Toll-like Receptor-4 Regulation of Hepatic Cyp3a11 Metabolism in a Mouse Model of LPS-induced CNS Inflammation

Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60–70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding the involvement of the hypothalamic-adrenal-pituitary axis. Endotoxin was detectable (1–10 ng/ml) in serum between 15 and 120 min after ICV dosing of 2.5 μg LPS. Peripheral administration of 2.5 μg LPS by intraperitoneal injection produced similar serum endotoxin levels and a similar loss (60%) in Cyp3a11 expression and activity in the liver. The loss of Cyp3a11 in response to centrally or peripherally administered LPS could not be evoked in Toll-like receptor-4 (TLR4)-mutant (C3H/ HeJ) mice, indicating that TLR4 signaling pathways are directly involved in the enzyme loss. In summary, we conclude that LPS is transferred from the brain to the circulation in significant quantities in a model of CNS infection or inflammation. Subsequently, LPS that has reached the circulation stimulates a TLR4-dependent mechanism in the periphery, evoking a reduction in Cyp3a11 expression and metabolism in the liver

Automating lichen monitoring in ecological studies using instance segmentation of time-lapse images

Lichens are symbiotic organisms composed of fungi, algae, and/or cyanobacteria that thrive in a variety of environments. They play important roles in carbon and nitrogen cycling, and contribute directly and indirectly to biodiversity. Ecologists typically monitor lichens by using them as indicators to assess air quality and habitat conditions. In particular, epiphytic lichens, which live on trees, are key markers of air quality and environmental health. A new method of monitoring epiphytic lichens involves using time-lapse cameras to gather images of lichen populations. These cameras are used by ecologists in Newfoundland and Labrador to subsequently analyze and manually segment the images to determine lichen thalli condition and change. These methods are time-consuming and susceptible to observer bias. In this work, we aim to automate the monitoring of lichens over extended periods and to estimate their biomass and condition to facilitate the task of ecologists. To accomplish this, our proposed framework uses semantic segmentation with an effective training approach to automate monitoring and biomass estimation of epiphytic lichens on time-lapse images. We show that our method has the potential to significantly improve the accuracy and efficiency of lichen population monitoring, making it a valuable tool for forest ecologists and environmental scientists to evaluate the impact of climate change on Canada's forests. To the best of our knowledge, this is the first time that such an approach has been used to assist ecologists in monitoring and analyzing epiphytic lichens.Comment: 6 pages, 3 Figures, 8 Tables, Accepted for publication in IEEE International Conference on Machine Learning and Applications (ICMLA), copyright IEE

Relationship between antidepressant therapy and risk for cardiovascular events in patients with and without cardiovascular disease

Objective: The American Heart Association has endorsed depression as a cardiac risk factor and recommends screening as part of routine practice. This has been met with controversy due to inconsistencies in the data linking depression treatment to better cardiovascular outcomes. Our objective was to prospectively assess the association between depression treatment (defined as being prescribed antidepressant medication) and major adverse cardiovascular events (MACE) in patients referred for exercise stress tests. Methods: 2385 consecutive patients presenting for myocardial perfusion exercise stress tests underwent a sociodemographic, medical, and psychiatric interview (PRIME-MD) and completed the Beck Depression Inventory (BDI). History of CVD and antidepressant use was self-reported and verified via chart review. Participants followed over an 8.8 year follow-up, and information regarding MACE incidence (including cardiac mortality, non-fatal myocardial infarction, revascularization procedures, cerebrovascular events) was obtained from provincial administrative databases. Results: 8% (n=190) of the sample were taking antidepressants at baseline, 41% (n=916) had a history of CVD, and 38.7% (n=921) had depression according to the PRIME-MD or BDI. Antidepressant treatment was associated with a 30% reduced risk of MACE (HR=0.697; 95%CI=0.504-0.964; p=.029). A 46% reduction in risk was associated with antidepressant treatment among those without CVD (HR=0.542; 95%CI=0.299-0.981; p=.043). In depressed patients, a 33% reduction in risk of MACE associated with antidepressant use was seen (adjusted HR=0.674; 95%CI=0.440-1.033; p=.07). Conclusions: Antidepressants may be cardio-protective among patients presenting for stress testing independent of risk factors including CVD and depression. Results support treating depression with antidepressants in this population to reduce risk of MACE

Positive and negative affect is related to experiencing chest pain during exercise-induced myocardial ischemia

© 2017 by the American Psychosomatic Society. Objective: Silent myocardial ischemia is thought to be associated with worse cardiovascular outcomes due to a lack of perception of pain cues that initiate treatment seeking. Negative affect (NA) has been associated with increased pain reporting and positive affect (PA) with decreased pain reporting, but these psychological factors have not been examined within the context of myocardial ischemia. This study evaluated the associations between PA, NA, and chest pain reporting in patients with and without ischemia during exercise testing. Methods: A total of 246 patients referred for myocardial perfusion single-photon emission computed tomography exercise stress testing completed the positive and negative affect schedule-expanded version, a measure of PA and NA. Presence of chest pain and myocardial ischemia were evaluated using standardized protocols. Results: Logistic regression analyses revealed that for every 1-point increase in NA, there was a 13% higher chance for ischemic patients (odds ratio [OR] = 1.13; 95 % confidence interval [CI] = 1.02 to 1.26) and an 11% higher chance in nonischemic patients (OR = 1.11; 95% CI = 1.03 to 1.19) to report chest pain. A significant interaction of PA and NA on chest pain reporting (ß = 0.02; 95% CI = 0.002 to 0.031) was also observed; nonischemic patients with high NA and PA reported more chest pain (57%) versus patients with low NA and low PA (13%), with high NA and low PA (17%), and with high PA and low NA (7%). Conclusions: Patients who experience higher NA are more likely to report experiencing chest pain. In patients without ischemia, high NA and PA was also associated with a higher likelihood of reporting chest pain. Results suggest that high levels of PA as well as NA may increase the experience and/or reporting of chest pain

Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak