Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

The relationship between expressive suppression, therapeutic bond, and treatment outcomes of a positive affect intervention for adults with anxiety and/or depression.

Expressive suppression (ES; reducing emotional expression) is linked with reduced social connectedness in individuals with anxiety or depression. One implication is that people who use ES may have difficulty establishing a bond with their therapist which may impede clinical improvement. We examined this hypothesis in 33 adults with clinically elevated anxiety or depression receiving treatment focused on enhancing positive thoughts, emotions, and behaviors. At baseline, participants rated ES for positive and negative emotions during a standardized conversation task designed to generate connectedness. They also rated measures of early (session 3) perceived therapeutic bond and treatment outcomes (i.e. positive affect and social connectedness). ES of positive (r = -.39, p = .018), but not negative (r = .06, p = .747), emotions was negatively associated with therapeutic bond. Therapeutic bond mediated the relationship between greater ES of positive emotions during affiliation and lower post-treatment positive affect, 95% bias-corrected bootstrap confidence interval [-0.021, -0.000], adjusted for pre-treatment positive affect, as well as lower post-treatment social connectedness [-0.397, -0.015]; however, the indirect effect was not significant when accounting for pre-treatment social connectedness (p > .05). ES of positive emotions may be an important factor in the development of therapeutic bond and therefore treatment outcomes for individuals with anxiety or depression.

Validation of the Approach-Avoidance Temperament Questionnaire in Individuals with Anxiety and Depression.

The Approach-Avoidance Temperament Questionnaire (ATQ) is a well-established measure assessing heightened sensitivity and reactivity to reward/positive stimuli (approach temperament) and to punishment/negative stimuli (avoidance temperament). These basic dimensions of personality are believed to be important for understanding the etiology and maintenance of anxiety and depressive disorders. Despite the ATQ's potential utility in clinical psychology research, its psychometric properties and factor structure have yet to be examined in a psychiatric sample. The aims of the present study were to 1) conduct confirmatory factor analysis to replicate the ATQ's factor structure in individuals diagnosed with an anxiety or depressive disorder (N = 244), 2) assess internal consistency and convergent and divergent validity, and 3) explore differences in approach and avoidance temperaments in individuals with versus without a diagnosis of anxiety or depression. Results confirmed the original two-factor structure of the ATQ in a clinical sample, with approach and avoidance temperaments representing orthogonal dimensions. The measure demonstrated strong internal consistency, convergent and divergent validity, and predictive validity. Individuals with anxiety and depression scored higher on avoidance items and lower on approach items compared to those without clinical diagnoses. This study supports the use of the ATQ in clinical populations.

Social network size and personality traits independently and prospectively predict distress disorders and suicidal behavior in U.S. Army soldiers.

BACKGROUND: Personality traits (e.g. neuroticism) and the social environment predict risk for internalizing disorders and suicidal behavior. Studying these characteristics together and prospectively within a population confronted with high stressor exposure (e.g. U.S. Army soldiers) has not been done, yet could uncover unique and interactive predictive effects that may inform prevention and early intervention efforts. METHODS: Five broad personality traits and social network size were assessed via self-administered questionnaires among experienced soldiers preparing for deployment (N = 4645) and new soldiers reporting for basic training (N = 6216). Predictive models examined associations of baseline personality and social network variables with recent distress disorders or suicidal behaviors assessed 3- and 9-months post-deployment and approximately 5 years following enlistment. RESULTS: Among the personality traits, elevated neuroticism was consistently associated with increased mental health risk following deployment. Small social networks were also associated with increased mental health risk following deployment, beyond the variance accounted for by personality. Limited support was found for social network size moderating the association between personality and mental health outcomes. Small social networks also predicted distress disorders and suicidal behavior 5 years following enlistment, whereas unique effects of personality traits on these more distal outcomes were rare. CONCLUSIONS: Heightened neuroticism and small social networks predict a greater risk for negative mental health sequelae, especially following deployment. Social ties may mitigate adverse impacts of personality traits on psychopathology in some contexts. Early identification and targeted intervention for these distinct, modifiable factors may decrease the risk of distress disorders and suicidal behavior.

Livestock plants and COVID-19 transmission.

Policy responses to the COVID-19 outbreak must strike a balance between maintaining essential supply chains and limiting the spread of the virus. Our results indicate a strong positive relationship between livestock-processing plants and local community transmission of COVID-19, suggesting that these plants may act as transmission vectors into the surrounding population and accelerate the spread of the virus beyond what would be predicted solely by population risk characteristics. We estimate the total excess COVID-19 cases and deaths associated with proximity to livestock plants to be 236,000 to 310,000 (6 to 8% of all US cases) and 4,300 to 5,200 (3 to 4% of all US deaths), respectively, as of July 21, 2020, with the vast majority likely related to community spread outside these plants. The association is found primarily among large processing facilities and large meatpacking companies. In addition, we find evidence that plant closures attenuated county-wide cases and that plants that received permission from the US Department of Agriculture to increase their production-line speeds saw more county-wide cases. Ensuring both public health and robust essential supply chains may require an increase in meatpacking oversight and potentially a shift toward more decentralized, smaller-scale meat production.

The neuroanatomical consequences and pathological implications of bilingualism.

In recent years, there has been a rise in the number of people who are able to speak two or more languages. This has been paralleled by an increase in research related to bilingualism. Despite this, much of the neuroanatomical consequences and pathological implications of bilingualism are still subject to discussion. This review aims to evaluate the neuroanatomical structures related to language and to the acquisition of a second language as well as exploring how learning a second language can alter one's susceptibility to and the progression of certain cerebral pathologies. A literature search was conducted on the Medline, Embase, and Web of Science databases. A total of 137 articles regarding the neuroanatomical or pathological implications of bilingualism were included for review. Following analysis of the included papers, this review finds that bilingualism induces significant gray and white matter cerebral changes, particularly in the frontal lobes, anterior cingulate cortex, left inferior parietal lobule and subcortical areas, and that native language and acquired language largely recruit the same neuroanatomical structures with however, subtle functional and anatomical differences dependent on proficiency and age of language acquisition. There is adequate evidence to suggest that bilingualism offsets the symptoms and diagnosis of dementia, and that it is protective against both pathological and age-related cognitive decline. While many of the neuroanatomical changes are known, more remains to be elucidated and the relationship between bilingualism and other neurological pathologies remains unclear.

Density estimation for circular data observed with errors.

Until now the problem of estimating circular densities when data are observed with errors has been mainly treated by Fourier series methods. We propose kernel-based estimators exhibiting simple construction and easy implementation. Specifically, we consider three different approaches: the first one is based on the equivalence between kernel estimators using data corrupted with different levels of error. This proposal appears to be totally unexplored, despite its potential for application also in the Euclidean setting. The second approach relies on estimators whose weight functions are circular deconvolution kernels. Due to the periodicity of the involved densities, it requires ad hoc mathematical tools. Finally, the third one is based on the idea of correcting extra bias of kernel estimators which use contaminated data and is essentially an adaptation of the standard theory to the circular case. For all the proposed estimators, we derive asymptotic properties, provide some simulation results, and also discuss some possible generalizations and extensions. Real data case studies are also included.

The Relationship Between Loneliness and Positive Affect in Older Adults.

OBJECTIVE: To establish whether positive affect (PA) is uniquely associated with loneliness and other social functioning variables beyond negative affect (NA) among older adults. METHODS: Four hundred and twenty-eight participants (aged 60+ years old, 82% White, and 48% female) were recruited using random digit-dialing and completed scales for loneliness (UCLA Loneliness Scale), companionship (PROMIS scale), satisfaction with discretionary social activities (PROMIS scale), PA (Center for Epidemiologic Studies [CES] Happiness Scale), and NA (CES-Depression scale and Brief Symptom Inventory-Anxiety Subscale). RESULTS: Multiple linear regression models found PA to be a significant predictor of lower loneliness where the effect of PA on loneliness is dependent on the level of NA; a large effect size at the mean level of NA, which becomes attenuated when NA increases. Although the direction of effect of PA on loneliness will change for NA > 5.10, which is 5 standard deviations away from 0, based on the model estimates, the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with lower loneliness, however this effect is attenuated for larger NA. Similarly, multiple linear regression models found that companionship was associated with PA and NA where the effect of PA is dependent on the level of NA; a medium effect size at the mean level of NA, which becomes attenuated when NA increases. As in the case of loneliness, the direction of effect of PA on companionship will change for NA > 3.52, which is 3.5 standard deviation away from 0, based on the model estimates, but the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with increased companionship, aand this effect is attenuated with greater NA. Satisfaction with social activities was associated with PA only (medium effect size). CONCLUSION: Results suggest PA appears to be uniquely associated with social functioning among older adults. These findings support the potential for treatments that target PA to decrease loneliness among older adults, or vice versa.

