Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: Role of enhanced brain reward functional connectivity and homeostasis redeeming joy

Background Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. Case presentations We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid “bad dreams” remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. Results The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient’s regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. Conclusions These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies

Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells

The per-protocol effect of immediate versus deferred antiretroviral therapy initiation

The START trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

EFFECT OF PYROLYSIS PARAMETERS ON SILICON CARBIDE-FORMING COMPOSITE MIXTURES

High-performance ceramics are often used for reusable spacecraft Thermal Protection Systems (TPS). Pre-ceramic polymers provide a suitable route for fabricating silicon carbide (SiC)–based TPS. It is known that different phases of SiC form upon pyrolysis depending on the temperature. This research investigates the effects of pyrolysis temperature and nucleation aids on SiC forming pre-ceramic polymers and how they influence the final phases. It is possible that the addition of seed powders consisting of microscale and nanoscale SiC powders can aid growth of crystalline SiC at lower temperatures and influence the final composition in mixtures of SiC-forming polymers with crystalline SiC powders and graphite. For this research, pre-ceramic polymer mixtures with various nucleation aids were cured slowly in a furnace and pyrolyzed at various temperatures into a ceramic. The effects of temperature were investigated for six different sample configurations: pure polymer sample, micron crystalline SiC powder layer with polymer fill, nano SiC powder with polymer fill, micron SiC powder and polymer mixture (85 wt%), 3D printed amorphous carbon-loaded polylactic acid layer with SiC polymer fill, and crystalline graphite mixed with a UV-curable polymer (65 wt.%) mixed with SiC polymer. Material characterization was conducted via SEM to identify the phases. These results can improve processing procedures for these ceramics with better strength and thermal diffusivity for TPS.Ensign, United States NavyApproved for public release. Distribution is unlimited

Association between quantitative varicella-zoster virus antibody levels and zoster reactivation in HIV-infected persons

Abstract Background Varicella-zoster virus (VZV) reactivation is common but difficult to predict in HIV-infected persons. Objective Since qualitative VZV antibodies can determine past VZV disease or vaccination, we evaluated whether quantitative VZV antibody levels over time can predict future zoster. Study design US Military HIV Natural History (NHS) participants with a zoster diagnosis at least 5 years after HIV diagnosis (n = 100) were included. Zoster-negative controls (n = 200) were matched by age, race, gender, and CD4 count at HIV diagnosis. Repository plasma specimens collected at baseline and prior to zoster diagnosis were evaluated using a quantitative anti-VZV ELISA assay. Differences in quantitative VZV levels were analyzed by Wilcoxon Mann–Whitney and Fisher’s exact tests. Results Median CD4 count at HIV diagnosis was similar for cases and controls (535 [IQR 384–666] vs. 523 [IQR 377–690] cells/μL; p = 0.940), but lower for cases at zoster diagnosis (436 [IQR 277–631] vs. 527 [IQR 367–744] cells/μL; p = 0.007). Antiretroviral therapy (ART) use prior to zoster diagnosis was lower for cases (52.0%) compared to controls (64.5%; p = 0.025). Cases had similar mean VZV antibody levels prior to zoster diagnosis compared to controls [2.25 ± 0.85 vs. 2.44 ± 0.96 index value/optical density (OD) ratio; p = 0.151] with no difference in the change in antibody levels over time (0.08 ± 0.71 vs. 0.01 ± 0.94 index value/OD per year; p = 0.276). Conclusion Quantitative VZV antibody levels are stable in HIV-infected persons and do not predict zoster reactivation. Low CD4 count and lack of ART use appear to be better predictors of future zoster diagnosis