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ObjectiveThis study aimed to identify differences in patient empowerment based on biopsychosocial patient-reported measures, the magnitude of those differences, and which measures best explain differences in patient empowerment.MethodsThis was a cross-sectional observational study of 6918 adults with arthritis in the US. Data were collected from March 2019 to March 2020 through the Arthritis Foundation Live Yes! INSIGHTS program. Patient empowerment, measured by the Health Care Empowerment Questionnaire, included 2 scales: Patient Information Seeking and Healthcare Interaction Results. Patient-reported outcomes were measured using the Patient Reported Outcomes Measurement Information System (PROMIS)-29 and PROMIS emotional support scale. ANOVA assessed differences between groups, and Spearman rank correlation assessed correlations between variables. Hierarchical regression analysis determined the contributions of sociodemographic characteristics, arthritis type, and patient-reported health measures in explaining patient empowerment (α = 0.05).ResultsEmpowerment was lower among those who were male, older, less educated, or who had lower income, osteoarthritis, less emotional support, or better physical function, although the effect was small-to-negligible for most of these variables in the final regression models. Empowerment did not differ by race/ethnicity in unadjusted or adjusted analysis. In final regression models, emotional support contributed the most to explaining patient empowerment.ConclusionEmotional support is important for patient empowerment. This suggests that programs that seek to improve patient empowerment should target and measure effects on emotional support.

Close relationships are consequential for youth depressive symptoms and suicide risk, but nuanced research examining intersecting factors is needed to improve identification and intervention. This study examines a clinical, residential sample of 939 adolescents and young adults ages 10 to 23 years old (M = 15.84, SD = 1.53; 97.7% white, 99.5% non-Hispanic, 55% female). The final model found that family conflict, parental criticism, verbal bullying, and interactions with friends were associated with depressive symptoms in the expected directions, and there were significant interactions with family, peer, and demographic variables. However, most associations with suicide risk were indirect. Associations involving family factors, peer factors, depressive symptoms, and suicide are not always straightforward, and should be understood within a microsystemic context.

Objective Despite considerable evidence that supports perceived burdensomeness (PB) and thwarted belongingness (TB) as risk factors for suicidal ideation (SI), far less is known about the direction of effects between these constructs in treatments for suicidal adolescents. The present study examined bidirectional relations between PB, TB, and adolescents' suicidal ideation (SI) during a 16-week randomized clinical trial. Method 129 depressed and suicidal adolescents completed PB, TB, and SI measures at three time points: baseline (T1), mid-treatment (T2), and treatment completion (T3). Random-intercept cross-lagged panel models (RI-CLPM) examined within-subject direction of effects between interpersonal variables (PB & TB) and suicidal ideation (SI) in the first and second halves of treatment. Results Within-subjects, autoregressive paths indicated significant carryover in PB and SI. In the first half of treatment, a significant cross-lagged path indicated that T1 PB predicted change in T2 SI, and in the last half of treatment change in T2 SI predicted change in T3 PB. There were no significant auto-regressive or cross-lagged effects for TB. Conclusions In the first half of treatment, baseline PB predicted fewer reductions in SI suggesting that PB initially moderated adolescents' response to treatment. However, in the last half of treatment, initial reductions in SI predicted subsequent reductions in PB suggesting that adolescents' initial response to treatment decreased their perceptions of burdening others. The clinical and treatment implications of these bidirectional findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The COVID‐19 pandemic has transformed so many aspects of our lives. For psychotherapists, telehealth is likely a permanent part of the future mental health landscape. For family therapists using a manualized treatment, this brings unique challenges and creative opportunities. In this article, we describe the adaptation of attachment‐based family therapy (ABFT) in the context of telehealth and COVID‐19. ABFT is an empirically supported treatment model designed for adolescents and young adults struggling with depression, anxiety, trauma, and suicide. ABFT is a semi‐structured, process‐oriented, and trauma‐informed family therapy model which presents its own unique challenges and benefits in telehealth environments. We present our adaptations based on years of telehealth clinical experience and address how this model supports the impact of COVID‐19 on families.

This study evaluates the relationship between substance use and impairment and current suicidal thoughts or behaviors in adolescent patients screened in a pediatric emergency department (ED).Data were collected between June 2013 and February 2018 from adolescent patients who presented to a single, urban, pediatric ED. Adolescents completed a computerized, self-administered assessment that evaluates depression, suicide, posttraumatic stress, violence, traumatic exposure, bullying, and substance use. Assessments are administered as standard care to all ED patients aged 14 to 18 years. We used binary logistic regression to estimate the odds of reporting current suicidal thoughts or behaviors associated with patient demographics (ie, age, sex, and race), substance use in the past month, and substance-related impairment.A total of 11,623 adolescent patients (65.4% female and 52.9% African American) completed the assessment. Participants were, on average, 15.7 years old (SD = 1.27). Younger age (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.74-0.84) and substance use impairment (OR, 0.44; 95% CI, 0.33-0.58) decreased the odds of reporting current suicidal thoughts or behaviors, whereas male sex (OR, 1.51; 95% CI, 1.28-1.79) and those with past-month substance use (OR, 1.85; 95% CI, 1.51-2.26) increased the odds.Recent substance use and male sex are associated with a higher likelihood of adolescents reporting current suicidal thoughts or behaviors during an ED visit. Standardized screening during pediatric ED visits may allow for more efficient evaluation of patients in higher-risk groups.

OBJECTIVE To investigate the impact of residual β-cell function on continuous glucose monitoring (CGM) outcomes following acute exercise in people with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Thirty participants with T1D for ≥3 years were recruited. First, participants wore a blinded CGM unit for 7 days of free-living data capture. Second, a 3-h mixed-meal test assessed stimulated C-peptide and glucagon. Peak C-peptide was used to allocate participants into undetectable (Cpepund 200 pmol/L) C-peptide groups. Finally, participants completed 45 min of incline treadmill walking at 60% VO2peak followed by a further 48-h CGM capture. RESULTS CGM parameters were comparable across groups during the free-living observation week. In the 12- and 24-h postexercise periods (12 h and 24 h), the Cpephigh group had a significantly greater amount of time spent with glucose 3.9–10 mmol/L (12 h, 73.5 ± 27.6%; 24 h, 76.3 ± 19.2%) compared with Cpeplow (12 h, 43.6 ± 26.1%, P = 0.027; 24 h, 52.3 ± 25.0%, P = 0.067) or Cpepund (12 h, 40.6 ± 17.0%, P = 0.010; 24 h, 51.3 ± 22.3%, P = 0.041). Time spent in hyperglycemia (12 h and 24 h glucose >10 and >13.9 mmol/L, P < 0.05) and glycemic variability (12 h and 24 h SD, P < 0.01) were significantly lower in the Cpephigh group compared with Cpepund and Cpeplow. Change in CGM outcomes from pre-exercise to 24-h postexercise was divergent: Cpepund and Cpeplow experienced worsening (glucose 3.9–10 mmol/L: −9.1% and −16.2%, respectively), with Cpephigh experiencing improvement (+12.1%) (P = 0.017). CONCLUSIONS Residual β-cell function may partially explain the interindividual variation in the acute glycemic benefits of exercise in individuals with T1D. Quantifying C-peptide could aid in providing personalized and targeted support for exercising patients.

Background The current study aimed to classify recent and lifetime suicide attempt history among youth presenting to medical settings using machine learning (ML) as applied to a behavioral health screen self-report survey. Methods In the current study, 13,325 (mean age = 17.06, SD = 2.61) pediatric primary care patients from rural, semi-urban, and urban areas of Pennsylvania and 12,001 (mean age = 15.79, SD = 1.40) pediatric patients from an urban children's hospital emergency department were included in the analyses. We used two methods of ML (decision trees, random forests) to (a) generate algorithms to classify suicide attempt history, and (b) validate generated algorithms within and across samples to assess model performance. We also employed ridge regression to evaluate performance of the ML approaches. Results Our findings demonstrate that ML approaches did not enhance our ability to classify lifetime or recent suicide attempt history among youth across medical care settings, suggesting that relationships may be mainly linear and non-interactive. In line with prior research, a history of suicide planning, active suicidal ideation, passive suicidal ideation, and nonsuicidal self-injury emerged as relatively important correlates of suicide attempt. Limitations The cross-sectional nature of the current study prevents us from determining the extent to which the important variables identified confer risk for future suicidal behavior. Conclusions The present study underscores the importance of suicide risk screenings that focus on the assessment of active and passive suicidal ideation and suicide planning, in addition to nonsuicidal self-injury, across pediatric medical settings.

