A facial expression for anxiety.

Anxiety and fear are often confounded in discussions of human emotions. However, studies of rodent defensive reactions under naturalistic conditions suggest anxiety is functionally distinct from fear. Unambiguous threats, such as predators, elicit flight from rodents (if an escape-route is available), whereas ambiguous threats (e.g., the odor of a predator) elicit risk assessment behavior, which is associated with anxiety as it is preferentially modulated by anti-anxiety drugs. However, without human evidence, it would be premature to assume that rodent-based psychological models are valid for humans. We tested the human validity of the risk assessment explanation for anxiety by presenting 8 volunteers with emotive scenarios and asking them to pose facial expressions. Photographs and videos of these expressions were shown to 40 participants who matched them to the scenarios and labeled each expression. Scenarios describing ambiguous threats were preferentially matched to the facial expression posed in response to the same scenario type. This expression consisted of two plausible environmental-scanning behaviors (eye darts and head swivels) and was labeled as anxiety, not fear. The facial expression elicited by unambiguous threat scenarios was labeled as fear. The emotion labels generated were then presented to another 18 participants who matched them back to photographs of the facial expressions. This back-matching of labels to faces also linked anxiety to the environmental-scanning face rather than fear face. Results therefore suggest that anxiety produces a distinct facial expression and that it has adaptive value in situations that are ambiguously threatening, supporting a functional, risk-assessing explanation for human anxiet

Measuring agreement between decision support reminders: the cloud vs. the local expert

Background: A cloud-based clinical decision support system (CDSS) was implemented to remotely provide evidence-based guideline reminders in support of preventative health. Following implementation, we measured the agreement between preventive care reminders generated by an existing, local CDSS and the new, cloud-based CDSS operating on the same patient visit data. Methods: Electronic health record data for the same set of patients seen in primary care were sent to both the cloud-based web service and local CDSS. The clinical reminders returned by both services were captured for analysis. Cohen’s Kappa coefficient was calculated to compare the two sets of reminders. Kappa statistics were further adjusted for prevalence and bias due to the potential effects of bias in the CDS logic and prevalence in the relative small sample of patients. Results: The cloud-based CDSS generated 965 clinical reminders for 405 patient visits over 3 months. The local CDSS returned 889 reminders for the same patient visit data. When adjusted for prevalence and bias, observed agreement varied by reminder from 0.33 (95% CI 0.24 – 0.42) to 0.99 (95% CI 0.97 – 1.00) and demonstrated almost perfect agreement for 7 of the 11 reminders. Conclusions: Preventive care reminders delivered by two disparate CDS systems show substantial agreement. Subtle differences in rule logic and terminology mapping appear to account for much of the discordance. Cloud-based CDSS therefore show promise, opening the door for future development and implementation in support of health care providers with limited resources for knowledge management of complex logic and rules

Deutetrabenazine for the treatment of chorea associated with Huntington’s disease

This is a comprehensive review of the literature regarding the use of Deutetrabenazine in treating chorea associated with Huntington’s disease. Unfortunately, treatment has been limited for many aspects of this neurodegenerative disease. The present investigation presents the background, evidence, and indications for the use Deutetrabenazine in the setting of Huntington’s disease. Huntington’s disease is characterized by a variety of motor, psychiatric, and cognitive symptoms with chorea being one of the more notable ones. Chorea is a movement disorder present in multiple neurologic diseases that causes involuntary and irregular muscle movements theorized to be stemming from high dopamine levels. Deutetrabenazine is thought to function as an inhibitor of the VMAT2 vesicular monoamine transporter resulting in decreased monoamine release, including dopamine, in the synaptic cleft which has a therapeutic effect in management of chorea. This drug was approved by the FDA in 2017 with a specific indication for tardive dyskinesia and choreiform movement in Huntington’s disease. Currently, there is no definitive treatment for Huntington’s disease. Thus, management is primarily focused on symptom management with the use of a variety of pharmaceutical agents. Chorea is one of the many manifestations that significantly alter the quality of life of many patients. Deutetrabenazine is a promising new option for the treatment of chorea in the setting of Huntington’s disease. Although studies so far have displayed mixed results, further research, including head-to-head studies, is necessary to elucidate the true potential of this drug

Functional characterization of a panel of high-grade serous ovarian cancer cell lines as representative experimental models of the disease.

Genomic analysis of ovarian cancer cell lines has revealed a panel that best represents the most common ovarian cancer subtype, high-grade serous ovarian cancer (HGSOC). However, these HGSOC-like cell lines have not been extensively applied by ovarian cancer researchers to date, and the most commonly used cell lines in the ovarian cancer field do not genetically resemble the major clinical type of the disease. For the HGSOC-like lines to serve as suitable models, they need to be characterized for common functional assays. To achieve that objective, we systematically studied a panel of HGSOC cells CAOV3, COV362, Kuramochi, OVCAR4, OVCAR5, OVCAR8, OVSAHO and SNU119 for migration, invasion, proliferation, clonogenicity, EMT phenotype and cisplatin resistance. They exhibited a range of efficacies and OVCAR5, OVCAR8 and Kuramochi were the most aggressive. SNU119 and OVSAHO cells demonstrated the lowest functional activities. Wide differences in expression of EMT markers were observed between cell lines. SNU119 were the most epithelial and OVCAR8 had the most mesenchymal phenotype. COV362 was the most resistant to cisplatin while CAOV3 was the most sensitive. Taken together, our systematic characterization represents a valuable resource to help guide the application of HGSOC cells by the cancer research community

Conservation Status of the Plains Spotted Skunk, Spilogale putorius interrupta, in Texas, with an Assessment of Genetic Variability in the Species

Robert C. Dowler, Department of Biology at Angelo State University is the corresponding author, robert dot dowler at angelo dot eduIn this report, we present results of research on the conservation status of the plains spotted skunk (Spilogale putorius interrupta) in Texas and an assessment of the genetic variability in populations throughout the range of the species. The conservation status portion of the study included (1) mapping the species’ potential habitat in Texas using maximum entropy modeling (Maxent) with historic museum specimen records, (2) field-based surveying of locations in 10 counties to determine occurrence of the plains spotted skunk, (3) seeking additional occurrence records in Texas through crowd sourcing and citizen scientist approaches (4) using all current (2001 – 2017) occurrences to produce a model of probable geographic distribution in Texas and (5) assessing anthropogenic changes in land use, which may threaten the species’ habitats, by mapping current and forecasted oil and gas development and urbanization within the species’ modeled range. The species distribution model, combined with the land-change assessment, was used to select sites in 10 representative counties for field-based surveys in the hopes of revealing patterns of current distribution. Field surveys were carried out using live traps, enclosed track plates, and camera traps. These methods documented detections of plains spotted skunks (n = 12) in 4 of the 10 sites sampled. All methods of detection were successful, but cameras and live traps out-performed track plates. Crowd-sourced approaches and citizen scientist camera trapping revealed an additional 82 occurrences in the state, 79 of which were since 2009. These recent records were used to produce a species distribution model that provides relative probability of occurrence for the plains spotted skunk in the state. Our land-change mapping revealed potential anthropogenic threats to habitats at 2 of the sites (Katy Prairie and Fort Hood), which also had robust populations of plains spotted skunks based on 25 and 51detections, respectively). For our genetic assessment, samples of tissue from three sources (i.e., field surveys, state agencies throughout the distribution of the eastern spotted skunk, and museum tissue collections) allowed a detailed assessment of the genetic variability in the species (S. putorius) using both microsatellite markers and cytochrome b gene sequence. Our analysis of 119 specimens was able to establish that genetic patterns were consistent with currently accepted taxonomy of the 3 recognized subspecies of S. putorius (S. p. putorius, S. p. ambarvalis, and S. p. interrupta). We also determined that there was no evidence for hybridization with the congener, S. gracilis (western spotted skunk), a species co-occurring with the eastern spotted skunk in parts of Texas. The differentiation between S. p. putorius and S. p. ambarvalis was less pronounced (FST = 0.178; cytochrome b sequence divergence = 1.2%) than between these subspecies and the plains spotted skunk (average FST = 0.278; cytochrome b sequence divergence = 2.9%). Overall, genetic variability (observed heterozygosity = 0.474) in the plains spotted skunk was lower than that seen in common carnivores (striped skunks, raccoons), but slightly higher than some endangered carnivores (black-footed ferret). The heterozygosity levels more closely resemble the levels found within the island spotted skunk (S. gracilis amphiala) from the Channel Islands of California and other vertebrates that have a “threatened” conservation status. Key findings of the study include: 1) the current geographic distribution of the plains spotted skunk in Texas is reduced relative to historic records; 2) the species distribution model based on recorded occurrences since 2001 suggests areas of the state that are in need of further survey efforts; 3) genetic variability of plains spotted skunks is lower than more common carnivores, but higher than some recognized endangered species; 4) the subspecies, S. p. interrupta is a distinct genetic subunit of the eastern spotted skunk; and 5) continued energy development and especially future urbanization in some parts of Texas may affect populations of the plains spotted skunk.Texas Comptroller of Public AccountsBureau of Economic Geolog

The Fake IQ Test: a novel measure of self-reflection in major depressive disorder

Background Excessive negative self-referential processing plays an important role in the development and maintenance of major depressive disorder (MDD). Current measures of self-reflection are limited to self-report questionnaires and invoking imagined states, which may not be suitable for all populations. Aims The current study aimed to pilot a new measure of self-reflection, the Fake IQ Test (FIQT). Method Participants with MDD and unaffected controls completed a behavioural (experiment 1, n = 50) and functional magnetic resonance imaging version (experiment 2, n = 35) of the FIQT. Results Behaviourally, those with MDD showed elevated negative self-comparison with others, higher self-dissatisfaction and lower perceived success on the task, compared with controls; however, FIQT scores were not related to existing self-report measures of self-reflection. In the functional magnetic resonance imaging version, greater activation in self-reflection versus control conditions was found bilaterally in the inferior frontal cortex, insula, dorsolateral prefrontal cortex, motor cortex and dorsal anterior cingulate cortex. No differences in neural activation were found between participants with MDD and controls, nor were there any associations between neural activity, FIQT scores or self-report measures of self-reflection. Conclusions Our results suggest the FIQT is sensitive to affective psychopathology, but a lack of association with other measures of self-reflection may indicate that the task is measuring a different construct. Alternatively, the FIQT may measure aspects of self-reflection inaccessible to current questionnaires. Future work should explore relationships with alternative measures of self-reflection likely to be involved in perception of task performance, such as perfectionism

Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder

Drugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy

Relationship of a big five personality questionnaire to the symptoms of affective disorders

Online assessments allow cost-effective, large-scale screening for psychiatric vulnerability (e.g., university undergraduates or military recruits). However, conventional psychiatric questionnaires may worsen mental health outcomes due to overmedicalizing normal emotional reactions. Personality questionnaires designed for occupational applications could circumvent this problem as they utilise non-clinical wording and it is well-established that personality traits influence susceptibility to psychiatric illness. Here we present a brief, free-to-use occupational personality questionnaire, and test its sensitivity to symptoms of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in an online sample. Our study used a cross-sectional, self-report design to assess the relationship between self-reported symptoms of affective disorders and scores on the personality dimensions of openness, conscientiousness, extraversion, agreeableness and neuroticism. We used SEM to compare affective symptoms in 8,470 individuals (mean age 25.6 ± 7.0 years; 4,717 male) with scores on an online adaption of the TSDI, a public-domain ‘Big Five’ personality questionnaire. ROC curve analyses assessed cut off scores for the best predictors of overall vulnerability to affective disorders (represented by a composite screening score). Neuroticism was the most robust predictor of QIDS-16 depression symptoms and MDQ Hypomania symptoms (β = 0.68 and 0.39 respectively, p < .0001). Extraversion was the most robust predictor of HCL-16 Hypomania symptoms (β = 0.34, p < .0001). ROC curve analyses suggest if the TSDI was used for screening in this sample, neuroticism cut offs of approximately 58 for men and 70 for women would provide the most useful classification of overall vulnerability to affective disorders