Experimental inoculation of pigs with monkeypox virus results in productive infection and transmission to sentinels.

Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.

Scoping Review: Transdiagnostic Measurement of Impulsivity Domains in Youth Using the UPPS Impulsive Behavior Scales.

OBJECTIVE: Impulsivity contributes to many clinically relevant behaviors impacting youth. A scoping review was conducted to characterize existing research using the Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking (UPPS) Impulsive Behavior Scales in youth populations, to review the psychometric and validity data of UPPS, and to summarize findings related to sex/gender and diagnostic populations of youth. METHOD: PubMed, Embase, and PsycNET databases were searched from January 1, 2001 (original UPPS publication) through October 2, 2022, according to PRISMA extension for Scoping Reviews guidelines. Articles were reviewed for inclusion/exclusion by 2 authors. Original research articles in English using any UPPS version or subscale in persons aged ≤21 years were included. RESULTS: Inclusion criteria were met by 45 articles, with low bias and moderate-to-high quality. Most were cross-sectional studies; studies investigated diverse community and clinical samples. The UPPS demonstrated consistent factor structure, good reliability, and good external validity with other measures of impulsive behaviors and conditions associated with impaired impulse control. Some studies observed differences in UPPS domain scores between sex/gender groups or differential patterns in relationships between UPPS domains and clinical variables. UPPS subscale scores often differed in youth with attention-deficit/hyperactivity disorder, conduct disorders, substance use, and excess weight/obesity compared with control youth. UPPS domains commonly had interactions with sex/gender, sociodemographic, and diagnosis-related variables. CONCLUSION: The current literature suggests that the UPPS has utility in measuring distinct components of impulsivity in clinical and nonclinical populations of youth. Specificity in discriminating diagnostic groups and predicting risk currently remains uncertain. Further research is needed to integrate UPPS measures with experimental models and additional neurobiological methods and to assess longitudinal developmental trajectories. PLAIN LANGUAGE SUMMARY: Impulsivity contributes to many clinically relevant behaviors and mental health disorders that impact youth. The Urgency, Premeditation, Perseverance, Sensation Seeking (UPPS) Impulsive Behavior Scale has been increasingly used in research to measure deficits in impulse control. In this scoping review the authors examined 45 studies that used versions of the UPPS to measure different domains of impulsivity in youth aged 21 years and younger. The authors found evidence in the literature for the validity and reliability of the UPPS and its variants in measuring impulsivity in youth. Certain patterns of UPPS subscale scores corresponded with clinical behaviors and diagnoses including attention-deficit/hyperactivity disorder (ADHD), conduct disorder, substance use, and excessive weight/obesity. Despite this, there remain gaps in the literature regarding the stability of UPPS measures over time and ability of the UPPS to predict clinical outcomes.

Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: A preliminary dose-finding study exploring safety and clinical effectiveness.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an intervention for treatment-resistant depression (TRD) that modulates neural activity. Deep TMS (dTMS) can target not only cortical but also deeper limbic structures implicated in depression. Although TMS has demonstrated safety in adolescents, dTMS has yet to be applied to adolescent TRD. OBJECTIVE/HYPOTHESIS: This pilot study evaluated the safety, tolerability, and clinical effects of dTMS in adolescents with TRD. We hypothesized dTMS would be safe, tolerable, and efficacious for adolescent TRD. METHODS: 15 adolescents with TRD (Age, years: M = 16.4, SD = 1.42) completed a six-week daily dTMS protocol targeting the left dorsolateral prefrontal cortex (BrainsWay H1 coil, 30 sessions, 10 Hz, 3.6 s train duration, 20s inter-train interval, 55 trains; 1980 total pulses per session, 80 % to 120 % of motor threshold). Participants completed clinical, safety, and neurocognitive assessments before and after treatment. The primary outcome was depression symptom severity measured by the Children's Depression Rating Scale-Revised (CDRS-R). RESULTS: 14 out of 15 participants completed the dTMS treatments. One participant experienced a convulsive syncope; the other participants only experienced mild side effects (e.g., headaches). There were no serious adverse events and minimal to no change in cognitive performance. Depression symptom severity significantly improved pre- to post-treatment and decreased to a clinically significant degree after 10 treatment sessions. Six participants met criteria for treatment response. LIMITATIONS: Main limitations include a small sample size and open-label design. CONCLUSIONS: These findings provide preliminary evidence that dTMS may be tolerable and associated with clinical improvement in adolescent TRD.

