TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4.

Recent findings indicate that TLR3 polymorphisms increase susceptibility to enteroviral myocarditis and inflammatory dilated cardiomyopathy (iDCM) in patients. TLR3 signaling has been found to inhibit coxsackievirus B3 (CVB3) replication and acute myocarditis in mouse models, but its role in the progression from myocarditis to iDCM has not been previously investigated. In this study we found that TLR3 deficiency increased acute (P = 5.9 × 10(-9)) and chronic (P = 6.0 × 10(-7)) myocarditis compared with WT B6.129, a mouse strain that is resistant to chronic myocarditis and iDCM. Using left ventricular in vivo hemodynamic assessment, we found that TLR3-deficient mice developed progressively worse chronic cardiomyopathy. TLR3 deficiency significantly increased viral replication in the heart during acute myocarditis from day 3 through day 12 after infection, but infectious virus was not detected in the heart during chronic disease. TLR3 deficiency increased cytokines associated with a T helper (Th)2 response, including IL-4 (P = 0.03), IL-10 (P = 0.008), IL-13 (P = 0.002), and TGF-ß(1) (P = 0.005), and induced a shift to an immunoregulatory phenotype in the heart. However, IL-4-deficient mice had improved heart function during acute CVB3 myocarditis by echocardiography and in vivo hemodynamic assessment compared with wild-type mice, indicating that IL-4 impairs cardiac function during myocarditis. IL-4 deficiency increased regulatory T-cell and macrophage populations, including FoxP3(+) T cells (P = 0.005) and Tim-3(+) macrophages (P = 0.004). Thus, TLR3 prevents the progression from myocarditis to iDCM following CVB3 infection by reducing acute viral replication and IL-4 levels in the heart.

Association of Hearing Loss and Loneliness in Older Adults.

OBJECTIVE: The objective of this study is to determine factors associated with loneliness in older adults presenting for hearing loss treatment. METHOD: A cross-sectional analysis was conducted of 145 participants (aged 50-94) who presented for hearing aids or cochlear implants and were enrolled in the Studying Multiple Outcomes After Aural Rehabilitative Treatment (SMART) study from 2011 to 2013. Social, communicative, physical, and mental health functioning were assessed using self-administered questionnaires, and loneliness using the University of California, Los Angeles (UCLA) Loneliness Scale. RESULTS: Younger age and greater hearing loss were significantly associated with greater loneliness. Metrics of depressive symptoms and hearing-related quality of life, communication difficulties, and emotional well-being, mental health, and 36-Item Medical Outcomes Study Short-Form (SF-36) scores were moderately or highly correlated with loneliness. DISCUSSION: Younger age and greater hearing loss are independently associated with higher levels of loneliness in older adults presenting to clinic for hearing loss treatment. Further studies needed to determine whether hearing treatment can reduce loneliness in older adults.

The Association of Alcohol Use Disorders with Suicidal Ideation and Suicide Attempts in a Population-Based Sample with Mood Symptoms.

Using population-based data, we examined associations between alcohol use disorders (AUD) and suicidality, assessing effect modification by mood disorders, and mediation by drinking level. Suicidality was assessed among current drinkers with 2-weeks of low mood (n = 9,173) in the National Epidemiologic Survey on Alcohol and Related Conditions. Independent of mood disorder, alcohol dependence, was associated with suicidal ideation (adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI] = 1.25-2.14), and suicide attempts (AOR = 2.02; CI = 1.43-2.85) relative to those without AUD. Findings indicate partial mediation by consumption. Associations between AUD and suicidality among those with low mood are not explained by comorbid mood disorder, but are partially mediated by drinking level. Future studies should evaluate transitions in suicidality with change in consumption.

Assessing Systemic Stress in Otolaryngology: Methodology and Feasibility of Hair and Salivary Cortisol Testing.

OBJECTIVE: Elevated systemic stress is a predictor of adverse health outcomes, and stress can be objectively quantified by cortisol concentration. Despite its utility, such testing is rarely performed in otolaryngology. This manuscript provides details on the principles, methodology, and feasibility of performing laboratory assessments of hair and salivary cortisol to inform researchers wishing to incorporate these novel tests in future otolaryngologic studies. METHODS: Participants were older adults with hearing impairment. One hair sample and eight saliva samples were collected. Feasibility of study design was assessed through rates of participation in hair and saliva sampling and protocol adherence for saliva collection. Area under the curve (AUC) was used to evaluate overall secretion, and cortisol awakening response (CAR) was used to evaluate the dynamic secretion response. RESULTS: From 9/1/2013 to 12/31/2013, 26/30 (86.7%) eligible participants agreed to hair sampling. All 30 subjects agreed to collect saliva, with 29 (96.7%) adhering to the collection protocol. Mean AUC was 401.2 nmol/L per hour, and CAR was 4.5 nmol/L. CONCLUSIONS: Evaluating systemic stress in an otolaryngologic population using hair and saliva is feasible with acceptable participation and adherence. Repeat measurements over time will allow for evaluation of changes in systemic stress in relation to treatment.