Sparse modelling of cancer patients' survival based on genomic copy number alterations.

Copy number alterations (CNA) are structural variation in the genome, in which some regions exhibit more or less than the normal two chromosomal copies. This genomic CNA profile provides critical information in tumour progression and is therefore informative for patients' survival. It is currently a statistical challenge to model patients' survival using their genomic CNA profiles while at the same time identify regions in the genome that are associated with patients' survival. Some methods have been proposed, including Cox proportional hazard (PH) model with ridge, lasso, or elastic net penalties. However, these methods do not take the general dependencies between genomic regions into account and produce results that are difficult to interpret. In this paper, we extend the elastic net penalty by introducing additional penalty that takes into account general dependencies between genomic regions. This new model produces smooth parameter estimates while simultaneously performs variable selection via sparse solution. The results indicate that the proposed method shows a better prediction performance than other models in our simulation study, while enabling us to investigate regions in the genome that are associated with the patients' survival with sensible interpretation. We illustrate the method using a real dataset from a lung cancer cohort and simulated data.

Dural tear repair surgery comparative analysis: a stitch in time saves nine.

PURPOSE: A dural tear is a common iatrogenic complication of spinal surgery associated with a several post-operative adverse events. Despite their common occurrence, guidelines on how best to repair the defect remain unclear. This study uses five post-operative outcomes to the compare repair methods used to treat 106 dural tears to determine which method is clinically favourable. METHODS: Data were retrospectively collected from Southampton General Hospital's online databases. 106 tears were identified and grouped per repair method. MANOVA was used to compare the following five outcomes: Length of stay, numbers of further admissions or revision surgeries, length of additional admissions, post-operative infection rate and dural tear associated neurological symptoms. Sub-analysis was conducted on patient demographics, primary vs non-primary closure and type of patch. Minimal clinically important difference (MCID) was calculated via the Delphi procedure. RESULTS: Age had a significant impact on patient outcomes and BMI displayed positive correlation with three-fifth of the predefined outcome measures. No significant difference was observed between repair groups; however, primary closure ± a patch achieved an MCID percentage improvement with regards to length of original stay, rate of additional admissions/surgeries and post-operative infection rate. Artificial over autologous patches resulted in shorter hospital stays, fewer readmissions, infections and neurological symptoms. CONCLUSION: This study reports primary closure ± dural patch as the most efficient repair method with regards to the five reported outcomes. This study provides limited evidence in favour of artificial over autologous patches and recommends that dural patches be used in conjunction with primary closure. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

The Current Accuracy, Cost-Effectiveness, and Uses of Musculoskeletal Telehealth and Telerehabilitation Services.

ABSTRACT: Musculoskeletal conditions are a major contributor to global morbidity. During the COVID-19 pandemic, clinicians needed to rapidly meet the evolving requirements of their patients, which resulted in an increased adoption of telehealth services. This area needs more research, as there is currently a paucity of studies, and telehealth practices are continuing to advance and evolve. This study subsequently aims to evaluate the ethics, health economics, and accuracy of current musculoskeletal telehealth services. This article combines three original studies; a telehealth accuracy systematic review; a cost-effectiveness scoping review; and a biopsychosocial narrative review. These studies were combined into one article. This article concludes that telehealth services achieve an average agreement with in-person assessments of 62% for the knee and 31% for the shoulder and that telerehabilitation services incur average cost savings per patient of £38.57 but that these savings are primarily a result of a reduced need to travel.

Non-invasive procedural planning using computed tomography-derived fractional flow reserve.

OBJECTIVES: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFRCT planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR. BACKGROUND: Advances in FFRCT technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses. METHODS: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFRCT was calculated using pre-PCI coronary CT angiography. Subsequently, FFRCT and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFRCT models in the same locations as PCI was performed. Relationships between invasive FFR and FFRCT , between post-PCI FFR and FFRCT planner, and between delta FFR and delta FFRCT were evaluated. RESULTS: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFRCT was 0.64 ± 0.13 (p = .34) with a mean difference of 0.015 (95% CI: -0.23-0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFRCT planner was 0.85 ± 0.07 (p < .001) with a mean difference of 0.040 (95% CI: -0.10-0.18). Delta invasive FFR and delta FFRCT were 0.23 ± 0.12 and 0.21 ± 0.12 (p = .09) with a mean difference of 0.025 (95% CI: -0.20-0.25). Significant correlations were found between pre-PCI FFR and FFRCT (r = 0.53, p < .001), between post-PCI FFR and FFRCT planner (r = 0.41, p = .001), and between delta FFR and delta FFRCT (r = 0.57, p < .001). CONCLUSIONS: The non-invasive FFRCT planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFRCT planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.

Computer-delivered behavioural activation and approach-avoidance training in major depression: Proof of concept and initial outcomes.

OBJECTIVES: Individuals with major depressive disorder (MDD) have problems with engaging in approach behaviour to potentially rewarding encounters, which contributes to the maintenance of depressive symptoms. Approach-avoidance training (AAT) retrains implicit approach tendencies, and behavioural activation (BA) promotes explicit approach behaviour in MDD. As a novel MDD treatment strategy, this study aimed to implement a brief, computerized version of BA integrated with implicit AAT. DESIGN: Adults with a principal diagnosis of MDD (N = 25) were randomly assigned to complete one of two versions of AAT - approach-positive faces (n = 12) or balanced approach of positive and neutral faces (n = 13) - concurrently with self-guided BA twice weekly for 2 weeks. METHODS: Outcomes included treatment completion rates; bias scores for automatic approach towards positive social cues; and symptom scales for depression, positive affect, social relationship functioning, anhedonia, and anxiety. RESULTS: Feasibility and acceptability of computerized BA + AAT were supported by moderate pre-treatment credibility and expectancy ratings and 80% treatment completion. Participants across both conditions displayed significant and large sized reductions in depression from pre- to post-assessment (Cohen's d = -1.23) that maintained three months later, as well as decreased anxiety and anhedonia and increased positive affect and social relationship functioning (medium to large effects). CONCLUSION: Results support the feasibility and potential efficacy of brief, computerized BA + AAT. Research is needed to determine whether AAT is additive to BA, and what AAT parameters best enhance treatment outcomes. PRACTITIONER POINTS: Brief, computerized behavioral activation plus approach/avoidance training (BA + AAT) may be acceptable and beneficial for some patients with moderate-to-severe major depression. Computer-delivered BA + AAT can be implemented as a largely self-guided program for MDD and could be administered remotely and/or with minimal clinician interaction. As this was a small proof of concept study, it cannot be determined which treatment components - AAT, BA, or both - contributed to positive clinical outcomes. Because BA + AAT was implemented in a research clinic, it remains unknown what treatment engagement and response would look like in community settings.

Evaluating the Efficacy and Optimisation of the Peer-Led Flipped Model Using TEL Resources Within Neuroanatomy.

The flipped classroom (where students prepare before and then develop understanding during class) and technology-enhanced learning (audio-visual learning tools) are increasingly used to supplement anatomy teaching. However, the supporting literature lacks robust methodology and is conflicting in demonstrating efficacy outcomes. Contrastingly, near-peer teaching (where senior students teach juniors on the same academic programme) is well researched and reported to be both effective and versatile. This provides an ideal vehicle in which to investigate and potentially optimise these approaches.This study aims to assess educational impact of the peer-led flipped model and student engagement and perceptions regarding traditional and TEL resources.A quasi-randomised, cross-sectional study was conducted with 281 second-year University of Southampton medical students. Students were randomly allocated to 3 groups: traditional lecture (control), flipped text resource, or flipped video resource. The first group received no pre-teaching material, but the flipped groups received a text or video pre-teaching resource. Objective outcomes measured were: Knowledge gain and retention via multiple-choice questionnaires and formative exams Student perceptions and engagement using questionnaires and 2 focus groups All groups demonstrated significant knowledge gain post-teaching (p < 0.0001). However, regardless of engagement with pre-teaching material, no significant difference was found in knowledge gain or retention between the groups. Students engaged 21.1% more with the text rather than video resource (p = 0.0019), but spent equal time using both (p = 0.0948). All resources and teaching approaches were perceived 'very useful' with no significant differences found between groups. A qualitative approach utilising thematic analysis of focus groups identified 4 themes, including 'Attitudes towards flipped classroom', which revealed mixed reviews and perceptions from participants.This study has found the peer-led flipped model is of no detriment to educational impact compared to peer-led traditional approaches in a well-established peer teaching programme in undergraduate medicine at the University of Southampton. Students value traditional and video resources but engage with them differently. Additionally, it was reported that in this experiment, NPT did not seem well suited to the flipped classroom, suggesting a rare limitation of the utility of NPT application within an anatomy curriculum.

The Association between Age and Experienced Emotions in Hoarding Disorder.

Objectives: Hoarding disorder (HD) is conceptualized as a fear-based disorder and exposure to sorting/discarding possessions is a core part of treatment. However, there has been no investigation of age-related differences in emotional reaction to sorting. The objective of this study was to explore the association between age and affective response during a sorting task.Methods: Forty-nine adults with HD completed a standardized sorting task. Participants reported their current emotion before and after the sorting task and reported their subjective distress throughout the task.Results: Older participants reported significantly lower distress ratings. Only 43% of participants reported fear prior to the task and 22% reported fear after the task. The probability of reporting fear before and after the task decreased significantly with age.Conclusions: Fear may not be the emotion experienced when discarding items, particularly for older adults with HD. Future work should focus on mechanisms of action in HD treatment.Clinical Implications: Clinicians should not assume fear or anxiety to be the primary emotional response in older adults with HD when engaged in an exposure to sorting/discarding. Older hoarding patients with a more fear-oriented aversion to sorting possessions may require a treatment emphasis on increasing the percentage of items discarded.

Proactive engagement of cognitive control modulates implicit approach-avoidance bias.

Implicit social-affective biases-reflected in a propensity to approach positive and avoid negative stimuli-have been documented in humans with paradigms, such as the Approach-Avoidance Task (AAT). However, the degree to which preemptively engaging cognitive control can help to down-regulate those behavioral tendencies remains poorly understood. While undergoing functional magnetic resonance imaging (fMRI), 24 healthy participants completed a cued version of the AAT, in which they responded to pictures of happy or angry faces by pulling a joystick toward themselves (approach) or pushing the joystick away (avoidance) based on the color of the stimulus frame. On some trials, they were cued to reverse the frame color/joystick action instructions. Before stimulus onset, a reverse cue was associated with deactivation of a visuo-spatial and motor planning network and subsequent slowing down in response to stimuli. During the stimulus phase, a reverse cue was associated with a) activation of cognitive control areas, including the right inferior frontal gyrus (IFG) and right inferior parietal lobule (IPL); and b) reduced right precentral gyrus activation when having to push (avoid) a happy face. Overall, these results suggest that proactively engaging cognitive control can help fine-tune behavioral and neural adjustment to emotionally incongruent behavioral conditions.

Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins.

The gabapentinoid drugs gabapentin and pregabalin (Neurontin and Lyrica) are mainstay treatments for neuropathic pain and preventing focal seizures. Both drugs have similar effects to each other in animal models and clinically. Studies have shown that a protein first identified as an auxiliary subunit of voltage-gated calcium channels (the α 2 δ-subunit type 1 [α 2 δ-1], or Ca V a2d1) is the high-affinity binding site for gabapentin and pregabalin and is required for the efficacy of these drugs. The α 2 δ-1 protein is required for the ability of gabapentin and pregabalin to reduce neurotransmitter release in neuronal tissue, consistent with a therapeutic mechanism of action via voltage-gated calcium channels. However, recent studies have revealed that α 2 δ-1 interacts with several proteins in addition to voltage-gated calcium channels, and these additional proteins could be involved in gabapentinoid pharmacology. Furthermore, gabapentin and pregabalin have been shown to modify the action of a subset of N-methyl-d-aspartate-sensitive glutamate receptors, neurexin-1α, and thrombospondin proteins by binding to α 2 δ-1. Thus, these effects may contribute substantially to gabapentinoid therapeutic mechanism of action. SIGNIFICANCE STATEMENT: It is widely believed that gabapentin and pregabalin act by modestly reducing the membrane localization and activation of voltage-gated calcium channels at synaptic endings in spinal cord and neocortex via binding to the α 2 δ-1 protein. However, recent findings show that the α 2 δ-1 protein also interacts with N-methyl-d-aspartate-sensitive glutamate receptors, neurexin-1α, thrombospondins (adhesion molecules), and other presynaptic proteins. These newly discovered interactions, in addition to actions at calcium channels, may be important mediators of gabapentin and pregabalin therapeutic effects.

Diagnostic and dimensional evaluation of implicit reward learning in social anxiety disorder and major depression.

OBJECTIVE: Increasing evidence supports the presence of an anhedonic endophenotype in major depressive disorder (MDD), characterized by impairments in various components of reward processing, particularly incentive motivation, effort-based decision making, and reward learning. In addition to its prominent role in MDD, reward processing dysregulation has been proposed as a transdiagnostic risk and/or maintenance factor for a range of other forms of psychopathology. Individuals with social anxiety disorder (SAD)-a condition that frequently co-occurs with MDD-demonstrate low trait positive affectivity and altered processing of rewards and positively valenced information. However, no studies to date have directly tested reward learning-the ability to modulate behavior in response to rewards-in this population. MATERIALS AND METHODS: The current study evaluated reward learning in MDD, SAD, and healthy control subjects (N = 90) using a well-validated signal detection task. Given increasing data supporting transdiagnostic features of psychopathology, we also evaluated associations between anhedonia and task performance transdiagnostically in the patient sample. RESULTS: Contrary to expectations, results indicated no significant group differences in response bias in the full sample, suggesting no diagnostic differences in reward learning. However, dimensional analyses revealed that higher self-reported anhedonia (but not general distress or anxious arousal) was associated with worse reward learning in both the MDD and SAD groups explaining about 11% of the variance. CONCLUSION: Deficits in implicit reward learning are associated with anhedonia but not necessarily with major depressive disorder as a diagnosis, which supports the use of transdiagnostic approaches to understanding psychopathology.

Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor.

Breast cancer cells experience a range of shear stresses in the tumor microenvironment (TME). However most current in vitro three-dimensional (3D) models fail to systematically probe the effects of this biophysical stimuli on cancer cell metastasis, proliferation, and chemoresistance. To investigate the roles of shear stress within the mammary and lung pleural effusion TME, a bioreactor capable of applying shear stress to cells within a 3D extracellular matrix was designed and characterized. Breast cancer cells were encapsulated within an interpenetrating network hydrogel and subjected to shear stress of 5.4 dynes cm-2 for 72 hr. Finite element modeling assessed shear stress profiles within the bioreactor. Cells exposed to shear stress had significantly higher cellular area and significantly lower circularity, indicating a motile phenotype. Stimulated cells were more proliferative than static controls and showed higher rates of chemoresistance to the anti-neoplastic drug paclitaxel. Fluid shear stress-induced significant upregulation of the PLAU gene and elevated urokinase activity was confirmed through zymography and activity assay. Overall, these results indicate that pulsatile shear stress promotes breast cancer cell proliferation, invasive potential, chemoresistance, and PLAU signaling.

Impact of sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues.