MHV68 Latency Modulates the Host Immune Response to Influenza A Virus

Murine gammaherpesvirus 68 (MHV68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. Like other herpesviruses, MHV68 causes acute infection and establishes life-long latency in the host. Recently, it has been shown that mice latently infected with MHV68 have resistance to unrelated pathogens in secondary infection models. We therefore hypothesized that latent MHV68 infection could modulate the host response to influenza A virus. To test this hypothesis, mice were infected intranasally with influenza virus following the establishment of MHV68 latency. Mice latently infected with MHV68 showed significantly higher survival to influenza A virus infection than did PBS mock-infected mice. Latent MHV68 infection led to lower influenza viral loads and decreased inflammatory pathology in the lungs. Alveolar macrophages of mice latently infected with MHV68 showed activated status, and adoptive transfer of those activated macrophages into mice followed the infection with influenza A virus had significantly greater survival rates than control mice, suggesting that activated alveolar macrophages are a key mechanistic component in protection from secondary infections.     

A prospective investigation of depression and adverse outcomes in patients undergoing vascular surgical interventions: A retrospective cohort study using a large mental health database in South London

BackgroundPatients with depression are more susceptible to cardiovascular illness including vascular surgeries. However, health outcomes after vascular surgery among patients with depression is unknown. This study aimed to investigate associations of depression with post-operative health outcomes for vascular surgical patients.MethodsA retrospective observational study was conducted using data from a large mental healthcare provider and linked national hospitalization data for the same south London geographic catchment. OPCS-4 codes were used to identify vascular procedures. Health outcomes were compared between those with/without depression including length of hospital stay (LOS), inpatient mortality, and 30 day emergency hospital readmissions. Predictors of these health outcomes were also assessed.ResultsVascular surgery was received by 9,267 patients, including 446 diagnosed with depression. Patients with depression had a higher risk of emergency admission for vascular surgery (odds ratio [OR] 1.28; 1.03, 1.59), longer index LOS (IRR 1.38; 1.33–1.42), and a higher risk of 30-day emergency readmission (OR 1.82; 1.35–2.47). Patients with depression had higher inpatient mortality after adjustment for sociodemographic status (1.51; 1.03, 2.23) but not on full adjustment, and had longer emergency readmission LOS (1.13; 1.04, 1.22) after adjustment for sociodemographic factors and cardiovascular disease. Correlates of vascular surgery hospitalization among patients with depression included admission through emergency route for longer LOS, inpatient mortality, and 30-day hospital readmission.ConclusionPatients with depression undergoing vascular surgery have substantially poorer health outcomes. Screening for depression prior to surgery might be indicated to target preventative measures.     

The immediate effects of open kinetic chain knee extensor exercise at different loads on knee anterior laxity in the uninjured

BackgroundThere is evidence that anterior laxity may be affected by knee extensor open kinetic chain (OKC) exercise with responses being load-dependent. The aim of this study is to evaluate the immediate and short-term changes in passive knee anterior laxity following a single session of OKC knee extensor exercise.MethodsThirty two participants were randomly allocated to perform either high load (20 sets of 2 repetitions) or low load (2 sets of 20 repetitions) knee extensor OKC exercise with knee anterior laxity assessed before exercise, immediately after exercise and 45 and 90 min after exercise with a KT-2000 arthrometer using a 133 N force.ResultsA significant effect of time was observed on knee laxity (p < 0.001). However, a significant interaction of time and group was not found (p = 0.54) and so the results presented here are for the combined (low and high load) group mean ± standard deviation knee anterior laxity (mm) in the exercised leg: 7.2 ± 2.2 (baseline), 8.2 ± 2.3 (immediate post exercise, 14% change from baseline), 8.1 ± 2.3 (45 min post exercise, 12% change from baseline), and 7.7 ± 2.2/0.29 (6.9) (90 min post exercise, 7% change from baseline).ConclusionOKC knee extensor exercise at high loads and low loads causes an immediate increase in knee laxity that begins to decrease within 90 min.     

Chemotherapy and peripheral neuropathy

Neurological Sciences - Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major dose-limiting side effect of many anti-cancer agents, including taxanes, platinums, vinca alkaloids,...     

Prevalence Rates and Correlates of Likely Post-Traumatic Stress Disorder in Residents of Fort McMurray 6 Months After a Wildfire

On May 3, 2016, mandatory evacuation order was declared for Fort McMurray region as wildfire threatened. Over 90,000 residents were evacuated and firefighters from Canada and abroad worked constantly to protect the municipality. Overall, fire consumed about 2400 homes and over 200,000 ha of forest, reaching into Saskatchewan. The evacuation order was lifted with residents returning to the Municipality in phases from June 1, 2016. The aim of this study is to assess likely prevalence of PTSD in residents of Fort McMurray 6 months after a wildfire and to determine the predictors of likely PTSD in the respondents. A quantitative cross-sectional survey was used to collect data through self-administered paper-based questionnaires to determine likely PTSD. The PTSD Checklist for DSM 5 Part 3 was used to assess the presence or absence of likely PTSD in respondents randomly selected from a variety of natural settings in Fort McMurray. Data were analyzed with SPSS version 20 using univariate analysis with the chi-squared test and binary logistic regression analysis. One-month prevalence rate among adult residents for likely PTSD 6 months after the disaster was 12.8% (14.9% for females and 8.7% for males). While controlling for other factors in the logistic regression model, corresponding odds ratios included 9.51 and 4.88 for those who received no or only limited support respectively from friends/family, 8.00 for those who had history of an anxiety disorder before the wildfire, and 4.01 for those who received counseling after the wildfire. Respondents who presented with likely PTSD were significantly more likely to self-report increased drug abuse, but not increased alcohol use, after the fire. Our study has established that while support from family/friends following wildfires may be protective against likely PTSD, a prior diagnosis of an anxiety disorder significantly increased risk for developing PTSD. Further studies are needed to explore whether receiving counseling after a wild fire alters the likelihood of individuals presenting with PTSD.

     

Bias and Precision of Parameter Estimates from Models Using Polygenic Scores to Estimate Environmental and Genetic Parental Influences

Behavior Genetics - In a companion paper Balbona et al. (Behav Genet, in press), we introduced a series of causal models that use polygenic scores from transmitted and nontransmitted alleles, the...     

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.