Dimensions of experienced gender and prospective self-injurious thoughts and behaviors in preadolescent children: A national study.

OBJECTIVES: Gender diverse youth face higher risk of engaging in self-injurious thoughts and behaviors (SITBs) compared to cisgender youth. Limitations in past research include a focus on older adolescents, an emphasis on specific gender identity labels that may not be inclusive of the range of youth gender experiences, and reliance on cross-sectional data. Thus, the current study prospectively evaluated dimensions of experienced gender in relation to first-onset SITBs among preadolescents. METHODS: Data were drawn from the Adolescent Brain Cognitive Development Study, a longitudinal study of youth across the United States. Youth (n = 7909) were aged 10-11 during initial assessment, and follow-up was conducted one year later. Two dimensions of experienced gender, felt-gender incongruence (not feeling aligned with the gender associated with one's sex assigned at birth) and gender non-contentedness (feeling dissatisfaction with the gender associated with one's sex assigned at birth), were assessed. Primary outcomes included non-suicidal self-injury (NSSI), suicidal ideation (SI), and suicide attempts (SA). RESULTS: Logistic regressions were conducted stratified by sex assigned at birth. For youth assigned female at birth, felt-gender incongruence was prospectively associated with first-onset NSSI and SI and gender non-contentedness was prospectively associated with first-onset of NSSI. For youth assigned male at birth, gender non-contentedness was prospectively associated with first-onset SI. Diverse experienced gender did not prospectively predict SA. CONCLUSIONS: Dimensions of experienced gender may be associated with subsequent first-onset SITBs among preadolescents. These findings support the need for future research on risk and protective factors that may mediate or moderate this relationship.

Assessment of suicidal thoughts and behaviors in adults: A systematic review of measure psychometric properties and implications for clinical and research utility.

High-quality clinical care and research on suicidal thoughts and behaviors (STBs) depends on availability and implementation of reliable and valid measures of STBs. In contrast to studies examining STB risk factors, screening instruments, or treatment, little research has rigorously examined the content, characteristics, and psychometric properties of STB measures themselves. This systematic review (1) identified STB measures that conform to empirically supported definitions of STBs, and (2) identified peer-reviewed papers reporting on the psychometric properties of these measures in adults. Data on psychometric properties and other measure characteristics were extracted. A total of 21 eligible measures were identified in the first stage. In the second stage, 70 articles (with 79 independent samples) were included with psychometric data in adult samples for 19 measures. Although there was support for strong internal consistency and content validity across many measures, face validity and clinical utility concerns were prevalent. Few measures comprehensively assessed suicidal behaviors, and interview-based assessments tended to show the strongest psychometric properties and clinical utility. Findings are discussed in the context of recommendations for improving existing measures, including future research to increase utility and translatability across clinical settings, delivery methods, and diverse populations.

Lessons Learned From a Retrospective Analysis of Medicolegal Risks for Physicians Treated Adolescents and Young Adults With Medical Complexity.

PURPOSE: Adolescent and young adult patients occupy a clinically transitional space between pediatric and adult care. Youth with chronic conditions and special healthcare needs may have trouble accessing and receiving appropriate care in this transition, which may lead to patient safety issues and medicolegal risks for physicians. The objectives of this article were to explore patient safety issues and identify medicolegal risks for physicians. METHODS: A national repository was retrospectively searched for medicolegal cases (MLCs) involving complaints from youth. The study included MLCs closed at the Canadian Medical Protective Association between 2013 and 2022 involving youth. The study participants were adolescents and young adults aged ≥ 15 and ≤ 21 years with medical complexity. The frequencies and proportions of patient safety events and medicolegal risks for physicians were calculated by exploring factors that contributed to each incident using established frameworks. RESULTS: A total of 182 eligible MLCs were identified. Of 206 involved physicians, 55 were psychiatrists. The most common reasons for patient complaints were deficient assessment, diagnostic error, and communication breakdown with the patient and/or family. More than half of the cases were related to a harmful incident. Peer experts reviewed the cases and identified factors such as a deficient assessment, a failure to perform a test or intervention, failure to refer the patient, and insufficient provider knowledge/skill as contributing to the patient safety event. DISCUSSION: The impact of our findings is to identify gaps in care delivery to youth that can inform practitioners of ways to mitigate the gaps and improve patient care and health outcomes.

