Release of live baitfish by recreational anglers drives fish pathogen introduction risk

Emerging diseases of wildlife are an existential threat to biodiversity, and human-mediated movements of live animals are a primary vector of their spread. Wildlife disease risk analyses offer an appealing alternative to precautionary approaches because they allow for explicit quantification of uncertainties and consideration of tradeoffs. Such considerations become particularly important in high-frequency invasion pathways with hundreds of thousands of individual vectors, where even low pathogen prevalence can lead to substantial risk. The purpose of this study was to examine the landscape-level dynamics of human behavior-mediated pathogen introduction risk in the context of a high-frequency invasion pathway. One such pathway is the use and release of live fish used as bait by recreational anglers. We used a stochastic risk assessment model parameterized by angler survey data from Minnesota, USA, to simulate one year of fishing in Minnesota and estimate the total number of risky trips for each of three pathogens: viral hemorrhagic septicemia virus, the microsporidian parasite Ovipleistophora ovariae, and the Asian fish tapeworm Schizocotyle acheilognathi. We assessed the number of introductions under four scenarios: current/baseline conditions, outbreak conditions (increased pathogen prevalence), source-focused control measures (decreased pathogen prevalence), and angler-focused control measures (decreased rates of release). We found that hundreds of thousands of introduction events can occur per year, even for regulated pathogens at low pathogen prevalence. Reducing the rate of illegal baitfish release had significant impact on risky trips in scenarios where a high number of anglers were involved, but was less impactful in circumstances with limited outbreaks and fewer affected anglers. In contrast, reducing pathogen prevalence in the source populations of baitfish had relatively little impact. In order to make meaningful changes in pathogen introduction risk, managers should focus efforts on containing local outbreaks and reducing illegal baitfish release to reduce pathogen introduction risk. Our study also demonstrates the risk associated with high-frequency invasion pathways and the importance of incorporating human behaviors into wildlife disease models and risk assessments

Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Factors Associated With Cannabis Use During the Reproductive Cycle: A Retrospective Cross-Sectional Study of Women in States With Recreational and Medical Cannabis Legalization.

IntroductionPassage of cannabis laws may impact cannabis use and the use of other substances. The suggested association is of particular concern in pregnant women where exposure to substances can cause harm to both the pregnant woman and fetus. The present study contributes to the minimal literature on factors associated with cannabis use during the preconception, prenatal, and postpartum periods including state legalization status, concurrent use of tobacco and e-cigarettes and adequacy of prenatal care.MethodsWe conducted a cross-sectional analysis using combined survey data from the 2016-2018 Pregnancy Risk Assessment Monitoring System (PRAMS) collected from 36,391 women. Logistic regression was used to estimate the impact of state-legalization, adequacy of prenatal care, and other substance use on cannabis use during the preconception, prenatal, and post-partum periods.ResultsIn the preconception model, residence in a recreationally legal state (OR: 2.37; 95% CI, 2.04-2.75) or medically legal state (OR:3.32; 95% CI, 2.90-3.80) compared to a non-legal state was associated with higher odds of cannabis use. In the prenatal model, residence in a recreationally legal state was associated with higher odds of cannabis use (OR: 1.51; 95% CI, 1.29-1.79) whereas there was no association with residence in a medically legal state. Tobacco use including e-cigarettes and moderate prenatal alcohol use were also significantly associated with cannabis use.ConclusionRecreational cannabis legalization is associated with the use of cannabis prior to, during, and after pregnancy. Renewed clinical and policy efforts may be warranted to update prenatal substance use prevention programs, educational campaigns, and provider education as cannabis legalization evolves

Factors associated with habitual sleep duration in US adults with hypertension: a cross-sectional study of the 2015-2018 National Health and Nutrition Examination Survey.

BackgroundThe relationship between inadequate sleep duration and hypertension risk has been established in the general population, but there is a gap in the literature on predictors of habitual sleep duration in adults with hypertension. This study examined factors associated with habitual sleep duration among adults with hypertension in the United States (US).MethodsData of 5660 adults with hypertension were obtained by combining the 2015-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey weighted multinomial logistic regression models were fit to examine factors associated with short (&lt; 7 h) and long (&gt; 9 h) sleep duration with adequate sleep duration (7-9 h) as the reference.ResultsThe prevalence of self-reported adequate sleep duration was 65.7%, while short sleep duration was 23.6%, and long sleep duration 10.7%. Short sleep duration (compared to adequate sleep duration) was positively associated with history of seeking help for sleeping difficulties (relative risk ratio [RRR], 1.25; 95% confidence interval [CI], 1.02-1.53), Non-Hispanic Black race/ethnicity (RRR, 2.08; 95% CI, 1.61-2.67), working ≥45 h/week (RRR, 1.81; 95% CI, 1.32-2.48), and negatively associated with older age ≥ 65 years (RRR, 0.63; 95% CI, 0.45-0.91) and female gender (RRR, 0.70; 95% CI, 0.56-0.88). Long sleep duration was positively associated with female gender (RRR, 1.24; 95% CI, 1.001-1.54), chronic kidney disease (RRR, 1.48; 95% CI, 1.14-1.92), moderate depressive symptoms (RRR, 1.62; 95% CI, 1.08-2.44), moderately severe to severe depressive symptoms (RRR, 1.89; 95% CI, 1.05-3.43), being in retirement (RRR, 3.46; 95% CI, 2.18-5.49), and not working due to health reasons (RRR, 4.87; 95% CI, 2.89-8.22) or other reasons (RRR, 3.29; 95% CI, 1.84-5.88).ConclusionThis population-based study identified factors independently associated with habitual sleep duration in adults with hypertension. These included help-seeking for sleeping difficulty, gender, age, chronic kidney disease, depressive symptoms, race/ethnicity, and employment status. These findings can help in the development of tailored approaches for promoting adequate sleep duration in adults with hypertension