Reducing (Behavioral) Restraint Use Through Simulation at the Bedside.

Hospitals are experiencing an influx of patients in active behavioral crises, leading to restraints as a behavior management strategy. Over 100 staff participated in simulation training designed to manage escalating patient behavior. The training had a direct impact on the reduction of restraint use and increased preparedness and confidence of participants managing escalating patient behavior. Results suggest simulation can be an effective strategy to train medical staff to manage challenging behavior and reduce restraint use.

Intranasal COVID-19 vaccine induces respiratory memory T cells and protects K18-hACE mice against SARS-CoV-2 infection.

Current COVID-19 vaccines prevent severe disease, but do not induce mucosal immunity or prevent infection with SARS-CoV-2, especially with recent variants. Furthermore, serum antibody responses wane soon after immunization. We assessed the immunogenicity and protective efficacy of an experimental COVID-19 vaccine based on the SARS-CoV-2 Spike trimer formulated with a novel adjuvant LP-GMP, comprising TLR2 and STING agonists. We demonstrated that immunization of mice twice by the intranasal (i.n.) route or by heterologous intramuscular (i.m.) prime and i.n. boost with the Spike-LP-GMP vaccine generated potent Spike-specific IgG, IgA and tissue-resident memory (TRM) T cells in the lungs and nasal mucosa that persisted for at least 3 months. Furthermore, Spike-LP-GMP vaccine delivered by i.n./i.n., i.m./i.n., or i.m./i.m. routes protected human ACE-2 transgenic mice against respiratory infection and COVID-19-like disease following lethal challenge with ancestral or Delta strains of SARS-CoV-2. Our findings underscore the potential for nasal vaccines in preventing infection with SARS-CoV-2 and other respiratory pathogen.

Elevated water temperature initially affects reproduction and behavior but not cognitive performance or physiology in Gambusia affinis.

Warming temperatures associated with climate change and urbanization affect both terrestrial and aquatic populations with freshwater fish being especially vulnerable. As fish rely on water temperature to regulate their body temperature, elevated temperatures can alter physiology and in turn behavioral and cognitive skills. We examined whether reproduction, physiology, behavior, and cognitive skills were altered by exposure to elevated water temperatures during one reproductive cycle in the live-bearing fish, Gambusia affinis. We found that within four days of exposure to a higher temperature (31°C), females were more likely to drop underdeveloped offspring than females maintained at 25°C. However, females did not show a change in cortisol release rates over time or altered fecundity and reproductive allotment, despite increased growth at the higher temperature. But in the heat treatment fish that started the experiment with higher baseline cortisol dropped their offspring sooner than fish with lower cortisol release rates. We used a detour test to explore behavior and cognitive skills at three time points after exposure to the heat treatments: early, midway, and at the end (day 7, 20 and 34). We found that on day 7, females were less likely to exit the starting chamber when maintained at 31°C but did not differ in their time to exit the starting chamber or in their motivation (reach the clear barrier). Similarly, females did not differ in their time to swim around the barrier to reach a female fish reward (solving skill). Nonetheless, we found a link between behavior and cognition, where females who were slower to exit the start chamber got around the barrier faster, indicating that they learned from prior experience. Together our results indicate that G. affinis is initially affected by elevated water temperatures but may partially cope with higher temperatures by not altering their hypothalamus-interrenal axis (baseline cortisol), and at the same time this might act to buffer their young. Acclimation may reduce costs for this species and potentially explain why they are successful invaders and tolerant species despite climate change.

Effect of reflex and mechanical decreases in skin perfusion on thermal- and agonist-induced eccrine sweating in humans.

In humans, skin blood flux (SkBF) and eccrine sweating are tightly coupled, suggesting common neural control and regulation. This study was designed to separate these two sympathetic nervous system end-organ responses via nonadrenergic SkBF-decreasing mechanical perturbations during heightened sudomotor drive. We induced sweating physiologically via whole body heat stress using a high-density tube-lined suit (protocol 1; 2 women, 4 men), and pharmacologically via forearm intradermal microdialysis of two steady-state doses of a cholinergic agonist, pilocarpine (protocol 2; 4 women, 3 men). During sweating induction, we decreased SkBF via three mechanical perturbations: arm and leg dependency to engage the cutaneous venoarteriolar response (CVAR), limb venous occlusion to engage the CVAR and decrease perfusion pressure, and limb arterial occlusion to cause ischemia. In protocol 1, heat stress increased arm cutaneous vascular conductance and forearm sweat rate (capacitance hygrometry). During heat stress, despite decreases in SkBF during each of the acute (3 min) mechanical perturbations, eccrine sweat rate was unaffected. During heat stress with extended (10 min) ischemia, sweat rate decreased. In protocol 2, both pilocarpine doses (ED50 and EMAX) increased SkBF and sweat rate. Each mechanical perturbation resulted in decreased SkBF but minimal changes in eccrine sweat rate. Taken together, these data indicate that a wide range of acute decreases in SkBF do not appear to proportionally decrease either physiologically- or pharmacologically induced eccrine sweating in peripheral skin. This preservation of evaporative cooling despite acutely decreased SkBF could have consequential impacts for heat storage and balance during changes in body posture, limb position, or blood flow restrictive conditions.

