Cytoskeletal genes regulation by chronic morphine treatment in rat striatum.

It has been previously suggested that morphine can regulate the expression and function of some proteins of the cytoskeleton. In the present study, we used real-time quantitative polymerase chain reaction to examine the effects of chronic morphine administration, in rat striatum, on 14 proteins involved in microtubule polymerization and stabilization, intracellular trafficking, and serving as markers of neuronal growth and degeneration. Chronic morphine treatment led to modulation of the mRNA level of seven of the 14 genes tested. Glial fibrillary acidic protein (Gfap) and activity-regulated cytoskeleton-associated protein (Arc) mRNA were upregulated, while growth associated protein (Gap43), clathrin heavy chain (Cltc), alpha-tubulin, Tau, and stathmin were downregulated. In order to determine if the regulation of an mRNA correlates with a modulation of the expression of the corresponding protein, immunoblot analyses were performed. With the exception of Gap43, the levels of Cltc, Gfap, Tau, stathmin, and alpha-tubulin proteins were found to be in good agreement with those from mRNA quantification. These results demonstrate that neuroadaptation to chronic morphine administration in rat striatum implies modifications of the expression pattern of several genes and proteins of the cytoskeleton and cytoskeleton-associated components.     

Autonomic Arousal During Actigraphically Estimated Waking and Sleep in Male Veterans With PTSD

Physiological hyperarousal is manifested acutely by increased heart rate, decreased respiratory sinus arrhythmia, and increased skin conductance level and variability. Yet it is uncertain to what extent such activation occurs with the symptomatic hyperarousal of posttraumatic stress disorder (PTSD). We compared 56 male veterans with current PTSD to 54 males who never had PTSD. Subjects wore ambulatory devices that recorded electrocardiograms, finger skin conductance, and wrist movement while in their normal environments. Wrist movement was monitored to estimate sleep and waking periods. Heart rate, but not the other variables, was elevated in subjects with PTSD equally during waking and during actigraphic sleep (effect sizes, Cohen's d, ranged from 0.63 to 0.89). The length of the sleep periods and estimated sleep fragmentation did not differ between groups. Group heart rate differences could not be explained by differences in body activity, PTSD hyperarousal symptom scores, depression, physical fitness, or antidepressant use.     

Strain-related brain injury in neonatal mice subjected to hypoxia–ischemia

The development of transgenic mice has led to an increase in the use of mice as models for human disease. We hypothesized that the degree of brain damage sustained by animals in a neonatal mouse model of hypoxia–ischemia depends on the strain used. We compared three strains of mice commonly used to generate transgenic strains (C57Bl/6, 129Sv and CD1), as well as three hybrids of these strains (C57Bl/6×129Sv, CD1×C57Bl/6, and CD1×129Sv). At postnatal day 7 (P7), pups were subjected to a modified Vannucci procedure for hypoxia–ischemia as follows: permanent ligation of right common carotid artery under halothane anesthesia, 2-h recovery period, exposure to 8% oxygen at 37°C for varying durations (30, 60 or 90 min). After 5 days, animals were perfused with 4% paraformaldehyde, brains were removed, postfixed and examined histologically with cresyl violet and Perl's iron stain to assess the degree of damage. Damage was assessed blindly using a score ranging from 0 (none) to 3 (infarct) in eight regions (ant-, mid-, and post- cortex, CA1, CA2, CA3 and dentate gyrus of the hippocampus, and striatum). We found significant differences in susceptibility to brain damage and mortality depending on the strain used. While determining the maximal degree of injury with the least amount of mortality for each strain, it was found that some strains (CD1) are particularly susceptible to brain damage in this model, while others (129Sv) are resistant.     

Regulation of genes involved in dopamine transporter modulation by acute cocaine in rat striatum

It is well established that acute administration of psychostimulants alters dopamine transport. However, the exact mechanism of this modulation is still unknown. In this study we examined the mRNA levels of several proteins involved in the various proposed processes following cocaine administration. The expression levels of several immediate early genes were also studied. This was performed in rat striatum using real-time quantitative PCR. As expected, a marked increase of the immediate early genes Fos, Egr1 and Egr3 was observed. Egr2 was also found up-regulated. Among the different genes studied only Synaptotagmin4 in the SNARE family and Synphilin1 in the synaptic vesicles binding family were modulated by acute cocaine treatment. Interestingly, acute amphetamine treatment did not increase either Synaptotagmin4 and Synphilin1 mRNA levels, although increases in early genes expression were noted.     

Rnd family genes are differentially regulated by 3,4-methylenedioxymethamphetamine and cocaine acute treatment in mice brain

Drugs of abuse induce alterations in cytoskeletal and cytoskeleton associated genes in several brain areas. We have previously shown that acute MDMA regulates the mRNA level of Rnd3, a Rho GTPase involved in actin cytoskeleton regulation, in mice striatum. In this study we investigated the effects of single administration of cocaine, another psychostimulant with a slightly different mechanism of action, on the mRNA levels of the three members of the Rnd genes family (Rnd1, Rnd2 and Rnd3). Mice were treated with either MDMA (9 mg/kg) or cocaine (20 mg/jg) and brain samples (i.e. hippocampus, striatum and prefrontal cortex) were processed for quantitative real-time PCR assay 1, 2, 4 and 6 h after the injections. The expression level of Rnd2 was differentially affected depending on the drug, brain area and time point after injection. Interestingly the two drugs up-regulate Rnd3 gene expression in the three structures tested with some differences in the timing. The effects of MDMA on Rnd3 appear earlier in the hippocampus as compared to cocaine, while it is the opposite in the prefrontal cortex. However, in the dorsal striatum, the two drugs induce an early and significant up-regulation of Rnd3 expression that is longer-lasting in the case of MDMA. In the case of cocaine contrarily to what was observed with MDMA, this modulation could not be blocked with the ERK activation inhibitor SL327 suggesting that the two drugs lead to the same effect on Rnd3 by two distinct pathways.     

Use of Video Telehealth Tablets to Increase Access for Veterans Experiencing Homelessness

BackgroundVeterans experiencing homelessness face substantial barriers to accessing health and social services. In 2016, the Veterans Affairs (VA) healthcare system launched a unique program to distribute video-enabled tablets to Veterans with access barriers.ObjectiveEvaluate the use of VA-issued video telehealth tablets among Veterans experiencing homelessness in the VA system.DesignGuided by the RE-AIM framework, we first evaluated the adoption of tablets among Veterans experiencing homelessness and housed Veterans. We then analyzed health record and tablet utilization data to compare characteristics of both subpopulations, and used multivariable logistic regression to identify factors associated with tablet use among Veterans experiencing homelessness.PatientsIn total, 12,148 VA patients receiving tablets between October 2017 and March 2019, focusing on the 1470 VA Veterans experiencing homelessness receiving tablets (12.1%).Main MeasuresTablet use within 6 months of receipt for mental health, primary or specialty care.Key ResultsNearly half (45.9%) of Veterans experiencing homelessness who received a tablet had a video visit within 6 months of receipt, most frequently for telemental health. Tablet use was more common among Veterans experiencing homelessness who were younger (AOR = 2.77; P <.001); middle-aged (AOR = 2.28; P <.001); in rural settings (AOR = 1.46; P =.005); and those with post-traumatic stress disorder (AOR = 1.64; P <.001), and less common among those who were Black (AOR = 0.43; P <.001) and those with a substance use disorder (AOR = 0.59; P <.001) or persistent housing instability (AOR = 0.75; P = .023).ConclusionsTelehealth care and connection for vulnerable populations are particularly salient during the COVID-19 pandemic but also beyond. VA’s distribution of video telehealth tablets offers healthcare access to Veterans experiencing homelessness; however, barriers remain for subpopulations. Tailored training and support for these patients may be needed to optimize telehealth tablet use and effectiveness.KEY WORDS: homelessness, Veterans, telemedicine, health services accessibility, mental health

The US Department of Veterans Affairs (VA) is a leader in clinical video telehealth to increase Veterans’ access to high-quality care.¹ In 2018 alone, VA healthcare systems provided more than 2.29 million telehealth episodes of video telehealth care to 12% of eligible Veterans.² The VA Video Connect (VVC) mobile application allows Veterans to securely stream live video sessions with their healthcare teams on the device of their choice.Studies have shown that video telehealth can offer effective delivery of mental healthcare,^3–5 primary care,^6,7 and specialty ambulatory care.^8–10 Patient populations who face sociodemographic and clinical challenges (e.g., travel distance to care for rural patients) can benefit from video telehealth.^11–16 Other vulnerable populations that have been shown to benefit from video telehealth include older adults,^17–21 African American and Hispanic adults,^22–25 and Native and Alaskan American adults;^26,27 and patients with mental health conditions such as anxiety and depression²⁸ or anxiety and alcohol use disorder,^29,30 post-traumatic stress disorder (PTSD),^31,32 substance use disorder (SUD);^33–35 or challenges with medication adherence.³⁶One VA patient population that could potentially benefit from virtual care is Veterans experiencing homelessness, representing 8% (n=37,085) of all US homeless adults. This population is a VA priority in part because it is characterized by elevated mortality due to high rates of suicide and fatal overdoses.^37,38 Veterans experiencing homelessness encounter health- and travel-related access barriers, while stigma may interfere with their willingness to seek care. Video telehealth could overcome some of these challenges, offering a mechanism for improved access to critical clinical services in this population.^39,40Little is known about video telehealth use among Veterans experiencing homelessness and how this technology influences their access to care. In 2016, the VA began the largest known program to distribute video telehealth tablets to Veterans facing access barriers. The tablets come with data plans and Wi-Fi connectivity.⁴¹ Between October 2017 and March 2019, the VA distributed 12,148 tablets to access-challenged Veterans. Tablets can be used for any clinical care that does not require physical contact, including mental health therapy and medication management, primary care, palliative care, and selective specialty and rehabilitation care.⁴²Previous evaluations have shown that the tablet distribution program successfully reached patients with clinical or social barriers and generated cost savings for such patients.^43,44 In this study, we sought to examine variation in sociodemographic and clinical characteristics with tablet recipients stratified by housed vs. homeless status, and by tablet users vs. non-users among Veterans experiencing homelessness, and factors associated with their tablet use. Our findings may contribute to an understanding of how video telehealth tablets and other devices can substitute for in-person healthcare encounters in the context of the COVID-19 pandemic and beyond.     

Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus

Opiates addiction is characterized by its long-term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used suppression subtractive hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases. Sensitization to the reinforcing effects of the drug occurred after three conditioning phases. After 25 days of treatment rats were euthanized and the complementary DNA (cDNA) from the hippocampus of morphine-dependent and saline-treated animals were then screened for differentially expressed cDNAs. The selected 177 clones were then subjected to a microarray procedure and 20 clones were found differentially regulated. The pattern of regulated genes suggests impairments in neurotransmitter release and the activation of neuroprotective pathways.     

Assessing sleep quality using self‐report and actigraphy in PTSD

Sleep disturbance is commonly reported by participants with post‐traumatic stress disorder, but objective evidence of poor sleep is often absent. Here we compared self‐report and actigraphic evaluations of sleep between veterans with post‐traumatic stress disorder and controls. Participants reported their sleep retrospectively for the month before the recording night and on the recording night. On the recording night, they wore an Actiwatch‐64 and were instructed to press the marker button upon getting into bed, each time they awoke, and at their final awakening. The post‐traumatic stress disorder group reported much worse sleep than controls on the Pittsburgh Sleep Quality Index for the previous month and somewhat poorer sleep on the recording night. However, on the recording night, neither diary nor actigraphic measures of number of awakenings, total time in bed, nor time lying awake after sleep onset differed between participants with and without post‐traumatic stress disorder. Diary‐reported number of awakenings was fewer than actigraphically captured awakenings. These results suggest a memory bias towards remembering worse sleep on the nights before the recording night.     

Broadband relaxation-optimized polarization transfer in magnetic resonance

Many applications of magnetic resonance are limited by rapid loss of spin coherence caused by large transverse relaxation rates. In NMR of large proteins, increased relaxation losses lead to poor sensitivity of experiments and increased measurement time. In this article, we develop broadband relaxation-optimized pulse sequences that approach fundamental limits of coherence transfer efficiency in the presence of very general relaxation mechanisms that include cross-correlated relaxation. These broadband transfer schemes use techniques of chemical shift refocusing (specific trajectory adapted refocusing echoes) that are tailored to specific trajectories of coupled spin evolution. We present simulations and experimental data indicating significant enhancement in the sensitivity of multidimensional NMR experiments of large molecules through these methods.