Prior cigarette smoke exposure does not affect acute post-stroke outcomes in mice

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally and is characterized by airflow limitation that is progressive and not fully reversible. Cigarette smoking is the major cause of COPD. Fifty percent of deaths in the COPD population are due to a cardiovascular event and it is now recognised that COPD is a risk factor for stroke. Whether COPD increases stroke severity has not been explored. The aim of this study was to investigate whether functional and histological endpoints of stroke outcomes in mice after transient middle cerebral artery occlusion (tMCAo) were more severe in mice exposed to cigarette smoke (CS). 7-week-old male C57BL/6 mice were exposed to room air or CS generated from 9 cigarettes/day, 5 days/week for 2, 8 and 12 weeks. Following air or CS exposure, mice underwent tMCAO surgery with an ischaemic period of 30–40 min or sham surgery. Mice were euthanised 24 h following the induction of ischaemia and bronchoalveolar lavage fluid (BALF), lungs and brains collected. Mice exposed to CS for 2 weeks and subjected to a stroke had similar BALF macrophages to air-exposed and stroke mice. However, CS plus stroke mice had significantly more BALF total cells, neutrophils and lymphocytes than air plus stroke mice. Mice exposed to CS for 8 and 12 weeks had significantly greater BALF total cells, macrophages, neutrophils and lymphocytes than air-exposed mice, but stroke did not affect CS-induced BALF cellularity. Prior CS exposure did not worsen stroke-induced neurological deficit scores, reduced foregrip strength, infarct and oedema volumes. Collectively, we found that although CS exposure caused significant BALF inflammation, it did not worsen acute post-stroke outcomes in mice. This data suggests that while patients with COPD are at increased risk of stroke, it may not translate to COPD patients having more severe stroke outcomes

Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation

Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. In addition, cerebral endothelial dysfunction (particularly at the level of the blood-brain barrier [BBB]) contributes to stroke pathogenesis. Therefore, we hypothesized that cigarette smoking may influence stroke, at least in part, by exacerbating ischaemia-induced BBB disruption. To test this, we examined the effect of CSE on the permeability of cerebral endothelial cells exposed to oxygen glucose deprivation and reoxygenation (OGD + RO). We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE. Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were however markedly lower. Furthermore, this occurred in association with elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defence response. Lastly, we found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β). Collectively, these results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, however, this is not linked to elevated ROS levels but may involve inflammatory mechanisms

Access to Transportation For Chittenden County Senior Citizens

Introduction. Elderly age often means a progressive loss of independence and mobility. Research has shown that this lack of mobility has a detrimental effect on health and well-being. It is estimated that 25% of Vermonters will be ?65 years by 2030. Thus, the rapid rise in the elderly population will translate into a greater need for reliable transportation. We sought to explore if and how lack of transportation compromised areas of seniors’ daily lives.https://scholarworks.uvm.edu/comphp_gallery/1201/thumbnail.jp

Tracheotomy care simulation training program for inpatient providers

Objectives: Tracheotomy complications can be life-threatening. Many of these complications may be avoided with proper education of health care providers. Unfortunately, access to high-quality tracheotomy care curricula is limited. We developed a program to address this gap in tracheotomy care education for inpatient providers. This study aimed to assess the efficacy of this training program in improving trainee knowledge and comfort with tracheotomy care. Methods: The curriculum includes asynchronous online modules coupled with a self-directed hands-on simulation activity using a low-cost tracheotomy care task trainer. The program was offered to inpatient providers including medical students, residents, medical assistants, nurses, and respiratory therapists. Efficacy of the training was assessed using pre-training and post-training surveys of learner comfort, knowledge, and qualitative feedback. Results: Data was collected on 41 participants. After completing the program, participants exhibited significantly improved comfort in performing tracheotomy care activities and 15% improvement in knowledge scores, with large effect sizes respectively and greater gains among those with little prior tracheotomy care experience. Conclusion: This study has demonstrated that completion of this integrated online and hands-on tracheotomy simulation curriculum training increases comfort and knowledge, especially for less-experienced learners. This training addresses an important gap in tracheotomy care education among health care professionals with low levels of tracheotomy care experience and ultimately aims to improve patient safety and quality of care. This curriculum is easily transferrable as it requires only access to the online modules and low-cost simulation materials and could be used in other hospitals, long-term care facilities, outpatient clinics, and home settings

