Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

Serum levels of TGF-ß1, cytokines, angiogenic, and anti-angiogenic factors in pregnant women who smoke.

INTRODUCTION: Women who smoke during pregnancy have a reduced risk of preeclampsia. The mechanism of this association is poorly understood. Preeclampsia is an anti-angiogenic and inflammatory state. Transforming growth factor beta 1 (TGF-ß1) is a multi-functional anti-inflammatory cytokine that activates membrane bound endoglin on endothelial cells causing a myriad of vascular actions including vasorelaxation. The objective of the study was to determine serum levels of cytokines, angiogenic factors, placental growth factor (PlGF), TGF-ß-1 and anti-angiogenic factors, soluble endoglin (sEng) and soluble vascular endothelial growth factor 1 (sVEGFR1) in smoking and non-smoking pregnant women. METHODS: Using enzyme-linked immunosorbent and multiplex assays we prospectively analyzed serum levels of PIGF, TGF-ß1, sEng, sVEGFR1 and cytokines in normotensive pregnant smokers and non-smokers. Exclusion criteria included maternal hypertension, autoimmune disorders, rupture of membranes, evidence of labor and drug use. RESULTS: There were 59 women in the smoking and 66 in the non-smoking group. Compared to non-smoking mothers. maternal age was lower in smoking mothers with no significant difference in other demographic variables. There was no difference in levels of cytokines, anti-angiogenic factors and PlGF between the two groups. Median TGF-ß1 levels were significantly higher in the smoking group (8120 pg/mL vs 6040 pg/mL, p < 0.001) and remained significant after controlling for confounders. TGF-ß1 levels correlated positively with cotinine levels in the smoking group. CONCLUSIONS: We speculate that higher TGF-ß1 levels may explain the reduced incidence of preeclampsia in mothers who smoke by being available for action on maternal endothelium even after inactivation by circulating maternal sEng.

10-Year Study of Christian Church Support for Domestic Violence Victims: 2005-2015.

Religious beliefs play a significant role in the lives of victims of domestic violence. Victims find strength in their faith and would rather endure the violence at all costs to keep a family or a marriage together, than to compromise their faith by leaving. This 10 -year study explored the climate of support for victims of domestic violence among Christian clergy and church members between 2005 and 2015. Using a convenience sample, surveys were sent out to congregations in the Upper Midwest in 2005 and 2015. The survey included demographics; two items measuring perception of domestic violence in the congregation and community; six Likert Scale items regarding agreement with statements concerning leaving an abusive marriage; four "Yes-No" items regarding the impact of faith in leaving, support of the congregation, community resources, and clergy as counselors. The clergy's survey had the same questions plus open-ended questions about their skills in counseling victims, their congregation's support for victims, community resources, and beliefs that could impact a victim's choice in leaving. Data were analyzed using descriptive statistics, simple frequencies, and bivariate correlations. Narrative data were analyzed using content analysis. The results of this study indicated that change is slow. Members want their clergy to become more educated in counseling and in speaking about domestic violence from the pulpit. Clergy felt comfortable in making referrals for professional counseling, while the majority of members would prefer counseling with their pastor if they were in a violent relationship. Both clergy and members want to create a safe and supportive environment for victims/survivors of violent relationships. Findings from this study exemplify the need for pastors to remove the silence about domestic violence in their congregations and address the misunderstood social religious beliefs that may bind a victim to the violence.

Proceedings From The 11th Annual University Of Calgary Leaders In Medicine Research Symposium.

On November 8th, 2019, the Cumming School of Medicine at the University of Calgary hosted the 11th annual Leaders in Medicine (LIM) Research Symposium. Dr. Donald A. Redelmeier, Professor at the University of Toronto and Canada Research Chair in Medical Decision Sciences, served as the keynote speaker with a talk entitled "Pitfalls of Reasoning and Clinical Medicine". In addition, there were five oral and 64 poster presentations. These presentations covered topics ranging from health promotion to neuroimaging. The event celebrated the continuing success and diversity of the LIM program and the training of clinician-scientists at the University of Calgary.

10-Year Study of Christian Church Support for Domestic Violence Victims: 2005-2015.

PURPOSE: This 10 -year study explored the climate of support for victims of domestic violence among Christian clergy and church members between 2005 and 2015. METHOD: Using a convenience sample, surveys were sent out to congregations in the Upper Midwest in 2005 and 2015. The survey included demographics; two items measuring perception of domestic violence in the congregation andcommunity; six Likert Scale items regarding agreement with statements concerning leaving an abusive marriage; four 'Yes-No' items regarding the impact of faith in leaving, support of the congregation, community resources,and clergy as counselors. The clergy's survey had the same questions, plus open-ended questions about their skills in counseling victims, their congregation's support for victims, community resources, and beliefs that could impact a victim's choice in leaving. ANALYSIS: Data were analyzed using descriptive statistics, simple frequencies, and bivariate correlations. Narrative data were analyzed using content analysis. RESULTS: The results of this study indicated that change is slow. Members want their clergy to become more educated in counseling and in speaking about domestic violence from the pulpit. Clergy felt comfortable in making referrals for professional counseling, while the majority of members would prefer counseling with their pastor if they were in a violent relationship. Both clergy and members want to create a safe and supportive environment for victims/survivors of violent relationships. Findings from this study exemplify the need for pastors to remove the silence about domestic violence in their congregations and address the misunderstood social religious beliefs that may bind a victim to the violence.

Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment.

Sepsis-associated encephalopathy manifesting as delirium is a common problem in critical care medicine. In this study, patients that had delirium due to sepsis had significant cognitive impairments at 12-18 months after hospital discharge when compared with controls and Cambridge Neuropsychological Automated Test Battery-standardized scores in spatial recognition memory, pattern recognition memory, and delayed-matching-to-sample tests but not other cognitive functions. A mouse model of S. pneumoniae pneumonia-induced sepsis, which modeled numerous aspects of the human sepsis-associated multiorgan dysfunction, including encephalopathy, also revealed similar deficits in spatial memory but not new task learning. Both humans and mice had large increases in chemokines for myeloid cell recruitment. Intravital imaging of the brains of septic mice revealed increased neutrophil and CCR2+ inflammatory monocyte recruitment (the latter being far more robust), accompanied by subtle microglial activation. Prevention of CCR2+ inflammatory monocyte recruitment, but not neutrophil recruitment, reduced microglial activation and other signs of neuroinflammation and prevented all signs of cognitive impairment after infection. Therefore, therapeutically targeting CCR2+ inflammatory monocytes at the time of sepsis may provide a novel neuroprotective clinical intervention to prevent the development of persistent cognitive impairments.