Adaptation of a mindfulness-based intervention for trauma-exposed, unhoused women with substance use disorder.

OBJECTIVE: Women experiencing homelessness (WEH) report exceedingly high rates of trauma exposure, posttraumatic stress disorder (PTSD), and substance use disorder (SUD). Mindfulness-based interventions including Mindfulness-based Stress Reduction (MBSR) may help lower traumatic stress-related symptoms and reduce SUD, but have been underexplored in community-based settings serving WEH with symptoms of PTSD and SUD. METHOD: We used a mixed-method, community-engaged approach that implemented a Community Advisory Board and the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework, including intervention demonstrations, to adapt and refine MBSR for WEH experiencing symptoms of PTSD/SUD. Trauma-exposed WEH (N = 28) living at a drug treatment site provided perspectives and feedback on an MBSR demonstration via quantitative questionnaires and four focus groups. RESULTS: Quantitative measures indicated high perceived acceptability and feasibility: Nearly all WEH reported MBSR activities (including yoga, meditation, body scans, class discussion, and home practice) would be at least "somewhat helpful"; between 71.43% to 89.29% reported each activity would be "a great deal helpful." Most reported the focus group sessions were useful for providing feedback relevant for improving program design and administration. Qualitative findings revealed four themes aligning with quantitative findings that provided useful suggestions to guide MBSR implementation with trauma-exposed WEH: (a) perception of feasibility and effectiveness of MBSR, (b) strategies for successful recruitment, (c) strategies for successful retention, and (d) characteristics of the MBSR trainer. CONCLUSIONS: Focus group recommendations could bolster intervention compliance, engagement, and completion for MBSR and community-based programs for WEH more generally. Results provide suggestions for implementing a trauma-sensitive approach when administering MBSR to trauma-exposed WEH. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A multi-method exploration of mindfulness as a coping tool: Perspectives from trauma-exposed, unhoused women residing at a drug treatment facility.

This multi-method study examined perspectives on mindfulness and coping strategies used by trauma-exposed women experiencing homelessness (WEH), residing in a state-funded residential drug treatment site in Southern California (United States). Questionnaires and in-depth focus group interviews were utilised to examine traumatic experiences over the lifespan, probable-posttraumatic stress disorder (PTSD), and coping strategies. Mindfulness was explored as a potential way to improve coping; potential benefits and challenges associated with implementing a mindfulness-based intervention (MBI) with trauma-exposed WEH were also investigated. A Community Advisory Board (CAB) was formed to identify key issues experienced by WEH and to develop a semi structured interview guide (SSIG). Using the SSIG, women participated in one of four focus groups (total N = 28; n = 7 per group). Quantitative data on demographic indicators, probable-PTSD, and trauma exposure were collected. Almost 90% of women met criteria for probable-PTSD; trauma exposure was exceedingly high; most women had experienced multiple traumas throughout their lives. Four main themes emerged from qualitative analyses, which drew from Grounded Theory and used open, selective, and axial coding: (1) ways of coping with trauma; (2) perspectives on mindfulness; (3) prior experiences with mindfulness; and (4) challenges for conducting a mindfulness programme. Overall, WEH used a variety of coping techniques to deal with their trauma, had some familiarity with mindfulness, and were optimistic an MBI would be helpful, despite identifying several challenges to implementation. MBIs may be helpful adjuncts to traditional care for trauma-exposed, WEH, recovering from substance use disorder. Population-specific considerations may improve implementation and participation.

Insights into intestinal regeneration signaling mechanisms.

