Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Personality dimensions harm avoidance and self-directedness predict the cortisol awakening response in military men

To account for individual differences in vulnerability for stress-related disorders, studies have examined the relationship between hypothalamic-pituitary-adrenal (HPA) axis functioning and personality. The present study examined the relationship between the free fraction of cortisol in saliva after awakening and personality as measured with Cloninger's Temperament and Character Inventory [Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., Wetzel, R.D., 1994. The Temperament and Character Inventory (TCI): A Guide to its Development and Use. Washington University, Center for Psychobiology of Personality, St. Louis, MO] in 107 healthy male soldiers. Harm avoidance explained 9% of variance in cortisol levels after awakening (AUCG), and harm avoidance and self-directedness predicted 10% of variance in mean cortisol increase. The cortisol awakening response (CAR) was lower in participants with low scores on harm avoidance, and mean cortisol increase after awakening was higher in soldiers high on self-directedness and harm avoidance. These results show that the CAR is related to personality and that it can be used to examine individual differences in HPA (re)activity. (C) 2009 Elsevier B.V. All rights reserved

Glucocorticoid receptor number predicts increase in amygdala activity after severe stress

Contains fulltext : 108044.pdf (publisher's version ) (Open Access)INTRODUCTION: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid receptor (GR) number in peripheral blood mononuclear cells (PBMCs) has been found to be a significant predictor for the development of PTSD symptoms. Research in rodents has shown that the response of basolateral amygdala neurons to corticosterone is mediated by GR. However, to the best of our knowledge, no previous study has investigated GR number in PBMCs and amygdala function in humans. METHODS: To investigate whether peripheral GR number is related to amygdala functioning, we assessed GR number in PBMCs of healthy soldiers before their deployment to Afghanistan. Amygdala functioning was assessed with fMRI before and after deployment. RESULTS: We found that pre-deployment GR number was significantly negatively correlated to pre-deployment amygdala activity. More importantly, pre-deployment GR number predicted the increase in amygdala activity by deployment. DISCUSSION: Our results demonstrate that peripheral GR number is associated with amygdala functioning and predicts the increase in amygdala activity following military deployment in healthy individuals who did not develop PTSD. It is uncertain how this relationship is mediated mechanistically, but future studies should examine the relation of GR and amygdala activity to determine whether this is part of a common pathway leading to increased vulnerability to stress-related disorders

Self-reported early trauma as a predictor of adult personality:A study in a military sample

Exposure to early trauma has frequently been linked to adult psychopathology, including personality disorders. This cross-sectional study explored the relationship between personality and retrospectively rated levels of early trauma in 242 soldiers. Multiple regression analyses showed a significant relationship between early trauma and adult personality as exposure to emotional trauma predicted levels of self-directedness and cooperativeness on the Temperament and Character Inventory (TCI; C. R. Cloninger, T. R. Przybeck, D. M. Svrakic, & R. D. Wetzel, 1994). Overall, these results suggest that early emotional trauma may be related to personality dimensions associated with poor impulse control and interpersonal behavior. These results are noteworthy considering that they were obtained in a healthy sample. They show that early trauma may become ingrained in personality and hamper the potential to effectively engage in social interactions, increasing the risk of emotional and cognitive problems. (c) 2008 Wiley Periodicals

The role of stress sensitization in progression of posttraumatic distress following deployment

Military personnel exposed to combat are at risk for experiencing post-traumatic distress that can progress over time following deployment. We hypothesized that progression of post-traumatic distress may be related to enhanced susceptibility to post-deployment stressors. This study aimed at examining the concept of stress sensitization prospectively in a sample of Dutch military personnel deployed in support of the conflicts in Afghanistan. In a cohort of soldiers (N = 814), symptoms of post-traumatic stress disorder (PTSD) were assessed before deployment as well as 2, 7, 14, and 26 months (N = 433; 53 %) after their return. Data were analyzed using latent growth modeling. Using multiple group analysis, we examined whether high combat stress exposure during deployment moderated the relation between post-deployment stressors and linear change in post-traumatic distress after deployment. A higher baseline level of post-traumatic distress was associated with more early life stressors (standardized regression coefficient = 0.30, p < 0.001). In addition, a stronger increase in posttraumatic distress during deployment was associated with more deployment stressors (standardized coefficient = 0.21, p < 0.001). A steeper linear increase in posttraumatic distress post-deployment (from 2 to 26 months) was predicted by more post-deployment stressors (standardized coefficient = 0.29, p < 0.001) in high combat stress exposed soldiers, but not in a less combat stress exposed group. The group difference in the predictive effect of post-deployment stressors on progression of post-traumatic distress was significant (χ²(1) = 7.85, p = 0.005). Progression of post-traumatic distress following combat exposure may be related to sensitization to the effects of post-deployment stressors during the first year following return from deploymen