Co-Circulating Monkeypox and Swinepox Viruses, Democratic Republic of the Congo, 2022.

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.

Domestic pigs are susceptible to experimental infection with non-human primate-derived Reston virus without the need for adaptation.

Domestic pigs are a critical component of the food supply and one of the most commonly raised production animals. Pork consumption has driven the intensification of pig production expanding into environments conducive to increased emergence and spread of infectious diseases, including the spillover of pathogens into human populations. One of these emerging viruses, Reston virus (RESTV), is an enigma among the Orthoebolavirus genus in that its lack of human pathogenicity is in stark contrast to the high virulence associated with most other ebolaviruses. RESTV is, however, associated with outbreaks of highly lethal hemorrhagic disease in non-human primates (NHP), as well as poorly understood clinical manifestations of mixed virulence and lethality in naturally and experimentally infected domestic pigs. Our results show it is possible for RESTV derived from an NHP to infect domestic pigs resulting in a spectrum of disease, from asymptomatic to severe respiratory distress. Further, we report on the first experimental transmission of RESTV between infected pigs and a co-housed, naïve animal, as well as the first report of the successful use of group oral fluids for the detection of RESTV RNA and virus-specific IgA antibodies.

Molecular and Pathological Characterization of Classical Swine Fever Virus Genotype 2 Strains Responsible for the 2013-2018 Outbreak in Colombia.

Classical swine fever (CSF) is a highly contagious transboundary viral disease of domestic and wild pigs. Despite mass vaccination and continuous eradication programs, CSF remains endemic in Asia, some countries in Europe, the Caribbean and South America. Since June 2013, Northern Colombia has reported 137 CSF outbreaks, mostly in backyard production systems with low vaccination coverage. The purpose of this study was to characterize the virus responsible for the outbreak. Phylogenetic analysis based on the full-length E2 sequence shows that the virus is closely related to CSF virus (CSFV) genotype 2.6 strains circulating in Southeast Asia. The pathotyping experiment suggests that the virus responsible is a moderately virulent strain. The 190 nucleotide stretch of the E2 hypervariable region of these isolates also shows high similarity to the CSFV isolates from Colombia in 2005 and 2006, suggesting a common origin for the CSF outbreaks caused by genotype 2.6 strains. The emergence of genotype 2.6 in Colombia suggests a potential transboundary spread of CSFV from Asia to the Americas, complicating the ongoing CSF eradication efforts in the Americas, and emphasizes the need for continuous surveillance in the region.

Event-Related Potential Markers of Suicidality in Adolescents.

BACKGROUND: Implicit cognitive markers may assist with the prediction of suicidality beyond clinical risk factors. The aim of this study was to investigate neural correlates associated with the Death/Suicide Implicit Association Test (DS-IAT) via event-related potentials (ERP) in suicidal adolescents. METHODS: Thirty inpatient adolescents with suicidal ideations and behaviors (SIBS) and 30 healthy controls from the community were recruited. All participants underwent 64-channel electroencephalography, DS-IAT, and clinical assessments. Hierarchical generalized linear models with spatiotemporal clustering were used to identify significant ERPs associated with the behavioral outcome of DS-IAT (D scores) and group differences. RESULTS: Behavioral results (D scores) showed that the adolescents with SIBS had stronger implicit associations between "death" and "self" than the healthy group (P = .02). Within adolescents with SIBS, participants with stronger implicit associations between "death" and "self" reported more difficulty in controllability of suicidal ideation in the past 2 weeks based on the Columbia-Suicide Severity Rating Scale (P = .03). For the ERP data, the D scores and N100 component over the left parieto-occipital cortex had significant correlations. Significant group differences without behavioral correlation were observed for a second N100 cluster (P = .01), P200 (P = .02), and late positive potential (5 clusters, all P ≤ .02). Exploratory predictive models combining both neurophysiological and clinical measures distinguished adolescents with SIBS from healthy adolescents. CONCLUSIONS: Our results suggest that N100 may be a marker of attentional resources involved in the distinction of stimuli that are congruent or incongruent to associations between death and self. Combined clinical and ERP measures may have utility in future refinements of assessment and treatment approaches for adolescents with suicidality.

Aldol Cleavage in Water and the Power of Citrate Lyase as a Catalyst.

Citrate lyase allows Klebsiella aerogenes to grow anaerobically on citrate as the sole carbon source. Arrhenius analysis of experiments at high temperatures indicates that citrate is cleaved nonenzymatically to acetate and oxaloacetate with a t1/2 of 6.9 million years in neutral solution at 25 °C, while malate cleavage occurs even more slowly (t1/2 = 280 million years). However, t1/2 is only 10 days for the nonenzymatic cleavage of 4-hydroxy-2-ketoglutarate, indicating that the introduction of an α-keto group enhances the rate of aldol cleavage of malate by a factor of 1010. The aldol cleavages of citrate and malate, like the decarboxylation of malonate (t1/2 = 180 years), are associated with a near-zero entropy of activation, and their extreme differences in rate reflect differences between their heats of activation. Citrate lyase enhances the rate of substrate cleavage 6 × 1015-fold, comparable in magnitude with the rate enhancement produced by OMP decarboxylase, although these enzymes are strikingly different in their mechanisms of action.

Comparative susceptibility of eastern cottontails and New Zealand white rabbits to classical rabbit haemorrhagic disease virus (RHDV) and RHDV2.

Rabbit haemorrhagic disease virus (RHDV) is associated with high morbidity and mortality in the European rabbit (Oryctolagus cuniculus). In 2010, a genetically distinct RHDV named RHDV2 emerged in Europe and spread to many other regions, including North America in 2016. Prior to this study it was unknown if eastern cottontails (ECT(s); Sylvilagus floridanus), one of the most common wild lagomorphs in the United States, were susceptible to RHDV2. In this study, 10 wild-caught ECTs and 10 New Zealand white rabbits (NZWR(s); O. cuniculus) were each inoculated orally with either RHDV (RHDVa/GI.1a; n = 5 per species) or RHDV2 (a recombinant GI.1bP-GI.2; n = 5 per species) and monitored for the development of disease. Three of the five ECTs that were infected with RHDV2 developed disease consistent with RHD and died at 4 and 6 days post-inoculation (DPI). The RHDV major capsid protein/antigen (VP60) was detected in the livers of three ECTs infected with RHDV2, but none was detected in the ECTs infected with RHDV. Additionally, RHD viral RNA was detected in the liver, spleen, intestine and blood of ECTs infected with RHDV2, but not in the ECTs infected with RHDV. RHD viral RNA was detected in urine, oral swabs and rectal swabs in at least two of five ECTs infected with RHDV2. One ECT inoculated with RHDV2 seroconverted and developed a high antibody titre by the end of the experimental period (21 DPI). ECTs inoculated with the classic RHDV did not seroconvert. In comparison, NZWRs inoculated with RHDV2 exhibited high mortality (five of five) at 2 DPI and four of five NZWRs inoculated with RHDV either died or were euthanized at 2 DPI indicating both of these viruses were highly pathogenic to this species. This experiment indicates that ECTs are susceptible to RHDV2 and can shed viral RNA, thereby suggesting this species could be involved in the epidemiology of this virus.

Livestock and Risk Group 4 Pathogens: Researching Zoonotic Threats to Public Health and Agriculture in Maximum Containment.

Maximum-containment laboratories are a unique and essential component of the bioeconomy of the United States. These facilities play a critical role in the national infrastructure, supporting research on a select set of especially dangerous pathogens, as well as novel, emerging diseases. Understanding the ecology, biology, and pathology at the human-animal interface of zoonotic spillover events is fundamental to efficient control and elimination of disease. The use of animals as human surrogate models or as target-host models in research is an integral part of unraveling the interrelated components involved in these dynamic systems. These models can prove vitally important in determining both viral- and host-factors associated with virus transmission, providing invaluable information that can be developed into better risk mitigation strategies. In this article, we focus on the use of livestock in maximum-containment, biosafety level-4 agriculture (BSL-4Ag) research involving zoonotic, risk group 4 pathogens and we provide an overview of historical associated research and contributions. Livestock are most commonly used as target-host models in high-consequence, maximum-containment research and are routinely used to establish data to assist in risk assessments. This article highlights the importance of animal use, insights gained, and how this type of research is essential for protecting animal health, food security, and the agriculture economy, as well as human public health in the face of emerging zoonotic pathogens. The utilization of animal models in high-consequence pathogen research and continued expansion to include available species of agricultural importance is essential to deciphering the ecology of emerging and re-emerging infectious diseases, as well as for emergency response and mitigation preparedness.

A Systematic Review of Neuromodulation Treatment Effects on Suicidality.

Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality. Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality. Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality. Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.

Preliminary Evidence for Anhedonia as a Marker of Sexual Trauma in Female Adolescents.

INTRODUCTION: Major depressive disorder (MDD) is a common condition with heterogeneous presentations that often include predominant anhedonia. Previous studies have revealed that childhood trauma is a potent risk factor for the development of MDD; however, the clinical implications of this finding are not fully understood. METHODS: Participants were adolescents (age 13-21 years) with a diagnosis of moderate-to-severe major depressive disorder and healthy controls. We used generalized linear models to assess the relationship between anhedonia severity and trauma severity in a cross-sectional dataset. RESULTS: This cross-sectional analysis of an adolescent sample that underwent clinical evaluations and a trauma assessment, suggested that anhedonia was associated with historical trauma severity. The association between anhedonia and sexual abuse was greater in female participants compared to male participants. DISCUSSION: Our results were partially in line with the reported literature in adult samples. Future studies aiming to characterize the trauma-anhedonia relationship in adolescents should utilize scales designed specifically to measure these constructs in young populations, and scales that assess specific subtypes of anhedonia.

Clinical Characteristics, Outcomes, Disposition, and Acute Care of Children and Adolescents Treated for Acetaminophen Toxicity.

OBJECTIVE: Acetaminophen is a common cause of intentional and inadvertent overdoses among children and adolescents worldwide. Little is known about characteristics and clinical outcomes of these youths. The primary goal of this naturalistic study was to describe the psychiatric characteristics, medical management, outcomes, and dispositions of children and adolescents evaluated for excessive acetaminophen exposure. METHODS: The Rochester Epidemiology Project database was searched for all patients ages 0-18 treated for excessive acetaminophen exposure in Olmsted County, Minnesota, during a 7-year period (2004-2010). Demographic factors, overdose intentionality, medical and psychiatric treatment, mental health and addiction history, and disposition from the emergency department (ED) were documented. RESULTS: Of 110 cases of acetaminophen overdose (89 female patients and 21 male patients), 97 (88%) were intentional and 13 (12%) were unintentional. Fifteen patients (14%) were discharged from the ED, and 69 (63%) required admission to a medical unit. Sixty-four (59%) received N-acetylcysteine. Ninety-eight (89%) were evaluated by psychiatry, and 80 (73%) were admitted for psychiatric hospitalization. Most had at least one psychiatric diagnosis, most commonly depression (55%); 22 (20%) had a prior suicide attempt. Substance use was common, notably alcohol dependence (N=16, 15%), alcohol abuse (N=18, 16%), and cannabis abuse (N=18, 16%). All survived and recovered without liver transplant. CONCLUSIONS: Among pediatric patients with acetaminophen overdoses, psychiatric comorbidities and substance use were common. Most received both inpatient medical and psychiatric treatment. Interventions that restrict acetaminophen access are needed for this population, as are suicide risk reduction interventions for delivery in emergency settings.

The Burden Borne by Protein Methyltransferases: Rates and Equilibria of Non-enzymatic Methylation of Amino Acid Side Chains by SAM in Water.

SAM is a powerful methylating agent, with a methyl group transfer potential matching the phosphoryl group transfer potential of ATP. SAM-dependent N-methyltransferases have evolved to catalyze the modification of specific lysine residues in histones and transcription factors, in addition to generating epinephrine, N-methylnicotinamide, and a quaternary amine (betaine) that is used to maintain osmotic pressure in plants and halophilic bacteria. To assess the catalytic power of these enzymes and their potential susceptibility to transition state and multisubstrate analogue inhibitors, we determined the rates and positions of the equilibrium of methyl transfer from the trimethylsulfonium ion to model amines in the absence of a catalyst. Unlike the methyl group transfer potential of SAM, which becomes more negative with an increase in pH throughout the normal pH range, equilibrium constants for the hydrolytic demethylation of secondary, tertiary, and quaternary amines are found to be insensitive to a change in pH and resemble each other in magnitude, with an average ΔG value of approximately -0.7 kcal/mol at pH 7. Thus, each of the three steps in the mono-, di-, and trimethylation of lysine by SAM is accompanied by a change in free energy of -7.5 kcal/mol in a neutral solution. Arrhenius analysis of the uncatalyzed reactions shows that the unprotonated form of glycine attacks the trimethylsulfonium ion (TMS+) with second-order rates constant of 1.8 × 10-7 M-1 s-1 at 25 °C (ΔH⧧ = 22 kcal/mol, and TΔS⧧ = -6 kcal/mol). Comparable values are observed for the methylation of secondary and tertiary amines, with k25 values of 1.1 × 10-7 M-1 s-1 for sarcosine and 4.3 × 10-8 M-1 s-1 for dimethylglycine. The non-enzymatic methylations of imidazole and methionine by TMS+, benchmarks for the methylation of histidine and methionine residues by SETD3, exhibit k25 values of 3.3 × 10-9 and 1.2 × 10-9 M-1 s-1, respectively. Lysine methylation by SAM, although slow under physiological conditions (t1/2 = 7 weeks at 25 °C), is accelerated 1.1 × 1012 -fold at the active site of a SET domain methyltransferase.

A pilot spectroscopy study of adversity in adolescents.

Background: Childhood adversity is a global health problem affecting 25-50% of children worldwide. Few prior studies have examined the underlying neurochemistry of adversity in adolescents. This cross-sectional study examined spectroscopic markers of trauma in a cohort of adolescents with major depressive disorder (MDD) and healthy controls. We hypothesized that historical adversity would have a negative relationship with spectroscopic measures of glutamate metabolites in anterior cingulate cortex. Methods: Adolescent participants (aged 13-21) underwent a semi-structured diagnostic interview and clinical assessment, which included the self-report Childhood Trauma Questionnaire (CTQ), a 28-item assessment of childhood adversity. Proton magnetic resonance spectroscopy (1H-MRS) scans at 3 Tesla of an anterior cingulate cortex (ACC) voxel (8 cm3) encompassing both hemispheres were collected using a 2-dimensional J-averaged sequence to assess N-acetylaspartate (NAA), Glx (glutamate+glutamine) and [NAA]/[Glx] concentrations. Generalized linear models assessed the relationships between CTQ scores and metabolite levels in ACC. Results: Thirty-nine participants (17 healthy controls, 22 depressed participants) underwent 1H-MRS and completed the CTQ measures. There were decrements in [NAA]/[Glx] ratio in the ACC of participants with childhood adversity while no significant relationship between CTQ total score and any of the ACC metabolites was found in the combined sample. Exploratory results revealed a positive association between Glx levels and CTQ scores in depressed participants. Conversely the [NAA]/[Glx] ratio had a negative association with total CTQ scores in the depressed participants. Emotional Abuse Scale showed a significant negative relationship with [NAA]/[Glx] ratio in the combined sample when adjusted for depression severity. Conclusions: Our findings suggest that childhood adversity may impact brain neurochemical profiles. Further longitudinal studies should examine neurochemical correlates of childhood adversity throughout development and in populations with other psychiatric disorders.

Susceptibility of Domestic Swine to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease, has been shown to infect several species. The role of domestic livestock and associated risks for humans in close contact with food production animals remains unknown for many species. Determining the susceptibility of pigs to SARS-CoV-2 is critical to a One Health approach to manage potential risk for zoonotic transmission. We found that pigs are susceptible to SARS-CoV-2 after oronasal inoculation. Among 16 animals, we detected viral RNA in group oral fluids and in nasal wash from 2 pigs, but live virus was isolated from only 1 pig. Antibodies also were detected in only 2 animals at 11 and 13 days postinoculation but were detected in oral fluid samples at 6 days postinoculation, indicating antibody secretion. These data highlight the need for additional livestock assessment to determine the potential role of domestic animals in the SARS-CoV-2 pandemic.

Challenges in Having Vaccines Available to Control Transboundary Diseases of Livestock.

The global human population is growing at a rapid rate leading to the need for continued expansion of food animal production to meet the world's increasing nutritional requirements. As a consequence of this increased production demand, the use of high volume, animal dense systems have expanded providing high quality protein at reduced costs. Backyard animal production has also expanded. This increased food animal production has facilitated the rapid spread, mutation, and adaptation of pathogens to new hosts. This scenario continues to drive the emergence and reemergence of diseases in livestock species increasing the urgency for development and availability of vaccines for transboundary animal diseases (TADs). Even though vaccines are widely recognized as being an essential tool for control of TADs, there are many scientific, economic, political, and logistical challenges to having vaccine available to control an outbreak. This article will focus on examples of the challenges associated with having vaccines available for emergency response, as well as the characteristics of 'ideal' TAD vaccines, the need for complementary diagnostic assays, and hurdles involved in bringing efficacious veterinary TAD vaccines to market including regulatory constraints and considerations for stockpiling vaccines for emergency use in non-endemic countries. Examples will also highlight the complicated interplay between animal health and human health and demonstrate the lasting benefits that can be gained from an efficacious vaccine.

Glutamatergic Correlates of Bipolar Symptoms in Adolescents.

Objectives: Prior studies demonstrate elevated cortical glutamate (Glu) in patients with bipolar disorder (BD). Studies assessing neurochemistry in early stages of bipolar illness before the emergence of manic symptoms are lacking. This study aimed to examine neurochemical correlates measured by proton magnetic resonance spectroscopy (1H-MRS) and a dimensional measure of bipolarity in a sample of depressed adolescents. Methods: Adolescent participants (aged 13-21 years) underwent a semistructured diagnostic interview and clinical assessment, which included the General Behavior Inventory Parent Version (P-GBI), a 73-item, parent-rated assessment of symptoms and behaviors. 1H-MRS scans of a left dorsolateral prefrontal cortex (L-DLPFC) voxel (8 cm3) were collected using a two-dimensional J-averaged sequence to assess N-acetylaspartate (NAA), Glu, Glx (glutamate + glutamine), and NAA/Glx concentrations. We used generalized linear models to assess the relationships between P-GBI scores and metabolite levels in L-DLPFC. Results: Thirty-six participants (17 healthy controls, 19 depressed) underwent 1H-MRS scans and clinical evaluation with the P-GBI. There was a significant negative relationship between P-GBI score and L-DLPFC NAA/Glx in the whole sample. However, the magnitude of the effect was small and statistical significance was lost after correcting for multiple comparisons. Conclusions: These preliminary results suggest that NAA/Glx may have utility as a marker of bipolar traits in healthy and depressed adolescents. If replicated, 1H-MRS measures of glutamatergic metabolism anomalies might have a role in identifying depressed adolescents at risk for mixed symptom presentations or BD. Identifying bipolarity in the early stages of the disease would have a significant impact on treatment planning and prognosis. Further longitudinal studies should examine neurochemical correlates of mood state during the developmental emergence of BD.

Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation.

The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (1H-MRS) at 3 T, utilizing a 2-dimensional J-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC, n = 16), depressed without SI (Dep/SI-, n = 13), and depressed with SI (Dep/SI+, n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and the N-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI- and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI- participants (padj = 0.012) and had lower NAA/Glx than both Dep/SI- (padj = 0.002) and HC adolescents (padj = 0.039). There were significant relationships between SI intensity and Glx (pFDR = 0.026), SI severity and NAA/Glx (pFDR = 0.012), and SI intensity and NAA/Glx (pFDR = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI- from Dep/SI+ participants. Uncoupled NAA-glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.

Impacts of dibenzopyrenes on bacterial community isolated from Gulf of Mexico sediment.

The presence of polycyclic aromatic hydrocarbons (PAHs) in marine environments as a result of contamination is an environmental concern, especially in regions where oil spills such as the Deepwater Horizon have occurred. While numerous PAHs have been studied for their effects on microbes, the family of dibenzopyrenes has yet to be investigated. In this preliminary study, the impacts of these molecules on the community structure of a bacterial consortium isolated from oil-impacted Gulf of Mexico sediment were examined using high-throughput sequencing, demonstrating intriguing negative impacts on species diversity and abundance. While no measurable degradation of the dibenzopyrenes was observed after 28-day incubation, the abundance of known oil-degrading bacteria from orders such as Oceanospirillales, Caulobacterales, Sphingomonadales, and Nitrosococcales were shown to be enhanced. Of the five isomers of dibenzopyrene studied, dibenzo[a,h]pyrene supported the fewer number of microbial species suggesting the isomer was more toxic compared to the other isomers.