Adverse Cardiovascular Effects with Acute Particulate Matter and Ozone Exposures: Interstrain Variation in Mice

OBJECTIVES: Increased ambient particulate matter (PM) levels are associated with cardiovascular morbidity and mortality, as shown by numerous epidemiology studies. Few studies have investigated the role of copollutants, such as ozone, in this association. Furthermore, the mechanisms by which PM affects cardiac function remain uncertain. We hypothesized that PM and O3 induce adverse cardiovascular effects in mice and that these effects are strain dependent. STUDY DESIGN: After implanting radiotelemeters to measure heart rate (HR) and HR variability (HRV) parameters, we exposed C57Bl/6J (B6), C3H/HeJ (HeJ), and C3H/HeOuJ (OuJ) inbred mouse strains to three different daily exposures of filtered air (FA), carbon black particles (CB), or O3 and CB sequentially [O3CB; for CB, 536 ± 24 µg/m3; for O3, 584 ± 35 ppb (mean ± SE)]. RESULTS: We observed significant changes in HR and HRV in all strains due to O3CB exposure, but not due to sequential FA and CB exposure (FACB). The data suggest that primarily acute HR and HRV effects occur during O3CB exposure, especially in HeJ and OuJ mice. For example, HeJ and OuJ mice demonstrated dramatic increases in HRV parameters associated with marked bradycardia during O3CB exposure. In contrast, depressed HR responses occurred in B6 mice without detectable changes in HRV parameters. CONCLUSIONS: These findings demonstrate that important interstrain differences exist with respect to PM- and O3-induced cardiac effects. This interstrain variation suggests that genetic factors may modulate HR regulation in response to and recuperation from acute copollutant exposures. KEY WORDS: air pollution, genetic susceptibility, heart rate variability, Toll-like receptor 4. Environ Health Perspect 116:1033–1039 (2008). doi:10.1289/ehp.10689 available vi

A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incident precluded development of subunit RSV vaccines for infants for over 30 years, because the mechanism of illness was never clarified. An RSV vaccine for infants is still not available

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Vicarious learning and case-based teaching: developing health science students' clinical reasoning skills

Developing expertise in clinical reasoning and diagnosis poses an enormous challenge to health science students. In a three-phase project, we identified the difficulties that health science students in initial training have with clinical reasoning, designed and implemented an online vicarious learning system to address those difficulties, and evaluated the outcomes in terms of learners' experiences, diagnostic skill development and use of professional language