The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestinal regenerative stages, suggesting that the Wnt/ß-catenin pathway is active during this process. Here, we used small molecules, putative disruptors of the Wnt pathway, to determine the potential role of the canonical Wnt pathway on intestine regeneration in the sea cucumber Holothuria glaberrima. We evaluated their effects in vivo by using histological analyses for cell dedifferentiation, cell proliferation and apoptosis. We found that iCRT14, an alleged Wnt pathway inhibitor, decreased the size of the regenerating intestine, while LiCl, a presumed Wnt pathway activator, increased its size. The possible cellular mechanisms by which signaling pathway disruptors affect the gut rudiment size were further studied in vitro, using cultures of tissue explants and additional pharmacological agents. Among the tested signaling activators, those that act through GSK-3 inhibition, LiCl, 1-Azakenpaullone, and CHIR99021 were found to increase muscle cell dedifferentiation, while the inhibitor iCRT14 blocked cell dedifferentiation. Differently, cell proliferation was reduced by all GSK-3 inhibitors, as well as by iCRT14 and C59, which interferes with Wnt ligand secretion. The in vivo temporal and spatial pattern of ß-catenin activity was determined using an antibody against phosphorylated ß-catenin and shown to correlate with cell proliferative activity. In vitro treatment using C59 decreased the number of cells immunostained for nuclear phosphorylated ß-catenin. Our results showed that the cell dedifferentiation observed during intestinal regeneration can be decoupled from the cell proliferation event and that these cellular processes can be modulated by particular signaling pathway inhibitors and activators. These results open the door for future studies where the cellular signaling pathways involved at each regeneration stage can be determined.

Adult T-cell leukemia/lymphoma can be indistinguishable from other more common T-cell lymphomas. The University of Miami experience with a large cohort of cases.

Adult T-cell leukemia/lymphoma, an aggressive T-cell neoplasm, is causally linked to human T-cell lymphotropic virus type 1 and based on this association has a distinct geographic distribution. In our United States-based practice, whose population is enriched for immigrants from human T-cell lymphotropic virus type 1 endemic areas, we have identified that a subset of adult T-cell leukemia/lymphoma, in the absence of human T-cell lymphotropic virus type 1 identification, are indistinguishable from other more common T-cell neoplasms. We retrospectively gathered serology results for anti-human T-cell lymphotropic virus type 1/2 antibody in patients diagnosed with T-cell neoplasms at our institution. A total of 220 human T-cell lymphotropic virus type 1/2 positive patients with T-cell neoplasms were identified; 199 (91%) were correctly classified as adult T-cell leukemia/lymphoma or provisionally as peripheral T-cell lymphoma (serology testing pending). Twenty-one cases (9%) were initially misclassified, including the following: 13 presenting with skin +/- peripheral blood involvement and misclassified as mycosis fungoides/Sezary syndrome; 7 with lymphomatous disease, absence of leukemic involvement, and diffuse CD30 expression, misclassified as ALK- negative anaplastic large-cell lymphoma; 1 thought to represent T-prolymphocytic leukemia with TCL-1 gene rearrangement and diffuse marrow involvement. We also present an example of adult T-cell leukemia/lymphoma, which mimicked lymphoepithelioid variant of peripheral T-cell lymphoma also with diffuse marrow involvement. A subset of adult T-cell leukemia/lymphoma can closely mimic a variety of other more common T-cell neoplasms. Due to its extreme clinicopathologic heterogeneity, identification of adult T-cell leukemia/lymphoma requires a high level of suspicion based on patient demographic alone, which should prompt anti-human T-cell lymphotropic virus type 1/2 serology testing in all T-cell neoplasms developing in patients of appropriate demographic. Absence of high level of suspicion, adult T-cell leukemia/lymphoma is easily misclassified.

Highly Sensitized Patients: Miami Transplant Institute Experience.

BACKGROUND: Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG). METHODS: Of the 42 highly sensitized kidney and 3 kidney-pancreas transplant recipients who underwent IVIG for desensitization from 2008-2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab ± IVIG ± plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted. RESULTS: Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 ± 0.6 and 50 ± 17 versus 1.1 ± 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047). CONCLUSIONS: In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival.

Mannose binding lectin (mbl2) haplotype frequencies in solid organ transplant patients and correlation with MBL protein levels--evaluation of complement-mediated effector pathway deficiency.

Mannose-binding lectin (MBL) is a protein critical in activating complement. Patients with wild-type and variant mbl2 genotypes have high or low concentrations of MBL protein, which is known to increase susceptibility to transplant rejection or infection, respectively. Our objective was to determine mbl2 genotype frequencies in future solid organ transplant recipients in order to optimize their induction and maintenance immunosuppressive therapies, and to provide MBL reference data for this unique population. We genotyped 1687 patients, and concurrently measured protein in 807 of them, during 2010-2011. Frequencies of the structural allele SNPs in our population were similar to those of other studied populations; however, Black patients with the same intermediate and deficient mbl2 genotypes as Caucasians produced significantly lower levels of MBL protein; therefore, within this population more genotypes should be considered MBL-deficient. Overall, the most critical parameter in determining serum MBL protein concentration was genotype, which was independent of other factors including ethnicity, gender, or diseased native organ type.

