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Previous research has examined risk factors associated with poorer treatment outcomes for military Veterans with PTSD. However, work has not examined risk for symptom worsening among Veterans with subthreshold PTSD. The aim of this study was to examine demographic, psychiatric, physical health, and pre-treatment PTSD symptom clusters associated with clinically significant worsening of PTSD among a nationally representative sample of United States (U.S.) Veterans with subthreshold PTSD. Participants were Veterans (weighted N = 3162; unweighted N = 236) with subthreshold PTSD entering a new episode of treatment at U.S. Veterans Affairs PTSD specialty clinics during fiscal years 2018 and 2019. Data was collected as part of the Veterans Outcome Assessment, a yearly baseline and 3-month follow-up telephone survey. Analyses used weighted calculations to support the use of VOA data to draw inferences about all eligible Veterans, and binary logistic regression was used to examine risk factors for symptom worsening. Over 1/3 (37.7%) of Veterans with subthreshold PTSD experienced clinically significant symptom worsening from baseline to follow-up. Adjusted analyses revealed several risk factors for symptom worsening, including demographic (e.g., male sex, White race), psychiatric (personality and anxiety disorders), health care utilization (e.g., more primary care encounters in the previous year), physical health disability, and specific baseline PTSD symptom clusters (negative affect and anxious arousal). Findings suggest that Veterans with subthreshold symptoms seeking treatment for PTSD are at risk for symptom worsening, and highlight the importance of assessment, prevention, and treatment in targeting veterans with PTSD symptoms below the diagnostic threshold.

The reported prevalence of military sexual trauma (MST) has increased over the past decades in the United States, yet scarce population-based studies have examined the prevalence, correlates, and health burden of MST in the general veteran population.Data were from the 2019-2020 National Health and Resilience in Veterans Study, a population-based survey of veterans (n = 4069).(1) estimated the prevalence of MST; (2) identified sex-stratified sociodemographic, military, and trauma characteristics associated with MST; and (3) examined sex-stratified associations between MST and psychiatric comorbidities, functioning, disability, and treatment utilization.Female veterans reported substantially higher rates of MST (44.2%) than male veterans (3.5%). Relative to male veterans without MST histories, male veterans with MST histories had nearly 3-fold increased odds of reporting future suicidal intent, 2-to-3-fold greater odds of screening positive for current posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder; and nearly 2-fold increased odds of being disabled. Male veterans with MST histories also scored lower on mental, physical, cognitive, and psychosocial functioning (d's = 0.16-0.29). Relative to female veterans without MST histories, female veterans with MST histories had 5-fold greater odds of current PTSD, 2-fold greater odds of engaging in mental health treatment, and scored lower on psychosocial functioning and higher on somatic symptoms (both d's = 0.25).Cross-sectional design precludes causal inference.A substantial proportion of veterans in the U.S. experience sexual trauma during their military service, and these experiences are associated with an elevated health burden.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N = 69; internal replication cohort: N = 77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Supplemental Digital Content is available in the text., Purpose To examine the psychological impact of the COVID-19 pandemic on medical trainees (residents and fellows) working at Mount Sinai Hospital (MSH) in New York City (NYC), the initial epicenter of the United States pandemic. Method The authors administered a survey to 991 trainees in frontline specialties working at MSH in NYC between April and May 2020. The instrument assessed symptoms of major depressive disorder, generalized anxiety disorder, COVID-19-related posttraumatic stress disorder, and burnout. Psychiatric screens were aggregated into 1 composite measure, and meeting criteria on any of the 3 scales was considered a positive screen for psychiatric symptoms. The survey also assessed COVID-19-related exposures, worries, coping strategies, and desired interventions. Multivariable logistic regressions were conducted to identify factors associated with psychiatric symptoms and burnout. Results Of the 560 respondents (56.6% response rate), 29.7% screened positive for psychiatric symptoms and 35.8% screened positive for burnout. History of a mental illness, COVID-19-related duties and personal/career worries, and coping by substance use were associated with increased likelihood of screening positive for psychiatric symptoms. Positive emotion-focused coping and feeling valued by supervisors were associated with decreased likelihood. Internal medicine and surgical specialties, a history of mental illness, increased duty hours, duty-related worries, personal/career worries, coping via self-blame and venting, and coping via substance use were associated with higher odds of burnout. Feeling valued by supervisors was associated with decreased burnout odds. The most common crisis-related needs included access to personal protective equipment, food provisions, and financial support. Conclusions Psychological distress and burnout affected approximately one-third of trainees sampled during the height of the pandemic in NYC. As the pandemic surged beyond NYC, these findings suggest that interventions should include addressing basic needs, promoting leadership affirmation, moderating duty hours, supporting trainees financially, and enhancing mental health support.

Heart failure (HF) is frequently accompanied with the sinoatrial node (SAN) dysfunction, which causes tachy-brady arrhythmias and increased mortality. MicroRNA (miR) alterations are associated with HF progression. However, the transcriptome of HF human SAN, and its role in HF-associated remodeling of ion channels, transporters, and receptors responsible for SAN automaticity and conduction impairments is unknown. We conducted comprehensive high-throughput transcriptomic analysis of pure human SAN primary pacemaker tissue and neighboring right atrial tissue from human transplanted HF hearts (n = 10) and non-failing (nHF) donor hearts (n = 9), using next-generation sequencing. Overall, 47 miRs and 832 mRNAs related to multiple signaling pathways, including cardiac diseases, tachy-brady arrhythmias and fibrosis, were significantly altered in HF SAN. Of the altered miRs, 27 are predicted to regulate mRNAs of major ion channels and neurotransmitter receptors which are involved in SAN automaticity (e.g. HCN1, HCN4, SLC8A1) and intranodal conduction (e.g. SCN5A, SCN8A) or both (e.g. KCNJ3, KCNJ5). Luciferase reporter assays were used to validate interactions of miRs with predicted mRNA targets. In conclusion, our study provides a profile of altered miRs in HF human SAN, and a novel transcriptome blueprint to identify molecular targets for SAN dysfunction and arrhythmia treatments in HF.

Smoking is a serious public health issue linked to more than 8 million deaths per year worldwide and may lead to nicotine dependence (ND). Although the epigenomic literature on smoking is well established, studies evaluating the role of epigenetics in ND are limited. In this study, we examined the epigenomic signatures of ND and how these differ from smoking exposure to identify biomarkers specific to ND. We investigated the peripheral epigenetic profile of smoking status (SS) and ND in a US male veteran cohort. DNA from saliva was collected from 1135 European American (EA) male US military veterans. DNAm was assessed using the Illumina Infinium Human MethylationEPIC BeadChip array. SS was evaluated as current smokers (n = 137; 12.1%) and non-current smokers (never and former; n = 998; 87.9%). ND

Arterial thromboembolic events (ATE) in COVID-19, similarly as venous thromboembolism (VTE), are observed mainly in severely ill patients. ATE include brain, heart, aortic, and peripheral ischemic complications which usually aggravate a course of the disease leading to lifethreatening conditions.The authors describe a case of a 53-year-old male with Duhring disease in the remission period admitted due to severe COVID-19 pneumonia. The patient was treated with ceftriaxone (2000 mg once daily), dexamethasone (8 mg once daily), enoxaparin (60 mg twice daily), baricitinib (4 mg once daily), and remdesivir (200 mg on the first day, followed by 100 mg within 4 consecutive days); he required high flow oxygen therapy. On day 5 of hospitalization, he began to suffer from pain of the right lower extremity; in physical examination the limb was cold with absent femoral, popliteal, and pedal pulses. Urgent computed tomography angiography revealed total occlusion of the right superficial femoral artery (SFA) in the absence of any atherosclerotic plaques in the aorta. The patient was intubated and transferred to department of vascular surgery, where a giant clot was removed from SFA. Unfortunately, the patient outcome was unfavorable due to respiratory failure progression. The authors underline that ATE may occur even in anticoagulated patients and that association of some therapeutic options of COVID-19, like janus kinase (JAK) inhibitors use with an increased risk of ATE, should not be excluded.

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

Introduction There has been a decade-long federal commitment to prevent and end homelessness among U.S. military veterans. Substantial progress has been made; so, a question that stakeholders ask is: Is veteran homelessness still a problem? Methods To answer this question, 2 different data sources were analyzed in 2020: (1) a nationally representative community survey of 4,069 veterans conducted in 2019 and (2) national administrative data from the U.S. Department of Veterans Affairs on >6 million healthcare and homeless services in 2019. Results In the community sample, the lifetime prevalence of adult homelessness was 10.2%, with the highest prevalence found in participants aged 30–44 years (19.9% prevalence). In the Veterans Affairs administrative data, 4.2% of all Veterans Affairs service users used homeless services (n=290,515 Veterans Affairs homeless services); 27.9% of these were first-time Veterans Affairs homeless service users. Veterans who were racial/ethnic minorities were more likely to report any lifetime adult homelessness, more likely to be identified as homeless in Veterans Affairs records, and more likely to have used any Veterans Affairs homeless program. There was no sex difference in the lifetime prevalence of homelessness, but Veterans Affairs records showed that male veterans were more likely to be identified as homeless and to use homeless programs, suggesting possible underidentification of female veteran homelessness. Across age, sex, and racial/ethnic groups, 35.1% of Veterans Affairs homeless service users used emergency department services in the same year. Conclusions There is a continued need to dedicate resources to address veteran homelessness across sociodemographic groups, and these data serve as a benchmark before and after the onset of the COVID-19 pandemic.

Epidemiological observations indicate that female flight attendants are exposed to some reproductive and endocrine system disturbances. The aim of the study was to determine the incidence of hyperprolactinemia among female flight attendants, and to identify factors affecting the secretion of prolactin in female flight attendants working within 1 time zone as well as on long-distance flights.The cross-sectional study covered 103 women aged 23-46 years. The study group (I) was divided into 2 subgroups: subgroup Ia comprising female flight attendants flying within 1 flight zone, and subgroup Ib composed of female flight attendants working on long-distance flights. The control group (II) included women of reproductive age who sought medical assistance due to marital infertility in whom the male factor was found to be responsible for problems with conception in the course of the diagnostic process. The assessment included: age, the body mass index, menstrual cycle regularity, the length of service, the frequency of flying, the prolactin, estradiol and progesterone concentrations, and the result of endometrial biopsy. Descriptive and inferential statistics methods were used to compile the data.The incidence of hyperprolactinemia in the female flight attendants (46%) was significantly higher than in the control group (9%), p0.001. Differences between subgroups Ia and Ib regarding individual concentrations were not statistically significant (p = 0.425). Hyperprolactinemia among the female flight attendants working ≥15 years is present slightly more often than in those working15 years: 46% vs. 45% (p0.05). No significant difference was revealed in the secretion of prolactin between the study participants spending60 h/month flying and those spending ≥60 h/month flying (p0.05).Hyperprolactinemia is more common in female flight attendants than in the general population. High values of prolactin concentration in flight attendants are rarely manifested in clinical symptoms. The frequency of flying and the length of service do not affect the development of hyperprolactinemia or the mean prolactin concentration. Int J Occup Med Environ Health. 2021;34(3):351-61.

One of the newest antiseizure medication is levetiracetam (LEV). It might be effective in various indications, not only related to convulsions. Central nervous system disorders are common during anticonvulsant therapy. The aim of this study was to assess the effect of LEV on various types of memory and anxiety in rats.Adult male Wistar rats (n = 58) were given LV p.o. as a single (100 mg/kg or 500 mg/kg) or repeated doses (300 mg/kg). The effect of the drug on memory was assessed in the Morris water maze (MWM) (spatial memory), the passive avoidance (PA) (emotional memory) and the novel object recognition (NOR) (recognition memory). The anxiety was evaluated in the elevated plus maze (EPM).LEV administered as repeated doses disturbed the long-term recognition memory in NOR and locomotor activity in EPM. A single dose affected emotional memory in PA. LEV did not alter spatial memory in MWM.LEV may cause memory and locomotor disturbances, but some of these adverse effects seem to be temporary and limited to the effect of acute dose.

Background: Chronic inflammation can lead to the development of obesity, diabetes and other chronic diseases. One of the factors causing inflammation is diet. The aim of this study was to assess the inflammatory potential of the diet, expressed by the DII index, in young physically active men. Methods: A total of 94 physically active students aged 19–23 participated in the study. The subjects’ diets were assessed on the basis of 4-day dietary records, which were then analyzed using the computer program “Diet 5.0”. The DII was calculated for each participant based on the individual consumption of the selected dietary components. The concentration of CRP protein was also determined. Results: Participants was divided into groups according to values of DII. Diets with different DIIs provided similar amounts of calories, but differed significantly in the content of many nutrients. Participants whose diets showed the most anti-inflammatory effects consumed significantly more protein, magnesium, iron, zinc, antioxidant vitamins, and B vitamins compared to others. The highest concentration of CRP protein was observed in men whose diet was described as the most pro-inflammatory (Q4 group). A significant relationship was found between DII and body fat (%) in men in the most anti-inflammatory (Q1 group) and neutral diet (Q2–Q3 group). Conclusions: The Dietary Inflammatory Index is a promising method of describing the effect of dietary intake on the risk of inflammation in young, healthy individuals engaging in regular physical activity.

Background Synaptic injury is a pathological hallmark of neurological impairment in people living with human immunodeficiency virus (HIV, PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). Measurement of synaptic density in living humans may allow better understanding of HIV neuropathogenesis and provide a dynamic biomarker for therapeutic studies. We applied novel synaptic vesical protein 2A (SV2A) positron emission tomographic (PET) imaging to investigate synaptic density in the frontostriatalthalamic region in PLWH and HIV-uninfected participants. Methods In this cross-sectional pilot study,13 older male PLWH on ART underwent magnetic resonance imaging (MRI) and PET scanning with the SV2A ligand [11C]UCB-J with partial volume correction and had neurocognitive assessments. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV-uninfected participants and assessed with respect to neurocognitive performance in PLWH. Results PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV-uninfected (PLWH: mean [SD], 3.93 [0.80]; HIV-uninfected: 4.59 [0.43]; P = .02, effect size 1.02). Differences were observed in widespread additional regions in exploratory analyses. Higher frontostriatalthalamic SV2A BPND associated with better grooved pegboard performance, a measure of motor coordination, in PLWH (r = 0.61, P = .03). Conclusions In a pilot study, SV2A PET imaging reveals reduced synaptic density in older male PLWH on ART compared to HIV-uninfected in the frontostriatalthalamic circuit and other cortical areas. Larger studies controlling for factors in addition to age are needed to determine whether differences are attributable to HIV or comorbidities in PLWH. SV2A imaging is a promising biomarker for studies of neuropathogenesis and therapeutic interventions in HIV., Understanding of the biological substrates of neurological impairment in people with human immunodeficiency virus (HIV) is limited. Here, novel in vivo SV2A positron emission tomographic (PET) imaging demonstrated lower synaptic density in older men with virologically suppressed HIV, potentially revealing a new biomarker of neurologic injury.

BACKGROUND Hydroxyapatite (HA) coated flexible intramedullary nailing (FIN) stimulates osteogenic activity. The role of HA-coated intramedullary nails remains unclear in normal bone lengthening. The goal of this study was to quantify the influence of FIN on the External Fixation Index (EFI) in patients with congenital lower limb discrepancy. METHODS Patients with femoral deficiency and fibular hemimelia underwent lengthening by the combined technique of external fixation with titanium (Ti) FIN or HA coated FIN and returned for follow-up at least 12 months after frame removal. RESULTS Seventy patients (mean age of 12.6 y) were included: 19 monofocal femoral lengthenings, 35 tibial monofocal lengthenings, 16 tibial bifocal lengthenings. The mean EFI's for those treated with and without HA-coated nails were not significantly different. The Conover posthoc analysis did not reveal a significant influence of the type of FIN on EFI in any subgroup. However, 2-way analysis of variance revealed simultaneous effects of nail types and age on the EFI in tibial bifocal lengthening.Significant positive correlation between the ratio "nail diameter/medullary shaft diameter" and EFI in tibial bifocal non-HA-coated FIN lengthening, and a significant positive correlation between age and EFI for femoral non-HA-coated FIN lengthening, tibial monofocal and bifocal HA-coated FIN lengthening were revealed.There were 4 cases of fracture at lengthening site required unscheduled surgery. In the non-HA-coated group, there was a statistically significant negative correlation between nail diameter and fracture occurrence at the lengthening site after frame removal. A ratio of

Objective Exposure to traumatic life events is associated with increased risk of posttraumatic stress disorder (PTSD) and other mental health problems such as suicidal ideation (SI), alcohol use disorder (AUD), and decreased quality of life (QOL). Mindfulness, which involves attending to the present moment, may help individuals cope with traumatic events by increasing acceptance of trauma-related experiences and decreasing trauma-related negative affect and avoidance of trauma reminders. The current study evaluated whether mindful attention to the present moment mediated the association between number of lifetime traumas and mental health. Method The sample consisted of 1,268 trauma-exposed U.S. veterans who participated in the National Health and Resilience in Veterans Study, a nationally representative study of U.S. veterans. On average, the sample was 60.6 years of age (SD = 15.2, range = 20-94), predominantly male (89.8%), Caucasian (75.0%), and noncombat veterans (59.2%). Results Path analyses revealed that mindfulness partially mediated the relation between number of lifetime traumas and PTSD symptoms (β = -.55), AUD (β = -.17), and QOL (β = .38), and fully mediated the relation between number of lifetime traumas and SI (β = -.36). Conclusions The relationship between lifetime trauma burden and various mental health issues of relevance to U.S. veterans may be mediated by mindfulness, or the ability to pay attention to the present moment. Interventions that bolster mindfulness may help mitigate the negative impact of cumulative traumas in this population. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur. This comorbidity negatively influences treatment outcomes, functioning, and quality of life. To better understand the relation between PTSD and AUD, research has begun to examine the influence of PTSD symptom clusters on alcohol-related problems. The current study is the first to analyze the associations between PTSD symptom clusters and alcohol consumption and AUD symptom severity in a treatment-seeking sample of Black/African American (AA) adults with co-occurring AUD and PTSD symptoms. Examination of these associations may help to facilitate greater recovery in this underserved population by identifying more precise targets for treatment. PTSD symptom clusters were identified from both the current 4-factor model identified in the DSM-5 and from a recently proposed 7-factor model. Participants were Black/AA adults (50.6% male) who endorsed trauma exposure and were seeking treatment for alcohol misuse. The majority (66%) were unemployed and almost half (45%) reported an income at or lower than $20,000. In the 4-factor model, results showed Cluster D symptoms of PTSD (i.e., negative alterations in cognitions and mood) were independently associated with alcohol consequences. Use of the 7-factor model, which divides Cluster D into symptoms of negative affect and anhedonia, further demonstrated that only anhedonic symptoms were independently associated with alcohol consequences. No symptom clusters were uniquely associated with alcohol consumption. Results suggest the absence of positive emotions, rather than the presence of negative emotions, are primarily associated with alcohol-related problems in a sample of trauma-exposed, Black/AA adults seeking treatment for alcohol misuse.

Background Nearly 20 years after the terrorist attacks of September 11, 2001, multiple studies have documented the adverse mental consequences among World Trade Center (WTC) rescue, recovery, and clean-up workers. However, scarce research has examined mental health stigma and barriers to care in WTC-exposed individuals, and no known study has examined whether rates of endorsement may differ between police and "nontraditional" responders, the latter comprising a heterogeneous group of workers and volunteers. Objective To identify the prevalence and correlates of mental health stigma and barriers to care in WTC responders. Methods Mental health stigma and barriers to care and their correlates were examined in 6,777 police and 6,272 nontraditional WTC responders. Results Nontraditional responders endorsed more stigma or barriers to care concerns than police responders. Within a subsample who screened positive for a psychiatric disorder, police were more likely than nontraditional responders to endorse "concerns that negative job consequences might result" (17.9% vs. 9.1%), while nontraditional responders were more likely to endorse "I don't know where to go to find counseling services" (18.4% vs.6.6%). Within this subsample, mental health service need and more severe WTC-related posttraumatic stress disorder symptoms were associated with increased likelihood of endorsing stigma or barriers; pre-9/11 psychiatric history and non-Hispanic Black race/ethnicity were associated with lower likelihood of endorsing stigma or barriers. Conclusions Results of this study underscore the burden of mental health stigma and barriers to care in WTC responders, and highlight the need for targeted interventions to address these concerns and promote mental healthcare utilization in this population.

Background Despite advances in the treatment of suicidality over the last decade, a significant proportion of veterans with suicidal ideation do not utilize mental health treatment. To date, however, few population-based studies have examined factors that may facilitate or impede mental healthcare engagement among veterans currently contemplating suicide. This study examined barriers and facilitators of current mental healthcare utilization in a nationally representative sample of U.S. military veterans who endorsed current suicidal ideation. Methods Using data from the National Health and Resilience in Veterans Study (n = 3157), collected in 2011, multivariable analyses were conducted to identify predisposing (e.g., age), enabling (e.g., social support), and need (e.g., psychiatric history) characteristics, as well as perceptions of stigma and barriers to care, associated with current mental healthcare utilization. Results A total of 7.3% (n = 231) of veterans endorsed current suicidal ideation, of which 36.1% (n = 84) were engaged in current mental health treatment. Younger age, female sex, current depression, lifetime suicide attempt(s), and number of lifetime traumas and medical problems were associated with treatment utilization. Mistrust of mental health providers and fear of treatment harming one's reputation were associated with lower likelihood of treatment engagement, over and above the effects of these predisposing, enabling, and need characteristics. Discussion More than 3 of 5 U.S. veterans endorsing current suicidal ideation are not engaged in mental health treatment. Results underscore the importance of multi-modal suicide prevention and treatment engagement efforts that target need-based factors, and perceptions of stigma and negative beliefs about mental healthcare in this population.

Objective Physical exercise may serve as a protective factor for posttraumatic stress disorder (PTSD), but little is known about whether physical exercise is associated with PTSD in population-based samples of military veterans. Methods We analyzed cross-sectional data on the relation between self-reported physical exercise frequency and the prevalence of probable PTSD in a nationally representative sample of 2832 U.S. military veterans who participated in the National Health and Resilience in Veterans Study. Results A "U-shaped" association best explained the relation between self-reported exercise frequency and the prevalence of probable PTSD. Compared to veterans without probable PTSD, those with probable PTSD were nearly twice as likely to report no weekly exercise (52.3% vs. 29.3%) or daily (7 days/week) exercise (15.2% vs. 8.5%) and were nearly half as likely to report exercising a median of 3.5 days/week (32.6% vs. 62.1%). No exercise was associated with greater severity of emotional numbing and lower severity of anxious arousal symptoms, while daily exercise was associated with greater severity of re-experiencing symptoms. Conclusions Results of this study suggest a "U-shaped" association between self-reported exercise frequency and the prevalence of probable PTSD among U.S. veterans. Veterans with probable PTSD were more likely than those without probable PTSD to report not exercising at all or exercising every day and were less likely to report exercising 1-6 days per week. Clinical implications of these findings are discussed.

Objective Depression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning. Methods One thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures. Results Depressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34–0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52–0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58–0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80–1.92), and objective measures of visual learning (d = 0.8–1.31) and working memory (d = 0.67). Conclusion Depression is associated with moderate decrements in cognitive functioning in older U.S. military veterans, and this association is moderated by BDNF Val66Met genotype and physical exercise. Prevention and treatment efforts designed to promote physical exercise may help preserve cognitive functioning in at-risk veterans.

Smoking and obesity are major public health concerns, though little is known about the mental and physical health burden of co-occurring obesity and smoking.Using a nationally representative sample of U.S. military veterans, we examined the prevalence of mental and physical co-morbidities, physical and mental functioning, and quality of life between obese only; smoking only; and obese smokers.Among current smokers, 31.7% were obese; among obese veterans, 16.4% were current smokers; and in the total sample, 5.4% were obese and current smokers. Relative to the obese-only group, obese smokers were more likely to be younger, male, non-white, non-married, unemployed and VA-served, and have lower household incomes. These also reported higher levels of perceived stress and trauma and were more likely to endorsed current suicidal ideation and lifetime suicide attempts (odds ratio [OR]=2.0), medical (2.3=OR=3.9) and psychiatric (1.5=OR=2.9) comorbidities, and lower overall health status and quality of life. Compared to the smoking-only group, obese smokers were more likely to endorse current suicidal ideation (OR=2.0) and nicotine dependence (OR=1.5), and reported poorer physical health and overall quality of life. Analyses were adjusted for sociodemographic and military characteristics.The cross-sectional study design precludes causal inference.These findings suggest that co-occurring obesity and smoking is associated with substantial mental and physical health burden in U.S. veterans. Collectively, they underscore the importance of multicomponent interventions targeting, obesity, smoking, and co-occurring issues, such as trauma and internalizing disorders, in this population.

Objectives Most studies of aging cognition have focused on risk factors for worse performance and on either genetic or environmental factors. In contrast, we examined whether 2 factors known to individually benefit aging cognition may interact to produce better cognition: environment-based positive age beliefs and the APOE ε2 gene. Method The sample consisted of 3,895 Health and Retirement Study participants who were 60 years or older at baseline and completed as many as 5 assessments of cognition over 8 years. Results As predicted, positive age beliefs amplified the cognitive benefit of APOE ε2. In contrast, negative age beliefs suppressed the cognitive benefit of APOE ε2. We also found that positive age beliefs contributed nearly 15 times more than APOE ε2 to better cognition. Discussion This study provides the first known evidence that self-perceptions can influence the impact of a gene on cognition. The results underscore the importance of combined psychosocial and biological approaches to understanding cognitive function in older adults.

BACKGROUND AND OBJECTIVES Alcohol use disorder (AUD) is highly prevalent in US military veterans, though little is known about whether the psychiatric comorbidities and functional outcomes (ie, clinical features) of AUD differ across race/ethnic groups. We aimed to identify differences in the clinical features of veterans with AUD by race/ethnicity. METHODS In a sample of veterans with AUD (n = 1212) from the nationally representative National Health and Resilience in Veterans Study, we compared the clinical features associated with AUD across racial/ethnic groups using analysis of covariance and logistic regression. RESULTS Black veterans (n = 60, 34.0%) were less likely to screen positive for lifetime AUD compared with white (n = 1099, 42.7%) and Hispanic (n = 53, 41.5%) veterans. Among those with lifetime AUD, Hispanic veterans were more likely than white veterans to have lifetime and current mood or anxiety disorders (adjusted odds ratio range [AORR] = 2.21-2.52, P

The Epstein-Barr virus (EBV) may directly cause the development of EBV-associated gastric cancer (EBVaGC). The prevalence of EBVaGC ranges from 4% to 18%, with a 2-fold higher frequency in males, and in tumors arising in the gastric cardia or corpus and 4 times higher frequency in gastric stump carcinoma. The vast majority of EBVaGC are lymphoepithelioma-like carcinomas. Despite extensive nodal involvement and distant metastases at initial diagnosis, EBVaGC seems to be a distinct etiologic entity with a favorable prognosis. However, the lymphoepithelioma-like carcinomas subtype in EBVaGC cannot be recognized in the current molecular classifications. Neither is there an association between EBV positivity and survival of patients after curative gastrectomy if they received standard adjuvant chemotherapy, nor EBV positivity and prediction of response to neoadjuvant platinum/5-FU-based chemotherapy. Alterations in chemokines and PD-L1 provide theoretical justification for clinical evaluation of immune checkpoint therapy in EBVaGC. Moreover, a higher degree of host immune response was demonstrated in EBVaGC. The current histologic and molecular GC classification does not influence clinical practice. Further research is expected to find convenient methods to assess gastric subtypes in day-to-day practice and to tailor therapy to improve overall survival.

Gastric cancer is one of the most common worldwide types of cancer. It is a multifactorial disease and both environmental and genetic factors play an important role in its etiology. Evaluation of the relative expression level of NFKB2 gene in two groups of patients: peptic ulcer and gastric cancer and its role in the pathomechanism of these diseases was the aim of this study. RNA was isolated from: 79 samples of peptic ulcer, 22 gastric cancer and 11 control tissue. The real-time PCR technique was used to study the expression of NFKB2 gene. The relative expression level of NFKB2 gene was a variable in all three studied groups. The relative NFKB2 gene expression depends on the type of a disease. Peptic ulcer cases showed the increased relative NFKB2 gene expression to control group (p = 0.0000). Cancer cases presented decreased relative NFKB2 gene expression to normal stomach tissue (p = 0.0183). There are statistically important differences in the investigated gene expression between peptic ulcer, where the expression level is higher comparing to gastric cancer and control tissue which confirmed that such an activation is connected with an inflammatory process. The relative expression level of NFKB2 is decreased in cancer cases as opposed to control tissue and peptic ulcer cases which could suggest that during carcinogenesis of gastric cancer inhibition of NF-kB pathway takes place which could be a promising factor for patients.

Significance The cell of origin and the temporal order of oncogenic events in tumors play important roles for disease state. This is of particular interest for PCa due to its highly variable clinical outcome. However, these features are difficult to analyze in tumors. We established an in vitro murine PCa organoid model taking into account the cell of origin and the temporal order of events. We found that TIP5 primes luminal prostate cells for Pten-loss mediated oncogenic transformation whereas it is dispensable once the transformation is established. Cross-species transcriptomic analyses revealed a PTEN-loss gene signature that identified a set of aggressive tumors with PTEN-del, or low PTEN expression, and high-TIP5 expression. This paper provides a powerful tool to elucidate PCa mechanisms., Prostate cancer (PCa) is the second leading cause of cancer death in men. Its clinical and molecular heterogeneities and the lack of in vitro models outline the complexity of PCa in the clinical and research settings. We established an in vitro mouse PCa model based on organoid technology that takes into account the cell of origin and the order of events. Primary PCa with deletion of the tumor suppressor gene PTEN (PTEN-del) can be modeled through Pten-down-regulation in mouse organoids. We used this system to elucidate the contribution of TIP5 in PCa initiation, a chromatin regulator that is implicated in aggressive PCa. High TIP5 expression correlates with primary PTEN-del PCa and this combination strongly associates with reduced prostate-specific antigen (PSA) recurrence-free survival. TIP5 is critical for the initiation of PCa of luminal origin mediated by Pten-loss whereas it is dispensable once Pten-loss mediated transformation is established. Cross-species analyses revealed a PTEN gene signature that identified a group of aggressive primary PCas characterized by PTEN-del, high-TIP5 expression, and a TIP5-regulated gene expression profile. The results highlight the modeling of PCa with organoids as a powerful tool to elucidate the role of genetic alterations found in recent studies in their time orders and cells of origin, thereby providing further optimization for tumor stratification to improve the clinical management of PCa.

Questions persist about how often potentially morally injurious events (PMIEs) are associated with posttraumatic stress disorder (PTSD) and depression.This study examined the overlap of morally injurious events with probable PTSD and depression in a nationally representative sample of U.S. combat veterans (n = 1,321, mean age 59.1, 93.7% male).Most veterans with probable PTSD (72.2%), probable depression (72.4%), and probable PTSD and/or depression (68.4%), endorsed experiencing PMIEs; 31.1-35.3% of these participants endorsed perpetration, 45.1-50.4% endorsed witnessing others, and 52.6-55.7% endorsed betrayal. The prevalence of PMIEs among veterans without current probable PTSD and/or depression was 33.7%, 32.3%, and 31.5%, respectively; 7.9-9.1% of these participants endorsed perpetration-based PMIEs, 19.2-20.3% witnessing, and 19.8-21.8% endorsed betrayal. PMIEs were more prevalent among veterans with probable PTSD or depression relative to those without (ORs ranging 2.14-3.32; p's lt; 0.001).This is the first nationally representative study to examine the prevalence of PMIEs among veterans with and without probable PTSD or depression. Results highlight the importance of understanding distress and functional impairment in these veterans to evaluate whether they may benefit from intervention. PMIEs were strikingly more prevalent among veterans with probable PTSD and depression, suggesting that veterans without PMIEs are the minority among combat veterans with these disorders.

The current study examined the nature and correlates of seven-year posttraumatic stress disorder (PTSD) symptom courses in a nationally representative, prospective cohort of U.S. military veterans. Data were analyzed from 2,307 trauma-exposed veterans who completed at least one follow-up assessment over a 7-year period, a subsample of n = 3,157 veterans who participated in the first wave of the National Health and Resilience in Veterans Study. Latent growth mixture modeling (LGMM) was used to identify PTSD symptom courses over four survey waves conducted in 2011, 2013, 2015, and 2018. Sociodemographic, health, and psychosocial variables were examined as potential correlates of symptomatic trajectories. PTSD symptoms were best characterized by three courses: No/Low (89.2%), Moderate Symptom (7.6%), and High Symptom (3.2%). Relative to the No/Low Symptom course, symptomatic courses were positively associated with a greater number of lifetime traumatic events, higher scores on measures of physical health difficulties and lifetime psychiatric history (relative risk ratio [RRR] range = 1.19–2.74), and were negatively associated with time since index trauma, household income, and social connectedness (RRR range = 0.14–0.97). Veterans in the Moderate Symptom course additionally had lower scores on a measure of protective psychosocial characteristics (RRR = 0.78) and were more likely to have received mental health treatment (RRR = 1.62), while those in the High PTSD Symptom course were more likely to be exposed to combat and to more traumas since Wave 1 (RRR range = 1.23–4.63). Three PTSD symptom courses in U.S. veterans were identified, with more than 10% of veterans exhibiting a moderate or high symptom course. Prevention and treatment efforts targeting modifiable correlates, such as social connectedness, may help mitigate symptomatic PTSD symptom courses in this population.

Obesity and alcohol use disorder (AUD) are two of the most prevalent and costly clinical conditions among U.S. military veterans, and these conditions often co-occur. However, little is known about the clinical correlates of co-occurring obesity and AUD, which is critical to informing effective interventions. The current study analyzed data from a nationally representative sample of 4069 (3463 males, 479 females) veterans, who completed an online survey. The Alcohol Use Disorder Identification Test was used to identify veterans who screened positive for probable AUD (pAUD) and self-reported height and weight was used to calculate body mass index and identify veterans with obesity. Multinomial logistic regression was used to examine differences between four groups: controls (no current AUD or obesity), pAUD only, obesity only, and pAUD + obesity. A total of 1390 (36.1%) veterans had obesity, 10.5% (n = 359) had pAUD, and 3.7% (n = 124) had pAUD and obesity. Relative to veterans without AUD, Veterans with pAUD were less likely to have normal/lean weight (14.6% versus 21.4%) and more likely to have overweight (49.6% versus 41.7%). Veterans with pAUD + obesity were nearly twice as likely than veterans with pAUD to report three or more adverse childhood experiences. The results of this study help inform the clinical presentation and needs of veterans with co-occurring obesity and AUD. They also underscore the importance of regularly monitoring weight among veterans with AUD, and considering the role of childhood adversity as a risk factor for co-occurring AUD and obesity.

Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the Esr1 gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of Esr2, Gper1, Ahr, Arnt, Cyp19a1, Cyp1a1, and Atg7, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.

The study aimed to show that including the brain region into the standard 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) study protocol may result in detecting clinically silent brain tumours. We retrospectively analyzed the group of 10,378 from the total of 12,011 consecutive patients who underwent the torso and brain [18F]FDG PET/CT scanning, considering an ability of the method to evaluate undetected before brain tumours in patients diagnosed and treated in our institution. While collecting the database, we followed the inclusion criteria: at least 1-year of follow-up, a full medical history collected in our institution, histopathologic examination or other studies available to confirm the type of observed lesion, and the most importantly—no brain lesions reported in the patients’ medical data. In this study, performing the torso and brain [18F]FDG PET/CT imaging helped to detect clinically silent primary and metastatic brain tumours in 129 patients, and the benign lesions in 24 studied cases, in whom no suspicious brain findings were reported prior to the examination. In conclusion, including the brain region into the standard [18F]FDG PET/CT protocol can be considered helpful in detecting clinically silent malignant and benign brain tumours.

Activation of c-Jun N-terminal kinases (JNKs) has been implicated in the development and persistence of inflammatory and neuropathic pain in animal models. Moreover, JNKs have been involved in the maintenance of chronic pain, as well as development of tolerance to antinociceptive agents in the opioid and cannabinoid class of compounds. In this study, we evaluated the antinociceptive effects of the JNK inhibitor SU 3327 (0.3–30 mg/kg) in the formalin pain model with an emphasis on the sex-specific actions of this compound. In wild-type C57BL6J mice, SU 3327 produced strong antinociceptive effects in the formalin pain model which were mediated by CB2 receptors in females, and both CB1 and CB2 receptors in males. SU 3327 at a dose of 10 mg/kg produced antinociception, hypothermia, motor impairment, and hypolocomotion to a similar extent in both males and females. The antinociceptive effects of SU 3327 were more potent in males at lower doses (1 and 3 mg/kg), while females were more sensitive to the hypothermic, and motor-suppression effects at lower (3 mg/kg) doses versus males. Analysis of spinal cords, using qPCR following SU 3327 administration in the formalin test, revealed changes in cannabinoid, tolerance and inflammatory markers in females only, and only in the high (10–30 mg/kg) dose conditions. Indeed, females showed an increase in mRNA levels of cannabinoid (CB2), but a decrease in tolerance (β-arrestin 1) and inflammatory (TNF-α, IL-1β, IL-6)-associated markers. The differences between males and females, in this study, support sex as an important factor in nociception and antinociceptive responses mediated by JNK and the endocannabinoid system.

Numerous studies assessed the quality of life (QoL) of adult patients after Cushing's disease (CD) treatment. Available professional literature reveals that hypercortisolemia caused by CD may negatively impact the mood and social life. However, data on QoL of adult patients after CD treatment in childhood are scarce. Aim of the study: To study the QoL of adult patients treated for CD in childhood.Eighteen out of 29 adult patients diagnosed in childhood with CD and/or treated at one center participated in a survey and completed WHO Quality of Life-BREF questionnaire. The influence of selected prognostic factors for the QoL has been analyzed. Patients data were compared with a control group with the same age and sex.Participants (10 women and 8 men) were at the mean age of 28.93 years (19.75-40.33). No significant difference in the QoL was noted between analyzed patients and controls. Patients with hypopituitarism had lower results in domain 4 in comparison with patients without hypopituitarism (p = 0.31) and lower results in domain 2 in comparison with the control group (p = 0.045). Patients with a higher age at disease onset had lower results of the QoL in domain 1 (p = 0.031).During long-term follow-up the QoL of patients after CD treatment in childhood is not significantly different wit QoL of healthy controls. Further studies are needed to expand the knowledge of factors that may contribute to the QoL in CD patients who were treated in childhood.Jakość życia (QoL) dorosłych pacjentów po leczeniu choroby Cushinga (CD) oceniano w wielu badaniach. Z dostępnej fachowej literatury wynika, że hiperkortyzolemia spowodowana CD może negatywnie wpływać na nastrój i życie społeczne. Jednak dane dotyczące jakości życia dorosłych pacjentów po leczeniu CD w dzieciństwie są ograniczone. Cel pracy: Zbadanie jakości życia dorosłych pacjentów leczonych z powodu CD w dzieciństwie.Osiemnastu z 29 dorosłych pacjentów z rozpoznaniem w dzieciństwie CD i/lub leczonych w jednym ośrodku wzięło udział w ankiecie i wypełniło kwestionariusz WHO Quality of Life-BREF. Przeanalizowano wpływ wybranych czynników prognostycznych na QoL. Wyniki porównano z grupą kontrolną osób zdrowych w tym samym wieku i płci.Uczestnicy (10 kobiet i 8 mężczyzn) byli w średnim wieku 28,93 roku (19,75–40,33 roku). Nie stwierdzono istotnej różnicy w QoL między analizowanymi pacjentami a grupą kontrolną. Pacjenci z niedoczynnością przysadki mieli niższe wyniki w domenie 4. w porównaniu z pacjentami bez niedoczynności przysadki (p = 0,31) oraz niższe wyniki w domenie 2 w porównaniu z grupą kontrolną (p = 0,045). Pacjenci starsi w momencie wystąpienia choroby mieli niższe wyniki QoL w domenie 1 (p = 0,031).W długoterminowej ocenie QoL pacjentów po leczeniu CD w dzieciństwie nie różni się istotnie od QoL osób zdrowych. Potrzebne są dalsze badania, aby poszerzyć wiedzę na temat czynników, które mogą wpływać na jakość życia pacjentów z CD leczonych w dzieciństwie.