A prospective study on personality and the cortisol awakening response to predict posttraumatic stress symptoms in response to military deployment

Few prospective studies on pre-trauma predictors for subsequent development of posttraumatic stress disorder (PTSD) have been conducted. In this study we prospectively investigated whether pre-deployment personality and the cortisol awakening response (CAR) predicted development of PTSD symptoms in response to military deployment. Furthermore, we hypothesized that potential effects of age, childhood trauma and previous deployment on development of PTSD symptoms were mediated via pre-deployment personality, CAR and PTSD symptoms. Path analysis was performed on data from 470 male soldiers collected before and six months after a 4-month deployment to Afghanistan. Before deployment, personality was assessed with the short-form Temperament-Character Inventory and the Cook-Medley Hostility scale. In addition, pre-deployment saliva sampling for assessment of the CAR was performed immediately after awakening and 15, 30 and 60min thereafter. Pre-deployment high hostility and low self-directedness represented intrinsic vulnerabilities for development of PTSD symptoms after deployment. The CAR assessed before deployment did not predict PTSD symptoms after deployment. Pre-deployment low-to-moderate PTSD symptoms were associated with PTSD symptoms after deployment. As hypothesized, the effects of age and childhood trauma on PTSD symptoms after deployment were mediated via personality and pre-deployment PTSD symptoms. However, the number of previous deployments was not related to development of PTSD symptoms. The total model explained 24% of variance in PTSD symptoms after military deploymen

Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting state magnetic resonance images were obtained from male veterans with (n = 31) and without (n = 25) PTSD, and healthy male civilian controls (n = 25). Veterans with and without PTSD (combat controls) had reduced functional connectivity compared to healthy controls between the caudal ACC and the precentral gyrus, and between the perigenual ACC and the superior medial gyrus and middle temporal gyrus. Combat controls had increased connectivity between the rostral ACC and precentral/middle frontal gyrus compared to PTSD patients and healthy civilian controls. The resting state functional connectivity differences in the perigenual ACC network reported here indicate that veterans differ from healthy controls, potentially due to military training, deployment, and/or trauma exposure. In addition, specific alterations in the combat controls may potentially be related to resilience. These results underline the importance of distinguishing trauma-exposed (combat) controls from healthy civilian controls when studying PTSD

fMRI data of PTSD patients with and without comorbid Major Depressive Disorder

<p>Patients were male veterans recruited from the Military Mental Health Care Center, the Netherlands. MDD_diagnosis = current depressive episode (1=yes, 0=no), CAPS_TOTAL_B = total scores from CAPS cluster B symptoms, CAPS_TOTAL_C = total scores from CAPS cluster C symptoms, CAPS_TOTAL_D = total scores from CAPS cluster D symptoms, MASQ_NA = negative affect scores, MASQ_PA = positive affect scores, MASQ_SA = somatic anxiety scores, RSFC=resting state functional connectivity, Hip = hippocampus, ACC= anterior cingulate cortex, sg= subgenual, Thal = thalamus, SSRI = current use of selective serotonin reuptake inhibitor (0=no, 1=yes), BENZO = current use of benzodiazepines (0=no, 1=yes), SARI = current use of serotonin antagonist and reuptake inhibitor (0=no, 1=yes), ISCED = international standard classification of education. Handedness presents right-handedness as 0, left-handedness as 2 and ambidexterity as 3. The code 9999 represents a missing value.</p