Multiplexed Proteome Dynamics Profiling Reveals Mechanisms Controlling Protein Homeostasis.

Protein degradation plays important roles in biological processes and is tightly regulated. Further, targeted proteolysis is an emerging research tool and therapeutic strategy. However, proteome-wide technologies to investigate the causes and consequences of protein degradation in biological systems are lacking. We developed "multiplexed proteome dynamics profiling" (mPDP), a mass-spectrometry-based approach combining dynamic-SILAC labeling with isobaric mass tagging for multiplexed analysis of protein degradation and synthesis. In three proof-of-concept studies, we uncover different responses induced by the bromodomain inhibitor JQ1 versus a JQ1 proteolysis targeting chimera; we elucidate distinct modes of action of estrogen receptor modulators; and we comprehensively classify HSP90 clients based on their requirement for HSP90 constitutively or during synthesis, demonstrating that constitutive HSP90 clients have lower thermal stability than non-clients, have higher affinity for the chaperone, vary between cell types, and change upon external stimuli. These findings highlight the potential of mPDP to identify dynamically controlled degradation mechanisms in cellular systems.

Efficacy of infliximab after loss of response of/intolerance to adalimumab in pediatric Crohn's disease: A retrospective multicenter cohort study of the "GETAID pédiatrique".

BACKGROUND: Infliximab (IFX) and adalimumab (ADA) are recommended for induction and maintenance of remission in pediatric Crohn's disease (CD). ADA is now often used in first line due to its efficacy and tolerability, but a loss of response (LOR) can occur over time. The aim was to assess the efficacy of IFX as second line therapy after LOR or intolerance to ADA in pediatric CD patients at 1 year. METHODS: We conducted a retrospective and multicenter study in France among the "GETAID pédiatrique" centers between April 2019 and April 2022. CD patients under 18 years old and treated with IFX after ADA failure or intolerance were included. We collected anthropometric, clinical, and biological data at baseline (start of IFX), at 6 and 12 months. Clinical remission was defined by a Weighted Pediatric CD Activity Index (wPCDAI) score less than 12.5 points. RESULTS: Of the 32 patients included in our study, 27 (84.4%) were still on IFX at 12 months of the switch. Among them, 13 had discontinued ADA because of a LOR, 12 for insufficient response and 2 due to primary nonresponse. At M12, 22 patients were in corticosteroid free clinical remission (68.7%). Under IFX, the wPCDAI decreased over time (47.5 ± 24.1, 16.6 ± 21.2 and 9.7 ± 19.0 at M0, M6 and M12 respectively). The only factor associated with clinical remission at 12 months was absence of perianal disease at the end of the IFX induction. CONCLUSIONS: IFX is effective in maintaining remission at 1 year in pediatric CD patients experiencing a LOR or intolerance with ADA, and IFX could be an interesting therapeutic choice instead of other biologics in this situation.

Longitudinal associations between interpersonal relationship functioning and posttraumatic stress disorder (PTSD) in recently traumatized individuals: differential findings by assessment method.

BACKGROUND: The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment. METHODS: The current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals. Participants were assessed at four time points over 1 year. RESULTS: Approximately 53% of the sample was diagnosed with PTSD at initial assessment, with declining rates of diagnostic status over time to 16%. Latent difference score (LDS) modeling revealed nonlinear declines in both clinician-assessed and self-reported PTSD symptom severity, with faster declines in earlier periods. Likewise, LDS models revealed nonlinear declines in negative (conflict) aspects of interpersonal relationship functioning, but linear declines in positive (support, depth) aspects. The relationship between PTSD and relationship functioning differed for clinician- and self-reported PTSD. Bivariate LDS modeling revealed significant cross-lagged effects from relationship conflict to clinician-assessed PTSD, and significant cross-lagged effects from self-reported PTSD to relationship conflict over time. CONCLUSIONS: These results highlight that the variability in prior results may be related to the method of assessing PTSD symptomatology and different relational constructs. Implications for theory and early intervention are discussed.

Social interactions in trauma disclosure: A multi-informant and multiconstruct investigation.