Importance A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objectives To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. Design, Setting, and Participants The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. Main Outcomes and Measures The PTSD Checklist forDSM-5was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. Results A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. Conclusions and Relevance The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.

Objective Lacosamide (LC) belongs to a new generation of antiepileptic drugs (AEDs) and demonstrates unique mechanism of action. The drug also shows neuroprotective activity on the hippocampus. In this study, the impact of LC on learning processes was assessed. Methods Adult male Wistar rats (n = 40) were used. Lacosamide was administered p.o. as a single (25 mg/kg or 75 mg/kg) or repeated doses (75 mg/kg). The effect of the drug was assessed in the Morris water maze (spatial memory) and the passive avoidance (PA) (emotional memory). Results Lacosamide administered at a single dose or repeatedly did not impair spatial memory in Morris water maze. Higher swimming speed was observed in rats after administration of acute doses of LC. In PA, the disturbance of emotional memory was observed only after the single high dose of LC. Conclusion Lacosamide does not impair memory and learning processes. The emotional memory impairment observed after the acute high dose appears to be temporary and did not occur after repeated administration.

Objective: US military veterans have high rates of suicide relative to civilians. However, little is known about the prevalence and correlates of suicidal behaviors in the general US veteran population. Methods: Data were from the National Health and Resilience in Veterans Study, a representative survey of US veterans conducted in 2019-2020 (n = 4,069). Analyses (1) estimated the prevalence of current suicidal ideation, lifetime suicide plans, and lifetime suicide attempts; (2) identified associated sociodemographic, military, DSM-5 psychiatric, and other risk correlates; and (3) examined mental health treatment utilization among veterans with suicidal ideation, suicide plans, or suicide attempts. Results: The prevalence of current suicidal ideation, lifetime suicide plans, and lifetime suicide attempts was 9.0%, 7.3%, and 3.9%, respectively. Suicidal behaviors were most prevalent among veterans aged 18-44 years, with 18.2%, 19.3%, and 11.1%, respectively, endorsing suicidal ideation, suicide plans, and suicide attempts. Major depressive disorder (MDD), age, posttraumatic stress disorder, and adverse childhood experiences (ACEs) emerged as the strongest correlates of suicidal ideation and suicide plans, while MDD, age, alcohol use disorder, and ACEs were the strongest correlates of suicide attempts. Only 35.5% of veterans with current suicidal ideation were engaged in mental health treatment, with veterans who used the US Veterans Administration (VA) as their primary source of health care more than twice as likely as VA non-users to be engaged in such treatment (54.7% vs 23.8%). Conclusions: Suicidal behaviors are highly prevalent among US veterans, particularly among young veterans. Results suggest that nearly two-thirds of veterans with current suicidal ideation are not engaged in mental health treatment, signaling the need for enhanced suicide prevention and outreach efforts.

Alcohol use disorder (AUD) is a prevalent public health concern in the U.S. that disproportionately affects veterans relative to civilians. Given changes to the demographic composition of the veteran population and AUD diagnostic criteria in the DSM-5, updated knowledge regarding the epidemiology of DSM-5 AUD in a national sample of veterans is critical to informing the population-based burden of this disorder.Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 U.S. veterans. Lifetime DSM-5 AUD (mild, moderate, severe) and past-year DSM-5 AUD were assessed using validated self-report measures, and sociodemographic, military, and psychiatric characteristics associated with lifetime and past-year AUD were evaluated.Prevalences of lifetime and past-year DSM-5 AUD were 40.8% (95% confidence interval [CI]=39.2-42.3%) and 10.5% (95%CI=9.6-11.5%), respectively. Lifetime prevalences of mild, moderate, and severe AUD were 20.5%, 8.3%, and 12.0%, respectively. Veterans with lifetime AUD had elevated rates of psychiatric disorders and suicidal behavior, which generally increased as a function of AUD severity. Lifetime AUD was also associated with being younger, male, white, unmarried, retired and experiencing more adverse childhood experiences and traumas. For past-year AUD, being younger, male, white, having more adverse childhood experiences, and experiencing lifetime PTSD were significant correlates.AUD is highly prevalent among U.S. veterans and associated with substantial psychopathology, including elevated odds of suicidal behaviors. Results underscore the importance of comprehensive screening and preventive efforts for AUD, and interventions that concurrently target overlapping alcohol use and psychiatric difficulties.

Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction.