Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.

The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses.

Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold.

Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl3) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl3 then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group - simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.

Is nurse-supervised exercise stress testing safe practice?

OBJECTIVE: Nurses have been performing exercise stress tests (EST) without medical supervision since 1978 in our hospital-based cardiac rehabilitation unit. This study was conducted to examine the incidence of cardiovascular complications and to describe the competency-based training program for the nurses performing the EST. DESIGN: Descriptive, retrospective audit of prospective data. SETTING: Single comprehensive cardiac rehabilitation center in a large tertiary referral hospital in western Sydney, Australia. SUBJECTS: Seventeen thousand, four hundred and sixty-seven patients were included in this study over a 12-year period. METHOD: Data were collected on all ESTs performed by the cardiac rehabilitation nurses from January 1986 to December 1997 in relation to serious cardiovascular complications and other EST parameters. RESULTS: In this study, 17,467 ESTs were performed on 5054 patients who had 6273 separate presentations. The most common entry diagnosis was after an acute myocardial infarction (50%). The mean age was 58 +/- 10.5 years (range 15 to 87 years; 80% male). The left ventricular ejection fraction (n = 2822) was 49% +/- 14%. In a subgroup analysis of 14,454 patients, 14% had a positive EST (ST segment >1.9 mm depression). There were no deaths associated with the EST, and there were 13 major complications in 12 patients. This figure included no cardiac arrests, 11 episodes of conscious sustained ventricular tachycardia, 1 reinfarction, and 1 mitral valve rupture, representing a 0% mortality rate and a 0.075% major morbidity rate. CONCLUSION: This study shows that nurse-supervised EST of higher risk patients in the hospital-based cardiac rehabilitation setting has been a safe practice from a mortality and morbidity rate perspective. This finding may be accounted for by the high training standard and reaccreditation of the nurses on the advanced practice of performing EST.