The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.

We have reported that D,L-thiol esters, including D-cysteine ethyl ester (D-CYSee), are effective at overcoming opioid-induced respiratory depression (OIRD) in rats. Our on-going studies reveal that co-injections of D-CYSee with multi-day morphine injections markedly diminish spontaneous withdrawal that usually occurs after cessation of multiple injections of morphine in rats. Chronically administered opioids are known (1) to alter cellular redox status, thus inducing an oxidative state, and (2) for an overall decrease in DNA methylation, therefore resulting in the transcriptional activation of previously silenced long interspersed elements (LINE-1) retrotransposon genes. The first objective of the present study was to determine whether D-CYSee and the one carbon metabolism with the methyl donor, betaine, would maintain redox control and normal DNA methylation levels in human neuroblastoma cell cultures (SH-SY5Y) under overnight challenge with morphine (100 nM). The second objective was to determine whether D-CYSee and/or betaine could diminish the degree of physical dependence to morphine in male Sprague Dawley rats. Our data showed that overnight treatment with morphine reduced cellular GSH levels, induced mitochondrial damage, decreased global DNA methylation, and increased LINE-1 mRNA expression. These adverse effects by morphine, which diminished the reducing capacity and compromised the maintenance of the membrane potential of SH-SY5Y cells, was prevented by concurrent application of D-CYSee (100 µM) or betaine (300 µM). Furthermore, our data demonstrated that co-injections of D-CYSee (250 µmol/kg, IV) and to a lesser extent, betaine (250 µmol/kg, IV), markedly diminished the development of physical dependence induced by multi-day morphine injections (escalating daily doses of 10-30 mg/kg, IV), as assessed by the lesser number of withdrawal phenomena elicited by the injection of the opioid receptor antagonist, naloxone (1.5 mg/kg, IV). These findings provide evidence that D-CYSee and betaine prevent the appearance of redox alterations and epigenetic signatures commonly seen in neural cells involved in opioid physical dependence/addiction, and lessen development of physical dependence to morphine.

A community treatment intervention advancing active treatment in the elderly (ACTIVATE): a pilot study.

A growing population of older adults receive treatment for depression but remain symptomatic. We report on a feasibility pilot study of an intervention (ACTIVATE) to improve depression care by encouraging the older person to take a step to intensify the existing treatment. Older adults (N = 43) receiving home-meal service and in depression treatment, but still symptomatic, participated in the ACTIVATE intervention. Assessments were conducted to evaluate change in treatment. Many (66.6%) participants took a step to change their treatment; the rate (88.2%) was higher among individuals with major depression. ACTIVATE may be a useful social work intervention to improve depression care.

Zinc cytotoxicity induces mitochondrial morphology changes in hela cell line.

Zinc (Zn2+) is important in cellular processes. In the cell, free zinc is tightly regulated and found in minuscule amounts. However, in an unhealthy cellular environment, such as hypoxia, zinc increases in the cell and zinc overload may occur. Studies have shown that zinc overload causes cellular and mitochondrial stress. Mitochondrial stress affects mitochondrial morphology. In normal cells, mitochondrial morphology resembles a long, tubular shape. In unhealthy cells, mitochondrial morphology resembles fragmented, circular shape. To address whether zinc overload contributes directly to the abnormal changes of mitochondrial morphology, we imaged and analyzed mitochondria that were treated with the application of exogenous zinc. In the first part of the study, exogenous zinc was applied to HeLa cells at 1 µM, 10 µM, 50 µM, 100 µM, or 200 µM zinc chloride along with 10 µM pyrithione. Mitochondrial morphology was analyzed with Mito-Morphology micro in ImageJ. Mitochondrial morphology changed from a healthy tubular shape to an unhealthy circular shape and fragmentation. Mitochondrial morphology changes were observed in a dose-dependent fashion. The second part of the study involved applying the metal ion chelator TPEN after applying 50 µM zinc chloride along with 10 µM pyrithione. TPEN reduced zinc-induced abnormal mitochondrial morphology after zinc treatment. This present study supports that zinc overload may cause morphology changes induced by mitochondrial stress that may lead to cell death.

Lessons Learned in Implementing VA Video Connect for Evidence-Based Psychotherapies for Anxiety and Depression in the Veterans Healthcare Administration.

A top priority for the Veteran's Healthcare Administration is improving access to high-quality mental healthcare. Mobile and telemental healthcare are a vital component of increasing access for veterans. The Veteran's Healthcare Administration is making efforts to further broaden how veterans receive their care through VA Video Connect, which allows veterans to connect with their provider from their residence or workplace. In this mixed-methods study, successes and challenges associated with the rapid implementation of VA Video Connect telemental health appointments are examined through (1) administrative data and (2) qualitative interviews at one medical center. Within 1 year of the telehealth initiative, the number of providers experienced with telemental health increased from 15% to 85%, and telehealth appointments increased from 5376 to 14,210. Provider reported barriers included administrative challenges and concerns regarding care. Having an implementation model of telehealth champions and a team of experienced mental health providers allowed for rapid adoption of telehealth. Utilizing a similar model in other settings will further enable more veterans with depression and anxiety to have access to evidence-based psychotherapy, regardless of location or national crisis. With the dramatic increase in both training for providers as well as veteran use of telemental healthcare during the COVID-19 pandemic response, future research should aim to better understand which teams were able to switch to telehealth easily versus those which struggled, along with examining system-wide and provider-level factors that facilitated continued use of telehealth after social distancing requirements related to COVID-19 were relaxed.