Transgender Youth Readiness for Health Care Transition: A Survey of Youth, Parents, and Providers.

Purpose: The purpose of this study was to identify health care transition (HCT) readiness and skills among transgender youth transitioning gender-affirming care from pediatric to adult providers. Methods: A convenience sample of youth, 14-21 years old, their parents, and health care providers recruited from a multidisciplinary transgender youth clinic in 2019 completed a modified version of the Got Transition readiness assessment with elements specific to gender-affirming care. Youth assessed their own readiness, parents assessed their child's readiness, and providers assessed their transgender patients' readiness overall. Results: Twenty-nine youth (mean age 17.0 years), 26 parents, and 5 health care providers participated. Ratings of the overall importance of preparing for HCT were similar across all participant groups, and there were few disagreements on the importance of individual skills included in the readiness assessment. Ratings of overall HCT readiness were similar for youth regardless of age, while parents of younger youth (<18 years old) reported lower readiness than did parents of older youth. Youth rated their own competence in several skills higher compared with parents or providers, including knowledge of hormone therapy side effects. All groups of participants reported that youth most frequently needed assistance with scheduling appointments and keeping records of health information. Conclusions: Survey of youth, parents, and providers suggests that youth and parents require additional support to navigate the HCT process, highlighting the importance of ongoing skills assessment and planning.

Warning signs for suicide attempts in psychiatric inpatients: Patient and informant perspectives.

OBJECTIVE: Warning signs can help prevent suicide attempts and death. It is important to develop an evidence base for warning signs that considers both self-perspectives (i.e., those at risk for suicide) and informant-perspectives (i.e., those who observe individuals at risk for suicide). METHODS: A questionnaire assessing a diverse set of 80 potential warning signs ("present in the minutes, hours, or days before the suicide attempts") was developed based on literature searches, lived experience consultations, and the American Association of Suicidology (AAS) expert consensus list. This questionnaire was administered to two samples: psychiatric inpatients who had attempted suicide (n = 476), and informants identified as friends, family, or caretakers of patients (n = 120). RESULTS: Hopelessness, anxiousness, and unbearable pain were each endorsed as warning signs by >80% of inpatients and informants. Warning signs were similar across patient and informant perspectives, and across sociodemographic and clinical characteristics. Some AAS warning signs were endorsed by few patients and informants (risky behaviors, alcohol or drug use, seeking revenge) and may warrant re-evaluation. CONCLUSIONS: Findings are consistent with models of suicide risk emphasizing pain, hopelessness, and anxiousness. Existing lists of warning signs may benefit from revision as the evidence base continues to develop.

Characterization of Poldip2 knockout mice: Avoiding incorrect gene targeting.

POLDIP2 is a multifunctional protein whose roles are only partially understood. Our laboratory previously reported physiological studies performed using a mouse gene trap model, which suffered from three limitations: perinatal lethality in homozygotes, constitutive Poldip2 inactivation and inadvertent downregulation of the adjacent Tmem199 gene. To overcome these limitations, we developed a new conditional floxed Poldip2 model. The first part of the present study shows that our initial floxed mice were affected by an unexpected mutation, which was not readily detected by Southern blotting and traditional PCR. It consisted of a 305 kb duplication around Poldip2 with retention of the wild type allele and could be traced back to the original targeted ES cell clone. We offer simple suggestions to rapidly detect similar accidents, which may affect genome editing using both traditional and CRISPR-based methods. In the second part of the present study, correctly targeted floxed Poldip2 mice were generated and used to produce a new constitutive knockout line by crossing with a Cre deleter. In contrast to the gene trap model, many homozygous knockout mice were viable, in spite of having no POLDIP2 expression. To further characterize the effects of Poldip2 ablation in the vasculature, RNA-seq and RT-qPCR experiments were performed in constitutive knockout arteries. Results show that POLDIP2 inactivation affects multiple cellular processes and provide new opportunities for future in-depth study of its functions.

Examining the Three-Step Theory (3ST) of Suicide in a Prospective Study of Adult Psychiatric Inpatients.

This study examined the validity and predictive utility of the three-step theory (3ST) of suicide in psychiatric patients. Participants were 190 consecutively admitted adult psychiatric inpatients (53% female, 60% White, ages 18-73) assessed at three time points: baseline, 4 weeks later (n = 112), and 3 months postdischarge (n = 102). Results were broadly supportive of the 3ST. First, at baseline, an interactive model of pain and hopelessness accounted for substantial variability in suicidal desire, even when controlling for depression and lifetime ideation. This result replicated in different genders and age ranges (i.e., 18-32 and 33-73). Further, pain and hopelessness were robust predictors of suicidal desire weeks and months into the future. Second, among those with pain and hopelessness, lower connectedness, as well as the extent to which pain exceeds connectedness, were robust predictors of higher suicidal desire. Last, a baseline measure of practical capability for suicide predicted suicide attempts both retrospectively and prospectively, even when controlling for lifetime ideation-however, dispositional and acquired contributors to capability were less predictive. Results support the validity and predictive utility of the 3ST, and suggest that the theory may have utility for guiding risk assessment and intervention.

Transition from Pediatric to Adult Care for Transgender Youth: A Qualitative Study of Patient, Parent, and Provider Perspectives.

Purpose: No information exists on the needs of transgender youth transitioning their gender-affirming health care from pediatric to adult settings. We obtained perspectives of transgender youth, their parents, and providers, and aimed to identify barriers and unmet needs during the transition of care. Methods: Five online focus groups were conducted between February and March 2019 with separate groups for transgender youth 13-17 and 18-21 years old; parents of transgender youth 13-17 and 18-21 years old; and gender-affirming health care providers. Thematic analysis of transcripts was conducted by two researchers. Pooled Cohen's κ was 0.83, indicating excellent inter-rater reliability. Results: Sixty-six participants (29 youth, 27 parents, and 10 providers) identified 10 themes. Themes related to barriers to transition included access and insurance challenges, patient readiness and hesitancy to transfer care, and multidisciplinary-system inefficiencies. Themes related to improving transition focused on prioritizing referrals from trusted sources, establishing gradual patient independence, aligning gender transition goals, and setting impetus for transferring care. Conclusion: Successful health care transition for transgender youth must consider the intricacies of a complex medical system and challenges that they pose to adolescents' perceived abilities to independently manage health care and willingness to prepare transfer of care. Given that patients, parents, and providers assume important roles during the process, each can uniquely contribute toward ensuring a smooth transition. Efforts to improve this process should focus on enhancing collaboration between clinics and families through crowdsourcing resources, continued verification of health goals, supporting greater patient autonomy, and delineating an explicit timeline for transition.

A Brief Measure of Unbearable Psychache.

OBJECTIVE: Psychache has been proposed to cause suicide when it becomes unbearable. However, existing measures of psychache do not directly target unbearable psychache. Thus, the purpose of the current study was to provide initial validation for a brief measure of unbearable psychache. METHOD: Three items were selected to create the Unbearable Psychache Scale (UP3). Psychometric properties were assessed in two populations: (1) an online sample composed of 1,006 adults (53% male) from various locations in the United States and (2) a sample of 190 psychiatric inpatient adults (47% male) from a hospital in Western Canada. RESULTS: In both samples, the UP3 demonstrated excellent internal reliability, and strong convergent and predictive validity. Additionally, the UP3 predicted significant variance in suicidal ideation over and above documented correlates of suicidal ideation including general psychache, hopelessness, perceived burdensomeness, and low belongingness. CONCLUSIONS: The UP3 is a brief, psychometrically sound measure of unbearable psychache that may be well-suited for use in research protocols and clinical assessments.

Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells.

Polymerase-δ-interacting protein 2 (Poldip2) controls a wide variety of cellular functions and vascular pathologies. To mediate these effects, Poldip2 interacts with numerous proteins and generates reactive oxygen species via the enzyme NADPH oxidase 4 (Nox4). We have previously shown that Poldip2 can activate the Rho family GTPase RhoA, another signaling node within the cell. In this study, we aimed to better understand how Poldip2 activates Rho family GTPases and the functions of the involved proteins in vascular smooth muscle cells (VSMCs). RhoA is activated by guanine nucleotide exchange factors. Using nucleotide-free RhoA (isolated from bacteria) to pulldown active RhoGEFs, we found that the RhoGEF epithelial cell transforming sequence 2 (Ect2) is activated by Poldip2. Ect2 is a critical RhoGEF for Poldip2-mediated RhoA activation, because siRNA against Ect2 prevented Poldip2-mediated RhoA activity (measured by rhotekin pulldowns). Surprisingly, we were unable to detect a direct interaction between Poldip2 and Ect2, as they did not coimmunoprecipitate. Nox4 is not required for Poldip2-driven Ect2 activation, as Poldip2 overexpression induced Ect2 activation in Nox4 knockout VSMCs similar to wild-type cells. However, antioxidant treatment blocked Poldip2-induced Ect2 activation. This indicates a novel reactive oxygen species-driven mechanism by which Poldip2 regulates Rho family GTPases. Finally, we examined the function of these proteins in VSMCs, using siRNA against Poldip2 or Ect2 and determined that Poldip2 and Ect2 are both essential for vascular smooth muscle cell cytokinesis and proliferation.

Attachment style and readiness for psychotherapy among psychiatric outpatients.

Ninety-two adults attending outpatient mental health services completed measures of attachment style and readiness to engage in psychotherapy. Correlation and linear regression analyses found anxious attachment to be positively associated with treatment-seeking distress and found avoidant attachment to be negatively associated with openness to personal disclosure in the therapy relationship. PRACTITIONER POINTS: Insecure attachment may influence prospective patients' readiness for psychotherapy. Patients with an avoidant attachment style may need assistance in preparing for the relational aspects of psychotherapy.

Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

OBJECTIVE: To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. METHODS: Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. RESULTS: Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. CONCLUSIONS: The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

Forecasting success: patients' expectations for improvement and their relations to baseline, process and outcome variables in group cognitive-behavioural therapy for depression.

UNLABELLED: There is growing evidence for the important role of patients' outcome expectations to the process and outcome of psychotherapy, yet its relevance to group cognitive-behavioural therapy (CBT) for depression has not been examined. In an effort to fill this void, the present study investigated expectations for improvement among 80 psychiatric outpatients attending a group CBT program for depression. The study addressed the following four questions: (1) Which baseline patient characteristics might be associated with patients' expectations for improvement? (2) Does providing a rationale and outline for treatment affect patients' expectations? (3) Are patients' expectations related to the quality of therapeutic alliance? and (4) Are patients' expectations associated with the outcome of treatment? The main findings of the study are as follows: (a) baseline symptoms of depression, quality of life and current suicidal ideations were consistently associated with outcome expectancies; (b) outcome expectancies were unrelated to treatment completion status; (c) although expectancy ratings did not change significantly for the group as a whole, there was some variability in how individual patient's expectancy ratings changed; (d) baseline expectancies were related to early-treatment alliance quality, but not to mid-treatment alliance, whereas early-treatment expectancies were significantly associated with mid-treatment alliance; and (e) baseline expectations of favourable outcome had a negative association with improvement in anxiety symptoms, yet expectancy ratings from session 3 had a positive association with improvement in quality of life and interpersonal problems. Increases in expectancy ratings were significantly related to improvement in anxiety, quality of life and interpersonal problems. KEY PRACTITIONER MESSAGE: Patients who present in a particularly hopeless and demoralized state are likely to have low expectations for a positive outcome of treatment. Efforts should be made in the first few sessions of therapy to mobilize patients' hope and expectation of success, for increases in one's expectations may facilitate a favourable treatment outcome. An optimistic outlook on the probability of success in treatment may contribute to the development of a strong working relationship between the patient and the therapist.

Endothelialized microfluidics for studying microvascular interactions in hematologic diseases.

Advances in microfabrication techniques have enabled the production of inexpensive and reproducible microfluidic systems for conducting biological and biochemical experiments at the micro- and nanoscales (1,2). In addition, microfluidics have also been specifically used to quantitatively analyze hematologic and microvascular processes, because of their ability to easily control the dynamic fluidic environment and biological conditions(3-6). As such, researchers have more recently used microfluidic systems to study blood cell deformability, blood cell aggregation, microvascular blood flow, and blood cell-endothelial cell interactions(6-13).However, these microfluidic systems either did not include cultured endothelial cells or were larger than the sizescale relevant to microvascular pathologic processes. A microfluidic platform with cultured endothelial cells that accurately recapitulates the cellular, physical, and hemodynamic environment of the microcirculation is needed to further our understanding of the underlying biophysical pathophysiology of hematologic diseases that involve the microvasculature. Here, we report a method to create an "endothelialized" in vitro model of the microvasculature, using a simple, single mask microfabrication process in conjunction with standard endothelial cell culture techniques, to study pathologic biophysical microvascular interactions that occur in hematologic disease. This "microvasculature-on-a-chip" provides the researcher with a robust assay that tightly controls biological as well as biophysical conditions and is operated using a standard syringe pump and brightfield/fluorescence microscopy. Parameters such as microcirculatory hemodynamic conditions, endothelial cell type, blood cell type(s) and concentration(s), drug/inhibitory concentration etc., can all be easily controlled. As such, our microsystem provides a method to quantitatively investigate disease processes in which microvascular flow is impaired due to alterations in cell adhesion, aggregation, and deformability, a capability unavailable with existing assays.

Depressive tendencies and pathological narcissism among psychiatric outpatients.

This study examined the relationship between components of pathological narcissism and types of depressive tendencies among a sample of 117 psychiatric outpatients. Findings revealed that depressive themes concerning dependency were associated with narcissistic grandiosity. Depressive tendencies concerning self-criticism were positively associated with narcissistic vulnerability.

In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology.

In hematologic diseases, such as sickle cell disease (SCD) and hemolytic uremic syndrome (HUS), pathological biophysical interactions among blood cells, endothelial cells, and soluble factors lead to microvascular occlusion and thrombosis. Here, we report an in vitro "endothelialized" microfluidic microvasculature model that recapitulates and integrates this ensemble of pathophysiological processes. Under controlled flow conditions, the model enabled quantitative investigation of how biophysical alterations in hematologic disease collectively lead to microvascular occlusion and thrombosis. Using blood samples from patients with SCD, we investigated how the drug hydroxyurea quantitatively affects microvascular obstruction in SCD, an unresolved issue pivotal to understanding its clinical efficacy in such patients. In addition, we demonstrated that our microsystem can function as an in vitro model of HUS and showed that shear stress influences microvascular thrombosis/obstruction and the efficacy of the drug eptifibatide, which decreases platelet aggregation, in the context of HUS. These experiments establish the versatility and clinical relevance of our microvasculature-on-a-chip model as a biophysical assay of hematologic pathophysiology as well as a drug discovery platform.

Assessment of learning gains associated with independent exam analysis in introductory biology.

This study evaluates the impact of an independent postmidterm question analysis exercise on the ability of students to answer subsequent exam questions on the same topics. It was conducted in three sections (∼400 students/section) of introductory biology. Graded midterms were returned electronically, and each student was assigned a subset of questions answered incorrectly by more than 40% of the class to analyze as homework. The majority of questions were at Bloom's application/analysis level; this exercise therefore emphasized learning at these higher levels of cognition. Students in each section answered final exam questions matched by topic to all homework questions, providing a within-class control group for each question. The percentage of students who correctly answered the matched final exam question was significantly higher (p < 0.05) in the Topic Analysis versus Control Analysis group for seven of 19 questions. We identified two factors that influenced activity effectiveness: 1) similarity in topic emphasis of the midterm-final exam question pair and 2) quality of the completed analysis homework. Our data suggest that this easy-to-implement exercise will be useful in large-enrollment classes to help students develop self-regulated learning skills. Additional strategies to help introductory students gain a broader understanding of topic areas are discussed.