Influenza virus immune imprinting dictates the clinical outcomes in ferrets challenged with highly pathogenic avian influenza virus H5N1

Zoonotic transmission of H5N1 highly pathogenic avian influenza virus (HPAIV) into the human population is an increasing global threat. The recent 2022 HPAIV outbreak significantly highlighted this possibility, increasing concern in the general population. The clinical outcomes of H5N1 influenza virus exposure can be determined by an individual’s primary influenza virus infection (imprinting) or vaccination status. Immunological imprinting with Group 1 - (H1N1, H2N2, and H2N3) increases survival rates following H5N1 viral infection compared to Group 2 - (H3N2) imprinted individuals. Vaccination against H5N1 influenza viruses can offer protection to at-risk populations; however, stockpiled inactivated H5N1 influenza vaccines are not readily available to the public. We hypothesize that the immunological response to vaccination and subsequent clinical outcome following H5N1 influenza virus infection is correlated with the immunological imprinting status of an individual. To test this hypothesis, our lab established a ferret pre-immune model of disease. Naïve ferrets were intranasally inoculated with seasonal influenza viruses and allowed to recover for 84 days prior to H5N1 virus infection. Ferrets imprinted following H1N1 and H2N3 virus infections were completely protected against lethal H5N1 influenza virus challenge (100% survival), with few to no clinical symptoms. In comparison, H3N2 influenza virus-imprinted ferrets had severe clinical symptoms, delayed disease progression, and a sublethal phenotype (40% mortality). Consecutive infections with H1N1 influenza viruses followed by an H3N2 influenza virus infection did not abrogate the immune protection induced by the original H1N1 influenza virus infection. In addition, ferrets consecutively infected with H1N1 and H2N3 viruses had no clinical symptoms or weight loss. H3N2 pre-immune ferrets were vaccinated with a broadly reactive H5 HA-based or H1 NA-based vaccine (Hu-CO 2). These ferrets were protected against H5N1 influenza virus challenge, whereas ferrets vaccinated with the H1N1 wild-type CA/09 rHA vaccine had similar phenotypes as non-vaccinated H3N2-imprinted ferrets with 40% survival. Overall, Group 2 imprinted ferrets, which were vaccinated with heterologous Group 1 HA vaccines, had redirected immune responses to Group 1 influenza viral antigens and rescued a sublethal phenotype to complete protection

Age-Related Pathology Associated with H1N1 A/California/07/2009 Influenza Virus Infection

Influenza virus infection causes a spectrum of diseases, ranging from mild upper respiratory tract infection to severe lower respiratory tract infection, that can lead to diffuse alveolar damage, interstitial and airspace inflammation, or acute respiratory failure. Mechanisms instructing disease severity are not completely understood, but host, viral, and bacterial factors influence disease outcome. With age being one host factor associated with a higher risk of severe influenza, we investigated regional pulmonary distribution and severity of pneumonia after 2009 H1N1 influenza virus infection in newly weaned, adult, and aged ferrets to better understand age-dependent susceptibility and pathology. Aged ferrets exhibited greater weight loss and higher rates of mortality than adult ferrets, whereas most newly weaned ferrets did not lose weight but had a lack of weight gain. Newly weaned ferrets exhibited minimal pneumonia, whereas adult and aged ferrets had a spectrum of pneumonia severity. Influenza virus-induced pneumonia peaked earliest in adult ferrets, whereas aged ferrets had delayed presentation. Bronchial severity differed among groups, but bronchial pathology was comparable among all cohorts. Alveolar infection was strikingly different among groups. Newly weaned ferrets had little alveolar cell infection. Adult and aged ferrets had alveolar infection, but aged ferrets were unable to clear infection. These different age-related pneumonia and infection patterns suggest therapeutic strategies to treat influenza should be tailored contingent on age