Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Endocannabinoid involvement in beneficial effects of caloric restriction in a rodent model of comorbid depression and epilepsy.

Clinically, patients with depression are at a heightened risk for developing epilepsy, and vice versa, suggesting shared mechanisms for this bidirectional comorbidity. Unfortunately, comorbid depression and epilepsy is associated with worsened quality of life and treatment refractoriness, highlighting the need for novel treatment targets and nonpharmacologic supplements to existing therapies. The present study used the Swim-Low Active rat, a well-validated model of depression and epilepsy comorbidity that was selectively bred based on forced swim test behavior, to assess the safety and efficacy of caloric restriction in treating this comorbidity.

An alcohol-related liver disease multi-stakeholder hub (ARMS-Hub) to enhance research activity in underserved communities in the UK.

Background: Alcohol use is the third leading risk factor of death and disability in the UK and costs the NHS £3.5 billion per year. Despite the high prevalence and healthcare burden of Alcohol-related Liver Disease (ArLD), there has been minimal research addressing prevention, morbidity and mortality.

Driving DNA Nanopore Membrane Insertion through Dipolar Coupling.

DNA nanopores appear to be a plausible alternative to the use of transmembrane proteins. The specificity and programmability of DNA interactions allow the design of synthetic channels that insert into lipid bilayers and can regulate the ionic transport across them. In this Communication, we investigate the dependence of insertion capabilities on the electrostatic properties of the nanopore and show that the presence of a permanent electric dipole is an important factor for the nanopore to insert into the membrane.

Voucher-based contingency management to promote treatment engagement in comorbid alcohol use disorder and alcohol-related liver disease: A pilot theory-informed qualitative study with service users.

Background: Effective interventions for the management of alcohol-related liver disease (ARLD) remain a gap in clinical practice, and patients' engagement with alcohol services is suboptimal. Based upon the principles of operant conditioning, contingency management (CM) is a psychosocial intervention th at involves gradual, increasing incentives upon completion of treatment-related goals such as treatment attendance.

Methods: A pilot feasibility trial was conducted with 30 adult patients recruited from an inpatient clinical setting.