Comparison of allogeneic vs autologous bone marrow­derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

CONTEXT: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. OBJECTIVE: To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. DESIGN, SETTING, AND PATIENTS: A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. INTERVENTION: Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. MAIN OUTCOME MEASURES: Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. RESULTS: Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. CONCLUSIONS: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01087996.

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

Small bowel transplantation (SBT) is becoming a preferred treatment for patients with irreversible intestinal failure. Despite continuous improvement of immunosuppression, SBT is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need for reliable detection markers and novel immunosuppressive strategies that can achieve better control of ACR. We hypothesized that particular transcriptomes provide critical regulation of the intragraft immune response. The aim of our study was to detect potential molecular biomarkers for identifying ACR in minute mucosal biopsies. We examined 30 intestinal mucosal biopsies (AR/NR; 17/13) obtained from recipients after SBT or multivisceral transplantation. We utilized TaqMan® Gene Signature Arrays (immune, inflammation and apoptosis) and investigated the expression of 280 genes. As one of our validations, we performed immunohistochemistry for selected targets. We detected 252 mRNAs in total, 92 of which were found with significantly different expression levels between the AR and NR groups. Immunohistochemistry showed significantly increased staining for IL1R2, ICAM1, GZMB, and CCL3 (P < 0.05) during ACR. For the first time, we characterize the potential molecular changes that are associated with modulation of histological appearances of intestinal ACR. These differences in transcriptome patterns can be used to identify robust biomarkers and potential novel therapeutic targets for immunosuppressive agents.

Cytofluorographic and molecular identification of a CD8-positive, TCR-alpha/beta-negative intraocular T cell lymphoma: a case report and review of the literature.

INTRODUCTION: Cytofluorographic and molecular techniques are effective adjuncts in diagnosing intraocular lymphoma. Primary intraocular lymphoma is an uncommon entity predominantly of B cell origin and rarely with a T cell phenotype. The aim of the present paper is to report a case of a CD8-positive, TCR-alpha/beta-negative intraocular T cell lymphoma and review the literature. CASE PRESENTATION: T cell neoplasia was detected based on flow cytometric demonstration of an abnormal T cell population and polymerase chain reactions for immunoglobulin and T-cell receptor rearrangements demonstrating evidence of monoclonality. Flow cytometry revealed a T cell population aberrantly expressing T-cell lineage markers. This T cell population expressed CD2, bright CD3, CD8, bright CD7, CD38, CD69, and variable CD25. T-cell receptor gamma gene rearrangement studies demonstrated evidence of T-cell gene rearrangement confirming that the T cells were monoclonal. CONCLUSION: We herein report the rare case of a TCR alpha/beta-negative CD8+ intraocular T-cell lymphoma suggestive of gamma/delta origin diagnosed by flow cytometry and polymerase chain reaction.

Burkitt s lymphoma variant of post-transplant lymphoproliferative disease (PTLD).

The occurrence of posttransplant lymphoproliferative disorder (PTLD) in solid organ allograft recipients can be quite varied in clinical presentation, histopathological characteristics and frequency. A variety of lymphomas can develop as a PTLD although some types appear infrequently and remain poorly understood in this clinical setting. In this report, we describe two cases of Burkitt s lymphoma presenting as a PTLD following liver transplantation. The recipients were 12 and 44 years of age and displayed gastrointestinal involvement by the tumors several years following transplant. The tumors displayed the typical histological features of Burkitt s lymphoma and were markedly positive for EBV. The tumors displayed similar immunophenotypic characteristics by flow cytometry and had rearrangements of the immunoglobulin J-H heavy chain. The tumors required aggressive chemotherapy and a cessation of immunosuppressive therapy. This report demonstrates that Burkitt s type lymphomas can develop in the posttransplant setting and that these tumors contain morphologic, cytofluorographic and molecular features identical to Burkitt s lymphomas that occur in non-transplant patients. Our experience is that these PTLD- Burkitt s lymphomas behave aggressively and require intensive chemotherapeutic intervention.