Research has established that social factors are integral to trauma recovery. Yet, there is relatively little data on the association between social interactions from different supports and posttraumatic stress disorder (PTSD) symptoms. Moreover, few studies have measured these factors from multiple informants. This paper examined social interactions from different sources (i.e., negative and positive reactions from a chosen close other [CO], family/friends, and general non-COs) and their association with PTSD symptoms using multi-informant reports of the social constructs (i.e., from the individual exposed to trauma [TI] and their CO). Participants (N = 104 dyads) were recruited from an urban center within 6 months of the TIs' exposure to a traumatic event. TIs were assessed using the Clinician-Administered PTSD Scale. TI self-report, t(97) = 2.58, p = .012, and CO collateral report of disapproval from family/friends, t(97) = 2.14, p = .035, and TI self-report of general disapproval, t(97) = 4.91, p < .001, emerged as significant predictors of PTSD symptoms when compared with other social constructs. Interventions that target family members' and friends' reactions to trauma survivors and societal discourse around trauma and reactions to trauma survivors are recommended. Clinical interventions that buffer against TIs' experiences of disapproval and guide COs on the provision of supportive responses are discussed.

Partner outcomes from an uncontrolled trial of Couple HOPES: A guided online couple intervention for posttraumatic stress disorder and relationship enhancement.

Posttraumatic stress disorder (PTSD) is associated with significant individual and relationship impairment for people with PTSD and their romantic partners. Conjoint treatments, such as cognitive behavioral conjoint therapy for PTSD (CBCT), are designed to address individual and relationship factors, yet significant barriers impede accessing in-person therapy. Couple HOPES (i.e., Helping Overcome PTSD and Enhance Satisfaction) is a coach-guided, online couple intervention for PTSD based on CBCT that was designed to address these barriers. Previous investigations have found preliminary efficacy of Couple HOPES for improving PTSD symptoms, relationship functioning, and some individual functioning domains for the partner with probable PTSD. However, no study to date has tested individual outcomes for romantic partners, which is needed to fully evaluate the intervention's promise. The current study tested these partner outcomes in a combined, uncontrolled sample of 27 couples. Intent-to-intervene analyses found significant improvements at postintervention in four of eight tested outcomes, including ineffective arguing, g = 0.74; anger, g = 0.32; perceived health, g = 0.67; and quality of life, g = 0.56. Depressive symptoms, generalized anxiety, alcohol misuse, and work functioning did not significantly change, gs = 0.17-0.42. Among participants who completed a 1-month follow-up assessment, generalized anxiety, g = 0.43, and perceived health, g = 0.73, significantly improved over follow-up, whereas anger, g = -0.48, lost gains previously made. Results were largely consistent in the completer sample. These findings show the potential of Couple HOPES to have broad benefits not only for individuals with probable PTSD but also for their romantic partners.

Orbital Compartment Syndrome in Severe Burns: Predictive Factors, Timing, and Complications of Intervention.

PURPOSE: Severe burn patients require high-volume fluid resuscitation, which increases risk for orbital compartment syndrome (OCS). We aimed to understand surgeons' practice patterns and to examine risk factors for OCS, timing of lateral canthotomy and cantholysis (LCC), and complications of intervention. METHODS: A survey of American Society of Ophthalmic Plastic and Reconstructive Surgery and North American Society of Academic Orbital Surgeons' practice patterns in burn patients was undertaken. In addition, a retrospective analysis was conducted of 107 patients with burns greater than 20% total body surface area at 1 institution from January 1, 2009, to June 1, 2018. Patients with Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, frostbite, or no ophthalmologic consultation were excluded. Risk factors for OCS, timing of LCC, and complications of the intervention were examined. RESULTS: In the survey, 37 of 54 respondents had treated burn patients, of which 29 followed no protocol. Threshold intraocular pressure for intervention varied widely, and nearly all reported having seen complications from LCC in burn patients. For the retrospective analysis, 107 patients met criteria, of which 22 (20.6%) required LCC. Renal failure, inhalation injury, eyelid burns, higher total body surface area, elevated lactate, increased number of escharotomies, and greater total fluid required were significantly associated with the clinical decision that the patient was at risk for OCS requiring LCC. Fluid resuscitation in excess of the Ivy Index (250 ml/kg) increased odds of LCC 8.6 times. Average time of LCC was 15.8 hours after burn. LCC patients experienced higher rates of complications including eyelid retraction, exposure keratopathy, and corneal ulceration. CONCLUSIONS: Severe burn patients should be monitored closely by an ophthalmologist during the first 48 hours for signs of OCS. Further studies should aim to recommend protocols guiding evaluation and intervention.

Potential processes of change in MDMA-Assisted therapy for social anxiety disorder: Enhanced memory reconsolidation, self-transcendence, and therapeutic relationships.

OBJECTIVE: Researchers have suggested that psychotherapy may be enhanced by the addition of 3,4-methylenedioxymethamphetamine (MDMA), particularly in the treatment of disorders wherein interpersonal dysfunction is central, such as social anxiety disorder. We review literature pertaining to three potential processes of change that may be instigated during sessions involving MDMA administration in the treatment of social anxiety disorder. DESIGN: This is a narrative review that integrates research on the etiology and maintenance of social anxiety disorder and mechanisms of action of MDMA to examine how MDMA may enhance psychotherapy outcomes. RESULTS: We first outline how MDMA may enhance memory reconsolidation in social anxiety disorder. We then discuss how MDMA may induce experiences of self-transcendence and self-transcendent emotions such as compassion, love, and awe; and how these experiences may be therapeutic in the context of social anxiety disorder. We subsequently discuss the possibility that MDMA may enhance the strength and effectiveness of the therapeutic relationship which is a robust predictor of outcomes across many disorders as well as a potential key ingredient in treating disorders where shame and social disconnection are central factors. CONCLUSION: We discuss how processes of change may extend beyond the MDMA dosing sessions themselves.

Anterior cervical spine surgery for the treatment of subaxial cervical spondylodiscitis: a report of 30 consecutive patients.

OBJECTIVEInfection of the cervical spine is a rare disease but is associated with significant risk of neurological deterioration, morbidity, and a poor response to nonsurgical management. The ideal treatment for cervical spondylodiscitis (CSD) remains unclear.METHODSHospital records of patients who underwent acute surgical management for CSD were reviewed. Information about preoperative neurological status, surgical treatment, peri- and postoperative processes, antibiotic treatment, repeated procedure, and neurological status at follow-up examination were analyzed.RESULTSA total of 30 consecutive patients (17 male and 13 female) were included in this retrospective study. The mean age at procedures was 68.1 years (range 50-82 years), with mean of 6 coexisting comorbidities. Preoperatively neck pain was noted in 21 patients (70.0%), arm pain in 12 (40.0%), a paresis in 12 (40.0%), sensory deficit in 8 (26.7%), tetraparesis in 6 (20%), a septicemia in 4 (13.3%). Preoperative MRI scan revealed a CSD in one-level fusion in 21 patients (70.0%), in two-level fusions in 7 patients (23.3%), and in three-level fusions in 2 patients (6.7%). In 16 patients an antibiotic treatment was initiated prior to surgical treatment. Anterior cervical discectomy and fusion with cervical plating (ACDF+CP) was performed in 17 patients and anterior cervical corpectomy and fusion (ACCF) in 12 patients. Additional posterior decompression was performed in one case of ACDF+CP and additional posterior fixation in ten cases of ACCF procedures. Three patients died due to multiple organ failure (10%). Revision surgery was performed in 6 patients (20.7%) within the first 2 weeks postoperatively. All patients received antibiotic treatment for 6 weeks. At the first follow-up (mean 3 month) no recurrent infection was detected on blood workup and MRI scans. At final follow-up (mean 18 month), all patients reported improvement of neck pain, all but one patients were free of radicular pain and had no sensory deficits, and all patients showed improvement of motor strength. One patient with preoperative tetraparesis was able to ambulate.CONCLUSIONSCSD is a disease that is associated with severe neurological deterioration. Anterior cervical surgery with radical debridement and appropriate antibiotic treatment achieves complete healing. Anterior cervical plating with the use of polyetheretherketone cages has no negative effect of the healing process. Posterior fixation is recommended following ACCF procedures.

Computer-Aided Detection of Pulmonary Nodules in Computed Tomography Using ClearReadCT.

This study evaluates the accuracy of a computer-aided detection (CAD) application for pulmonary nodular lesions (PNL) in computed tomography (CT) scans, the ClearReadCT (Riverain Technologies). The study was retrospective for 106 biopsied PNLs from 100 patients. Seventy-five scans were Contrast-Enhanced (CECT) and 25 received no enhancer (NECT). Axial reconstructions in soft-tissue and lung kernel were applied at three different slice thicknesses, 0.75 mm (CECT/NECT n = 25/6), 1.5 mm (n = 18/9) and 3.0 mm (n = 43/18). We questioned the effect of (1) enhancer, (2) kernel and (3) slice thickness on the CAD performance. Our main findings are: (1) Vessel suppression is effective and specific in both NECT and CECT. (2) Contrast enhancement significantly increased the CAD sensitivity from 60% in NECT to 80% in CECT, P = 0.025 Fischer's exact test. (3) The CAD sensitivity was 84% in 3 mm slices compared to 68% in 0.75 mm slices, P > 0.2 Fischer's exact test. (4) Small lesions of low attenuation were detected with higher sensitivity. (5) Lung kernel reconstructions increased the false positive rate without affecting the sensitivity (P > 0.05 McNemar's test). In conclusion, ClearReadCT showed an optimized sensitivity of 84% and a positive predictive value of 67% in enhanced lung scans with thick, soft kernel reconstructions. NECT, thin slices and lung kernel reconstruction were associated with inferior performance.

HIV-related stigma, racial discrimination, and gender discrimination: Pathways to physical and mental health-related quality of life among a national cohort of women living with HIV.

Social inequities compromise health-related quality of life (HR-QoL) among women living with HIV (WLWH). Little is known about health impacts of intersecting stigma based on HIV status, race and gender among WLWH or potential mechanisms to promote HR-QoL. We tested pathways from multiple types of stigma (HIV-related, racial, gender) to physical and mental HR-QoL utilizing baseline survey data from a national cohort of WLWH in Canada (2013-2015). Structural equation modeling was conducted using maximum likelihood estimation methods to test the direct effects of HIV-related stigma, racial discrimination, and gender discrimination on HR-QoL and indirect effects via social support and economic insecurity, adjusting for socio-demographic factors. Among 1425 WLWH (median age: 43years [IQR=35-50]), HIV-related stigma and gender discrimination had significant direct effects on mental HR-QoL. Social support mediated the relationship between HIV-related stigma and mental HR-QoL, accounting for 22.7% of the effect. Social support accounted for 41.4% of the effect of gender discrimination on mental HR-QoL. Economic insecurity accounted for 14.3% of the effect of HIV-related stigma, and 42.4% of the effect of racial discrimination, on physical HR-QoL. Fit indices suggest good model fit (χ2[1]=3.319, p=0.069; CFI=0.998; RMSEA=0.042 (90% CI: 0-0.069); SRMR=0.004). Findings reveal complex relationships between intersecting stigma and HR-QoL. Strategies that address intersecting stigma and economic insecurity among WLWH may prevent the harmful impacts of HIV-related stigma and gender discrimination on physical HR-QoL. Increasing social support may mitigate the impacts of stigma on mental health. Findings can inform multi-level interventions to promote health and wellbeing among WLWH.

Geographic differences in the experiences of HIV-related stigma for women living with HIV in northern and rural communities of Ontario, Canada.

INTRODUCTION: In Canada, individuals living in northern and rural regions report more barriers to health service access. For people living with HIV, these barriers may be exacerbated by experiences of HIV-related stigma, and women living with HIV can be disproportionately affected because of intersections of multiple forms of oppression, including racism, sexism and classism. To further understand the impact of geography on the wellbeing of women living with HIV, this study assessed geographic differences in HIV-related stigma experiences among women in the Canadian HIV Women's Sexual & Reproductive Health Cohort Study (CHIWOS). METHODS: CHIWOS is a multisite cohort study of women living with HIV in Canada that operates under community-based participatory research methodology along with GIPA (greater involvement of people with HIV/AIDS) and MIWA (meaningful involvement of women living with HIV/AIDS) principles. This analysis compared peer research associate-administered questionnaire data between participants in northern and southern Ontario, Canada, and between participants in rural and non-rural Ontario. Northern regions were defined by healthcare delivery jurisdiction. The primary outcome was the 10-item shortened HIV Stigma Scale score. Multivariable linear regression models assessed the association between rural and northern regions and stigma score. RESULTS: Sixteen women were excluded due to incomplete HIV Stigma Scale data. Of 701 women included in the analysis, 66 (9.4%) were from northern regions and 24 (3.4%) were from rural regions. Mean stigma scores were 23.9 (standard deviation (SD) 8.0) overall, 26.7 (SD 8.8) in northern regions, 23.6 (SD 7.9) in southern regions, 28.3 (SD 10.1) in rural regions, and 23.8 (SD 7.8) in non-rural regions. In multivariable analyses, northern and rural regions of residence were associated with a 3.05 (95% confidence interval (CI): 0.77, 5.32) and 4.83 (95% CI: 1.37, 8.28) point increase in stigma score, respectively. CONCLUSIONS: Living in both northern and rural regions of Ontario was associated with higher HIV Stigma Scale scores. These geographic discrepancies in experiences of HIV-related stigma highlight the need for region-specific programs to reduce HIV-related stigma and to support people living with HIV who are affected by HIV-related stigma, particularly those living in geographically isolated regions. Prior qualitative studies have documented the important impact of HIV-related stigma, and this study supports these observations with quantitative data from a population that is often under-represented in HIV research.

HIV-related stigma in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

HIV-related stigma is associated with many psychological challenges; however, minimal research has explored how perceived HIV-related stigma intersects with psychosocial issues that mothers living with HIV may experience including depression, perceived stress and social isolation. The present study aims to describe the correlates and predictors of HIV-related stigma in a cohort of women living with HIV (WLWH) from across Ontario, Canada during pregnancy and early postpartum. From March 2011 to December 2012, WLWH ≥ 18 years (n = 77) completed a study instrument measuring independent variables including sociodemographic characteristics, perceived stress, depression symptoms, social isolation, social support and perceived racism in the third trimester and 3, 6 and 12 months postpartum. Multivariable linear regression was employed to explore the relationship between HIV-related stigma and multiple independent variables. HIV-related stigma generally increased from pregnancy to postpartum; however, there were no significant differences in HIV-related stigma across all study time points. In multivariable regression, depression symptoms and perceived racism were significant predictors of overall HIV-related stigma from pregnancy to postpartum. The present analysis contributes to our understanding of HIV-related stigma throughout the pregnancy-motherhood trajectory for WLWH including the interactional relationship between HIV-related stigma and other psychosocial variables, most notably, depression and racism.

The role of people living with HIV as patient instructors - reducing stigma and improving interest around HIV care among medical students.

People living with HIV/AIDS (PHAs) are increasingly recognized as experts in HIV and their own health. We developed a simulated clinical encounter (SCE) in which medical students provided HIV pre- and post-test counselling and point-of-care HIV testing for PHAs as patient instructors (PHA-PIs) under clinical preceptor supervision. The study assessed the acceptability of this teaching tool with a focus on assessing impact on HIV-related stigma among medical students. University of Toronto pre-clerkship medical students participated in a series of SCEs facilitated by 16 PHA-PIs and 22 clinical preceptors. Pre- and post-SCE students completed the validated Health Care Provider HIV/AIDS Stigma Scale (HPASS). HPASS measures overall stigma, as well as three domains within HIV stigma: stereotyping, discrimination, and prejudice. Higher scores represented higher levels of stigma. An additional questionnaire measured comfort in providing HIV-related care. Mean scores and results of paired t-tests are presented. Post-SCE, students (n = 62) demonstrated decreased overall stigma (68.74 vs. 61.81, p < .001) as well as decreased stigma within each domain. Post-SCE, students (n = 67) reported increased comfort in providing HIV-related care (10.24 vs. 18.06, p < .001). Involving PHA-PIs reduced HIV-related stigma among medical students and increased comfort in providing HIV-related care.

Move the Neighbourhood: Study design of a community-based participatory public open space intervention in a Danish deprived neighbourhood to promote active living.

BACKGROUND: A limited amount of research has examined the effect of changing public open spaces on active living. This paper will present the study protocol of a community-based intervention study co-designed in an interdisciplinary collaboration with community members to develop urban installations highly tailored to promote active living among children (10-13-years-old) and seniors (>60-years-old) in a deprived neighbourhood in Copenhagen. METHODS: The study builds on a quasi-experimental study design with two sub-studies: 1) a children study and 2) a senior study. The interventions will be developed, designed and implemented in collaboration with local children and seniors, respectively, using different co-design tools and methods. We will evaluate the effect of the interventions on children's and senior's use of the new-built urban installations using accelerometers in combination with GPS as well as systematic observation using the System for Observing Play and Recreation in Communities (SOPARC). A process evaluation with focus groups consisting of the various stakeholders in the two sub-studies will be used to gain knowledge of the intervention processes. DISCUSSION: The paper presents new approaches in the field of public open space interventions through interdisciplinary collaboration, participatory co-design approach and combination of measurements. Using both effect and process evaluations the study will provide unique insights in the role and importance of the interdisciplinary collaboration, participatory processes, and tailoring changes in public open space to local needs and wishes. These results can be used to guide urban renewal projects in deprived neighbourhoods in the future. TRIAL REGISTRATION: Retrospectively registered with study ID ISRCTN50036837 . Date of registration: 16 December 2016.

The Role of Posttraumatic Growth in a Randomized Controlled Trial of Cognitive-Behavioral Conjoint Therapy for PTSD.

Posttraumatic growth (PTG) is defined as a positive psychological change that can emerge following a traumatic life event. Although documented in noninterventional studies of traumatized individuals, there are scant data on the potential for therapy to induce or improve PTG. Thus, the primary goal of this study was to examine changes in PTG in a controlled trial of cognitive-behavioral conjoint therapy for posttraumatic stress disorder versus waitlist (CBCT for PTSD; Monson & Fredman, 2012). We also examined whether pretreatment relationship satisfaction and PTSD symptomatology moderated change in PTG. There were 40 couples (75% with a female partner with PTSD) who were randomized to either immediate CBCT for PTSD or a 3-month waitlist (WL). Compared to WL, individuals who received treatment immediately demonstrated a significant increase in PTG. There was a moderate effect size between-group difference (Hedge's g = 0.45). There was a nonsignificant relationship with a moderate effect size (Hedge's g = 0.65) for the positive effect of pretreatment relationship satisfaction on the trajectory of PTG, but no effect of pretreatment PTSD symptoms. Results suggested that CBCT for PTSD facilitated PTG, even with a limited focus on PTG in this conjoint intervention. Future research should target PTG as a treatment goal and further examine the role of close others in facilitating development of PTG.

SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy.

Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H-2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX-A12. Control animals received a nonfunctional Spiegelmer (revNOX-A12). Samples were retrieved at different time points and analysed by histology, RT-PCR and proliferation assay. Blockade of SDF-1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 ± 0.1 vs. 1.8 ± 0.1, P < 0.001 AoTx; 0.35 ± 0.05 vs. 1.13 ± 0.27, P < 0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX-A12 showed a significant reduction in proliferation (0.42 ± 0.04 vs. 0.24 ± 0.03, P < 0.05). TGF-ß, TNF-α and IL-6 levels were significantly reduced under SDF-1 inhibition (3.42 ± 0.37 vs. 1.67 ± 0.33, P < 0.05; 2.18 ± 0.37 vs. 1.0 ± 0.39, P < 0.05; 2.18 ± 0.26 vs. 1.6 ± 0.1, P < 0.05). SDF-1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF-1 with NOX-A12 may represent a therapeutic option to ameliorate chronic rejection changes.

Health care provider attitudes and beliefs about people living with HIV: Initial validation of the Health Care Provider HIV/AIDS Stigma Scale (HPASS).

HIV stigma is a pressing concern for people living with HIV, and particularly when it is perpetuated by health care providers, as it may affect quality of life and access to health care services. The current study describes the development and initial validation of a contextually appropriate HIV stigma scale for health care providers in North America. A ground-up qualitative approach was used to develop the scale, and it was assessed psychometrically with health care trainees across Canada. The measure demonstrates excellent internal consistency reliability and test-retest reliability, as well as convergent and divergent validity. The study supports a tripartite model of HIV stigma consisting of stereotyping, prejudice and discrimination. The scale provides a new tool to assess HIV stigma in health care providers and can be used to inform training, intervention and self-evaluation of stigmatizing attitudes, beliefs and behaviors among providers.

Biochar Reduces Zinc and Cadmium but not Copper and Lead Leaching on a Former Sewage Field.

The leaching of trace metals from anthropogenically contaminated sites poses the risk of groundwater pollution. Biochar has recently been proposed as a soil additive to reduce trace-metal concentrations in the soil solution and to increase water retention, thus reducing drainage. However, field studies on the effects of biochar addition on trace-metal leaching are scarce. Therefore, we added 0, 1, 2.5, and 5 g 100 g of biochar derived from giant miscanthus ( × J.M. Greef & Deuter ex Hodk. & Renvoize) to soil contaminated by former wastewater irrigation and examined water retention and cumulative leaching of Zn, Cd, Cu, and Pb in a 2-yr field study. Cumulative trace-metal leaching was determined by self-integrating accumulators (SIAs) based on ion-exchange resins and compared with data calculated from mean concentrations in the soil solution collected with tension lysimeter plates and groundwater recharge rate. The highest rate of biochar addition increased water retention and thus reduced the amount of drainage water. Mean cumulative Zn and Cd fluxes decreased due to both reduced concentrations in the soil solution and reduced drainage. Although Cu and Pb concentrations in the soil solution increased with biochar addition, the reduced drainage resulted in similar fluxes in the biochar and the control treatment. The cumulative Zn, Cd, and Cu fluxes determined with SIAs were in the same range as the calculated values, while SIA-based Pb fluxes were much higher than those calculated. Since the suction plates excluded colloids, the high SIA-based Pb fluxes indicate colloidal transport and reveal the importance to elucidate the colloidal pathway for risk assessment.

A Comparison of Teleburn to In-Person Consultation of Pediatric Patients in a Children's Emergency Department.

BACKGROUND: Pediatric burn care is an essential component to emergency care and there are disparities in access to regional burn centers. Teleburn is a tool that enables providers without a certified burn center to provide photos of a burn to experts and receive recommendations. The purpose of this study is to evaluate the effectiveness of a Teleburn system to the in-person consultation regarding burn infection rate, clinic follow up rate, post-burn admission rate, and 72-hour bounce back rate. DESIGN/METHODS: Data was collected from December 2019-March 2022 through the electronic medical record. A total of 416 patient encounters that met criteria were analyzed. A non-inferiority study was designed comparing proportional outcomes of Teleburn initial visits to emergency department visits regarding burn infection rate, clinic follow up rate, post-burn admission rate, and 72-hour bounce back rate. The data were compared with a difference of greater than 10% being considered inferior. RESULTS: No differences were identified in rates of readmission - 1.67% difference (95% CI -27%< x< 23.8%) and return within 72 hours - 0.7% difference (-18.4%< x< 19.7%). Teleburn patients were 12.6% less likely to follow up (2.7%< x< 22.40%). Only one infection was identified, which was insufficient to conclude non-inferiority. CONCLUSION: While convenient, Teleburn consult could not be demonstrated to be non-inferior to in-person consultation. No differences in infection rates were identified, and difference in readmission and return were clinically insignificant. This study demonstrates that Teleburn may be effective and feasible to regional burn centers if follow up can be improved.

Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder.

Background: MDMA-assisted psychotherapy (MDMA-AP) is a combined psychotherapeutic and pharmacologic intervention that shows promise in the treatment of posttraumatic stress disorder (PTSD). Although therapeutic alliance has been established as a key predictor across psychotherapies and is emphasised within MDMA-AP treatment manuals, research has not yet examined the relationship between therapeutic alliance and MDMA-AP treatment outcomes.Objective: Examine whether therapeutic alliance predicts changes in PTSD symptoms following MDMA-AP.Method: Twenty-three individuals with chronic PTSD participated in a MDMA-AP clinical trial that included a randomised (MDMA vs. placebo) and open-label phase. The present analyses focused on participants who were administered MDMA over the course of the randomised and open-label phases (n = 22). Therapeutic alliance was assessed using the Working Alliance Inventory at sessions baseline (pre-session 3) and sessions 4 and 9. PTSD symptoms were assessed using the Clinician Administered PTSD Scale and the Impact of Events Scale-Revised.Results: Controlling for baseline clinician-assessed PTSD severity, therapeutic alliance at sessions 4 and 9 (but not baseline) significantly predicted post-MDMA-AP clinician-assessed PTSD severity. Controlling for baseline self-reported PTSD severity, therapeutic alliance at baseline (although this did not survive correction for multiple comparisons) and sessions 4 and 9 predicted post-MDMA-AP self-reported PTSD severity.Conclusions: The present results provide the first preliminary evidence for the relationship between the therapeutic alliance and treatment outcomes within MDMA-AP for PTSD. These findings highlight the important role of psychotherapy, and common psychotherapeutic factors, within MDMA-AP. Replication in studies with larger and more diverse clinical samples remain necessary.Trial registration: ClinicalTrials.gov identifier: NCT00090064.

Among individuals with chronic posttraumatic stress disorder, therapeutic alliance predicted changes in posttraumatic stress disorder severity following MDMA-assisted psychotherapy.Therapeutic alliance may play a key role in facilitating therapeutic improvement within MDMA-assisted psychotherapy.Further research remains necessary to confirm these preliminary findings and the role of therapeutic alliance in MDMA-assisted psychotherapy.