspid mechanical valve prostheses developed marked weight gain with increasing abdominal girth and facial plethora 4 weeks after anticoagulation was temporarily interrupted for abdominal surgery. Transthoracic and transesophageal echocardiography documented severe tricuspid stenosis and regurgitation. The two discs of the tricuspid prosthesis were immobilized, half open and half closed. The prosthesis was replaced and the patient did well.