Perceived value of computed tomography imaging for patients with inflammatory bowel disease in the emergency department: a Canadian survey.

Background: There are high rates of computed tomography (CT) utilization in the emergency department (ED) for patients with inflammatory bowel disease (IBD), despite guidelines recommending judicious use. We performed a national survey to better understand perceptions and practice patterns of Canadian physicians related to CT imaging in the ED. Methods: Our survey was developed by a multistep iterative process with input from key stakeholders between 2021 and 2022. It evaluated Canadian gastroenterologists', surgeons', and emergency physicians' (1) perceived rates of IBD findings detected by CT, (2) likelihood of performing CT for specific presentations and (3) comfort in diagnosing IBD phenotypes/complications without CT. Results: A total of 208 physicians responded to our survey: median age 44 years (IQR, 37-50), 63% male, 68% academic, 44% emergency physicians, 39% gastroenterologists, and 17% surgeons. Compared with emergency physicians and surgeons, gastroenterologists more often perceived that CT would detect inflammation alone and less often IBD complications. Based on established rates in the literature, 13 (16%) gastroenterologists, 33 (40%) emergency physicians, and 21 (60%) surgeons overestimated the rates of at least one IBD complication. Although most physicians were more comfortable diagnosing inflammation compared to IBD complications without CT, gastroenterologists were significantly less likely to recommend CT imaging for non-obstructive/penetrating presentations compared with emergency physicians and surgeons with results that varied by IBD subtype. Conclusion: This national survey demonstrates differences in physician perceptions and practices regarding CT utilization in the ED and can be used as a framework for educational initiatives regarding appropriate usage of this modality.

Psychopathy measurement practices moderate psychopathy's association with anxiety and depression: A comprehensive meta-analysis.

Theories of psychopathy development traditionally emphasize that individuals high in psychopathy experience diminished internalizing symptoms (e.g., anxiety and depression). However, many studies find null or even positive relationships between psychopathy and internalizing. The current meta-analysis therefore aimed to provide a comprehensive understanding of heterogeneity in psychopathy-anxiety/depression relationships by examining measurement and sample-related variables that may moderate these associations (e.g., psychopathy subdimensions assessed, different measures/operationalizations of psychopathy and anxiety/depression, and demographic characteristics). Results suggest that psychopathy demonstrates a small, positive overall association with anxiety/depression (r = 0.09), which may indicate that psychopathy is unrelated to subjective experiences of anxiety and sadness, but results could also reflect that varying psychopathy and anxiety/depression assessment practices contribute to heterogeneity in psychopathy-anxiety/depression associations. Most notably, results indicate that associations vary substantially across different measures/operationalizations of psychopathy, even when controlling for sample type and informant. Some psychopathy scales could therefore inadvertently capture anxiety/depression symptoms or broader psychopathology in addition to psychopathic traits. Findings from the current meta-analysis can inform future efforts to understand how measurement-related considerations influence relationships between psychopathy and anxiety/depression.

Creatinine clearance is maintained in a range of wet-bulb globe temperatures and work-rest ratios during simulated occupational heat stress.

We tested the hypothesis that compliance with the National Institute for Occupational Safety and Health (NIOSH) heat stress recommendations will prevent reductions in glomerular filtration rate (GFR) across a range of wet bulb globe temperatures (WBGTs) and work-rest ratios at a fixed work intensity. We also tested the hypothesis that non-compliance would result in a reduction in GFR compared to a work-rest matched compliant trial. Twelve healthy adults completed five trials (four NIOSH compliant, one non-compliant) that consisted of four hours of exposure to a range of WBGTs. Subjects walked on a treadmill (Hprod: ~430 W) and work-rest ratios (work per hour: 60, 45, 30, 15 min) were prescribed as a function of WBGT (24°C, 26.5°C, 28.5°C, 30°C, 36°C), and subjects drank a sport drink ad libitum. Peak core temperature (TC) and percentage change in body weight (%DBW) were measured. Creatinine clearance measured pre- and postexposure provided a primary marker of GFR. Peak TC did not differ among NIOSH compliant trials (p=0.065) but differed between compliant vs. non-compliant trials (p<0.001). %DBW did not differ among NIOSH compliant trials (p=0.131) or between compliant vs. non-compliant trials (p=0.185). Creatinine clearance did not change or differ among compliant trials (p³0.079). Creatinine clearance did not change or differ between compliant vs. non-compliant trials (p³0.661). Compliance with the NIOSH recommendations maintained GFR. Surprisingly, despite a greater heat strain in a non-compliant trial, GFR was maintained highlighting the potential relative importance of hydration.

Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by 1 h of head-out cold-water immersion.

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia ([Formula: see text] = 0.21) or normobaric hypoxia ([Formula: see text] = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI.NEW & NOTEWORTHY Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures.

Relation between resting spleen volume and apnea-induced increases in hemoglobin mass.

Introduction: Indigenous populations renowned for apneic diving have comparatively large spleen volumes. It has been proposed that a larger spleen translates to heightened apnea-induced splenic contraction and elevations in circulating hemoglobin mass (Hbmass), which, in theory, improves O2 carrying and/or CO2/pH buffering capacities. However, the relation between resting spleen volume and apnea- induced increases in Hbmass is unknown. Therefore, we tested the hypothesis that resting spleen volume is positively related to apnea-induced increases in total Hbmass. Methods: Fourteen healthy adults (six women; 29 ± 5 years) completed a two-minute carbon monoxide rebreathe procedure to measure pre-apneas Hbmass and blood volume. Spleen length, width, and thickness were measured pre-and post-five maximal apneas via ultrasound. Spleen volume was calculated via the Pilström equation (test-retest CV:2 ± 2%). Hemoglobin concentration ([Hb]; g/dl) and hematocrit (%) were measured pre- and post-apneas via capillary blood samples. Post-apneas Hbmass was estimated as post-apnea [Hb] x pre-apnea blood volume. Data are presented as mean ± SD. Results: Spleen volume decreased from pre- (247 ± 95 mL) to post- (200 ± 82 mL, p<0.01) apneas. [Hb] (14.6 ± 1.2 vs. 14.9 ± 1.2 g/dL, p<0.01), hematocrit (44 ± 3 vs. 45 ± 3%, p=0.04), and Hbmass (1025 ± 322 vs. 1046 ± 339 g, p=0.03) increased from pre- to post-apneas. Pre-apneas spleen volume was unrelated to post-apneas increases in Hbmass (r=-0.02, p=0.47). O2 (+28 ± 31 mL, p<0.01) and CO2 (+31 ± 35 mL, p<0.01) carrying capacities increased post-apneas. Conclusion: Larger spleen volume is not associated with a greater rise in apneas-induced increases in Hbmass in non-apnea-trained healthy adults.

Cool head-out water immersion does not alter cerebrovascular reactivity to hypercapnia despite elevated middle cerebral artery blood velocity: A pilot study.

Episodic increases in cerebral blood flow (CBF) are thought to contribute to improved cerebrovascular function and health. Head-out water immersion (HOWI) may be a useful modality to increase CBF secondary to the hydrostatic pressure placed on the body. However, it is unclear whether water temperatures common to the general public elicit similar cerebrovascular responses. We tested the hypothesis that mean middle cerebral artery blood velocity (MCAvmean) and cerebrovascular reactivity to CO2 (CVRCO2) would be higher during an acute bout of thermoneutral (TN; 35°C) vs. cool (COOL; 25°C) HOWI. Ten healthy participants (age: 23±3 y; 4 women) completed two randomized HOWI visits. Right MCAvmean, end-tidal CO2 (PETCO2) mean arterial pressure (MAP), and MCA conductance (MCAvmean/MAP) were continuously recorded. CVRCO2 was assessed using a stepped hypercapnia protocol before (PRE), at 30 minutes of HOWI (HOWI), immediately after HOWI (POST-1), and 45 minutes after HOWI (POST-2). Absolute values are reported as mean ± SD. MCAvmean, PETCO2, MAP, and CVRCO2 were not different between conditions at any timepoint (all P≥0.17). In COOL, MCAvmean increased from PRE (61±9 cm/s) during HOWI (68±11 cm/s), at POST-1 (69±11 cm/s), and POST-2 (72±8 cm/s) (all P<0.01), and in TN from PRE to POST-1 (66±13 vs. 71±14 cm/s; P = 0.05). PETCO2 did not change over time in either condition. In COOL, MAP increased from PRE (85±5 mmHg) during HOWI (101±4 mmHg), at POST-1 (97±7 mmHg), and POST-2 (96±9 mmHg), and in TN from PRE (88±5 mmHg) at HOWI (98±7 mmHg) and POST-1 (99±8 mmHg) (all P<0.01). In COOL, CVRCO2 increased from PRE to HOWI (1.66±0.55 vs. 1.92±0.52 cm/s/mmHg; P = 0.04). MCA conductance was not different between or within conditions. These data indicate that 30 minutes of cool HOWI augments MCAvmean and that the increase in MCAvmean persists beyond cool HOWI. However, cool HOWI does not alter CVRCO2 in healthy young adults.

Activation of cardiac parasympathetic and sympathetic activity occurs at different skin temperatures during face cooling.

Sufficiently cold-water temperatures (<7°C) are needed to elicit the sympathetic response to the cold pressor test using the hand. However, it is not known if stimulating the trigeminal nerve via face cooling, which increases both sympathetic and cardiac parasympathetic activity, also has a threshold temperature. We tested the hypothesis that peak autonomic activation during a progressive face cooling challenge would be achieved when the stimulus temperature is ≤7°C. Twelve healthy participants (age: 25 ± 3 yr, four women) completed our study. Six pliable bags, each containing water or an ice slurry (34°C, 28°C, 21°C, 14°C, 7°C, and 0°C) were applied sequentially to participants' forehead, eyes, and cheeks for 5 min each. Mean arterial pressure (photoplethysmography; index of sympathetic activity) and heart rhythm (3-lead ECG) were averaged in 1-min increments at the end of baseline and throughout each temperature condition. Heart rate variability in the time [(root mean square of successive differences (RMSSD)] and frequency [high-frequency (HF) power] domains was used to estimate cardiac parasympathetic activity. Data are presented as the increase from baseline ± SD. Mean arterial pressure only increased from baseline in the 7°C (13.1 ± 10.3 mmHg; P = 0.018) and 0°C (25.2 ± 7.8 mmHg; P < 0.001) conditions. Only the 0°C condition increased RMSSD (160.6 ± 208.9 ms; P = 0.009) and HF power (11,450 ± 14,555 ms2; P = 0.014) from baseline. Our data indicate that peak increases in sympathetic activity during face cooling are initiated at a higher forehead skin temperature than peak increases in cardiac parasympathetic activity.

Diagnostic accuracy of thermal, hydration, and heart rate assessments in discriminating positive acute kidney injury risk following physical work in the heat.

Occupational heat stress increases the risk of acute kidney injury (AKI). This study presents a secondary analysis to generate novel hypotheses for future studies by investigating the diagnostic accuracy of thermal, hydration, and heart rate assessments in discriminating positive AKI risk following physical work in the heat in unacclimatized individuals. Unacclimatized participants (n = 13, 3 women, age: ∼23 years) completed four trials involving 2 h of exercise in a 39.7 ± 0.6 °C, 32 ± 3% relative humidity environment that differed by experimental manipulation of hyperthermia (i.e., cooling intervention) and dehydration (i.e., water drinking). Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Positive AKI risk was identified when the product of concentrations insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinase-2 [IGFBP7∙TIMP-2] exceeded 0.3 (ng∙mL-1)2∙1000-1. Peak absolute core temperature had the acceptable discriminatory ability (AUC = 0.71, p = 0.009), but a relatively large variance (AUC 95% CI: 0.57-0.86). Mean body temperature, urine specific gravity, urine osmolality, peak heart rate, and the peak percent of both maximum heart rate and heart rate reserve had poor discrimination (AUC = 0.66-0.69, p ≤ 0.051). Mean skin temperature, percent change in body mass and plasma volume, and serum sodium and osmolality had no discrimination (p ≥ 0.072). A peak increase in mean skin temperature of >4.7 °C had a positive likelihood ratio of 11.0 which suggests clinical significance. These data suggest that the absolute value of peak core temperature and the increase in mean skin temperature may be valuable to pursue in future studies as a biomarker for AKI risk in unacclimatized workers.

Renal vascular control during normothermia and passive heat stress does not differ between healthy younger men and women.

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.

Proposed Specifiers for Conduct Disorder (PSCD): Further validation of the parent-report version in a nationally representative U.S. sample of 10- to 17-year-olds.

The Proposed Specifiers for Conduct Disorder (PSCD; Salekin & Hare, 2016) is a new self-report and informant measure designed to assess psychopathic characteristic domains along with symptoms of conduct disorder in youth. Previous factor analytic studies on the PSCD have found that the items are accounted for by a four-factor model reflecting grandiose-manipulative, callous-unemotional, daring-impulsive, and conduct disorder (CD) symptoms. The present study examined the factor structure, psychometric properties, and criterion-related validity of the parent-report version of the PSCD (PSCD-P) in a nationally representative U.S. sample of children and adolescents (N = 1,091, Mage = 13.39, SD = 2.20, range age = 10-17; 50.0% boys, 76% White). Confirmatory factor analyses for the full (24-item) and a shortened (13-item) PSCD-P revealed good internal reliability estimates and support for the four-factor model (grandiose-manipulative, callous-unemotional, daring-impulsive, CD). Results also provided evidence for (a) measurement invariance of the PSCD-P items across sex, race/ethnicity, and age of the child; (b) convergent validity with CD/oppositional defiant disorder symptoms and discriminant validity with a measure of neuroticism; and (c) criterion-related validity with respect to prosociality, peer and family functioning, reactive and proactive aggression, delinquency, academic performance, and substance use. The prevalence for psychopathic personality propensity was found to be 2%. We discuss clinical and research implications regarding the use of the parent-report version of the PSCD for school-aged children. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Use of the Buffalo Concussion Treadmill Test in community adult patients with mild traumatic brain injury.

BACKGROUND: The Buffalo Concussion Treadmill Test (BCTT) is used to establish exercise tolerance for rehabilitation and identify injury subtypes for youth athletes after mild traumatic brain injury (mTBI). Its utility in adult community members is unknown. OBJECTIVE: Primary: To describe how adults with and without mTBI tolerate the BCTT. Secondary: To explore relationships between baseline factors, mTBI-related symptoms, and BCTT duration. DESIGN: Prospective, observational, longitudinal. SETTING: Academic medical center. PARTICIPANTS: Thirty-seven adults treated in a level 1 trauma center emergency department with mTBI; 24 uninjured controls (UC). INTERVENTIONS: N/A. MAIN MEASURES: Participants completed two visits 3 weeks apart (1 week and 1 month after mTBI) including a 15-minute BCTT, the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and preinjury International Physical Activity Questionnaire. Analyses characterized BCTT response and associations between baseline factors, RPQ scores, and BCTT duration. RESULTS: Persons with mTBI discontinued earlier than UC at 1-week postinjury using standard discontinuation criteria for exercise intolerance. The percentage of mTBI participants with signs of possible mTBI-related intolerance was 55.6% at 1 week (36.1% for mTBI-related symptom exacerbation, 19.4% for exertion/fatigue before reaching 85% of one's age-predicted maximum heart rate [HR]) and 48.0% at 1 month (40.0% mTBI-related symptom exacerbation, 8.0% exertion without reaching the target HR). Thirty percent of UCs completed the BCTT at both assessments. UCs met discontinuation criteria for increased nonspecific symptoms (eg, pain/general discomfort and increased Visual Analog Scale ratings; 39-61%) and physical exertion (9-26%). Shorter duration was associated with higher body mass index (r = -0.42 - -0.45), shorter height (r = 0.22-0.29), female gender (r = -0.26 - -0.27), and greater RPQ symptoms (r = -0.28 - -0.47). CONCLUSION: The BCTT exacerbates mTBI-related symptoms in adult community members. Participant characteristics and noninjury factors influence performance. The findings imply the BCTT could be useful in clinical assessments of adults with mTBI. Interpretation should account for the unique characteristics of nonathletes.

Utility of Structured Oculomotor, Balance, and Exercise Testing in Civilian Adults With Mild Traumatic Brain Injury.

PURPOSE: Assessments of oculomotor, balance, and exercise function detect different responses to mild traumatic brain injury in sports-related mild traumatic brain injury. These assessments are understudied in the adult community mild traumatic brain injury population. We evaluated level 1 trauma center patients with nonsports-related mild traumatic brain injury on oculomotor functioning (near point of convergence and accommodation), balance (Balance Error Scoring System), and exercise tolerance (Buffalo Concussion Treadmill Test). METHODS: A prospective, cohort study of adults with mild traumatic brain injury ( n = 36) were assessed at 1 wk and 1-mo post-mild traumatic brain injury ( n = 26) using near point of convergence, near point of accommodation, Balance Error Scoring System, Buffalo Concussion Treadmill Test, and the Rivermead Post Concussion Symptoms Questionnaire. Prevalence of test impairment and association between performance and mild traumatic brain injury-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire scores) were characterized. RESULTS: Participants demonstrated varying levels of impairment (e.g., 33.3% oculomotor, 44.1% balance, and 55.6% exercise impairment at 1 wk). Participants displayed diverse impairment profiles across assessments. We observed medium-to-large correlations between poorer near point of convergence and Buffalo Concussion Treadmill Test performance and greater mild traumatic brain injury symptom burden. CONCLUSIONS: Clinical examinations of oculomotor function, balance, and exercise adopted from sports-related concussion assessments detect impairment in adult community members with mild traumatic brain injury. While findings warrant larger-scale replication, they imply that incorporating these simple, structured examinations into the assessment of mild traumatic brain injury may facilitate more personalized management strategies.

Moderators of the relationship between callous-unemotional traits and externalizing problems in youth.

[Correction Notice: An Erratum for this article was reported online in Personality Disorders: Theory, Research, and Treatment on Oct 26 2023 (see record 2024-19662-001). In the original article, the authors changed the order of authorship from "Blair D. Batky, Allison N. Shields, Jennifer L. Tackett, and Randall T. Salekin" to "Blair D. Batky, Allison N. Shields, Randall T. Salekin, and Jennifer L. Tackett." All versions of this article have been corrected. The names appear correctly in this record.] Callous-unemotional (CU) traits (i.e., tendencies to experience low levels of guilt and empathy) are associated with severe and persistent conduct problems in youth. However, some youth with elevated CU traits do not exhibit severe externalizing problems, and further research is needed to identify conditions under which CU traits are more versus less strongly associated with higher levels of externalizing behavior. To this end, the current preregistered study examined whether internalizing problems, five-factor model personality traits, and parenting practices moderated associations between CU traits and externalizing problems. Caregivers of 1,232 youth ages 6-18 (Mage = 11.46) reported on youths' CU traits, externalizing, internalizing, and five-factor model traits as well as on their own parenting practices. We found that the relationship between CU traits and externalizing was robust to the moderating effects of internalizing problems and parenting practices, but CU traits were more strongly related to externalizing problems at higher levels of neuroticism and at lower levels of agreeableness and conscientiousness. Results contribute to a more comprehensive understanding of externalizing problems among youth high in CU traits and may inform future longitudinal and intervention research seeking to identify factors that reduce externalizing behavior among high-CU youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Role of bradykinin and prostaglandin EP4 receptors in regulating TRPV1 channel sensitization in rat dorsal root ganglion neurons.

Transient receptor potential vanilloid type-1 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9-amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP3 and EP4 ) modulate the sensitisation of TRPV1-mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re-sensitization of TRPV1 by bradykinin, then to explore the role EP3 and EP4 receptors in mediating these bradykinin-dependent effects. Immunocytochemistry was used to study the co-expression and distribution of EP4, TRPV1, COX-1 and B2 in rat DRG neurons. Desensitization was seen upon repeated capsaicin application, we show that bradykinin-mediated sensitization of capsaicin-evoked calcium responses in rat DRG neurons occurs is dependent on COX-1 activity and utilizes a pathway that involves EP4 but not EP3 receptors. Immunocytochemical techniques revealed that EP4, TRPV1, COX-1 and B2 proteins are expressed mainly in small diameter (<1000 µm2 ) cell bodies of rat DRG neurons which are typically nociceptors. The present study provides suggestive evidence for a potential signalling pathway through which bradykinin may regulate TRPV1 ion channel function via EP4 receptors. In addition to confirming existing knowledge, the anatomical distribution and colocalization of these proteins in DRG neurons as revealed by this study offer valuable insight.

Proposed Specifiers for Conduct Disorder (PSCD) self-report: Factor structure and validation in a community sample of Belgian youth.

The current study examined the psychometric properties of the Proposed Specifiers for Conduct Disorder (PSCD) in a sample of school-attending adolescent Belgian youth (N = 599; M age = 16.51 years, SD = 1.27). Given the recent interest in the PSCD-Short Version (PSCD-SV), this study focused on the 13-item variant of the PSCD. Study findings showed that the PSCD-SV had a hierarchical four-factor structure including the components of grandiose-manipulative (GM), callous-unemotional (CU), daring-impulsive (DI), and conduct disorder (CD). These interrelated factors were found to be internally consistent. The study also showed that the PSCD-SV total score was positively and significantly related to an alternate measure of psychopathy. Further, the study revealed the PSCD-SV was meaningfully related to the five-factor personality domains (i.e., extraversion, conscientiousness, agreeableness) as well as peer functioning and prosocial behavior. Bivariate correlations demonstrated that the dimensions differed in their associations with external correlates (e.g., peer functioning). Regression analyses showed that the GM, CU, and CD components of the PSCD-SV were uniquely associated to externalizing difficulties, whereas only the GM and CU components of the PSCD-SV were associated with low prosocial behaviors. These findings shed light on the conceptual and developmental models for the consideration of psychopathy and conduct problems. The use of the broader psychopathy condition as well as its underpinning dimensions may have important implications for assessment, treatment, and diagnostic manuals. The implications of the current study are further discussed.

Aerobic exercise performance is reduced following prolonged cold-water immersion.

Background: We tested the hypotheses that self-paced aerobic exercise performance is reduced following four hours of cold-water immersion when breathing air and further reduced when breathing 100% oxygen (O2). Nine healthy adults (four women; age 24 ± 3 years; body fat 17.9 ± 6.4%; VO2max 48±9 mL • kg • minute⁻¹) completed three visits: a no-immersion control trial and two experimental trials consisting of a four-hour cold-water immersion (20.1±0.3°C) either breathing air (FIO2 = 0.21) or O2 (FIO2 = 1.0). During the no-immersion control trial and following immersion in the experimental trials, subjects first completed a 60-minute ruck-march carrying 20% of body mass in a rucksack, immediately followed by an unweighted, self-paced 5-km time trial on a motorized treadmill. Core temperature, heart rate, and rating of perceived exertion were recorded every 1,000 meters during the 5-km time trial. Data are presented mean± SD. Time trial performance was reduced following immersion in both the 100% O2 trial (32±6 minutes; p=0.01) and air trial (32±5 minutes; p=0.01) compared to the control trial (28± 4 minutes). However, there was no difference between the 100% O2 and air trials (p=0.86). Heart rate, core temperature, and rating of perceived exertion increased during the time trial (time effect: p≺0.01), but were not different between trials (trial effect: p≥0.33). These findings suggest that prolonged cold-water immersion attenuates self-paced aerobic exercise performance, but does not appear to be further affected by breathing gas type.

Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms.

Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role of individual genes in disease-relevant mechanisms. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observe that diseases are significantly associated with gene modules expressed in relevant cell types, and our approach is accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we find that functionally important players lack associations but are prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.

The modulatory role of cannabis use in subconcussive neural injury.

Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

Dissolved Algal Toxins along the Southern Coast of British Columbia Canada.

Harmful algal blooms (HABs) in coastal British Columbia (BC), Canada, negatively impact the salmon aquaculture industry. One disease of interest to salmon aquaculture is Net Pen Liver Disease (NPLD), which induces severe liver damage and is believed to be caused by the exposure to microcystins (MCs). To address the lack of information about algal toxins in BC marine environments and the risk they pose, this study investigated the presence of MCs and other toxins at aquaculture sites. Sampling was carried out using discrete water samples and Solid Phase Adsorption Toxin Tracking (SPATT) samplers from 2017-2019. All 283 SPATT samples and all 81 water samples tested positive for MCs. Testing for okadaic acid (OA) and domoic acid (DA) occurred in 66 and 43 samples, respectively, and all samples were positive for the toxin tested. Testing for dinophysistoxin-1 (DTX-1) (20 samples), pectenotoxin-2 (PTX-2) (20 samples), and yessotoxin (YTX) (17 samples) revealed that all samples were positive for the tested toxins. This study revealed the presence of multiple co-occurring toxins in BC's coastal waters and the levels detected in this study were below the regulatory limits for health and recreational use. This study expands our limited knowledge of algal toxins in coastal BC and shows that further studies are needed to understand the risks they pose to marine fisheries and ecosystems.