Mental health services in restricted housing: Do we know what's going on behind the steel doors?

The use of administrative segregation (AS) in North American prisons remains a common but contentious practice that is currently at the forefront of human rights and legal discussions. While extant research is mixed regarding the direct links between segregation and psychological functioning, it is clear these individuals are worse off in many ways. Mental and behavioral health interventions appear especially limited for people incarcerated in secure units, yet little is known about the extent of services offered or existing barriers to service provision. Using a standardized survey, we attempted to obtain a nationally representative sampling of mental health practices for people incarcerated in segregation and frontline provider perspectives across 24 state prisons. Survey results suggest that, while most facilities offer some form of mental health services to clients in restrictive units, most do not provide structured, manualized interventions. An even smaller number provide interventions specifically tailored to this unique population. Perceptions of service delivery barriers fell into four categories: (a) the nature of the restrictive environment, (b) lack of available programs, (c) staff-related concerns, and (d) client/inmate-related concerns. We conclude with recommendations to improve program accessibility and delivery on segregated units. Focused intervention efforts may reduce the number and duration of restricted placements. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Complete Genome Sequences of Actinobacteriophages Anaysia and Caviar.

Anaysia and Caviar are temperate siphoviruses isolated from soil using Gordonia terrae 3612 and Mycobacterium smegmatis mc2155, respectively. Anaysia's 52,861-bp genome carries 102 genes, while Caviar's 47,074-bp genome carries 79 genes. Based on gene content similarity, Anaysia and Caviar are assigned to phage clusters A15 and A3, respectively.

Passive immunization with equine RBD-specific Fab protects K18-hACE2-mice against Alpha or Beta variants of SARS-CoV-2.

Emergence of variants of concern (VOC) during the COVID-19 pandemic has contributed to the decreased efficacy of therapeutic monoclonal antibody treatments for severe cases of SARS-CoV-2 infection. In addition, the cost of creating these therapeutic treatments is high, making their implementation in low- to middle-income countries devastated by the pandemic very difficult. Here, we explored the use of polyclonal EpF(ab')2 antibodies generated through the immunization of horses with SARS-CoV-2 WA-1 RBD conjugated to HBsAg nanoparticles as a low-cost therapeutic treatment for severe cases of disease. We determined that the equine EpF(ab')2 bind RBD and neutralize ACE2 receptor binding by virus for all VOC strains tested except Omicron. Despite its relatively quick clearance from peripheral circulation, a 100µg dose of EpF(ab')2 was able to fully protect mice against severe disease phenotypes following intranasal SARS-CoV-2 challenge with Alpha and Beta variants. EpF(ab')2 administration increased survival while subsequently lowering disease scores and viral RNA burden in disease-relevant tissues. No significant improvement in survival outcomes or disease scores was observed in EpF(ab')2-treated mice challenged using the Delta variant at 10µg or 100µg doses. Overall, the data presented here provide a proof of concept for the use of EpF(ab')2 in the prevention of severe SARS-CoV-2 infections and underscore the need for either variant-specific treatments or variant-independent therapeutics for COVID-19.

SARS-CoV-2 Delta variant induces enhanced pathology and inflammatory responses in K18-hACE2 mice.

The COVID-19 pandemic has been fueled by SARS-CoV-2 novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal dose of Delta was higher than Alpha or Beta strains. To characterize the differences in the Delta strain's pathogenesis, a time-course experiment was performed to evaluate the overall host response to Alpha or Delta variant challenge. qRT-PCR analysis of Alpha- or Delta-challenged mice revealed no significant difference between viral RNA burden in the lung, nasal wash or brain. However, histopathological analysis revealed high lung tissue inflammation and cell infiltration following Delta- but not Alpha-challenge at day 6. Additionally, pro-inflammatory cytokines were highest at day 6 in Delta-challenged mice suggesting enhanced pneumonia. Total RNA-sequencing analysis of lungs comparing challenged to no challenge mice revealed that Alpha-challenged mice have more total genes differentially activated. Conversely, Delta-challenged mice have a higher magnitude of differential gene expression. Delta-challenged mice have increased interferon-dependent gene expression and IFN-γ production compared to Alpha. Analysis of TCR clonotypes suggested that Delta challenged mice have increased T-cell infiltration compared to Alpha challenged. Our data suggest that Delta has evolved to engage interferon responses in a manner that may enhance pathogenesis. The in vivo and in silico observations of this study underscore the need to conduct experiments with VOC strains to best model COVID-19 when evaluating therapeutics and vaccines.

RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge.

The ongoing COVID-19 pandemic has contributed largely to the global vaccine disparity. Development of protein subunit vaccines can help alleviate shortages of COVID-19 vaccines delivered to low-income countries. Here, we evaluated the efficacy of a three-dose virus-like particle (VLP) vaccine composed of hepatitis B surface antigen (HBsAg) decorated with the receptor binding domain (RBD) from the Wuhan or Beta SARS-CoV-2 strain adjuvanted with either aluminum hydroxide (alum) or squalene in water emulsion (SWE). RBD HBsAg vaccines were compared to the standard two doses of Pfizer mRNA vaccine. Alum-adjuvanted vaccines were composed of either HBsAg conjugated with Beta RBD alone (ß RBD HBsAg+Al) or a combination of both Beta RBD HBsAg and Wuhan RBD HBsAg (ß/Wu RBD HBsAg+Al). RBD vaccines adjuvanted with SWE were formulated with Beta RBD HBsAg (ß RBD HBsAg+SWE) or without HBsAg (ß RBD+SWE). Both alum-adjuvanted RBD HBsAg vaccines generated functional RBD IgG against multiple SARS-CoV-2 variants of concern (VOC), decreased viral RNA burden, and lowered inflammation in the lung against Alpha or Beta challenge in K18-hACE2 mice. However, only ß/Wu RBD HBsAg+Al was able to afford 100% survival to mice challenged with Alpha or Beta VOC. Furthermore, mice immunized with ß RBD HBsAg+SWE induced cross-reactive neutralizing antibodies against major VOC of SARS-CoV-2, lowered viral RNA burden in the lung and brain, and protected mice from Alpha or Beta challenge similarly to mice immunized with Pfizer mRNA. However, RBD+SWE immunization failed to protect mice from VOC challenge. Our findings demonstrate that RBD HBsAg VLP vaccines provided similar protection profiles to the approved Pfizer mRNA vaccines used worldwide and may offer protection against SARS-CoV-2 VOC. IMPORTANCE Global COVID-19 vaccine distribution to low-income countries has been a major challenge of the pandemic. To address supply chain issues, RBD virus-like particle (VLP) vaccines that are cost-effective and capable of large-scale production were developed and evaluated for efficacy in preclinical mouse studies. We demonstrated that RBD-VLP vaccines protected K18-hACE2 mice against Alpha or Beta challenge similarly to Pfizer mRNA vaccination. Our findings showed that the VLP platform can be utilized to formulate immunogenic and efficacious COVID-19 vaccines.

Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge.

SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®). The vaccine is adjuvanted with Bacterial Enzymatic Combinatorial Chemistry (BECC), BECC470. Intranasal (IN) administration of BreC-CoV-2 in K18-hACE2 mice induced a strong systemic and localized immune response in the respiratory tissues which provided protection against the Washington strain of SARS-CoV-2. Protection provided after IN administration of BReC-CoV-2 was associated with decreased viral RNA copies in the lung, robust RBD IgA titers in the lung and nasal wash, and induction of broadly neutralizing antibodies in the serum. We also observed that BReC-CoV-2 vaccination administered using an intramuscular (IM) prime and IN boost protected mice from a lethal challenge dose of the Delta variant of SARS-CoV-2. IN administration of BReC-CoV-2 provided better protection than IM only administration to mice against lethal challenge dose of SARS-CoV-2. These data suggest that the IN route of vaccination induces localized immune responses that can better protect against SARS-CoV-2 than the IM route in the upper respiratory tract.

Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice.

SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta VoC in the K18 human angiotensin converting enzyme 2 (hACE2) transgenic mouse model. HCP protected mice from challenge with the original WA-1 SARS-CoV-2 strain; however, only partially protected mice challenged with the Alpha VoC (60% survival) and failed to save Beta challenged mice from succumbing to disease. HCP treatment groups had elevated receptor binding domain (RBD) and nucleocapsid IgG titers in the serum; however, Beta VoC viral RNA burden in the lung and brain was not decreased due to HCP treatment. While mice could be protected from WA-1 or Alpha challenge with a single dose of HCP, six doses of HCP could not decrease mortality of Delta challenged mice. Overall, these data demonstrate that VoC have enhanced immune evasion and this work underscores the need for in vivo models to evaluate future emerging strains. IMPORTANCE Emerging SARS-CoV-2 VoC are posing new problems regarding vaccine and monoclonal antibody efficacy. To better understand immune evasion tactics of the VoC, we utilized passive immunization to study the effect of early-pandemic SARS-CoV-2 HCP against, Alpha, Beta, and Delta VoC. We observed that HCP from a human infected with the original SARS-CoV-2 was unable to control lethality of Alpha, Beta, or Delta VoC in the K18-hACE2 transgenic mouse model of SARS-CoV-2 infection. Our findings demonstrate that passive immunization can be used as a model to evaluate immune evasion of emerging VoC strains.

Recalibrating the epigenetic clock after exposure to trauma: The role of risk and protective psychosocial factors.

BACKGROUND: Epigenetic aging is associated with a plethora of negative health outcomes and increased mortality. Yet, the dynamicity of epigenetic age after exposure to trauma and the factors that influence epigenetic age are not fully understood. This research evaluated longitudinal changes in epigenetic age before and after exposure to work-related trauma among paramedicine students. We further investigated psychological and social risk (psychological distress, posttraumatic stress disorder/PTSD symptom severity, professional quality of life) and protective factors (social support and organisational membership) that drive epigenetic aging at both time points. METHODS: The study comprised of 80 samples of University paramedicine students including 40 individuals at two time points - t0 (baseline) and t1 (post-trauma exposure). Epigenome-wide analysis was performed from t0 and t1 saliva using the Illumina EPIC arrays that cover >860k probes. Data analysis was performed using R via generalized regression models. The epigenetic age was calculated based on the Horvath algorithm, GrimAge and SkinBloodAge were calculated using the Horvath online calculator, and p-value for significance was corrected using the FDR method for multiple testing corrections. RESULTS: The epigenetic age at t0 and t1 were highly correlated with chronological age and with each other (r = 0.84-0.94). Baseline epigenetic age and follow-up epigenetic age were significantly associated with risk factors of psychological distress and PTSD symptom severity. Among the protective factors, a sense of psychological organisational membership at the start of the paramedicine course as measured at baseline significantly reduced epigenetic age at baseline and post-trauma exposure. On the other hand, receiving social support acted as a protective factor only after exposure to trauma (follow-up), decreasing epigenetic aging at follow-up. GrimAge acceleration at follow-up was significantly associated with increased PTSD symptom severity at baseline and follow-up. Moreover, increased social support at baseline and follow-up was associated with reduced follow-up GrimAge acceleration. CONCLUSION: These results demonstrate that epigenetic aging is dynamic and changes after exposure to trauma. Additionally, results demonstrate that different risk and protective factors influence epigenetic aging at different times. In conclusion, the research identified risk and protective factors associated with epigenetic aging pre- and post-trauma exposure, with implications for health and well-being among individuals exposed to trauma.

Activation of acid-sensing ion channels by carbon dioxide regulates amygdala synaptic protein degradation in memory reconsolidation.

Reconsolidation has been considered a process in which a consolidated memory is turned into a labile stage. Within the reconsolidation window, the labile memory can be either erased or strengthened. Manipulating acid-sensing ion channels (ASICs) in the amygdala via carbon dioxide (CO2) inhalation enhances memory retrieval and its lability within the reconsolidation window. Moreover, pairing CO2 inhalation with retrieval bears the reactivation of the memory trace and enhances the synaptic exchange of the calcium-impermeable AMPA receptors to calcium-permeable AMPA receptors. Our patch-clamp data suggest that the exchange of the AMPA receptors depends on the ubiquitin-proteasome system (UPS), via protein degradation. Ziram (50 µM), a ubiquitination inhibitor, reduces the turnover of the AMPA receptors. CO2 inhalation with retrieval boosts the ubiquitination without altering the proteasome activity. Several calcium-dependent kinases potentially involved in the CO2-inhalation regulated memory liability were identified using the Kinome assay. These results suggest that the UPS plays a key role in regulating the turnover of AMPA receptors during CO2 inhalation.

Differences in Lower Extremity Kinematics Between High School Cross-Country and Young Adult Recreational Runners.

BACKGROUND: While previous research has assessed running kinematics for age-related differences that could increase the risk of a running-related injury, none of these studies have included high school aged runners or assessed running kinematics using 2-dimensional video analysis. PURPOSE: The purpose of this study was to compare sagittal plane kinematics during treadmill running in high school cross-country and young adult recreational runners using 2-dimensional motion analysis techniques. METHODS: Twenty-five high school cross-country runners (13 women, 12 men) and 25 young adult recreational runners (12 women, 13 men) consented to participate in this study. Reflective markers were placed on each lower extremity over multiple anatomical landmarks. After a five-minute acclimation period in which the participants ran on a treadmill at their preferred running speed, video data were recorded at 240 frames per second for all participants while they continued to run on the treadmill. RESULTS: There were no significant differences between left and right extremities. The young adult recreational runners exhibited significantly greater vertical excursion of the center of mass (t = 4.64, p = .0001) compared to the high school runners. There was no significant difference between the two age groups regarding the six other sagittal plane variables. CONCLUSIONS: The young adult recreational runners demonstrated an increased center-of-mass vertical excursion in comparison to high school cross-country runners. In addition, the results obtained in this study for kinematic variables using 2-dimensional motion analysis were similar to previously reported studies using 3-dimensional motion analysis, demonstrating that 2-dimensional motion analysis could be used for analyzing sagittal plane running kinematics in clinical settings. LEVEL OF EVIDENCE: 4, Controlled laboratory study.

Actor perspective and moral reasoning: Do levels of criminal thinking moderate this relationship among non-criminals?

A large body of literature has explored moral decision-making; however, fewer have examined the explicit role of criminal thinking (CT). This study sought to determine whether moral judgment is influenced by CT in the general population and if this relationship further depends on the type of scenario (i.e., immoral vs. illegal) and/or the actor orientation (i.e., self vs. other). Using a sample of 239 U.S. adults and hypothetical case vignettes, results showed that those who endorsed higher levels of CT rated socially deviant behaviors, regardless of the type of scenario, as significantly more morally acceptable than participants who endorsed lower levels of CT. However, this difference was more pronounced for the immoral dilemma compared to the illegal dilemma. Specifically, proactive CT processes led to higher justification for the immoral dilemma. Neither general nor reactive CT were significantly associated with moral reasoning for the illegal dilemma. Among a mostly non-offending sample, this finding makes sense as it appears participants' levels of criminal thinking may have been high enough to rationalize an immoral dilemma but not so high as to allow for rationalization of an illegal dilemma. No significant differences were found concerning actor orientation. This research not only has important implications for better understanding traits associated with moral decision-making in everyday choices, but it may also have practical application in legal contexts. However, further research is needed in these contexts. Findings were also limited by a lack of racial diversity among participants.

Targeting macrophages by an aza-anthrapyrazole to ameliorate experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease in the central nerve system, in which both innate and adaptive immune cells are involved. BBR3378, an aza-anthrapyrazole prevents experimental autoimmune encephalomyelitis (EAE), an inflammatory condition similar to MS, by antagonizing T cell autoimmune responses. Here, we report BBR3378's regulatory effect on macrophages. METHODS: EAE was induced in ten-week-old female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptides followed by BBR3378 or sham treatment administered intraperitoneally, and clinical signs were assessed using a 0-5 scoring system. These mice were subjected to serum ELISA for cytokine IFNγ and TNFα levels, RT qPCR analysis of macrophage markers in isolated monocytes, and flow cytometry analysis for macrophage infiltration in the brain. Macrophages derived from primary monocytes and macrophage cell line RAW 264.7 were used to investigate BBR3378's effect on LPS-stimulated pro-inflammatory cytokine induction. RAW 264.7 cells expressing NF-κB-driven luciferase reporter were treated with LPS with or without BBR3378, and luciferase assays performed to assess the inhibition on NF-κB activation. LPS-induced activation of mitogen-activated protein kinases (MAPKs) with or without the presence of BBR3378 was also investigated by Western blot analysis. RESULTS: BBR3378 down-regulated cytokine-induced macrophage differentiation and activation in EAE mice, contributing to protection against macrophage infiltration in the brain and clinical symptoms from EAE. Treating macrophages with BBR3378 counteracted LPS-induced cytokine production via blocking activation of key signal molecules mediating inflammatory responses, such as NF-κB and MAPKs. CONCLUSIONS: These data suggest that in addition to T cells, BBR3378 can also target macrophages to attenuate the inflammation associated with EAE.

Impact of Malaria in Pregnancy on Risk of Malaria in Young Children: Systematic Review and Meta-Analyses.

BACKGROUND: Our objective was to quantify the risk of acquiring malaria among progeny of women with malaria during pregnancy. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for eligible prospective studies. The primary predictor was malaria during pregnancy defined as placental malaria, parasitemia, clinical malaria, or pregnancy-associated malaria. Primary outcomes were parasitemia or clinically defined malaria of young children. We performed meta-analyses to pool adjusted risk estimates using a random-effects model. RESULTS: Nineteen of 2053 eligible studies met inclusion criteria for the systemic review. Eleven of these studies were quantitative and were included in the meta-analyses. The pooled adjusted odds ratio (aOR) or adjusted hazard ratio (aHR) of malaria during pregnancy for detection of parasitemia in young children were 1.94 (95% confidence interval [CI], 0.93-4.07; P = .08) and 1.46 (95% CI, 1.07-2.00; P < .001), respectively. The pooled aOR or aHR for clinically defined malaria in young children were 2.82 (95% CI, 1.82-4.38; P < .001) and 1.31 (95% CI, 0.96-1.79; P = .09), respectively. CONCLUSIONS: Our results confirmed that malaria during pregnancy significantly increased the overall risk of malaria in young children via indeterminate mechanisms and emphasize the urgent need to implement safe and highly effective strategies to prevent malaria during pregnancy.

DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience.

OBJECTIVE: Understandings of the biological mechanisms underpinning posttrauma responses are limited. This pilot study aimed to expand research in this area by examining the relationship between DNA methylation of stress genes nuclear receptor subfamily 3 group C member 1 (NR3C1) and FK06 binding protein 5 (FKBP5) with an array of posttrauma responses of posttraumatic stress disorder (PTSD) symptom severity, posttraumatic growth (PTG), and resilience. METHOD: First-year paramedicine students (N = 47) completed self-report measures of PTSD symptom severity, PTG, and resilience and provided a saliva sample for methylation analysis. Surrogate variable analyses identified covariates after which generalized regression models were performed to identify genomic sites significantly associated with PTSD symptom severity, PTG, or resilience. RESULTS: Methylation of different FKBP5 and NR3C1 sites was significantly associated with PTSD symptom severity, PTG, and resilience. Methylation in FKBP5 site cg07485685 was a predictor of both PTSD symptom severity and resilience in opposite directions. CONCLUSIONS: This is the first study investigating methylation changes in PTG, and overall the results suggest that NR3C1 and FKBP5 methylation is associated with both positive and negative posttrauma responses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A Systematic Review of DNA Methylation and Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic Growth, and Resilience.

Most people will experience a traumatic event within their lifetime. One commonly recognized response to trauma exposure is posttraumatic stress disorder (PTSD). The biological underpinnings of PTSD, including epigenetic mechanisms of DNA methylation and gene expression, have been studied intensively. However, psychological posttrauma responses vary widely and can include positive outcomes, such as posttraumatic growth (PTG) and, more commonly, resilience. The aim of this systematic review was to summarize the current DNA methylation and gene expression data with respect to three potential posttrauma responses: PTSD, PTG, and resilience. A literature search identified 486 studies, 51 of which were deemed eligible for inclusion (total N = 10,633). All included studies examined PTSD and consistently implicated DNA methylation and gene expression changes in hypothalamic-pituitary-adrenal axis and inflammatory genes. Ten studies acknowledged resilience as a posttrauma response, but only two studies examined epigenetics and gene expression using a scale to measure resilience. Low resilience was associated with gene expression patterns in immune and dopamine genes, and high resilience was associated with a blunted inflammatory response. No studies examined epigenetic or gene expression changes associated with PTG. These findings highlight a focus on pathogenic research, which has failed to adequately acknowledge and measure positive posttrauma outcomes of PTG and resilience. Future research should examine DNA methylation and gene expression changes associated with PTG and resilience in addition to PTSD in order to gain a more comprehensive picture of an individual's well-being following exposure to trauma.