Analyzing the accuracy of a cross-mounting technique utilizing digitized interocclusal records.

PURPOSE: To compare the accuracy of a partially digital cross-mounting workflow of direct scans of interocclusal records to a conventional workflow by analyzing the deviations of sequentially cross-mounted casts. MATERIALS AND METHODS: A set of reference casts, comprising maxillary and mandibular full-arch prepared casts and interim prostheses, was articulated, mounted, and scanned to generate four reference casts for cross-mounting. In the conventional approach, 15 sets of these four casts were printed. Polyvinylsiloxane (PVS) records were made using the reference casts and utilized for sequential cross-mounting. In the partially digital group, the same PVS interocclusal records were scanned and used for digital cross-mounting via design software. The mean deviations of both groups from the reference cast were analyzed using a 3D inspection software program. Statistical tests, including paired t-test and analysis of variance (ANOVA), were conducted to compare the average discrepancies between the two groups and to evaluate discrepancies in the anterior and posterior regions (α = 0.05). RESULTS: The range of discrepancies was similar in both the conventional and partially digital groups. The final set of related casts had a mean deviation of 201.58 ± 136.98 mm in the conventional workflow and 248.69 ± 164.71 mm in the partially digital workflow. No statistically significant difference was found between conventional and partially digital groups (p = 0.091). Error propagation was examined by comparing discrepancies at each step within the cross-mounting process. In the conventional group, no significant difference was found (p = 0.148), but a significant difference was found among groups in the partially digital group at each step of sequential mounting (p < 0.001). A significant difference was observed between anterior and posterior deviations in the partially digital group (p < 0.001), but not in the conventional group (p = 0.143). CONCLUSIONS: The study reveals that there is no statistically significant difference between conventional and partially digital cross-mounting workflows. However, within the partially digital group, a significant difference in deviation emerges across cross-mounting steps, with increased deviation in the anterior region.

Concerto of movement: how expertise shapes the synergistic control of upper limb muscles in complex motor tasks with varying tempo and dynamics.

Objective. This research aims to reveal how the synergistic control of upper limb muscles adapts to varying requirements in complex motor tasks and how expertise shapes the motor modules.Approach. We study the muscle synergies of a complex, highly skilled and flexible task-piano playing-and characterize expertise-related muscle-synergy control that permits the experts to effortlessly execute the same task at different tempo and force levels. Surface EMGs (28 muscles) were recorded from adult novice (N= 10) and expert (N= 10) pianists as they played scales and arpeggios at different tempo-force combinations. Muscle synergies were factorized from EMGs.Main results. We found that experts were able to cover both tempo and dynamic ranges using similar synergy selections and achieved better performance, while novices altered synergy selections more to adapt to the changing tempi and keystroke intensities compared with experts. Both groups relied on fine-tuning the muscle weights within specific synergies to accomplish the different task styles, while the experts could tune the muscles in a greater number of synergies, especially when changing the tempo, and switch tempo over a wider range.Significance. Our study sheds light on the control mechanism underpinning expertise-related motor flexibility in highly skilled motor tasks that require decade-long training. Our results have implications on musical and sports training, as well as motor prosthetic design.

A systematic review and Bayesian meta-analysis of 30 years of stress generation research: Clinical, psychological, and sociodemographic risk and protective factors for prospective negative life events.

Stress generation posits that (a) individuals at-risk for psychopathology may inadvertently experience higher rates of prospective dependent stress (i.e., stressors that are in part influenced by their thoughts and behaviors) but not independent stress (i.e., stressors occurring outside their influence), and (b) this elevated dependent stress, in some measure, is what places these individuals at-risk for future psychopathology. In recognition of 30 years of stress generation research, we conducted a systematic review and meta-analysis using frequentist and Bayesian approaches (102 articles with 104 eligible studies, N = 31,541). Generally strong support was found for psychopathology predicting dependent stress (e.g., dsOverall psychopathology = 0.36-0.52, BF10 = 946.00 to 4.65 × 10¹8). Moderator analyses for dependent stress revealed larger effects for briefer assessments periods, shorter follow-ups, and self-report measures than for interviews. Among risk factors, depressogenic cognitive styles (ds = .26-.50, BF10 = 47.50 to 1.00 × 105) and general interpersonal vulnerability (ds = .26-.44, BF10 = 2.72 to 2708.00) received the strongest support as stress generation mechanisms, and current evidence is modest for protective factors predicting dependent stress. Overall, larger effects were generally found for prospective prediction of dependent stress than independent stress. Evaluations of mediation in the research literature were relatively few, limiting the current review to qualitative analysis of the mediation component of stress generation. General support was found, however, for dependent stress as a mediator for psychopathology and associated risk factors in relation to subsequent psychopathology. The current review ends with recommendations for future research and integration of stress generation within minority stress frameworks. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Reckoning With Our Past and Righting Our Future: Report From the Behavior Therapy Task Force on Sexual Orientation and Gender Identity/Expression Change Efforts (SOGIECEs).

Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible with modern standards for clinical practice. Despite evidence linking SOGIECEs with serious iatrogenic effects, and despite support for LGBTQ+-affirmative care alternatives, SOGIECE practices persist. In the 1970s and 1980s, Behavior Therapy published articles testing and/or endorsing SOGIECEs, thereby contributing to their overall development, acceptance, and use. The Behavior Therapy Task Force on SOGIECEs was assembled to conduct a rigorous review of the SOGIECE articles published in Behavior Therapy and to decide whether, and what, formal action(s) should be taken on these articles. This report provides a detailed review of the historic SOGIECE literature published in Behavior Therapy and outlines the Task Force's deliberative and democratic processes resulting in actions to: (1) add prominent advisory information to k = 24 SOGIECE papers in the form of digital "black box" disclaimers that caution readers that the SOGIECE practices tested or described in these papers are inconsistent with modern standards, (2) offset organizational financial benefits from the publication of these papers, and (3) promote LGBTQ+-affirmative practices. SOGIECEs are not the only concerning practices across the field's history, and the pages of today's scientific journals include practices that will be at odds with tomorrow's moral standards and ethical guidelines. This report calls for precautionary measures and editorial safeguards to minimize the future likelihood and impact of problematic published scholarship, including the need to fully include those with relevant lived experiences in all aspects of clinical science and peer review.

Incidentally Discovered 99mTc-MDP Uptake on Bone Scan in Otosclerosis.

Otosclerosis is a poorly understood clinical entity causing progressive conductive hearing loss. Here we present the first known evidence of otosclerosis demonstrating 99mTc-MDP uptake on bone scan. This presents an opportunity to explore the role of nuclear medicine imaging in early detection, staging, and even informing treatment and prognosis of this condition. Laryngoscope, 134:4763-4765, 2024.

Cardiometabolic Co-morbidity Burden and Circulating Biomarkers in Patients With Chronic Coronary Disease in the ISCHEMIA Trials.

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.

The effects of adverse and positive experiences on cardiovascular health in Australian children.

BACKGROUND: Limited evidence suggests that positive experiences in childhood may promote cardiovascular health, providing additional opportunities for prevention and early intervention. This study aimed to examine the effects of adverse and positive experiences on cardiovascular health in late childhood. METHODS: Data sources: Longitudinal Study of Australian Children (N = 1874). EXPOSURES: Adverse and positive experiences assessed repeatedly (age 0-11 years). OUTCOMES: Cardiovascular health (high versus low or moderate) quantified by four health behaviors (diet, physical activity, cigarette smoking, and sleep) and four health factors (body mass index, non-high-density lipoprotein, blood pressure, and blood glucose) (age 11-12 years) as per the American Heart Association's Life's Essential 8 metrics. ANALYSES: Separate generalized linear models with log-Poisson links were used to estimate the effects of adverse and positive experiences on cardiovascular health, adjusting for confounders. RESULTS: Children exposed to multiple adverse experiences (≥ 2) were less likely to have high cardiovascular health (RR = 0.82, 95% CI = 0.67 to 1.02) than those not exposed. Children exposed to multiple positive experiences (≥ 2) were more likely to have high cardiovascular health (RR = 1.14, 95% CI = 0.94 to 1.38) than those not exposed. Stratified analyses suggested that exposure to multiple positive experiences might buffer the detrimental effects of multiple adverse experiences on cardiovascular health. CONCLUSIONS: Both adverse and positive experiences were found to be modestly associated with cardiovascular health in Australian children. Future research and practice should not only consider addressing childhood adversity but also use a strengths-based approach to promoting positive experiences to improve cardiovascular health.

Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome.

Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.

Prospective Relations between Life Stress, Emotional Clarity, and Suicidal Ideation in an Adolescent Clinical Sample.

OBJECTIVE: Although life stress has been linked to adolescent suicidal ideation, most past research has been cross-sectional, and potential processes characterizing this relation remain unclear. One possibility may be a lack of emotional clarity. Informed by stress generation, the current study examined prospective relations between episodic life stress, lack of emotional clarity, and suicidal ideation in an adolescent clinical sample. METHODS: The sample consisted of 180 youths (Mage = 14.89; SD = 1.35; 71.7% female; 78.9% White; 43.0% sexual minority) recruited from a psychiatric inpatient facility. Suicidal ideation severity was assessed at baseline and 18-month follow-up. Lack of emotional clarity and life stress were assessed at baseline, as well as 6-, and 12-month follow-ups. Two random-intercepts cross-lagged panel models were created to estimate within-person relations for variables of interest. RESULTS: At the within-person level, lack of emotional clarity at baseline predicted greater 6-month impact of interpersonal dependent stressors (b = 0.29, p = .012, 95% CI [0.07, 0.52]), which subsequently predicted a greater 12-month lack of emotional clarity (b = 0.41, p = .005, 95% CI [0.12, 0.70]). Next, a 12-month lack of emotional clarity but not interpersonal dependent stress, predicted greater 18-month suicidal ideation (b = 0.81, p = .006, 95% CI [0.23, 1.30]; R2 = .24, p < .001). No significant relations were found for the lack of emotional clarity and independent stress. CONCLUSIONS: Results support the stress generation hypothesis and suggest that future research should be conducted evaluating whether bolstering youth's understanding of their emotional experiences may reduce subsequent suicidal ideation.

Acidification of α-granules in megakaryocytes by vacuolar-type adenosine triphosphatase is essential for organelle biogenesis.

BACKGROUND: Platelets coordinate blood coagulation at sites of vascular injury and play fundamental roles in a wide variety of (patho)physiological processes. Key to many platelet functions is the transport and secretion of proteins packaged within α-granules, organelles produced by platelet precursor megakaryocytes. Prominent among α-granule cargo are fibrinogen endocytosed from plasma and endogenously synthesized von Willebrand factor. These and other proteins are known to require acidic pH for stable packaging. Luminal acidity has been confirmed for mature α-granules isolated from platelets, but direct measurement of megakaryocyte granule acidity has not been reported. OBJECTIVES: To determine the luminal pH of α-granules and their precursors in megakaryocytes and assess the requirement of vacuolar-type adenosine triphosphatase (V-ATPase) activity to establish and maintain the luminal acidity and integrity of these organelles. METHODS: Cresyl violet staining was used to detect acidic granules in megakaryocytes. Endocytosis of fibrinogen tagged with the pH-sensitive fluorescent dye fluorescein isothiocyanate was used to load a subset of these organelles. Ratiometric fluorescence analysis was used to determine their luminal pH. RESULTS: We show that most of the acidic granules detected in megakaryocytes appear to be α-granules/precursors, for which we established a median luminal pH of 5.2 (IQR, 5.0-5.5). Inhibition of megakaryocyte V-ATPase activity led to enlargement of cargo-containing compartments detected by fluorescence microscopy and electron microscopy. CONCLUSION: These observations reveal that V-ATPase activity is required to establish and maintain a luminal acidic pH in megakaryocyte α-granules/precursors, confirming its importance for stable packaging of cargo proteins such as von Willebrand factor.

A phase 2, single-arm trial evaluating 131 I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131 I-PSMA-1095 (also known as 131 I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment. METHODS: We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131 I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18 F-DCFPyL PET and 18 F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131 I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed. RESULTS: Eleven patients were screened for inclusion and nine patients received 131 I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia. CONCLUSION: 131 I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131 I-PSMA-1095 compared to 177 Lu-PSMA-617.

Measures of Suicidal Thoughts and Behaviors in Children and Adolescents: A Systematic Review and Recommendations for Use in Clinical and Research Settings.

Empirically supported measures of suicidal thoughts and behaviors (STBs) are needed to serve as reference outcomes for suicide risk screening tools and to monitor severity and treatment progress in children and adolescents with STBs. The present paper systematically reviewed existing measures of STBs in youth and studies evaluating their psychometric properties and clinical utility. Measures were then evaluated on reliability, validity, and clinical utility. Sixteen articles (20 independent samples) were found with psychometric data with youth samples for eight measures. Interview-based measures were found to have the strongest psychometric support and clinical utility. Significant limitations exist for all self-report measures due to inherent characteristics of these measures that cannot be remedied through additional psychometric study. There is an urgent need for the development and validation of new self-report measures of STBs, particularly for preadolescent children, sexual and gender minority youth, and racial/ethnic minority youth.

Rectified Latent Variable Model-Based EMG Factorization of Inhibitory Muscle Synergy Components Related to Aging, Expertise and Force-Tempo Variations.

Muscle synergy has been widely acknowledged as a possible strategy of neuromotor control, but current research has ignored the potential inhibitory components in muscle synergies. Our study aims to identify and characterize the inhibitory components within motor modules derived from electromyography (EMG), investigate the impact of aging and motor expertise on these components, and better understand the nervous system's adaptions to varying task demands. We utilized a rectified latent variable model (RLVM) to factorize motor modules with inhibitory components from EMG signals recorded from ten expert pianists when they played scales and pieces at different tempo-force combinations. We found that older participants showed a higher proportion of inhibitory components compared with the younger group. Senior experts had a higher proportion of inhibitory components on the left hand, and most inhibitory components became less negative with increased tempo or decreased force. Our results demonstrated that the inhibitory components in muscle synergies could be shaped by aging and expertise, and also took part in motor control for adapting to different conditions in complex tasks.

Family dementia caregivers with suicidal ideation improve with mentalizing imagery therapy: Results from a pilot study.

Background: Family caregivers of persons living with dementia often experience increased depression and suicidal ideation (SI). However, the feasibility and impact of therapies on caregiver SI has remained largely unexplored. Mentalizing imagery therapy (MIT) helps reduce psychological symptoms through mindfulness and guided imagery. This pilot study examined the feasibility of participation by caregivers with SI in a randomized controlled trial (RCT) of MIT versus a psychosocial support group (SG), and the respective impact of group on SI, depression, and secondary outcomes. Methods: A secondary analysis of data from an RCT of 4-week MIT or SG for caregivers (n = 46) was performed, identifying SI (n = 23) and non-SI (n = 23) cohorts. Group attendance and home practice were compared between cohorts. In the SI cohort (total n = 23, MIT n = 11, SG n = 12), group differences in SI, depression, and secondary outcomes were evaluated post-group and at 4-month follow-up. Results: Attendance in both groups and home practice in MIT were similar between SI and non-SI cohorts. In the SI cohort, MIT evinced greater improvements relative to SG in SI (p=.02) and depression (p=.02) post-group, and other secondary outcomes at follow-up. Limitations: Limitations include small sample size and single-item assessments of SI from validated depression rating scales. Conclusions: Participation in an RCT was feasible for caregivers with SI. MIT resulted in important benefits for SI and depression, while SG showed no acute SI benefit. The role of MIT in improving SI should be confirmed with adequately powered trials, as effective therapies to address caregiver SI are critical.

The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway.

There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18-65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = -229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium.

Assessing Adverse Outcomes and Learning Needs in Canadian Psychiatric Independent Medical Examinations.

Despite the importance of independent medical examinations (IMEs), there is virtually no literature on the risks to the IME assessor nor the learning needs of psychiatrists in this area. To address this deficit, a retrospective chart review of nearly 38,000 cases from the Canadian Medical Protective Association (CMPA) identified 108 files involving complaints or legal actions against psychiatrists performing IMEs. Most complaints identified by the CMPA were to regulatory bodies, including biased opinion, inadequate assessment, inappropriately relying on a requester's information without independent evaluation, nonadherence to regulatory body policies, cursory documentation lacking relevant details, and communication breakdowns. A survey by the Canadian Academy of Psychiatry and the Law (CAPL) and the Canadian Psychiatric Association (CPA) had 306 Canadian psychiatrist respondents. About 37 percent of psychiatrists completing IMEs reported medico-legal consequences, including complaints to regulatory authorities. Only 40 percent of those doing IMEs and 20 percent of all psychiatrists had formal training in doing IMEs. The studies confirm that despite a low but important risk of medico-legal consequences, many psychiatrists performing IMEs do not have formalized training. Using the new CAPL Canadian Guidelines for Forensic Psychiatry Assessment and Report Writing is a step to reduce the risk of such evaluations.