Nocturnal autonomic nervous system activity and morning proinflammatory cytokines in young adult African Americans.

Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C-reactive protein (CRP) and interleukin (IL)-6. Ninety-four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening. Cardiac tracings from the second sleep recording were analysed for heart rate variability (HRV). Body mass index was the only non-HRV measure correlated with cytokine levels. Indicators of SNS activity for the presleep, and first non-rapid eye movement (REM) and REM sleep periods were correlated independently with morning IL-6 levels. Altered autonomic balance during sleep may be a modifiable factor that influences immune activation.

Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.

Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2ß3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the development of impulsivity and excessive alcohol consumption.

Recreational cannabis use is associated with poorer sleep outcomes in young adult African Americans.

INTRODUCTION: The present study sought to determine the relationship between self-reported cannabis use dosage in grams per day with (1) objective sleep outcomes: sleep efficiency (SE), sleep onset latency SOL and number of night-time awakenings (NWAK) (2) if objective and subjective sleep measures, using the PSQI, differed between cannabis users and non-cannabis users. METHODS: Our sample included 178 participants, aged 18-35 years. We collected demographic information, cannabis use in dosage per day and frequency of use, depressive symptoms through the CESD, and subjective sleep reports using the PSQI. After the survey assessment, we monitored sleep using the Phillips Actiwatch Spectrum watch for a minimum of 5 nights. RESULTS: The amount of cannabis consumed per day was inversely related to SOL and SE, and positively related to NWAK. After controlling for covariates, regression models were statistically significant for predicting SOL (ß = -0.369, p <.001), SE (ß = -0.232, p <.05) and NWAK, (ß = -0.318, p <.001), indicating cannabis dosage per day is the strongest predictor for the sleep parameters. Subjective sleep measures did not differ from cannabis users versus non-cannabis users. CONCLUSION: Recreational cannabis use is beneficial for SOL but may be detrimental to SE as those who reported increased cannabis use also had more NWAK. Cannabis may be useful for sleep onset, results suggest that increased use does not aid in sleep maintenance.

Educational initiative in an NCATS TL1 training program to address the impact of systemic racism on human health, biomedical research, and the translational scientist.

Introduction: The goal of clinical and translational science (CTS) is to fill gaps in medical knowledge toward improving human health. However, one of our most pressing challenges does not reside within the biological map we navigate to find sustainable cures but rather the moral compass to recognize and overcome racial and ethnic injustices that continue to influence our society and hinder diverse research rigor. The Georgetown-Howard Universities Center for Clinical and Translational Science includes an inter-institutional TL1-funded training program for predoctoral/postdoctoral trainees in Translational Biomedical Science (TBS). Methods: In the fall of 2020, the TBS program responded to the national social justice crisis by incorporating a curriculum focused on structural racism in biomedical research. Educational platforms, including movie reviews, Journal Clubs, and other workshops, were threaded throughout the curriculum by ensuring safe spaces to discuss racial and ethnic injustices and providing trainees with practical steps to recognize, approach, and respond to these harmful biases in the CTS. Workshops also focused on why individuals underrepresented in science are vital for addressing and closing gaps in CTS. Results: Paring analysis using REDCap software de-identified participants after invitations were sent and collected in the system to maintain anonymity for pre- and post-analysis. The Likert scale evaluated respondents' understanding of diverse scientific circumstances. The pre/Fall and post/Spring surveys suggested this curriculum was successful at raising institutional awareness of racial and ethnic biases. Evaluating the effectiveness of our program with other training Clinical and Translational Science Awards (CTSA) consortiums will strengthen both the academic and professional TBS programs.

Emotional response to perceived racism and nocturnal heart rate variability in young adult African Americans.

BACKGROUND: Heightened autonomic nervous system (ANS) arousal is a well-established contributor to the effect of stress on adverse cardiovascular health outcomes which disproportionately affect African Americans. ANS arousal is normally attenuated during sleep and compromise of this shift is associated with multiple adverse cardiovascular outcomes. Parasympathetic nervous system (PNS) dominance during sleep can be altered by stress. Racism has been recognized to have many negative health consequences in African Americans. Perceived racism has been linked to ANS activity, however, we are not aware of prior research on racism and nocturnal ANS balance. OBJECTIVE: To examine relationships between perceived racism and nocturnal ANS activity indexed by heart rate variability (HRV) in healthy African American men and women age 18-35. METHODS: Fifty-four participants completed the Perceived Racism Scale and had 24-hour ambulatory electrocardiogram recordings in their homes. Power spectral analysis was used to derive normalized high frequency (nHF) to index PNS activity which was computed by 5-minute epochs during wake and sleep. RESULTS: Endorsement of racism and negative emotional reactions during the past year were inversely related to nHF during time in bed. Multiple regression analysis indicated that negative emotional reactions were a significant predictor of nHF during the sleep period F(2,54) = 4.213, p = .020, R2 = 0.135 (adjusted R2 = 0.103). Relationships during wake were not statistically significant. CONCLUSION: Findings suggest that perseverative thoughts triggered by negative emotional reactions to racism influencing nocturnal ANS activity may be a pathway by which perceived racism affects health. Support: 3UL1TR001409-02S1 and R01HL087995 to Dr. Mellman.

A Novel, Highly Related Jumbo Family of Bacteriophages That Were Isolated Against Erwinia.

Erwinia amylovora is a plant pathogen from the Erwiniaceae family and a causative agent of the devastating agricultural disease fire blight. Here we characterize eight lytic bacteriophages of E. amylovora that we isolated from the Wasatch front (Utah, United States) that are highly similar to vB_EamM_Ea35-70 which was isolated in Ontario, Canada. With the genome size ranging from 271 to 275 kb, this is a novel jumbo family of bacteriophages. These jumbo bacteriophages were further characterized through genomic and proteomic comparison, mass spectrometry, host range and burst size. Their proteomes are highly unstudied, with over 200 putative proteins with no known homologs. The production of 27 of these putative proteins was confirmed by mass spectrometry analysis. These bacteriophages appear to be most similar to bacteriophages that infect Pseudomonas and Ralstonia rather than Enterobacteriales bacteria by protein similarity, however, we were only able to detect infection of Erwinia and the closely related strains of Pantoea.

CRF-amplified neuronal TLR4/MCP-1 signaling regulates alcohol self-administration.

Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking. It has a 50-60% risk contribution from inherited susceptibility genes; however, their exact identity and function are still poorly understood. We report that alcohol-preferring P rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol self-administration. The signal was sustained during alcohol drinking by increased expression of corticotropin-releasing factor and its feedback regulation of TLR4 expression, likely contributing to the transition to alcohol dependence.