Multimodal smoking cessation treatment combining repetitive transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths remain the leading cause of preventable death in the United States. Veterans suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies suggest the insula is integrally involved in the neurocircuitry of TUD. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a form of repetitive transcranial magnetic stimulation (rTMS) called intermittent theta burst stimulation (iTBS). iTBS has the advantage of allowing for a patterned form of stimulation delivery that we will administer at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the right post-central gyrus and the right posterior insula, withdrawal symptoms and short-term smoking cessation outcomes will improve. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n = 25) or sham-iTBS + CBT + NRT (n = 25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD.

BACKGROUND: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared to individuals without SCD. METHODS: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. RESULTS: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared to the veterans without SCD, whereby SCD patients were aging approximately 0.7 months more per year than those without SCD (p=4.49x10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with PTSD from the non-SCD group (p=2.18x10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sß0 thalassemia genotypes (p=1.61x10-10). CONCLUSIONS: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

Two cases of Angiostrongylus vasorum, a cardiopulmonary nematode, in a wild black bear and coyote of Tennessee.

Angiostrongylus vasorum, commonly known as the French heartworm, is a metastrongyloid parasitic nematode that infects wild and domestic canids. In North America, A. vasorum is endemic to the Canadian island of Newfoundland, but has been expanding to new areas including Nova Scotia, Prince Edward Island, and West Virginia (USA). Two cases of A. vasorum are reported from the state of Tennessee. The first case in a black bear (Ursus americanus) and the second case in a coyote (Canis latrans). The black bear was found dead in Sevier County in November of 2022, while the coyote was trapped and euthanized as part of a predator control program in Campbell County in January of 2023. Histology of the lungs revealed both animals had verminous pneumonia. DNA was extracted from the lungs of both, and PCR was performed using NC1 and NC2 primers. Sequencing results of the PCR products from the bear and coyote samples indicated that they were 95% and 96% similar, respectively, to European strains of A. vasorum. This report marks the first time A. vasorum has been reported in Tennessee as well as only the second and third report of autochthonous A. vasorum infection in the United States and the first report in an ursid. These two cases confirm the spread of A. vasorum further into North America. This nematode is highly pathogenic to wild and domestic canids, and thus these cases represent an emerging threat to both and underscore the need for further surveillance for the parasite.

Multisystemic inflammatory disease in Pheasantshell (Unionidae, Actinonaias pectorosa) associated with Yokenella regensburgei infection at sites experiencing seasonal mass mortality events.

Freshwater mussels are integral components of riverine ecosystems, influencing water quality, nutrient cycling, and habitat characteristics. Enigmatic freshwater mussel declines, often characterized by sudden mass mortality events, pose significant challenges to conservation efforts. The Clinch River, a freshwater biodiversity hotspot in Virginia and Tennessee, USA, has experienced several enigmatic mass mortality events since 2016. Studies have reported bacteria associated with moribund Pheasantshell (Actinonaias pectorosa) during mortality events in the Clinch River, specifically Yokenella regensburgei. Despite reports of bacterial infection, little is known about their role as pathogens. Through a multiyear case-control study, combining in-situ experiments, field surveys, histology, bacterial isolation, and high-throughput sequencing, we assessed the role of bacteria in Pheasantshell (Actinonais pectorosa) mortality at three sites in the Clinch River. Between May 2021 and December 2023, we collected 21 wild moribund free-living A. pectorosa and 68 hatchery-reared A. pectorosa maintained in silos at the same sites and investigated differences in pathology and microbiologye between groups. No silo mussels presented clinical signs of disease, or gross or microscopic lesions associated with pathological conditions leading to mortality. Our findings reveal a significant association between Yokenella regensburgei and severe multisystemic and multifocal infiltrative hemocytosis with necrosis, consistent with sepsis. Lesions associated with yokenellosis were of sufficient severity and physiological significance to explain mortality in infected hosts. Although our study does not explain the cause of these infections, it confirms that mussels at our study sites are ultimately dying with an infectious disease and that Y. regensburgei can be pathogenic in free-living mussels. Our results underscore the importance of considering bacterial diseases in wild mussel populations and emphasize the need for further research to elucidate the epidemiology and pathogenicity of Y. regensburgei. Overall, our study highlights the importance of integrated approaches combining pathology, microbiology, and epidemiology in freshwater mussel conservation efforts.

Verminous bronchitis and pneumonia by nasal trematodes in Greater Caribbean manatees from Puerto Rico.

Five adult Greater Caribbean manatees Trichechus manatus manatus were found stranded on various coasts of Puerto Rico; 2 stranded alive and 3 stranded dead. Clinical signs observed in live-stranded manatees included emaciation, weakness, bradypnea, arrhythmia, and nasal mucus discharge. Postmortem examinations revealed serosanguinous, mucohemorrhagic, or suppurative exudate in bronchi associated with luminal adult Pulmonicola cochleotrema (range: 18-182 trematodes), accompanied by pulmonary abscesses in 2 cases. Histologically, we observed eosinophilic bronchopneumonia of varying severity (n = 4) and chronic erosive to eosinophilic tracheobronchitis (n = 4) with squamous metaplasia (n = 3) and intralesional trematodes and eggs. The trematode identity was confirmed and compared through molecular analysis for the amplified 18S rDNA fragment. Comorbidities included enteric chiorchosis (n = 5), gastric heterocheilosis (n = 4), malnutrition (n = 4), trauma related to watercraft collision (n = 3), systemic toxoplasmosis (n = 1), acute bacterial peritonitis (n = 1), and interstitial nephritis (n = 1), suggesting that immunosuppression was a predisposing factor for lower respiratory tract pulmonicolosis. Based on lesion severity, clinical signs, and the presence and absence of other findings to explain death, this condition was considered the primary cause of death in 1 manatee, a contributory cause of death in 3 manatees, and an incidental finding in 1 individual. These clinicopathological descriptions will facilitate the diagnosis and clinical management of pulmonicolosis in T. manatus, a species endangered with extinction.

Debilitating Musculoskeletal Disease in Two Free-Ranging Juvenile American Black Bears (Ursus americanus).

Severe musculoskeletal disease characterized by marked joint laxity was the cause of euthanasia in two wild juvenile American black bears (Ursus americanus) admitted to a rehabilitation facility in eastern Tennessee in 2023. Previously, almost all reported musculoskeletal diseases in this population were of traumatic etiology, even in malnourished yearlings. Case 1 was an orphaned 11-month-old male cub exhibiting disproportionate dwarfism, progressive immobility, and joint laxity. Necropsy findings suggested either chondrodysplasia or rickets, and imaging findings supported a skeletal dysplasia. Case 2 was a 14-month-old emaciated male yearling exhibiting joint laxity and immobility. Necropsy findings showed osteoporosis and serous atrophy of fat, and imaging findings were inconsistent with a skeletal dysplasia. Both cases were clinically inconsistent with rickets based on normal calcium, phosphorous, and parathyroid hormone concentrations; however, Case 1 had hypovitaminosis D (9 nmol/L) compared to healthy juvenile black bears. We hypothesize that Case 1 had a genetic chondrodysplasia while the osteoporosis of Case 2 was due to chronic malnutrition. The goal of this case report is to inform wildlife agencies and facilities to monitor for similar, non-trauma-related debilitating musculoskeletal disease in free-ranging bears and evaluate cases that allow us to further understand the disease processes involved.

Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: A meta-analysis of 23 military and civilian cohorts.

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels. Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.

Demographic characteristics and epigenetic biological aging among post-9/11 veterans: Associations of DunedinPACE with sex, race, and age.

Measures of epigenetic aging derived from DNA methylation (DNAm) have enabled the assessment of biological aging in new populations and cohorts. In the present study, we used an epigenetic measure of aging, DunedinPACE, to examine rates of aging across demographic groups in a sample of 2,309 United States military veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study. As assessed by DunedinPACE, female veterans were aging faster than male veterans (ß = 0.39, 95 % CI [0.29, 0.48], p < .001), non-Hispanic Black veterans were aging faster than non-Hispanic White veterans (ß = 0.58, 95 % CI [0.50, 0.66], p < .001), and older veterans were biologically aging faster than younger veterans (ß = 0.21, 95 % CI [0.18, 0.25], p < .001). In secondary analyses, these differences in rates of aging were not explained by a variety of biopsychosocial covariates. In addition, the percentage of European genetic admixture in non-Hispanic Black veterans was not associated with DunedinPACE. Our findings suggest that female and non-Hispanic Black veterans are at greater risk of accelerated aging among post-9/11 veterans. Interventions that slow aging might provide relatively greater benefit among veterans comprising these at-risk groups.

Genome-wide DNA methylation analysis of cannabis use disorder in a veteran cohort enriched for posttraumatic stress disorder.

Cannabis use has been increasing over the past decade, not only in the general US population, but particularly among military veterans. With this rise in use has come a concomitant increase in cannabis use disorder (CUD) among veterans. Here, we performed an epigenome-wide association study for lifetime CUD in an Iraq/Afghanistan era veteran cohort enriched for posttraumatic stress disorder (PTSD) comprising 2,310 total subjects (1,109 non-Hispanic black and 1,201 non-Hispanic white). We also investigated CUD interactions with current PTSD status and examined potential indirect effects of DNA methylation (DNAm) on the relationship between CUD and psychiatric diagnoses. Four CpGs were associated with lifetime CUD, even after controlling for the effects of current smoking (AHRR cg05575921, LINC00299 cg23079012, VWA7 cg22112841, and FAM70A cg08760398). Importantly, cg05575921, a CpG strongly linked to smoking, remained associated with lifetime CUD even when restricting the analysis to veterans who reported never smoking cigarettes. Moreover, CUD interacted with current PTSD to affect cg05575921 and cg23079012 such that those with both CUD and PTSD displayed significantly lower DNAm compared to the other groups. Finally, we provide preliminary evidence that AHRR cg05575921 helps explain the association between CUD and any psychiatric diagnoses, specifically mood disorders.

In-nest mortality and pathology of hawksbill sea turtle (Eretmochelys imbricata) embryos and hatchlings in St. Kitts and Nevis.

Strategies to improve the hatch success and survival of critically endangered hawksbill turtles (Eretmochelys imbricata) require knowledge of threats to them including pathological conditions. The objective of this study was to describe the mortality and pathology of embryos and dead-in-nest hatchlings on St. Kitts and Nevis. Over the 2019/20 and 2020/21 nesting seasons, the combined mean (SD) hatch success for the two islands was 81.9% (13.2%) and deceased individuals within excavated nests were early-stage embryos (70.7%), late-stage embryos (17.7%), pipped-hatchlings (8.2%) or dead-in-nest hatchlings (3.4%). From 2017 to 2021, a post-mortem examination was performed on 183 turtles, including histology for 116. Anatomical malformations affected 77 (42.1%) examined turtles and included abnormal scute shape or number (22.4%), dysmelia (8.7%), schistosomus reflexus (7.7%) and compressed carapace (7.7%). Microscopic lesions were found in 49.1% of turtles and included tissue mineralization (26.7%, including renal, fetal membrane, liver, heart or muscle), chorioallantoitis (16.2%) and skeletal muscle degeneration and necrosis (10%). Inflammatory lesions associated with fungal or bacterial infections were in the skin (n = 3), chorioallantois (n = 4), lung (n = 3) or yolk sac (n = 1). These lesions may reflect non-specific terminal conditions but their presence in-nest helps explain some of the mortality and pathology documented in hatchlings that die during rehabilitative care. All of the gonads adequately represented for histological determination of sex were female (n = 62), supporting concern for feminization of Caribbean hawksbill turtle nests. The study identifies lesions that could affect hatch and emergence success. The high frequency of skeletal malformations indicates the need for investigations addressing regional impact and pathogenesis, especially genetic and environmental aetiologies including nest temperature. Immediate examination of live hatchlings on nest emergence is warranted to better determine the prevalence of non-fatal malformations that could impact fitness and population genetics.

Posttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.

People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military veterans who participated in the VISN 6 MIRECC's Post-Deployment Mental Health Study, we tested whether PTSD and trauma exposure were associated with accelerated rate of biological aging, assessed using a validated DNA methylation (DNAm) measure of epigenetic aging-DunedinPACE. Veterans with current PTSD were aging faster than those who did not have current PTSD, ß = 0.18, 95% CI [0.11, 0.27], p < .001. This effect represented an additional 0.4 months of biological aging each year. Veterans were also aging faster if they reported more PTSD symptoms, ß = 0.13, 95% CI [0.09, 0.16], p < 0.001, or higher levels of trauma exposure, ß = 0.09, 95% CI [0.05, 0.13], p < 0.001. Notably, veterans with past PTSD were aging more slowly than those with current PTSD, ß = -0.21, 95% CI [-0.35, -0.07], p = .003. All reported results accounted for age, gender, self-reported race/ethnicity, and education, and remained when controlling for smoking. Our findings suggest that an accelerated rate of biological aging could help explain how PTSD contributes to poor health and highlights the potential benefits of providing efficacious treatment to populations at increased risk of trauma and PTSD.

Development of Mobile Contingency Management for Cannabis Use Reduction.

Many interventions for cannabis use disorder (CUD) are associated with decreases in frequency and quantity of use but fail to increase overall rates of sustained abstinence. It is currently unknown whether reductions in use (in the absence of sustained abstinence) result in clinically significant improvements in functioning. The objective of this study was to refine a mobile contingency management approach to reduce cannabis use to ultimately evaluate whether reductions in frequency and quantity of cannabis are related to improvements in functional and mental health status. Three cohorts of participants (n = 18 total, n = 10 women) were enrolled and completed 2 weeks of ecological momentary assessment (EMA) during a baseline ad lib cannabis use period, followed by a 6-week reduction period. Participants completed EMA assessments multiple times per day and were prompted to provide videotaped saliva cannabis testing 2-3 times daily. Data from participants who were at least 80% adherent to all EMA prompts were analyzed (13 out of 18). During the ad lib phase, participants were using cannabis on 94% of the days and reported using a mean of 1.42 grams daily. The intervention was a mobile application that participants used to record cannabis use by saliva tests to bioverify abstinence and participants completed electronic diaries to report their grams used. During the 6-week intervention phase, participants reported reducing their use days to 47% of the days with a reported mean of .61 grams daily. In the last cohort, at least 50% of the heavy users were able to reduce their cannabis use by at least 50%. The effect of cannabis reduction (versus abstinence) is largely unknown. Observations suggest that it is possible to develop a mobile intervention to reduce cannabis use among heavy users, and this paradigm can be utilized in future work to evaluate whether reductions in cannabis use among heavy users will result in improvements in functional and mental health status.

Development and Implementation of Web-Based Safety Planning Intervention Training for Firefighter Peer Support Specialists.

Background: Recent findings indicate that firefighters may be at increased risk for death by suicide; however, there has been only limited suicide prevention work in fire service to date. Aim: The objective of this program evaluation project was to develop and evaluate a web-based Safety Planning Intervention (SPI) training course for firefighter peer support specialists. Method: Peer support specialists who completed the web-based SPI training were administered evaluation questionnaires before the training and then again at a 3-month follow-up assessment. Results: A total of 213 peer support specialists completed the SPI training. Most participants took 2-3 h to complete the training. Participants generally reported high levels of satisfaction with the course, with the vast majority (94.4%) indicating they would recommend it to their peers. Course completers also demonstrated significant gains in SPI knowledge and self-efficacy from baseline to 3-month follow-up (all p's < .001). Moreover, the percentage of participants who reported completing a safety plan with someone they suspected at being of risk for suicide increased approximately 7-fold from baseline (3.5%) to 3-month follow-up (25.2%; p < .001). Participants further reported that 97.6% of the safety plans that they completed resulted in a positive outcome. Limitations: This was a program evaluation project that did not include a control group. Thus, causality cannot be inferred. Conclusions: The present findings suggest that web-based SPI training is a feasible and scalable approach for training peer support specialists to deliver the SPI to at-risk individuals.

Spinal disease in a captive population of Panthera species: Review of 86 cases (2003-2021).

This retrospective study aimed to characterize and determine the prevalence of spinal disease in nondomestic felids within a sanctuary population. A review of 304 postmortem examination reports in Panthera species from 2003 to 2021 revealed that 86/304 (28%) were diagnosed with spinal disease. Spinal lesions were categorized according to pathologic process: degenerative (78/86, 91%), developmental (8/86, 9%), inflammatory (6/86, 7%), or neoplastic (8/86, 9%). Degenerative lesions included intervertebral disk disease (IVDD; 66/78, 85%), spondylosis without concurrent IVDD (4/78, 5%), and idiopathic (noncompressive) degenerative myelopathies (8/78, 10%). Fourteen individuals had lesions in more than 1 category. Developmental cases were vertebral (4/8) or spinal cord (3/8) malformations or both (1/8). Inflammatory lesions included meningitis (4/6) and meningomyelitis (2/6). Neoplasia included vertebral multiple myeloma (4/8) and others (4/8). IVDD often involved multiple disks but primarily affected the cervical (41/66, 62%) and thoracic spine (32/66, 48%). A multivariate binary logistic model predicted the diagnosis of IVDD at postmortem examination, where odds of being affected were highest for males, lions (Panthera leo), and geriatric age group (>14 years). The spinal lesions documented in this study provide insight into high-risk signalment categories and predominant associated lesions affecting captive Panthera populations. Specifically, spinal disease, especially cervical IVDD, is common among Panthera species, and lions, males, and older felids are at increased risk.

First molecular identification of the trematode Pulmonicola cochleotrema (Platyhelminthes: Opisthotrematidae) in West Indian manatees (Trichechus manatus, Sirenia: Trichechidae) from Puerto Rico and Florida.

West Indian manatees (Trichechus manatus) harbor a variety of endoparasites, including the nasal trematode Pulmonicola cochleotrema, which infects the respiratory tract, especially the nasal passages. Previous studies have described and identified this digenean using morphological data only. This study presents the first molecular identification of P. cochleotrema in West Indian manatees from Puerto Rico and Florida. Samples of the trematode were collected from seven manatees found stranded dead at both locations. The small subunit ribosomal DNA (18S rDNA) was amplified from each sample using universal primers for different regions of the gene, resulting in a consensus sequence of 1871 base pairs. The phylogenetic reconstruction was carried out using DNA sequences of other species of digenean parasites from other hosts, including a trematode of the same taxonomic family from another sirenian species. Specimens collected from both locations show the same molecular identity using SSU rDNA sequence data. The identity of P. cochleotrema was confirmed using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information database, yielding a high similarity of 98.8 % with Opisthotrema dujonis and 98.2 % with Lankatrema mannarense located in the same clade in our analysis. The latter two digeneans belong to the Opisthotrematidae as does P. cochleotrema and previous studies reported them infecting the Eustachian tubes, esophagus, and digestive tract in dugongs (Dugong dugon). These findings evidence that the nasal trematode of manatees in Florida and Puerto Rico and the dugong, all inhabiting and feeding in marine environments, will have a marine mollusk as an intermediate host, probably a gastropod. The question remains, which species of nasal trematode are harbored by lotic-dwelling manatees in other parts of their distribution like South America.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Multimodal smoking cessation treatment combining transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement therapy in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths exceed those resulting from homicides, suicides, motor vehicle accidence, alcohol consumption, illicit substance use, and acquired immunodeficiency syndrome (AIDS), combined. Amongst U.S. veterans, this trend is particularly concerning given that those suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies have revealed the insula as integrally involved in the neurocircuitry of TUD, specifically showing that individuals with brain lesions involving this region had drastically improved quit rates. Some of these studies show a probability of quitting up to 5 times greater compared to non-insula lesioned regions). Altered activity of the insula may be involved in the disruption of the salience network's (SN) connectivity to the executive control network (ECN), which compromises that patient's ability to switch between interoceptive states focused on cravings to executive and cognitive control. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a patterned form of repetitive transcranial magnetic stimulation (rTMS), intermittent theta burst stimulation (iTBS), at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the SN with the ECN to enhance executive control and by decreasing connectivity with the default mode network (DMN) to reduce interoceptive focus on withdrawal symptoms, we will improve smoking cessation outcomes. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to two conditions: active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n=25) or sham-iTBS + CBT + NRT (n=25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

An introduction to lesions and histology of scleractinian corals.

Stony corals (Scleractinia) are in the Phylum Cnidaria (cnidae referring to various types of stinging cells). They may be solitary or colonial, but all secrete an external, supporting aragonite skeleton. Large, colonial members of this phylum are responsible for the accretion of coral reefs in tropical and subtropical waters that form the foundations of the most biodiverse marine ecosystems. Coral reefs worldwide, but particularly in the Caribbean, are experiencing unprecedented levels of disease, resulting in reef degradation. Most coral diseases remain poorly described and lack clear case definitions, while the etiologies and pathogenesis are even more elusive. This introductory guide is focused on reef-building corals and describes basic gross and microscopic lesions in these corals in order to serve as an invitation to other veterinary pathologists to play a critical role in defining and advancing the field of coral pathology.