Significance Genome-wide association studies have identified genetic variation at the ARMS2/HTRA1 locus as a risk factor for the development and progression of age-related macular degeneration (AMD). We have developed a potent anti-HtrA1 Fab inhibitor of HtrA1 proteolytic activity in the retina as a potential therapeutic for treating AMD. A set of proteomic analytical tools was established to characterize HtrA1 activity and discover in vivo HtrA1 substrates. These efforts led to the identification of an eye-specific and clinically applicable pharmacodynamic biomarker of anti-HtrA1 Fab activity. Analysis of HtrA1-mediated cleavage of Dickkopf-related protein 3 in the aqueous humor of patients with geographic atrophy provided evidence of anti-HtrA1 Fab activity and information on duration of activity in a phase 1 study., Genetic polymorphisms in the region of the trimeric serine hydrolase high-temperature requirement 1 (HTRA1) are associated with increased risk of age-related macular degeneration (AMD) and disease progression, but the precise biological function of HtrA1 in the eye and its contribution to disease etiologies remain undefined. In this study, we have developed an HtrA1-blocking Fab fragment to test the therapeutic hypothesis that HtrA1 protease activity is involved in the progression of AMD. Next, we generated an activity-based small-molecule probe (ABP) to track target engagement in vivo. In addition, we used N-terminomic proteomic profiling in preclinical models to elucidate the in vivo repertoire of HtrA1-specific substrates, and identified substrates that can serve as robust pharmacodynamic biomarkers of HtrA1 activity. One of these HtrA1 substrates, Dickkopf-related protein 3 (DKK3), was successfully used as a biomarker to demonstrate the inhibition of HtrA1 activity in patients with AMD who were treated with the HtrA1-blocking Fab fragment. This pharmacodynamic biomarker provides important information on HtrA1 activity and pharmacological inhibition within the ocular compartment.

Objective Suicide is a leading cause of death in adolescence. The mechanisms of adolescent suicidality, however, are not fully understood. Although the Interpersonal-Psychological Theory of Suicide, as assessed by the Interpersonal Needs Questionnaire-15 (INQ), may be a promising framework, systematic study of its utility during adolescence is lacking. Method To this end, we utilized factor analyses and hierarchical regression analyses to test the factor structure, correlates, and predictive validity of the INQ in a sample of clinically depressed and suicidal adolescents (N = 120, aged 12-18). The sample was mostly female (81.9%), ethnically diverse (68.2% non-White) and with nearly a third identifying as a sexual minority (31.8%). Results Contrary to studies including adult samples in which a two-factor solution is identified, results within this sample indicated three factors: perceived burdensomeness, thwarted belongingness, and perceived isolation. Perceived burdensomeness and the interaction between perceived burdensomeness and perceived isolation predicted suicide ideation above and beyond depression, but thwarted belongingness and perceived isolation did not. Conclusion Perceived burdensomeness appears to play a role in adolescent suicidality and may be a point of intervention, yet the notable deviation from previous findings and the relative weakness of two of the factors warrant further study.

ObjectiveA subset of patients at the time of transcatheter mitral valve repair (TMVR) will have normal left atrial pressure (LAP) (MethodsA single-centre retrospective cohort of consecutive patients who underwent transcatheter edge-to-edge mitral valve clip and continuous LAP monitoring between 5/1/2014 and 5/1/2018 was analysed. One-year mortality was compared by Kaplan–Meier survival curves. Multivariable analysis was performed to identify predictors of normal LAP and 1 year mortality.ResultsOf the 204 patients undergoing TMVR, 65% were men and the mean age was 81. Of these patients, 31 (15%) had normal LAP (mean LAP 10.5 mm Hg, mean V wave 16.5 mm Hg) and 173 had elevated LAP (mean LAP 19 mm Hg, mean V wave 32.5 mm Hg). The prevalence of severe MR was not different between groups, although the normal LAP group had significantly lower effective regurgitant orifice area and regurgitant volume. Other notable baseline characteristics including prior cardiac surgery, atrial fibrillation, hypertension, diabetes, congestive heart failure, body mass index, mechanism of MR and ejection fraction were similar between groups. However, there was an increased prevalence of chronic lung disease (CLD) (45.2% vs 17.3%, pConclusionNormal LAP at the time of TMVR is associated with a higher incidence of CLD which independently predicts increased 1-year mortality. In patients with CLD and apparently severe MR, measurement of LAP may help identify those with lower likelihood of benefit from TMVR.

Human immunodeficiency virus (HIV) testing is a cornerstone in preventing HIV infections and accessing treatment for HIV. However, HIV testing remains low among men in the Democratic Republic of Congo (DRC). The purpose of this study was to assess the correlates of HIV testing among men in the DRC. Data from the 2014 DRC Demographic Health Survey were analyzed to assess the relationships between HIV testing and the correlates of HIV testing among 7830 men aged 15-59 years. Although more than half (4763 or 63.7%) knew of an HIV testing site, only one-sixth (1187 or 16.6%) reported ever being tested for HIV. The multivariate logistic regression indicated that men aged between 25 and 34 years were more likely to have tested for HIV than those aged between 15 and 24 years (aOR = 1.70; 95% CI: [1.23-2.34]). In addition, men with college experience were 5.47 more likely to have tested for HIV than men with no formal education (aOR = 5.47; 95% CI: [2.53-11.84]). The results highlight the need for a national HIV testing awareness and uptake campaign for Congolese men to increase HIV testing among this group and prevent HIV infections.

Objective Although there are currently several efficacious treatments for depressed and suicidal adolescents, less is known about predictors and moderators of adolescents' treatment response. A growing literature has identified family functioning as a prognostic indicator of adolescents' likelihood of benefiting from treatment. The current study tested both observational and perceived measures of family functioning as indicators of adolescents' response to 2 treatment conditions. Method The sample consisted of 129 depressed and suicidal adolescents (Mage = 14.96, 82.9% female, 56% Black/African American) who were randomized to attachment-based family therapy or family-enhanced nondirective supportive therapy (Diamond et al., 2019). Baseline assessments of family functioning included ratings of parent-adolescent communication coded with the Goal-Corrected Partnership in Adolescence Coding System (Lyons-Ruth, Hennighausen, & Holmes, 2005) and adolescent and parent reports of Family Conflict and Cohesion from the Self-Report of Family Functioning (Bloom, 1985). Results Adolescents who engaged in more uncooperative communication with their parents during a 10-min conflict discussion showed greater reductions in depressive symptoms in both treatments. Adolescents from traditionally underserved (non-White or lower income) families showed greater reductions in suicidal ideation in both treatments. Conclusions Attachment-based family therapy and family-enhanced nondirective supportive therapy were most effective for adolescents from traditionally underserved families and adolescents who engaged in less cooperative communication with their caregivers. Observational ratings of parent-adolescent communication were better prognostic indicators of treatment response than were self-reported indicators of global family functioning. Implications for generalizing these results to other treatments for depressed and suicidal adolescents are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Purpose To study the use of iris-claw Artisan intraocular lenses (IOLs) in patients with uveitis. Setting Moorfields Eye Hospital, London, England. Design Retrospective case series. Methods Data on all patients with anterior uveitis, intermediate uveitis, and panuveitis who had anterior-fixated Artisan IOL insertion between January 2014 and July 2019 at Moorfields Eye Hospital were assessed. Patients who had less than 2 months of follow-up were excluded from the analysis. Results The study comprised 11 patients. The mean age of the 7 women and 4 men was 61 years ± 14 (SD). The mean follow-up was 1.7 years. After Artisan IOL insertion, the corrected distance visual acuity (CDVA) improved significantly from 20/200 to 20/50 (P = .02). No patients had a significant flare-up of their uveitis after the surgery, and there were no intraocular pressure-related events. One patient developed cystoid macular edema, which responded to treatment. Conclusion This case series showed the efficacy and safety of Artisan-style IOLs in patients with a history of uveitis. After the Artisan IOL insertions, these patients experienced a significant improvement in CDVA with minimal side effects.

