Reduced Vagal Tone in Women With The Premutation Is Associated With MRNA but Not Depression or Anxiety

BACKGROUND: Autonomic dysfunction is implicated in a range of psychological conditions, including depression and anxiety. The () premutation is a common genetic mutation that affects ~1:150 women and is associated with psychological vulnerability. This study examined cardiac indicators of autonomic function among women with the premutation and control women as potential biomarkers for psychological risk that may be linked to . METHODS: Baseline inter-beat interval and respiratory sinus arrhythmia (a measure of parasympathetic vagal tone) were measured in 35 women with the premutation and 28 controls. The women completed anxiety and depression questionnaires. genetic indices (i.e., CGG repeat, quantitative FMRP, mRNA, activation ratio) were obtained for the premutation group. RESULTS: Respiratory sinus arrhythmia was reduced in the premutation group relative to controls. While depression symptoms were associated with reduced respiratory sinus arrhythmia among control women, these variables were unrelated in the premutation. Elevated mRNA was associated with higher respiratory sinus arrhythmia. CONCLUSIONS: Women with the premutation demonstrated autonomic dysregulation characterized by reduced vagal tone. Unlike patterns observed in the general population and in study controls, vagal activity and depression symptoms were decoupled in women with the premutation, suggesting independence between autonomic regulation and psychopathological symptoms that is atypical and potentially specific to the premutation. The association between vagal tone and mRNA suggests that molecular variation associated with plays a role in autonomic regulation

Effect of a specially formulated diet on progression of heart enlargement in dogs with subclinical degenerative mitral valve disease

BackgroundPrevious studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. Hypothesis/ObjectivesA specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. AnimalsOne hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. MethodsRandomized double-blinded controlled multicenter clinical trial. ResultsThe study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). Conclusions and Clinical ImportanceFeeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control

Chronic Wasting Disease Prions in Elk Antler Velvet

Residue 226 of cervid prion proteins may be a determinant of CWD pathogenesis

Susceptibilities of Nonhuman Primates to Chronic Wasting Disease

A species barrier may protect humans from this disease

Transmission of Chronic Wasting Disease Identifies a Prion Strain Causing Cachexia and Heart Infection in Hamsters

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD