Correction to: Amanita Mushroom Toxin Poisoning in Los Angeles County.

[This corrects the article DOI: 10.14309/crj.0000000000001246.].

Amanita Mushroom Toxin Poisoning in Los Angeles County.

Mushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis. We report a case of amatoxin poisoning in Los Angeles causing severe liver injury without acute liver failure treated successfully using medical therapies, gallbladder drainage, and plasma exchange.

Association between anesthesia technique and death after hip fracture repair for patients with COVID-19.

PURPOSE: Patients with COVID-19 undergoing hip fracture surgeries have a 30-day mortality of up to 34%. We aimed to evaluate the association between anesthesia technique and 30-day mortality after hip fracture surgery in patients with COVID-19. METHODS: After ethics approval, we performed a retrospective cohort analysis of the American College of Surgeons National Surgical Quality Improvement Program data set from January to December 2021. Inclusion criteria were age ≥ 19 yr, laboratory-confirmed SARS-CoV-2 infection within 14 days preoperatively, and hip fracture surgery under general anesthesia (GA) or spinal anesthesia (SA). Exclusion criteria were American Society of Anesthesiologists Physical Status V, ventilator dependence, international normalized ratio ≥ 1.5, partial thromboplastin time > 35 sec, and platelet count < 80 × 109 L-1. The primary outcome was all-cause 30-day mortality. The adjusted association between anesthetic technique and 30-day mortality was analyzed using multivariable logistic regression. RESULTS: Of 23,045 patients undergoing hip fracture surgery, 331 patients met the study criteria. The median [interquartile range] age was 82 [74-88] yr, and 32.3% were male. The 30-day mortality rate was 10.0% (33/331) for the cohort (10.7%, 29/272 for GA vs 6.8%, 4/59 for SA; P = 0.51; standardized mean difference, 0.138). The use of SA, compared with GA, was not associated with decreased mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.21 to 1.8; E-value, 2.49). CONCLUSION: Anesthesia technique was not associated with mortality in patients with COVID-19 undergoing hip fracture surgery. The findings were limited by a small sample size. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT05133648); registered 24 November 2021.

RéSUMé: OBJECTIF: Les personnes atteintes de COVID-19 bénéficiant d'une chirurgie de fracture de la hanche ont une mortalité à 30 jours allant jusqu'à 34 %. Notre objectif était d'évaluer l'association entre la technique d'anesthésie et la mortalité à 30 jours après une chirurgie de fracture de la hanche chez les personnes atteintes de COVID-19. MéTHODE: Après l'approbation du comité d'éthique, nous avons réalisé une analyse de cohorte rétrospective de l'ensemble de données du Programme national d'amélioration de la qualité chirurgicale de l'American College of Surgeons de janvier à décembre 2021. Les critères d'inclusion étaient un âge ≥ 19 ans, une infection par le SRAS-CoV-2 confirmée en laboratoire dans les 14 jours préopératoires et une chirurgie de fracture de la hanche sous anesthésie générale (AG) ou rachianesthésie (RA). Les critères d'exclusion étaient un statut physique V selon l'American Society of Anesthesiologists, la dépendance à une assistance ventilatoire, un ratio international normalisé ≥ 1,5, un temps de thromboplastine partielle > 35 sec, et une numération plaquettaire < 80 × 109 L−1. Le critère d'évaluation principal était la mortalité à 30 jours toutes causes confondues. L'association ajustée entre la technique anesthésique et la mortalité à 30 jours a été analysée à l'aide d'une régression logistique multivariée. RéSULTATS: Sur 23 045 patient·es opéré·es pour une fracture de la hanche, 331 répondaient aux critères de l'étude. L'âge médian (écart interquartile) était de 82 [74­88] ans et 32,3 % étaient des hommes. Le taux de mortalité à 30 jours était de 10,0 % (33/331) pour la cohorte (10,7 %, 29/272 pour l'AG vs 6,8 %, 4/59 pour la RA; P = 0,51; différence moyenne standardisée, 0,138). L'utilisation de la RA, par rapport à l'AG, n'a pas été associée à une diminution de la mortalité (rapport de cotes ajusté, 0,61; intervalle de confiance à 95 %, 0,21 à 1,8; valeur E, 2,49). CONCLUSION: La technique d'anesthésie n'a pas été associée à la mortalité chez les personnes atteintes de COVID-19 bénéficiant d'une chirurgie de fracture de la hanche. Les résultats ont été limités par la petite taille de l'échantillon. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT05133648); enregistrée le 24 novembre 2021.

Australian dental practitioners experience of burnout.

BACKGROUND: The aim of this study was to investigate factors associated with burnout in Australian dental practitioners. METHODS: A cross-sectional survey of 1483 Australian dental practitioners was conducted from Oct to Dec 2021. Participants reported burnout using the Sydney Burnout Measure, and aspects of mental health including psychological distress, depression, and anxiety disorders. Predictors of burnout were explored using a generalized linear model with a stepped approach including demographic, health and risk factor variables. RESULTS: One in four participants were classified as likely to be experiencing burnout. Burnout was associated with working in a regional/rural location (ß = 2.82, p < 0.001), an academic/non-clinical role (ß = 5.01, p = 0.037), more years of experience as a dental practitioner (ß = 0.08, p = 0.022), a current diagnosis of depression (ß = 2.38, p = 0.049), moderate/severe psychological distress (ß = 7.16, p < 0.001), poor self-rated physical health (ß = 5.84, p < 0.001) and increasing alcohol consumption (ß = 0.17, p = 0.020). Participants who scored high on resilience (ß = -0.23, p = 0.002) or perfectionism (ß = -0.24, p < 0.001) had lower burnout scores. CONCLUSION: Australian dental practitioners appear to be at high risk of burnout which may impact on their health and wellbeing and ability to deliver patient care. There is a need for support services to manage burnout and education to address workplace and environmental factors that may contribute to burnout.

Mental health, psychological distress and burnout in Australian dental practitioners.

BACKGROUND: Dental practitioners are known to experience a high level of stress, but little is known about the mental health of Australian dental practitioners. The aim of this study was to investigate the prevalence of mental health conditions among Australian dental practitioners. METHODS: A cross sectional survey of 1483 Australian dental practitioners was carried out from October to December 2021. Participants reported aspects of mental health including depression, anxiety disorder, burnout (Sydney Burnout Measure) and psychological distress (Kessler Psychological Distress Scale and General Health Questionnaire 12). RESULTS: Self-reported psychological distress was high, with 32.0% rated as having moderate or severe psychological distress and 59.4% a high likelihood of minor (or more severe) psychological distress. One in four participants (24.8%) were classified as likely to be experiencing burnout, with 25.9% reporting ever having a diagnosis of depression, 11.4% a current diagnosis of depression, 23.1% ever having a diagnosis of anxiety disorder and 12.9% a current diagnosis of anxiety disorder. CONCLUSION: Australian dental practitioners reported a high burden of psychological distress, burnout and mental health issues, suggesting a need for education and programmes to support their mental health and wellbeing. © 2023 Australian Dental Association.

Changes in white matter microstructure and MRI-derived cerebral blood flow after 1-week of exercise training.

Exercise is beneficial for brain health, inducing neuroplasticity and vascular plasticity in the hippocampus, which is possibly mediated by brain-derived neurotrophic factor (BDNF) levels. Here we investigated the short-term effects of exercise, to determine if a 1-week intervention is sufficient to induce brain changes. Fifteen healthy young males completed five supervised exercise training sessions over seven days. This was preceded and followed by a multi-modal magnetic resonance imaging (MRI) scan (diffusion-weighted MRI, perfusion-weighted MRI, dual-calibrated functional MRI) acquired 1 week apart, and blood sampling for BDNF. A diffusion tractography analysis showed, after exercise, a significant reduction relative to baseline in restricted fraction-an axon-specific metric-in the corpus callosum, uncinate fasciculus, and parahippocampal cingulum. A voxel-based approach found an increase in fractional anisotropy and reduction in radial diffusivity symmetrically, in voxels predominantly localised in the corpus callosum. A selective increase in hippocampal blood flow was found following exercise, with no change in vascular reactivity. BDNF levels were not altered. Thus, we demonstrate that 1 week of exercise is sufficient to induce microstructural and vascular brain changes on a group level, independent of BDNF, providing new insight into the temporal dynamics of plasticity, necessary to exploit the therapeutic potential of exercise.

The Interface between Cell Signaling Pathways and Pregnane X Receptor.

Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity.

The Frontal Aslant Tract and Supplementary Motor Area Syndrome: Moving towards a Connectomic Initiation Axis.

Connectomics is the use of big data to map the brain's neural infrastructure; employing such technology to improve surgical planning may improve neuro-oncological outcomes. Supplementary motor area (SMA) syndrome is a well-known complication of medial frontal lobe surgery. The 'localizationist' view posits that damage to the posteromedial bank of the superior frontal gyrus (SFG) is the basis of SMA syndrome. However, surgical experience within the frontal lobe suggests that this is not entirely true. In a study on n = 45 patients undergoing frontal lobe glioma surgery, we sought to determine if a 'connectomic' or network-based approach can decrease the likelihood of SMA syndrome. The control group (n = 23) underwent surgery avoiding the posterior bank of the SFG while the treatment group (n = 22) underwent mapping of the SMA network and Frontal Aslant Tract (FAT) using network analysis and DTI tractography. Patient outcomes were assessed post operatively and in subsequent follow-ups. Fewer patients (8.3%) in the treatment group experienced transient SMA syndrome compared to the control group (47%) (p = 0.003). There was no statistically significant difference found between the occurrence of permanent SMA syndrome between control and treatment groups. We demonstrate how utilizing tractography and a network-based approach decreases the likelihood of transient SMA syndrome during medial frontal glioma surgery. We found that not transecting the FAT and the SMA system improved outcomes which may be important for functional outcomes and patient quality of life.

Time-resolved nanosecond optical pyrometry of the vapor to plasma transitions in exploding bridgewires.

Electrically exploded wires find uses throughout high-energy physics. For example, they are commonly used as high-temperature sources, X-ray generators, and in precision timing detonators. However, the detailed and complete physics that occurs is complex and still poorly understood. A full mechanistic description of these complex phenomena is beyond the scope of a single paper. Instead, we focus on the formation of metal vapor and its transition to plasma. This single transition is commonly assumed to comprise "bridge-burst". We use a suite of diagnostics including a novel, fiber-based, high-speed, optical pyrometer to better characterize this transition. The primary finding from this project is that peak light output from an exploding wire does not temporally match the peak temperature. Additionally, it is found that peak light does not align with peak bridge-burst voltage and that the peak temperature is not voltage-dependent. These findings are non-intuitive and will allow for the correction of false assumptions previously made about this topic.

Acoustic shock: an update review.

BACKGROUND: This paper discusses the concept of acoustic shock based on a literature review and the results of our own research into cases seen in both clinical and medicolegal practice. With the demise of traditional 'metal bashing' and 'smoke stack' heavy industries, there has been a decline in the incidence of noise-induced hearing loss and tinnitus in this form of employment. However, with the increasing establishment of call centre work, the emergence of acoustic shock has been noted. Acoustic shock is recognised as a clinical entity distinct from noise-induced hearing loss and acoustic trauma. OBJECTIVE: This article discusses clinical implications, medicolegal considerations in light of a recent high-profile court case and proposed criteria for diagnosis.

Best practices for after-action review: turning lessons observed into lessons learned for preparedness policy.

All-hazards preparedness and response planning requires ongoing individual, organisational and multi-jurisdictional learning. Disaster after-action reviews are an established emergency management practice to acquire knowledge through a process of analysing what happened and why, to improve the emergency response before the next crisis. After-action reviews help individuals and organisations learn, and are an essential step in the preparedness cycle. Human and animal health authorities have begun to employ after-action reviews for disaster preparedness and response among public health and Veterinary Services. The World Organisation for Animal Health (OIE) encourages Members to establish after-action reviews and share best practice. The adoption of afteraction review is an essential step for all provincial, national and multinational emergency management authorities to mitigate the impact of disasters on human and animal health. Emerging and re-emerging infectious diseases with pandemic potential pose unique preparedness challenges, requiring high-level policy attention to close long-standing gaps. A review of after-action reports from the 2001 anthrax bioterror attacks and of naturally occurring infectious disease crises, from the 2003 outbreak of severe acute respiratory syndrome (SARS) to the 2014 Ebola epidemic, reveal a similar pattern of repeated weakness and failures. These phenomena are described as 'lessons observed but not lessons learned'. Most infectious disease outbreaks with pandemic potential are zoonotic and require a One Health approach to prevent, prepare for and respond to global health security crises. After-action reviews in a One Health security context are essential to improve the pandemic preparedness of public health and Veterinary Services. After-action reviews can also provide the evidence-based 'feedback loop' needed to galvanise public policy and political will to translate lessons observed into sustained and applied lessons learned.

La planification de la préparation et de la réponse à tous les risques est un processus qui exige un apprentissage permanent tant à l'échelle des individus que des organisations et des différentes autorités compétentes. Les retours d'expérience (ou « revues après action¼) suite à une catastrophe constituent un exercice éprouvé de gestion des urgences visant à acquérir de nouvelles connaissances en procédant à l'analyse de ce qui est arrivé et des raisons pour lesquelles c'est arrivé, dans le but d'améliorer les capacités d'intervention d'urgence avant que ne survienne la prochaine crise. Les individus et les organisations trouvent dans ces retours un cadre pour tirer des enseignements de leur expérience, ce qui constitue une étape essentielle du cycle de préparation. Les autorités en charge de la santé humaine et de la santé animale ont commencé à utiliser les retours d'expérience pour planifier la préparation et la réponse au sein des Services de santé publique et des Services vétérinaires. L'Organisation mondiale de la santé animale (OIE) encourage ses Membres à mettre en place des retours d'expérience et à partager les meilleures pratiques en la matière. L'analyse des retours d'expérience est une étape cruciale pour que les autorités en charge de la gestion des urgences à l'échelle provinciale, nationale et internationale puissent atténuer l'impact des catastrophes sur la santé humaine et animale. Les maladies émergentes et ré-émergentes ayant un potentiel pandémique posent des défis exceptionnels en termes de préparation et exigent des prises de décision de haut niveau afin de pallier des lacunes souvent anciennes. L'examen des retours d'expérience datant des attentats terroristes à l'anthrax de 2001 et des crises sanitaires dues à des maladies infectieuses d'origine naturelle (depuis l'épidémie du syndrome respiratoire aigu sévère [SRAS] en 2003 jusqu'à l'épidémie d'Ebola en 2014) révèle des caractéristiques toujours similaires, avec à chaque fois les mêmes faiblesses et les mêmes écueils. Ce phénomène correspond à ce que l'on peut appeler des « leçons observées mais non apprises ¼. Compte tenu de la nature zoonotique de la plupart des foyers de maladies infectieuses ayant un potentiel pandémique, c'est l'approche Une seule santé qui doit prévaloir en matière de prévention, de préparation et de réponse aux crises de sécurité sanitaire d'envergure mondiale. Les retours d'expérience dans un contexte de sécurité Une seule santé sont essentiels pour améliorer la préparation des Services de santé publique et des Services vétérinaires aux pandémies. En outre, les « boucles de réaction¼ fondées sur des éléments factuels résultant des retours d'expérience apportent un éclairage indispensable pour inciter les pouvoirs publics à élaborer des mesures appropriées et pour créer la volonté politique de traduire les leçons observées en leçons durablement apprises et appliquées.

La planificación de las labores de preparación y respuesta ante toda clase de peligros exige un permanente aprendizaje tanto personal como institucional y desde múltiples competencias. El examen de las intervenciones tras un desastre constituye un arraigado proceder de gestión de emergencias que sirve para aprender de la experiencia analizando el cómo y el porqué de lo sucedido y, a partir de ahí, mejorar los procesos de respuesta de emergencia antes de que advenga la siguiente crisis. Estos exámenes posteriores a las intervenciones, que ayudan a las personas y organizaciones a aprender, son una etapa fundamental del ciclo de preparación. Las autoridades sanitarias y zoosanitarias han empezado a utilizarlos en los servicios de salud pública y los Servicios Veterinarios con fines de preparación y respuesta para casos de desastre. La Organización Mundial de Sanidad Animal (OIE) alienta a sus Miembros a que establezcan este tipo de exámenes y pongan en común prácticas óptimas al respecto. La implantación del examen posterior a las intervenciones es un paso esencial para que todas las autoridades provinciales, nacionales e internacionales de gestión de emergencias estén en condiciones de mitigar los efectos sanitarios y zoosanitarios de un desastre. Las enfermedades infecciosas emergentes y reemergentes con potencial pandémico plantean singulares problemas de preparación, que requieren una atención y una labor normativa de alto nivel para solventar carencias históricas. El examen de los informes posteriores a las actuaciones de respuesta a los ataques bioterroristas perpetrados en 2001 con bacterias de carbunco (ántrax) y a crisis infecciosas de origen natural, desde el brote registrado en 2003 de síndrome respiratorio agudo severo (SRAS) hasta la epidemia causada por el virus del Ébola en 2014, revela un parecido patrón de fallos y carencias que se van repitiendo, fenómeno que se describe como «hechos observados sin enseñanzas extraídas¼. La mayoría de los brotes de enfermedades infecciosas con potencial pandémico son zoonóticos y exigen la aplicación de la lógica de Una sola salud para prevenir crisis sanitarias de dimensión mundial, prepararse para ellas y darles respuesta. Los exámenes posteriores a una intervención inscritos en el contexto de seguridad sanitaria de Una sola salud son esenciales para mejorar la preparación de los servicios de salud pública y los Servicios Veterinarios para episodios de pandemia. Estos procesos de examen también pueden alimentar con datos científicos el «ciclo de retroalimentación¼ que se requiere para galvanizar las políticas públicas y la voluntad política de traducir los hechos observados en enseñanzas extraídas que sean duraderas y se apliquen en la práctica.

Predicting vertical ground reaction force during running using novel piezoresponsive sensors and accelerometry.

Running is a common exercise with numerous health benefits. Vertical ground reaction force (vGRF) influences running injury risk and running performance. Measurement of vGRF during running is now primarily constrained to a laboratory setting. The purpose of this study was to evaluate a new approach to measuring vGRF during running. This approach can be used outside of the laboratory and involves running shoes instrumented with novel piezoresponsive sensors and a standard accelerometer. Thirty-one individuals ran at three different speeds on a force-instrumented treadmill while wearing the instrumented running shoes. vGRF was predicted using data collected from the instrumented shoes, and predicted vGRF were compared to vGRF measured via the treadmill. Per cent error of the resulting predictions varied depending upon the predicted vGRF characteristic. Per cent error was relatively low for predicted vGRF impulse (2-7%), active peak vGRF (3-7%), and ground contact time (3-6%), but relatively high for predicted vGRF load rates (22-29%). These errors should decrease with future iterations of the instrumented shoes and collection of additional data from a more diverse sample. The novel technology described herein might become a feasible way to collect large amounts of vGRF data outside of the traditional biomechanics laboratory.

An Eyebrow, Supracarotid Triangle Approach for Lesions at the Ventral Thalamopeduncular Junction: A Technical Report.

BACKGROUND: Lesions arising at the ventral thalamopeduncular junction are difficult to resect. In addition to being relatively inaccessible, these lesions are located in one of the most sensitive areas of the brain. A critical question is whether new approaches could be developed to allow surgeons to adequately resect these lesions with reasonable outcomes. In the present report, we describe our approach to resect lesions in this region of the brain using an eyebrow craniotomy approach with a trajectory through the supracarotid triangle. METHODS: Through retrospective data collection, we present a small series of patients who had undergone an eyebrow, supracarotid triangle approach to resect lesions located at the thalamopeduncular junction. We describe our surgical technique and report patient outcomes using this approach. RESULTS: Three patients had undergone an eyebrow, supracarotid approach for resection of a lesion arising at the ventral thalamopeduncular junction. Two patients had presented with a cavernoma and one with a pilocytic astrocytoma. Complete resection of all 3 lesions was achieved during surgery without any intraoperative complications. No patient developed permanent contralateral weakness despite entering the peduncle during surgery. One patient developed permanent paresthesia in his left hand. CONCLUSIONS: Lesions arising at the ventral thalamopeduncular junction can be adequately resected with reasonable outcomes using an eyebrow, supracarotid triangle approach. This operative technique establishes another potential operative corridor by which neurosurgeons can resect lesions arising within this relatively inaccessible part of the brain.

Refined diagnostic criteria for the bipolar disorders: phase two of the AREDOC project.

OBJECTIVE: As limitations exist across DSM criteria sets for defining and differentiating the bipolar disorders generally and their component bipolar I (BP-1) and bipolar II (BP-II) sub-types, we sought to generate empirically based criteria. METHOD: We formed an international Task Force (TF) comprising members with bipolar disorder expertise, and who recruited 74 patients with a TF-diagnosed bipolar I and 104 with a bipolar II condition (with patients responding to definitional queries and symptom questionnaires), while 33 unipolar depressed patients recruited by the first author also completed the symptom questionnaire. A factor analysis sought to determine granular hypo/manic constructs. RESULTS: The bipolar disorder subjects strongly affirmed a new general definition of a bipolar disorder (capturing both manic and hypomanic episodes). While DSM-5 requires impaired functioning, we established that a high percentage of individuals with a BP-I or a BP-II disorder reported improved functioning and therefore modified this criterion. Analyses identified syptoms with differential high rates in individuals with bipolar disorder and its sub-types (and thus not simply capturing happiness), while a factor analysis generated seven symptom constructs both linked with and differing from DSM-5 bipolar symptom criteria. CONCLUSION: This second-stage report details a new set of criteria for differentiating the bipolar disorders from unipolar depressive conditions, while arguing for BP-I and BP-II disorders being differentiated principally by the respective presence or absence of psychotic features. Future studies will evaluate whether further modifications are required and examine for differential treatment benefits for those with a BP-I versus a BP-II condition.

Uncovering a Role for the Dorsal Hippocampal Commissure in Recognition Memory.

The dorsal hippocampal commissure (DHC) is a white matter tract that provides interhemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted magnetic resonance imaging (DW-MRI) and white matter tractography to reconstruct the DHC in both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings demonstrate a close consistency between the known anatomy and tract reconstructions of the DHC. Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in nonhuman primates. Finally, we derived diffusion tensor MRI metrics from the DHC in a large sample of human subjects to investigate whether interindividual variation in DHC microstructure is predictive of memory performance. The mean diffusivity of the DHC correlated with performance in a standardized recognition memory task, an effect that was not reproduced in a comparison commissure tract-the anterior commissure. These findings highlight a potential role for the DHC in recognition memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease.

Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage.

Tyrosyl-tRNA synthetase ligates tyrosine to its cognate tRNA in the cytoplasm, but it can also be secreted through a noncanonical pathway. We found that extracellular tyrosyl-tRNA synthetase (YRS) exhibited proinflammatory activities. In addition to acting as a monocyte/macrophage chemoattractant, YRS initiated signaling through Toll-like receptor 2 (TLR2) resulting in NF-κB activation and release of tumor necrosis factor α (TNFα) and multiple chemokines, including MIP-1α/ß, CXCL8 (IL8), and CXCL1 (KC) from THP1 monocyte and peripheral blood mononuclear cell-derived macrophages. Furthermore, YRS up-regulated matrix metalloproteinase (MMP) activity in a TNFα-dependent manner in M0 macrophages. Because MMPs process a variety of intracellular proteins that also exhibit extracellular moonlighting functions, we profiled 10 MMPs for YRS cleavage and identified 55 cleavage sites by amino-terminal oriented mass spectrometry of substrates (ATOMS) positional proteomics and Edman degradation. Stable proteoforms resulted from cleavages near the start of the YRS C-terminal EMAPII domain. All of the MMPs tested cleaved at ADS386↓387LYV and VSG405↓406LVQ, generating 43- and 45-kDa fragments. The highest catalytic efficiency for YRS was demonstrated by MMP7, which is highly expressed by monocytes and macrophages, and by neutrophil-specific MMP8. MMP-cleaved YRS enhanced TLR2 signaling, increased TNFα secretion from macrophages, and amplified monocyte/macrophage chemotaxis compared with unprocessed YRS. The cleavage of YRS by MMP8, but not MMP7, was inhibited by tyrosine, a substrate of the YRS aminoacylation reaction. Overall, the proinflammatory activity of YRS is enhanced by MMP cleavage, which we suggest forms a feed-forward mechanism to promote inflammation.

Differentiating clinical and non-clinical depression: a heuristic study offering a template for extension studies.

OBJECTIVE: To differentiate clinical and non-clinical depression via a set of symptoms. METHODS: A sample of 140 patients attending a clinical service for those with mood disorders together with 40 subjects denying ever experiencing a clinical episode of depression were compared, with participants completing a questionnaire capturing many symptoms of depression as well as illness correlates. RESULTS: A latent class analysis of symptom data identified two classes and with class assignment corresponding strongly with initial clinical vs. non-clinical assignment. Univariate analyses identified the extent to which individual symptoms contributed to differentiation. Study data suggested DSM criteria that would benefit from re-writing or of reassignment. Two models for classifying clinical depression were generated. The first involved individuals feeling hopeless and also being suicidal or at risk of self-harm. The second involved a symptom set corresponding to DSM-5 criteria but with only five making significant independent contributions to diagnostic differentiation. CONCLUSION: The study is heuristic in offering a strategy for more precisely differentiating clinical and non-clinical depression in more representative samples, so allowing resolution of key features, and determining whether a monothetic or polythetic diagnostic symptom criterion model is optimal.

Parcellation-based tractographic modeling of the ventral attention network.

INTRODUCTION: The ventral attention network (VAN) is an important mediator of stimulus-driven attention. Multiple cortical areas, such as the middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and temporo-parietal junction have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity. METHODS: Using relevant task-based fMRI studies, an activation likelihood estimation (ALE) of the VAN was generated Regions of interest corresponding to the HCP cortical parcellation scheme were co-registered onto this ALE in MNI coordinate space and visually assessed for inclusion in the network. DSI-based fiber tractography was performed to determine the structural connections between cortical areas comprising the VAN. RESULTS: Fourteen regions within the right cerebral hemisphere were found to overlap the ALE of the VAN: 6a, 6r, 7AM, 7PM, 8C, AVI, FOP4, MIP, p9-46v, PCV, PFm, PGi, TPOJ1, and TPOJ2. Regions demonstrated consistent U-shaped interconnections between adjacent parcellations, and the SLF was found to connect frontal and parietal areas of the network. CONCLUSIONS: We present a tractographic model of the VAN. This model comprises parcellations within the frontal and parietal cortices that are linked via the SLF. Future studies may refine this model with the ultimate goal of clinical application.

Differentiating borderline personality disorder (BPD) from bipolar disorder: diagnostic efficiency of DSM BPD criteria.

OBJECTIVE: We sought to determine the differential diagnostic efficiency of all DSM-IV borderline personality disorder (BPD) criteria by studying a sample of those with BPD and a contrast group with a bipolar disorder (BP). METHOD: Participants were clinically assessed and assigned diagnoses based on DSM criteria - with prevalence rates and diagnostic efficiency values calculated. RESULTS: Fifty-three participants were assigned a BPD diagnosis, 83 a BP diagnosis, with comorbid participants excluded. The mean number of DSM BPD criteria assigned was 6.6 (SD = 1.0) in the BPD group and 1.9 (SD = 1.3) in the BP group. The most prevalent criterion in the BPD group was 'affective instability' (AI) (92.5%), with 'inappropriate anger' least endorsed (49%). The highest specificity criterion was 'abandonment fears', which displayed the greatest positive predictive value (PPV) = 0.9, and with AI offering the lowest specificity. 'Unstable relationships' had the highest overall negative predictive value (NPV) = 0.91. The highest percentage accuracy of classification was provided by 'identity disturbance' and 'abandonment fears' criteria, both 85%. CONCLUSION: The transdiagnostic nature of 'affective instability' means it is less useful for diagnostic decisions, whereas 'abandonment fears' and 'identity disturbance' offer superior diagnostic efficiency in distinguishing BPD from BP.