Introduction Argatroban is licensed for patients with heparin-induced thrombocytopenia and is conventionally monitored by activated partial thromboplastin time (APTT) ratio. The target range is 1.5 to 3.0 times the patients’ baseline APTT and not exceeding 100 s, however this baseline is not always known. APTT is known to plateau at higher levels of argatroban, and is influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. It has been used as a treatment for COVID-19 and Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Some recent publications have favored the use of anti-IIa methods to determine the plasma drug concentration of argatroban. Methods Plasma of 60 samples from 3 COVID-19 patients and 54 samples from 5 VITT patients were tested by APTT ratio and anti-IIa method (dilute thrombin time dTT). Actin FS APTT ratios were derived from the baseline APTT of the patient and the mean normal APTT. Results Mean APTT ratio derived from baseline was 1.71 (COVID-19), 1.33 (VITT) compared to APTT ratio by mean normal 1.65 (COVID-19), 1.48 (VITT). dTT mean concentration was 0.64 µg/ml (COVID-19) 0.53 µg/ml (VITT) with poor correlations to COVID-19 baseline APTT ratio r2 = 0.1526 p 2 = 0.2188 p 2 = 0.04 p 2 = 0.0064 p Conclusions We believe that dTT is a superior method to monitor the concentration of argatroban, we have demonstrated significant differences between APTT ratios and dTT levels, which could have clinical impact. This is especially so in COVID-19 and VITT.

Although treatments for youth at risk for suicide have been successful, they are not similarly effective for everyone. Anxiety may interfere with adolescents' ability to engage with therapy and explain why some adolescents do not respond as well as others to treatment. The current study tested whether an anxiety diagnosis predicted treatment outcome among a sample of adolescents with suicidal ideation and depressive symptoms participating in either attachment-based family therapy or family-enhanced nondirective supportive therapy (N = 129; M age = 14.87, SD = 1.68; 81.9% female). The data set that the current study used had a high representation of Black/African American adolescents (48.8% of sample), which is valuable, as few studies have included adequate representation of this population. A significant indirect effect (.88; 95% confidence interval [.01, 2.64]) showed that across both treatment conditions, participants who met criteria for an anxiety disorder had greater difficulties engaging in goal-directed behavior midtreatment, and these difficulties, in turn, predicted more posttreatment suicidal ideation. The effect of anxiety on treatment outcome via difficulties with goal-directed behavior was nonspecific to the treatment condition. However, attachment-based family therapy was superior to family-enhanced nondirective supportive therapy in improving this aspect of emotion regulation among adolescents who did not have anxiety. In addition, difficulties with goal-directed behavior on treatment outcome were worse for adolescents' who reported greater attachment avoidance to their parents. Future research should test whether targeting goal-directed behavior and attachment avoidance would result in better treatment outcome for adolescents with suicidal ideation and anxiety. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Exercise mobilizes angiogenic cells, which stimulate vascular repair. However, limited research suggests exercise-induced increase of endothelial progenitor cell (EPCs) is completely lacking in type 1 diabetes (T1D). Clarification, along with investigating how T1D influences exercise-induced increases of other angiogenic cells (hematopoietic progenitor cells; HPCs) and cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), is needed. Thirty T1D patients and 30 matched non-diabetes controls completed 45 min of incline walking. Circulating HPCs (CD34+, CD34+CD45dim) and EPCs (CD34+VEGFR2+, CD34+CD45dimVEGFR2+), and subsequent expression of CXCR4 and CXCR7, were enumerated by flow cytometry at rest and post-exercise. Counts of HPCs, EPCs and expression of CXCR4 and CXCR7 were significantly lower at rest in the T1D group. In both groups, exercise increased circulating angiogenic cells. However, increases was largely attenuated in the T1D group, up to 55% lower, with CD34+ (331 ± 437 Δcells/mL vs. 734 ± 876 Δcells/mL p = 0.048), CD34+VEGFR2+ (171 ± 342 Δcells/mL vs. 303 ± 267 Δcells/mL, p = 0.006) and CD34+VEGFR2+CXCR4+ (126 ± 242 Δcells/mL vs. 218 ± 217 Δcells/mL, p = 0.040) significantly lower. Exercise-induced increases of angiogenic cells is possible in T1D patients, albeit attenuated compared to controls. Decreased mobilization likely results in reduced migration to, and repair of, vascular damage, potentially limiting the cardiovascular benefits of exercise.Trial registration: ISRCTN63739203.

PurposeElevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes.MethodsIn a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5–10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen.ResultsWP reduced PPG area under the curve [AUC0–60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects.ConclusionPre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual’s insulin resistance, their obese state, or other obesity-related ailments needs further investigation.Clinical Trial RegistrationISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

Objective Although several treatments have been shown to be effective in treatment of youth suicidal thoughts and behaviors (STBs), there is a pressing need to account for the substantial variation in adolescents’ response to and outcomes from these treatments. Method Secondary analyses of data from a 16-week randomized trial of Attachment-Based Family Therapy (ABFT) and Family-Enhanced NonDirective Supportive Therapy (FE-NST) identified distinct classes of adolescents’ treatment response. Established risk factors for STBs, along with treatment condition and sociodemographic variables, were then tested as predictors of class membership. Results Three patterns of adolescents’ treatment response and outcome were identified: a) nonresponders (15.8%), b) good responders (57.5%), and c) partial responders (26.7%). After controlling for initial symptom severity, nonresponders were more likely to have higher levels of nonsuicidal self-injury and pessimism and were more likely to meet diagnostic criteria for major depressive disorder (MDD) than good or partial responders. Partial responders were more likely than good responders to meet criteria for MDD and to have higher perceived burdensomeness. Conclusion Although most adolescents showed significant symptom reductions with both treatments, adolescents with higher pretreatment levels of pessimism, MDD, nonsuicidal self-injury, and perceived burdensomeness were less likely to show an optimal pattern of treatment benefit. The findings point to heterogeneity in treatment response that may require adapting treatments for adolescents with these pretreatment profiles. Clinical trial registration information Attachment-Based Family Therapy for Suicidal Adolescents; http://clinicaltrials.gov ; NCT01537419 .

Assessing firearm access among adolescents with behavioral health risk factors is important for the primary prevention of suicide and interpersonal violence. We describe self-reported firearm access and the associated behavioral risk factors and demographic characteristics in a cross-sectional study conducted in the emergency department of an urban pediatric hospital from June 2013 to June 2014. A total of 2258 adolescents received a behavioral health survey to assess access to firearms inside and outside the home, mental health symptoms, and risk behaviors. One of 6 patients in our sample (15%) endorsed access to a firearm. Male gender, lifetime alcohol use, lifetime marijuana use, and lifetime other drug use were associated with access. Participants reporting access were more likely to report clinical levels of lifetime suicidality and depression. The odds of current suicidality were highest in those with 24-h access (OR 2.77 CI 1.73-4.46), compared to those who did not endorse access.

Objective: To evaluate the efficacy of attachment-based family therapy (ABFT) compared with a family-enhanced nondirective supportive therapy (FE-NST) for decreasing adolescents’ suicide ideation and depressive symptoms. Method: A randomized controlled trial of 129 adolescents who are suicidal ages 12- to 18-years-old (49% were African American) were randomized to ABFT (n = 66) or FE-NST (n = 63) for 16 weeks of treatment. Assessments occurred at baseline and 4, 8, 12, and 16 weeks. Trajectory of change and clinical recovery were calculated for suicidal ideation and depressive symptoms. Results: There was no significant between-group difference in the rate of change in self-reported ideation (Suicidal Ideation Questionnaire-Jr; F1,127 = 181, p = .18). Similar results were found for depressive symptoms. However, adolescents receiving ABFT showed a significant decrease in suicide ideation (t127 = 12.61, p < .0001; effect size, d = 2.24). Adolescents receiving FE-NST showed a similar significant decrease (t127 = 10.88, p < .0001; effect size, d = 1.93). Response rates (ie, ≥50% decrease in suicide ideation symptoms from baseline) at post-treatment were 69.1% for ABFT versus 62.3% for FE-NST. Conclusion: Contrary to expectations, ABFT did not perform better than FE-NST. The 2 treatments produced substantial decreases in suicidal ideation and depressive symptoms that were comparable to or better than those reported in other more intensive, multicomponent treatments. The equivalent outcomes could be attributed to common treatment elements, different active mechanisms, or regression to the mean. Future studies will explore long-term follow up, secondary outcomes, and potential moderators and mediators. Clinical trial registration information: Attachment-Based Family Therapy for Suicidal Adolescents; http://clinicaltrials.gov; NCT01537419. Published (Publication status)

Productive emotional processing is considered a key change mechanism in attachment-based family therapy (ABFT). This study examined the impact of attachment-based family therapy therapist interventions aimed to promote productive emotional processing of primary adaptive emotions in a sample of 30 depressed and suicidal adolescents who had participated in a larger randomized clinical trial. Results of sequential analyses revealed that relational reframes and therapists' focus on primary adaptive emotions were associated with the subsequent initiation of adolescents' productive emotional processing of primary adaptive emotions. In contrast, interpretations, reassurances, and therapists' focus on adolescents' rejecting anger toward their parents were all followed by the discontinuation of adolescents' emotional processing that had already begun. Finally, therapists' general encouragement of affect and focus on adolescents' unmet attachment/identity needs were associated with both the initiation of adolescents' productive emotional processing, and with the discontinuation of such processing once it had already begun. Theoretical and clinical implications are discussed.El procesamiento emocional productivo (Greenberg, Auszra y Hermann, 2007) se considera un mecanismo de cambio clave en la terapia familiar centrada en apego (ABFT en inglés; Diamond, Diamond,Levy, 2014). Este estudio examinó el impacto de intervenciones terapéuticas ABFT dirigidas a promover el procesamiento emocional productiva de emociones adaptativas primarias en una muestra de 30 estudiantes deprimidos y suicidas que participaron en un ensayo clínico aleatorio de mayor escala. Los resultados de los análisis secuenciales revelaron que los reencuadres relacionales y el enfoque de los terapistas en las emociones adaptativas primarias se asociaron al inicio subsiguiente del procesamiento emocional productivo de emociones adaptativas primarias por parte de los adolescentes. En cambio, las interpretaciones, afirmaciones y el enfoque de los terapistas en el enojo rechazador de los adolescentes hacia sus padres fueron seguidas por la suspensión del procesamiento emocional que había ya comenzado. Por último, la motivación general por parte de los terapistas del afecto y enfoque en las necesidades insatisfechas de apego/identidad de los adolescentes se asociaron tanto al inicio del procesamiento emocional productivo de los adolescentes como a la suspensión de dicho procesamiento cuando había ya comenzado. Se discuten las implicaciones teóricas y clínicas.建设性情绪处理(Greenberg, AuszraHermann, 2007) 被认为是基于亲情的家庭治疗中的关键改变机制。 (ABFT; Diamond, DiamondLevy, 2014)。本研究调查ABFT治疗师介入的影响,旨在促进对于主要调适性情感的建设性情绪处理。参与者是30名抑郁且有自杀倾向的青少年,选自于较大规模的任意性临床取样。序列分析结果表明重新看待关系和诊疗师对主要调适性情绪的关注与随后引起的的青少年对主要调适性情绪的建设性情感处理 之间有关联。与之相反,安慰和治疗师对青少年拒绝父母的生气情绪 的关注全都是在已经开始的青少年情绪处理的中断之后。治疗师的情感鼓励和关注青少年未实现的 情感/身份需求和两方面都有相关性。一是青少年建设性情绪处理的启动,一是建设性情绪处理开始一段时间后的中断。理论和临床方面的意义都有讨论。.

Eating disorders are a serious, life-threating condition impacting adolescents and young adults. Providers in primary care settings have an important role in identifying disordered eating (DE) symptoms. Unfortunately, symptoms go undetected in 50% of patients in medical settings. Using the behavioral health screen, this study identified DE risk profiles in a sample of 3620 female adolescents and young adults (ages 14–24), presenting in primary care. A latent class analysis with twenty psychosocial factors identified three DE risk groups. The group at highest risk for DE was characterized by endorsement of internalizing symptoms and a history of trauma. The next risk group consisted of those with externalizing symptoms, particularly substance use. The group at lowest risk for DE reported more time spent with friends compared to their peers. Primary care providers and psychiatric teams can benefit from knowing the psychosocial risk patterns affiliated with DE, and using brief, comprehensive screening tools to identify these symptoms. Published (Publication status)

To review our experience with balloon testing prior to atrial septal defect (ASD) closure in adults with left ventricular (LV) diastolic dysfunction.ASD closure in patients with LV diastolic dysfunction may precipitate LV failure. Temporary ASD occlusion has been used in this scenario but data are limited.Retrospective review of 27 patients age ≥ 50 years undergoing temporary ASD balloon occlusion between 2000 and 2018 for suspected LV diastolic dysfunction or elevated LV end-diastolic pressure (LVEDP).Median age was 72 years (IQR 66.7; 75.2). Atrial fibrillation was seen in 58% of patients, hypertension in 58%, and coronary artery disease in 26%; 52% were females. Median ASD size was 13 mm (10; 18) and Qp/Qs 1.8 (1.6; 2.2). Median LVEDP was 14 mmHg (12; 22); pulmonary artery wedge pressure (PAWP) 12 mmHg (9; 16.5) and left atrial pressure (LAP) 13.5 mmHg (8; 16.3). After a median of 5 min (3; 10) of balloon occlusion, patients with baseline LVEDP ≥15 mmHg had more significant increases in LVEDP (9 [6; 12] vs. 2 mmHg [0.5; 5]; p = 0.03) and LAP/PAWP (10.5 [8.3; 16.3] vs. 1.5 mmHg [-1.5; 3]; p = 0.0003) than those with baseline LVEDP15 mmHg. None of those with a baseline LVEDP15 mmHg had a LAP/PAWP15 mmHg during balloon testing compared to 92% of patients with a baseline LVEDP ≥15 mmHg.LVEDP might be used to predict LAP post-ASD closure. Comorbidities typically associated with LV diastolic dysfunction are common in these patients and should be considered in their management.

Purpose: This study examined whether a higher protein diet following strenuous exercise can alter markers of muscle damage and inflammation in older adults. Methods: Using a double-blind, independent group design, 10 males and eight females (age 57 ± 4 years; mass 72.3 ± 5.6 kg; height 1.7 ± 6.5 m) were supplied with a higher protein (2.50 g·kg−1·day−1) or moderate protein (1.25 g·kg−1·day−1) diet for 48 hr after 140 squats with 25% of their body mass. Maximal isometric voluntary contractions, muscle soreness, creatine kinase, Brief Assessment of Mood Adapted, and inflammatory markers were measured preexercise, and 24 hr and 48 hr postexercise. Results: The maximal isometric voluntary contractions decreased postexercise (p = .001, ), but did not differ between groups (p = .822, ). Muscle soreness peaked at 24 hr post in moderate protein (44 ± 30 mm) and 48 hr post in higher protein (70 ± 46 mm; p = .005; ); however, no group differences were found (p = .585; ). Monocytes and lymphocytes significantly decreased postexercise, and eosinophils increased 24 hr postexercise (p p > .05). Conclusion: In conclusion, 2.50 g·kg−1·day−1 of protein is not more effective than 1.25 g·kg−1·day−1 for attenuating indirect markers of muscle damage and inflammation following strenuous exercise in older adults.

Central nervous system ischemic injury features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here we show that activation of endothelial caspase-9 after hypoxia-ischemia is a critical event in subsequent dysfunction of the blood-retina barrier, using a panel of interrelated ophthalmic in vivo imaging measures in a mouse model of retinal vein occlusion (RVO). Rapid nonapoptotic activation of caspase-9 and its downstream effector caspase-7 in endothelial cells promotes capillary ischemia and retinal neurodegeneration. Topical eye-drop delivery of a highly selective caspase-9 inhibitor provides morphological and functional retinal protection. Inducible endothelial-specific caspase-9 deletion phenocopies this protection, with attenuated retinal edema, reduced inflammation and preserved neuroretinal morphology and function following RVO. These results reveal a non-apoptotic function of endothelial caspase-9 which regulates blood-retina barrier integrity and neuronal survival, and identify caspase-9 as a therapeutic target in neurovascular disease.

The Freiburg monosyllabic test (FBE) has been an important German speech audiometry test for years. It is nowadays also used to assess the benefit of hearing aids in noise (FBE-S). This study investigates hearing in noise using the FBE at different sound pressure levels and a signal to noise ratio of 5 dB to generate a recognition curve.In autumn 2018, 60 normal-hearing German native speakers (age 18-31 years) participated in the study at the military hospital in Hamburg. Using one FBE test list, speech intelligibility was measured from sound pressure levels of 15 to 90 dB in 5‑dB steps with a noise level 5 dB lower in each case. Subsequently, the average of all intelligibility rates and 95% confidence intervals (CI) were determined.Participants comprised 29 female and 31 male subjects. Average age was 24.32 years (±3.29 years). The fixed effects analysis of variance with recognition as the dependent variable demonstrated a highly significant correlation between the levels of sounds/noise and the intelligibility of speech (p 0.0001). The average intelligibility rates with 95% CI and the frequency distributions were presented tabularly and graphically.In comparison to the normative curve, the FBE‑S recognition curve is shifted to the right. The average values of the FBE‑S reach the saturation area at a volume of 70/65 dB with an intelligibility rate of 90% (for comparison: the point of saturation for 100% intelligibility of the FBE without noise is reached at 55 dB). Using these averaged values of the FBE‑S enables better interpretation of individual results without and with hearing aids. In the future, the benefit of hearing aids should be measured at lower noise levels than it is today.

T follicular helper (Tfh) cells are crucial for B cell-mediated humoral immunity(1). Although transcription factors, such as Bcl6, drive Tfh cell differentiation(2,3), whether and how posttranscriptional and metabolic programs enforce Tfh cell programming are unclear. Here, we show that the cytidine diphosphate (CDP)-ethanolamine pathway coordinates the expression and localization of CXCR5 with Tfh responses and humoral immunity. Using in vivo CRISPR-Cas9 screening and functional validation, we uncover Etnk1, Pcyt2 and Selenoi – enzymes in the CDP-ethanolamine pathway for de novo phosphatidylethanolamine (PE) synthesis – as selective posttranscriptional regulators of Tfh cell differentiation, by promoting CXCR5 surface expression and functional effects. Tfh cells show unique lipid metabolic programs and PE distribution to the plasma membrane outer layer where it co-localizes with CXCR5. De novo PE synthesis via the CDP-ethanolamine pathway coordinates these events to prevent CXCR5 internalization and degradation. Genetic deletion of Pcyt2, but not the CDP-choline pathway enzyme Pcyt1a, in activated T cells impairs Tfh cell differentiation, associated with reduced humoral immune responses. Surface PE levels and CXCR5 expression on B cells also depend upon Pcyt2. Our results reveal that phospholipid metabolism coordinates posttranscriptional mechanisms for Tfh cell differentiation and humoral immunity, highlighting metabolic control of context-dependent immune signaling and effector programs.

BACKGROUND Transcatheter edge-to-edge repair with MitraClip is only approved for treatment of mitral regurgitation but is increasingly used to treat concomitant tricuspid regurgitation (TR) due to its common coexistence and association with poor outcomes. This study aimed to describe the learning curve associated with the challenge of off-label treatment of concomitant TR. METHODS This is a retrospective review of initial and consecutive patients who underwent combined edge-to-edge repair of mitral and tricuspid valves (TVs) at our institution from August 2017 to October 2019. RESULTS Repair of both valves with MitraClip was performed in 22 patients (median age 81.5 years, 32% female). Mean procedure time was 176 ± 47 min; mean fluoroscopy time was 65 ± 24 min. Procedure duration in the first tertile was significantly longer (223 ± 13 min) than in the third tertile (143 ± 23 min, p = .0003). Median number of total clips placed per case was 3; in 15 patients (68%), the anterior and septal leaflets of the TV were clipped. The average changes in mean right atrial (RA) and left atrial (LA) pressures were -1.7 ± 2.5 mmHg (p = .0080) and -3.2 ± 4.6 mmHg (p = .0045), respectively. The average changes in RA and LA V-wave heights were -3.3 ± 4.0 mmHg (p = .0009) and -8.1 ± 9.9 mmHg (p = .038), respectively. There was a significant trend toward decreasing residual TR over the course of the series (p = .046). At 30 days, survival was 100% and mean NYHA class decreased from 2.8 to 1.8 (p

Child welfare systems (CWSs) worldwide show increased interest in adopting empirically informed clinical strategies to increase treatment effectiveness. Many empirically supported treatments (ESTs) exist, but little is known about EST implementation barriers and facilitators in CWS. This study explored CWS providers' experiences of implementing attachment-based family therapy (ABFT) in home-based services of the Flemish CWS (in Belgium). Sixteen CWS providers (twelve counselors and four supervisors) involved in three home-based services were interviewed. The Consolidated Framework for Implementation Research (CFIR) was used to guide collection, coding, and analysis of interview data. Findings revealed that implementation success was related to ABFT's fit with the CWS's mission, philosophy, and existing practices. CWS providers' belief in the compatibility between ABFT and CWS increased investment in implementation efforts and persistence to overcome challenges and setbacks. Some barriers pertained to the learning of ABFT and some barriers pertained to systems level challenges such as lack of leadership and support, poor coordination with referral sources and other youth care partners, and lack of policy support. For successful expansion of ESTs into CWS settings, various barriers at multiple systemic levels need to be addressed.Los sistemas de asistencia de menores de todo el mundo demuestran cada vez más interés en adoptar estrategias clínicas empíricamente informadas para aumentar la eficacia de los tratamientos. Existen muchos tratamientos respaldados empíricamente, pero se sabe poco acerca de los elementos obstaculizadores y facilitadores para la implementación de dichos tratamientos en los sistemas de asistencia de menores. Este estudio analizó las experiencias de los prestadores de sistemas de asistencia de menores a la hora de implementar la terapia familiar basada en el apego en los servicios domiciliarios del sistema flamenco de asistencia de menores (en Bélgica). Se entrevistó a dieciséis prestadores de sistemas de asistencia de menores (doce terapeutas y cuatro supervisores) implicados en tres servicios domiciliarios. Se utilizó el “Marco Consolidado para la Investigación de Implementación” (Consolidated Framework for Implementation Research,CFIR) para guiar la recopilación, la codificación y el análisis de los datos de las entrevistas. Los resultados revelaron que el éxito de la implementación estuvo relacionado con la adecuación de la terapia familiar basada en el apego con la misión, la filosofía y las prácticas existentes de los sistemas de asistencia de menores. La confianza de los prestadores de sistemas de asistencia de menores en la compatibilidad entre la terapia familiar basada en el apego y los sistemas de asistencia de menores aumentó la inversión en los esfuerzos de implementación y en la perseverancia para superar dificultades y contratiempos. Algunos obstáculos estuvieron relacionados con el aprendizaje de la terapia familiar basada en el apego y algunos otros con dificultades a nivel de los sistemas, como la falta de liderazgo y apoyo, la mala coordinación con fuentes de derivaciones y con otros acompañantes en el cuidado de los jóvenes, y con la falta de apoyo a las políticas. Para diseminar satisfactoriamente los tratamientos respaldados empíricamente en el marco de los sistemas de asistencia de mejores es necesario abordar diferentes obstáculos en múltiples niveles sistémicos.世界儿童福利系统(CWSs)的研究表明越来越多研究者把兴趣放在采用经验主义的临床策略来增加治疗的有效性。已有很多实证支持的治疗方法(ESTs)为人所知,但是人们对于EST在实施过程中遇到哪些障碍和哪些起到促进作用还知之甚少。本研究探索的是比利时的以弗兰德人家庭为基础的服务中,CWS供应者实施的以情感依恋为基础的家庭治疗(ABFT)的经验。服务于三家以家庭为基础的服务机构的16位CWS供应者(12位咨询师和4位管理者)接受了采访。在采访数据搜集,解码和分析过程中使用了实践研究强化框架(CFIR)来给予指导。研究结果表明实施成功与否和ABFT是否与CWS的使命,哲学和已有的措施有关联。 CWS提供者越来越相信ABFT和CWS的相互兼容性,这有助于执行过程中的不断付出和在遭遇挑战和挫折时仍能坚持应对。 有些障碍是和ABFT的学习有关, 有些是和系统水平的挑战有关,比如缺乏领导力和支持,外推的转诊资源和青少年医疗合作者之间协调不得力,缺乏政策支持等。对于ESTs成功得拓展应用到CWS情境中,还有不同系统层面的各种障碍有待于探索解决方法。.

HIV status disclosure among people living with HIV/AIDS has been shown to have a number of both personal and public health benefits, but rates of HIV status disclosure remain low in many African countries, including the Democratic Republic of the Congo (DRC). This systematic review uses the Disclosure Process Model to examine the factors involved in serostatus disclosure and nondisclosure to various persons in the lives of people living with HIV/AIDS (PLWHA) in the DRC, as well as the specific outcomes of their disclosure or nondisclosure. MEDLINE/PubMed, Embase, Web of Science, Global Health, and PsycINFO were searched and research studies were included if: (i) the study discussed disclosure of HIV status; (ii) the study population included HIV-infected people in DRC; and (iii) the study was published in English. Fourteen articles met the inclusion criteria and were included in the study. Factors contributing to nondisclosure were generally associated with high stigma of HIV in adults and concern for emotional wellbeing when disclosing to HIV positive minors. Factors contributing to disclosure among adults were increased social support and religion. In disclosing to HIV positive minors, increasing age and health benefits were identified as approach goals that supported disclosure. The findings highlight the importance of understanding the avoidance and approach goals involved in HIV status disclosure among populations living in the DRC. Interventions and future research directed at increasing HIV disclosure among Congolese PLWHA should move beyond individual-level to consider multilevel factors including circumstantial social behaviors.

Objective Little is known about the extent to which previous weeks' stressful events spill over and influence adolescents' abilities to derive insight from treatment sessions. Even less is known about factors that moderate clients' vulnerabilities to these spillover effects. The current study examined the spillover of negative interpersonal events to postsession insight and the role of difficulties in emotion regulation in this spillover effect. Method Participants were 129 adolescents with moderate to severe depressive symptoms and suicidal ideation (Mage = 14.96, 83% female, 56% African American/Black) participating in a comparative efficacy trial of Attachment-Based Family Therapy (ABFT) and Family-Enhanced Nondirective Supportive Therapy (FE-NST). A within-subject mediation model tested presession negative affect as a mediator of spillover of past week's events on postsession insight. We then examined baseline difficulties in emotion regulation (DERS) as a between-subjects moderator of the mediation model. Results Negative affect partially mediated (44%) the spillover of the past week's negative events on adolescents' ratings of postsession insight (p = .03, 95% confidence interval, CI [-.09., -.002]). Baseline DERS increased adolescents' vulnerabilities to spillover effects (p = .01, 95% CI [-.28, -.03]). Negative interpersonal events from the past week influence presession negative affect and spill over to adolescents' abilities to gain insight from their treatment sessions. Adolescents who began treatment with greater DERS were particularly vulnerable to these spillover effects. Findings indicate the need for therapists to adapt sessions to individual differences in depressed and suicidal adolescents' exposure to negative interpersonal events preceding treatment and in their vulnerabilities to spillover and emotion dysregulation. (PsycINFO Database Record

In patients with unexplained cardiomyopathy, electroanatomical mapping can identify abnormal tissue to target during electrophysiology-guided endomyocardial biopsy (EP-guided EMB). The objective of this study is to determine whether catheter ablation performed in the same setting as EP-guided EMB increases procedural risk. Sixty-seven patients (mean age 54.4 ± 13.8, 57% male) undergoing EP-guided EMB were included. Radiofrequency catheter ablation was performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for typical atrial flutter. Femoral arterial access was obtained in 90% ablation patients and 40% biopsy-only patients; vascular access complications were more common in the ablation group than in the EMB-only group (p = 0.02). There were no significant differences in rate of tricuspid regurgitation, thromboembolism, or pericardial effusion, whether procedural anticoagulation was used. In conclusion, catheter ablation and procedural anticoagulation can be combined with EP-guided EMB with an increased risk of vascular access complications, but no significant increase in intracardiac complications.

Depressive symptoms and self-harm, i.e. non-suicidal self-injury and suicidal behaviors, are highly prevalent in youngsters involved in Child Welfare System (CWS) services. Little research investigates, however, why these CWS youngsters are at risk. We explored whether trust in caregiver support and communication about experiences with primary caregivers, are associated with CWS youngsters’ depressive symptoms and/or self-harm. An anonymous online survey of 271 CWS youngsters (10-21 years of age, 57.2% female) was used to assess trust and communication, and depressive symptoms/self-harm. Results showed significant negative associations between self-reported trust in maternal and paternal support, and depressive symptoms/self-harm. Communication about experiences with one’s biological mother mediated the relationship between trust in maternal support and depressive symptoms/self-harm. Furthermore, the presence of an additional trustworthy caregiver buffered the impact of low trust in maternal or paternal support on depressive symptoms/self-harm. Implications for interventions targeting CWS youngsters’ depressive symptoms and self-harm are discussed. ispartof: Child Abuse & Neglect vol:77 pages:155-167 ispartof: location:England status: published

Members of the SCY1-like (SCYL) family of protein kinases are evolutionarily conserved and ubiquitously expressed proteins characterized by an N-terminal pseudokinase domain, centrally located Huntingtin, elongation factor 3, protein phosphatase 2A, yeast kinase TOR1 repeats, and an overall disorganized C-terminal segment. In mammals, three family members encoded by genesScyl1,Scyl2, andScyl3have been described. Studies have pointed to a role for SCYL1 and SCYL2 in regulating neuronal function and viability in mice and humans, but little is known about the biological function of SCYL3. Here, we show that the biochemical and cell biological properties of SCYL3 are similar to those of SCYL1 and both proteins work in conjunction to maintain motor neuron viability. Specifically, although lack ofScyl3in mice has no apparent effect on embryogenesis and postnatal life, it accelerates the onset of the motor neuron disorder caused byScyl1deficiency. Growth abnormalities, motor dysfunction, hindlimb paralysis, muscle wasting, neurogenic atrophy, motor neuron degeneration, and loss of large-caliber axons in peripheral nerves occurred at an earlier age inScyl1/Scyl3double-deficient mice than inScyl1-deficient mice. Disease onset also correlated with the mislocalization of TDP-43 in spinal motor neurons, suggesting that SCYL1 and SCYL3 regulate TDP-43 proteostasis. Together, our results demonstrate an overlapping role for SCYL1 and SCYL3in vivoand highlight the importance the SCYL family of proteins in regulating neuronal function and survival. Only male mice were used in this study.SIGNIFICANCE STATEMENTSCYL1 and SCYL2, members of the SCY1-like family of pseudokinases, have well established roles in neuronal function. Herein, we uncover the role of SCYL3 in maintaining motor neuron viability. Although targeted disruption ofScyl3in mice had little or no effect on embryonic development and postnatal life, it accelerated disease onset associated with the loss ofScyl1, a novel motor neuron disease gene in humans.Scyl1andScyl3double-deficient mice had neuronal defects characteristic of amyotrophic lateral sclerosis, including TDP-43 pathology, at an earlier age than didScyl1-deficient mice. Thus, we show that SCYL1 and SCYL3 play overlapping roles in maintaining motor neuronal viabilityin vivoand confirm that SCYL family members are critical regulators of neuronal function and survival.

PURPOSE: To investigate long-term visual acuity (VA) outcomes and complication rates in vitrectomised eyes undergoing anterior chamber intraocular lens (ACIOL) insertion. PATIENTS AND METHODS: A single-centre, retrospective case series including all patients who had undergone ACIOL placement at the time of vitrectomy surgery or having had previous vitrectomy, between January 2007 and January 2013. Patients were identified using an electronic database and paper casefile notes were analysed for all patients. Patients were excluded if they had

AIMS The differential diagnosis of intracardiac masses (ICM) is wide. While imaging modalities can suggest a diagnosis, clinical decision making usually requires histopathologic diagnosis. The aim of this study was to describe the procedural technique, safety outcomes, diagnostic accuracy and clinical utility of percutaneous transcatheter biopsy (TCB) for histopathologic diagnosis of ICM. The records of all patients undergoing TCB of ICM at the Mayo Clinic catheterisation laboratories in Rochester, Minnesota, between 2002 and 2017 were retrieved and reviewed. METHODS AND RESULTS TCB of ICM to establish histopathologic diagnosis was performed in 29 patients. Masses were located in the right-sided chambers in 93% of cases. Echocardiographic guidance was used. Ventricular arrhythmias requiring immediate cardioversion occurred in 7% of patients. No other complications were noted. The average number of samples retrieved per procedure was 7±3.6. A histopathologic diagnosis was made by TCB in 72% and altered clinical decision making in 52% of patients overall. Eleven patients (38%) who would otherwise have required excisional biopsy were able to avoid cardiovascular surgery. Each additional biopsy sample was associated with an increase in the likelihood of making a histopathologic diagnosis (OR 1.74, 95% CI: 1.05-2.87, p=0.032). CONCLUSIONS Echo-guided percutaneous TCB of ICM provides an accurate diagnosis and alters clinical management in the majority of cases. The procedural complication rate is low. An increase in the number of samples retrieved markedly improves the ability to render a diagnosis. TCB may therefore be considered as a first-line approach for the histopathologic diagnosis of ICM.

OBJECTIVE The objective of this study was to determine the accuracy of left atrial pressure (LAP) measurement through the manufacturer provided steerable guiding catheter (SGC) during transcatheter mitral valve repair (TMVR). BACKGROUND LAP measurement during TMVR has been shown to be associated with clinical improvement when measured through a dedicated catheter. METHODS Simultaneous LAP was performed in consecutive patients using an independent fluid-filled 4F multipurpose catheter and compared to LAP waveforms measured through the manufacturer-provided MitraClip SGC during TMVR (Abbott, Santa Clara, CA). RESULTS Mean age of 10 consecutive subjects with primary mitral regurgitation undergoing TMVR was 83 ± 3 years (60% female). Left atrial v wave and mean pressures through the dedicated catheter were 42 ± 7 and 24 ± 3 mmHg vs. 35 ± 7 and 23 ± 3 mmHg through the SGC (P

Donor-derived malignancy, particularly melanoma, is a rare but known complication of organ transplantation. Here we describe a case of metastatic melanoma in a deceased-donor kidney transplant recipient. After diagnosis, the patient was successfully treated with cessation of immunosuppression, explantation of the renal allograft, and novel melanoma therapies, including the mutation-targeted agents dabrafenib and trametinib and the immune checkpoint inhibitor nivolumab. These 2 new classes of melanoma therapy have revolutionized the course of metastatic melanoma, altering it from one of nearly certain mortality to one of potential cure. This case reviews the mechanisms of action of these therapies and reports our experience with them in the rare setting of donor-derived melanoma in a dialysis-dependent patient.

Background Data on the clinical utility of left atrial (LA) hemodynamic monitoring during percutaneous mitral interventions are limited. Objectives To evaluate the association between intraprocedural LA pressures during percutaneous mitral paravalvular leak (PVL) closure and long term survival. Methods Patients who underwent mitral PVL repair with invasive LA pressure monitoring were divided at baseline to three tertiles based on their mean final LA pressure ( 30% of mean systolic blood pressure). Primary outcome was all-cause mortality. Results 134 patients (mean age 68 ± 12 years) were studied. Over 3 year mean follow-up, 81 (38%) patients died. The cumulative probability of death at 3 years was significantly higher among patients in the highest LA pressure tertile (56 ± 8% vs. 28 ± 5%, log rank P

Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is complex and can be divided into two phases: early-MDV-IS associated with cytolytic infection in the lymphoid organs in chickens lacking maternal antibodies against MDV (MAbs) and late-MDV-IS that appears later in the pathogenesis and occurs even in chickens bearing MAbs. We have recently developed a model to reproduce late-MDV-IS under laboratory conditions. This model evaluates late-MDV-IS indirectly by assessing the effect of MDV infection on the efficacy of infectious laryngotracheitis (ILT) vaccines against challenge with ILT virus. In the present study, we have used this model to investigate the role of two factors (MDV pathotype and host sex) on the development of late-MDV-IS. Five MDV strains representing three different pathotypes: virulent (vMDV; 617A, GA), very virulent (vvMDV; Md5), and very virulent plus (vv+MDV; 648A, 686), were evaluated. Only vv+ strains were able to induce late-MDV-IS. An immunosuppression rank (IS-rank) was established based on the ability of MDV to reduce the efficacy of chicken embryo origin vaccine (values go from 0 to 100, with 100 being the highest immunosuppressive ability). The IS-rank of the evaluated MDV strains ranged from 5.97 (GA) to 20.8 (617A) in the vMDV strains, 5.97 to 16.24 in the vvMDV strain Md5, and 39.08 to 68.2 in the vv+ strains 648A and 686. In this study both male and female chickens were equally susceptible to MDV-IS by vv+MDV 686. Our findings suggest that late-MDV-IS is a unique feature of vv+ strains.

PurposeThe purpose of the study was to investigate the role of ethnicity on idiopathic macular holes (IMH) structure and surgical outcome. This was a retrospective review.Patients and methodsConsecutive patients undergoing primary IMH surgery at two surgical sites of Moorfields Eye Hospital (London, UK) between April 2012 and June 2013. The main outcome measure was post surgical anatomical closure of IMH.ResultsTwo hundred and twenty two primary IMH surgeries were undertaken. A standard procedure including pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade was undertaken for all cases. 61.3% of patients were Caucasian, 21.2% were South Asian, and 16% were Afro-Caribbean. The mean minimum linear diameter (MLD) for our cohort was 434.6 mcm. Mean MLD was 395.3 mcm in Caucasian patients, 490.0 mcm in South Asians (P=0.006), and 491.4 mcm in Afro-Caribbeans (P=0.007). Regression analysis demonstrated that MLD and Afro-Caribbean ethnicity were independent significant risk factors for surgical failure (OR: 1.01, P0.001 and OR: 5.73, P=0.008, respectively).ConclusionSouth Asian and Afro-Caribbean patients present with larger IMH than Caucasians. In addition to IMH diameter, Afro-Caribbean ethnicity is an independent risk factor for surgical failure.

Insecure attachment styles have consistently been identified as risk factors for adolescent psychopathology and, more specifically, suicidal ideation. However, much less is known about the mechanisms that account for the relationship between attachment styles and severity of suicidal ideation within clinical samples. In the current study, adolescents’ expectancies for caregiver availability and responsiveness were coded from transcripts of the Suicide Narrative Interview in a clinical sample of one hundred and twenty-nine depressed and suicidal adolescents. Results indicated that negative expectancies for caregiver availability in the Suicide Narrative Interview were associated both with attachment insecurity and with the intensity of adolescents’ suicidal ideation. The implications of adolescents’ expectancies for caregiver availability as targets for clinical intervention are discussed.

Summary: Neutrophil granule serine proteases contribute to immune responses through cleavage of microbial toxins and structural proteins. They induce tissue damage and modulate inflammation if levels exceed their inhibitors. Here, we show that the intracellular protease inhibitors Serpinb1a and Serpinb6a contribute to monocyte and neutrophil survival in steady-state and inflammatory settings by inhibiting cathepsin G (CatG). Importantly, we found that CatG efficiently cleaved gasdermin D (GSDMD) to generate the signature N-terminal domain GSDMD-p30 known to induce pyroptosis. Yet GSDMD deletion did not rescue neutrophil survival in Sb1a.Sb6a−/− mice. Furthermore, Sb1a.Sb6a−/− mice released high levels of pro-inflammatory cytokines upon endotoxin challenge in vivo in a CatG-dependent manner. Canonical inflammasome activation in Sb1a.Sb6a−/− macrophages showed increased IL-1β release that was dependent on CatG and GSDMD. Together, our findings demonstrate that cytosolic serpins expressed in myeloid cells prevent cell death and regulate inflammatory responses by inhibiting CatG and alternative activation of GSDMD. : Burgener et al. show that cytosolic protease inhibitors Serpinb1a and Serpinb6a inhibit the granule serine protease cathepsin G to prevent neutrophil and monocyte death and cytokine release upon LPS challenge. Mechanistically, activation of gasdermin D by cathepsin G is required for inflammation but not for neutrophil death. Keywords: inflammation, cell death, neutrophil, pyroptosis, apoptosis, serpin, proteinase, cathepsin, elastase, gasdermin

OBJECTIVE. Children of parents with depression are at increased risk for developing psychopathology. The purpose of the current longitudinal study was to examine the dynamic relations between parents’ depressive symptoms and children’s cognitions, specifically their attributions for the causes of life events. METHOD. Participants were 227 parent-child dyads with one parent (Mean(age)=42.19, SD=6.82, 76% female) and one child (Mean(age)=12.53, SD=2.33; 53% female) per family. Parents were either diagnosed with a current Major Depressive Disorder (n=129; 72.9% female) or were lifetime-free of mood disorders (n=98; 79.6% female). The Beck Depression Inventory II was used to obtain a dimensional measure of parents’ depressive symptoms, and the Children’s Attributional Style Questionnaire – Revised was used to assess children’s attributions of negative and positive events. Evaluations were conducted five times across 22 months. RESULTS. We used latent difference score modeling to examine the relations between changes in parents’ depressive symptoms and changes in children’s attributional style over time. The final model provided a close fit to the data: χ(2) =35.22, df=30, p=.24, comparative fit index=.995; root mean square error of approximation=.028, 90% confidence interval=.000 and .060; standardized root mean square residual=.024. Parents’ levels of depressive symptoms significantly predicted the worsening of children’s attributions (i.e., becoming more pessimistic) over the 22 months, whereas children’s attributions did not significantly predict changes in parents’ depressive symptoms at the next time point. CONCLUSIONS. Preventive interventions should aim to both reduce parents’ depression and teach children strategies for examining the accuracy of their beliefs regarding the causes of life events.

Abstract. Background: Adolescent suicidality is a growing public health concern. Although evidence supports a link between anxiety and suicidality, little is known about risk associated with specific anxiety disorders. Aims: This study examined the prevalence of anxiety disorders in a sample of adolescents with depression and suicidal ideation and the associations between specific anxiety disorders and suicide ideation severity and attempt history. Method: The sample consisted of 115 adolescents ( Mage = 14.96 years; 55.8% African American) entering a clinical trial for suicidal ideation and depressive symptoms. Prior to treatment, adolescents completed self-report and interview measures. Results: In all, 48% of the sample met criteria for an anxiety disorder, 22% met criteria for social anxiety disorder (SAD), and 40% met criteria for major depressive disorder (MDD). SAD was uniquely associated with more severe suicidal ideation. Limitations: Findings may not generalize to all suicidal adolescents, and non-measured variables may account for the observed relationships. Conclusion: Future research should examine whether targeting social anxiety would improve treatment response for suicidal adolescents.

The pyroptotic cell death effector gasdermin D (GSDMD) is required for murine models of hereditary inflammasome-driven, IL-1β–dependent, autoinflammatory disease, making it an attractive therapeutic target. However, the importance of GSDMD for more common conditions mediated by pathological IL-1β activation, such as gout, remain unclear. In this study, we address whether GSDMD and the recently described GSDMD inhibitor necrosulfonamide (NSA) contribute to monosodium urate (MSU) crystal–induced cell death, IL-1β release, and autoinflammation. We demonstrate that MSU crystals, the etiological agent of gout, rapidly activate GSDMD in murine macrophages. Despite this, the genetic deletion of GSDMD or the other lytic effector implicated in MSU crystal killing, mixed lineage kinase domain-like (MLKL), did not prevent MSU crystal–induced cell death. Consequently, GSDMD or MLKL loss did not hinder MSU crystal–mediated release of bioactive IL-1β. Consistent with in vitro findings, IL-1β induction and autoinflammation in MSU crystal–induced peritonitis was not reduced in GSDMD-deficient mice. Moreover, we show that the reported GSDMD inhibitor, NSA, blocks inflammasome priming and caspase-1 activation, thereby preventing pyroptosis independent of GSDMD targeting. The inhibition of cathepsins, widely implicated in particle-induced macrophage killing, also failed to prevent MSU crystal–mediated cell death. These findings 1) demonstrate that not all IL-1β–driven autoinflammatory conditions will benefit from the therapeutic targeting of GSDMD, 2) document a unique mechanism of MSU crystal–induced macrophage cell death not rescued by pan-cathepsin inhibition, and 3) show that NSA inhibits inflammasomes upstream of GSDMD to prevent pyroptotic cell death and IL-1β release.

Introduction The Democratic Republic of the Congo (DRC) had the second-highest mother-to-child HIV transmission rate in Sub-Saharan Africa at 29% in 2013, however the uptake of preventive services for mother-to-child transmission of HIV (PMTCT) remains suboptimal. This systematic review explores socio-cultural and structural factors influencing PMTCT service uptake in the DRC. Methods We conducted a search of electronic databases. The PEN-3 model was used as a framework to synthesize factors influencing PMTCT service uptake into perceptions, enablers, and nurturers. Results Sixteen studies, 14 quantitative and two qualitative, were retained. Maternal, socio-economic, structural, and cultural factors were found to influence PMTCT service uptake in the DRC. Cost, accessibility, and quality of PMTCT services were key barriers to service uptake. Integration, male partner involvement, and evolving PMTCT policies improved PMTCT service delivery and uptake. This review also revealed several socio-cultural challenges in involving male partners in PMTCT programs. Discussion Findings highlight the need to address barriers and reinforce enablers of PMTCT uptake. Creating culturally appropriate, male-friendly, and family-oriented PMTCT programs will improve service uptake in the DRC.

IntroductionExercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls.Research design and methodsParticipants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (β-C-terminal cross-linked telopeptide of type 1 collagen, β-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance.ResultsBaseline concentrations of P1NP and β-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but β-CTx decreased (p0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (pConclusionsFollowing exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted.

HIV testing serves as the gateway to HIV prevention and treatment. However, research examining men’s HIV testing behaviors in the Caribbean remains limited. The Andersen Behavioral Model of Health Services Utilization was used to examine factors associated with HIV testing among 7,354 men who participated in the 2012 Demographic and Health Survey conducted in Haiti. Few men (35%) reported having ever been tested for HIV. Logistic regression analyses revealed that HIV testing increased with education and wealth. Marital status was associated with HIV testing, with married men more likely to have been tested (adjusted odds ratio: 2.57, 95% CI [2.07, 3.19]) than unmarried men. Positive attitudes toward people living with HIV, indicated by willing to care for a relative who has HIV/AIDS, was also correlated with higher odds of having been tested (adjusted odds ratio: 1.28, 95% CI [1.08, 1.51]). Men who reported condom use during last sex were more likely to have been tested (odds ratio: 1.58, 95% CI [1.33, 1.88). The findings indicate that HIV testing rates remain low among men in Haiti and more efforts are needed to increase HIV testing among men who are not married, have low level of education, and engage in unprotected sex.