Mental Health, Race, and Social Support among Women Survivors of Intimate Partner Violence.

Women with mental health (MH) symptoms are more vulnerable to the adverse effects of intimate partner violence (IPV). Social support (SS) helps those women cope with adversities and regain their overall well-being. Examining specific sources and functions of SS will help expand knowledge about resources for and barriers to MH services for women IPV survivors. However, few studies examined functional and relational SS among women IPV survivors residing in shelters. This cross-sectional study examined how 31 racially diverse women IPV survivors with different MH symptoms perceive relational SS from various sources as they stay in a shelter that provides functional SS. Cluster analyses were performed to classify participants into two groups: more MH or fewer MH symptoms. Results showed that the women with more MH symptoms reported higher tangible support than those with fewer MH symptoms. Results from ANCOVA showed a significant cross-over interaction between MH and race for overall SS, indicating that women of color with more MH symptoms were less likely to perceive overall SS than Caucasians when controlling for functional SS. MANCOVA analyzed the specific sources of overall SS, such as family, friends, and others. There was a significant cross-over interaction of MH and race on SS from others when controlling for functional SS. These findings suggest that women IPV survivors of color who experience more MH symptoms perceive support from others as less supportive and trustworthy. Social service providers must provide culturally sensitive and strengths-based SS programs to help women of color who have experienced social isolation, stigma, and shame associated with IPV and mental illnesses (MIs). They also must engage in community outreach programs by educating community members about the needs and rights of women IPV survivors with MIs and collaborating to build communities that promote safety, trust, diversity, equity, and inclusion.

Targeting the Retinoid X Receptor Pathway Prevents and Ameliorates Murine Chronic Graft-Versus-Host Disease.

Most allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients receive peripheral blood stem cell grafts resulting in a 30%-70% incidence of chronic graft-versus-host disease (cGVHD), a major cause of mortality and morbidity in long-term survivors. While systemic steroids remain the standard of care for first-line therapy, patients may require long-term administration, and those with steroid-resistant or refractory cGVHD have a worse prognosis. Although durable and deep responses with second-line therapies can be achieved in some patients, there remains an urgent need for new therapies. In this study, we evaluated the efficacy of IRX4204, a novel agonist that activates RXRs and is in clinical trials for cancer treatment to prevent and treat cGVHD in two complementary murine models. In a major histocompatibility complex mismatched, non-sclerodermatous multiorgan system model with bronchiolitis obliterans, IRX4204 prevented and reversed cGVHD including associated pulmonary dysfunction with restoration of germinal center T-follicular helper: T-follicular regulatory cell balance. In a minor histocompatibility antigen disparate sclerodermatous model, IRX4204 treatment significantly prevented and ameliorated skin cGVHD by reducing Th1 and Th17 differentiation due to anti-inflammatory properties. Together, these results indicate that IRX4204 is a promising therapeutic option to treat cGVHD with bronchiolitis obliterans or sclerodermatous manifestations.

BET-bromodomain and EZH2 inhibitor-treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes.

Despite advances in the field, chronic graft-versus-host-disease (cGVHD) remains a leading cause of morbidity and mortality following allogenic hematopoietic stem cell transplant. Because treatment options remain limited, we tested efficacy of anticancer, chromatin-modifying enzyme inhibitors in a clinically relevant murine model of cGVHD with bronchiolitis obliterans (BO). We observed that the novel enhancer of zeste homolog 2 (EZH2) inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 each improved pulmonary function; impaired the germinal center (GC) reaction, a prerequisite in cGVHD/BO pathogenesis; and JQ5 reduced EZH2-mediated H3K27me3 in donor T cells. Using conditional EZH2 knockout donor cells, we demonstrated that EZH2 is obligatory for the initiation of cGVHD/BO. In a sclerodermatous cGVHD model, JQ5 reduced the severity of cutaneous lesions. To determine how the 2 drugs could lead to the same physiological improvements while targeting unique epigenetic processes, we analyzed the transcriptomes of splenic GCB cells (GCBs) from transplanted mice treated with either drug. Multiple inflammatory and signaling pathways enriched in cGVHD/BO GCBs were reduced by each drug. GCBs from JQ5- but not JQ1-treated mice were enriched for proproliferative pathways also seen in GCBs from bone marrow-only transplanted mice, likely reflecting their underlying biology in the unperturbed state. In conjunction with in vivo data, these insights led us to conclude that epigenetic targeting of the GC is a viable clinical approach for the treatment of cGVHD, and that the EZH2 inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 demonstrated clinical potential for EZH2i and BETi in patients with cGVHD/BO.

Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.

The therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the development of graft-versus-host disease (GVHD). In GVHD, rigorous pre-conditioning regimen resets the immune landscape and inflammatory milieu causing immune dysregulation, characterized by an expansion of alloreactive cells and a reduction in immune regulatory cells. In acute GVHD (aGVHD), the release of damage- and pathogen- associated molecular patterns from damaged tissue caused by the conditioning regimen sets the stage for T cell priming, activation and expansion further exacerbating tissue injury and organ damage, particularly in the gastrointestinal tract. Studies have shown that donor T cells utilize multiple energetic and biosynthetic pathways to mediate GVHD that can be distinct from the pathways used by regulatory T cells for their suppressive function. In chronic GVHD (cGVHD), donor T cells may differentiate into IL-21 producing T follicular helper cells or tissue resident T helper cells that cooperate with germinal center B cells or memory B cells, respectively, to produce allo- and auto-reactive antibodies with subsequent tissue fibrosis. Alternatively, donor T cells can become IFN- γ/IL-17 cytokine expressing T cells that mediate sclerodermatous skin injury. Patients refractory to the first line standard regimens for GVHD treatment have a poor prognosis indicating an urgent need for new therapies to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect. Emerging data points toward a role for metabolism in regulating these allo- and auto-immune responses. Here, we will discuss the preclinical and clinical data available on the distinct metabolic demands of acute and chronic GVHD and recent efforts in identifying therapeutic targets using metabolomics. Another dimension of this review will examine the changing microbiome after allo-HSCT and the role of microbial metabolites such as short chain fatty acids and long chain fatty acids on regulating immune responses. Lastly, we will examine the metabolic implications of coinhibitory pathway blockade and cellular therapies in allo-HSCT. In conclusion, greater understanding of metabolic pathways involved in immune cell dysregulation during allo-HSCT may pave the way to provide novel therapies to prevent and treat GVHD.

Husserlian phenomenology in Korean nursing research: analysis, problems, and suggestions.

PURPOSE: This paper is a critical review of the descriptive phenomenological methodology in Korean nursing research. We propose constructive suggestions for the improvement of descriptive phenomenological methodology in light of Husserl's phenomenological approaches. METHODS: Using the keywords of 'phenomenology,' 'experience,' and 'nursing,' we identify and analyze 64 Korean empirical phenomenological studies (selected from 282 studies) published in 14 Korean nursing journals from 2005 to 2018. The PubMed and the Korea Citation Index were used to identify the studies. RESULTS: Our analysis shows that all the reviewed articles used Giorgi's or Colaizzi's scientific phenomenological methodology, without critical attention to Husserl's philosophical phenomenological principles. CONCLUSIONS: The use of scientific phenomenology in nursing research, which originated in North America, has become a global phenomenon, and Korean phenomenological nursing research has faithfully followed this scholarly trend. This paper argues that greater integration of Husserlian phenomenological principles into scientific phenomenological methodology in nursing research, such as participant-centered bracketing and eidetic reduction, is needed to ensure that scientific phenomenology lives up to its promise as a research methodology.

Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease.

Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.

Husserlian Phenomenology in Korean Nursing Research: Analysis, Problems, and Suggestions / 한국간호교육학회지

This paper is a critical review of descriptive phenomenological methodology in Korean nursing research. We propose constructive suggestions for the improvement of descriptive phenomenological methodology in light of Husserl's phenomenological approaches. Methods: Using the key words of 'phenomenology,' 'experience,' and 'nursing,' we identify and analyze 64 Korean empirical phenomenological studies (selected from 282 studies) published in 14 Korean nursing journals from 2005 to 2018. The PubMed and the Korea Citation Index were used to identify the studies. Results: Our analysis shows that all the reviewed articles used Giorgi's or Colaizzi's scientific phenomenological methodology, without critical attention to Husserl's philosophical phenomenological principles. Conclusions: The use of scientific phenomenology in nursing research, which originated in North America, has become a global phenomenon, and Korean phenomenological nursing research has faithfully followed this scholarly trend. This paper argues that greater integration of Husserlian phenomenological principles into scientific phenomenological methodology in nursing research, such as participant-centered bracketing and eidetic reduction, is needed to ensure that scientific phenomenology lives up to its promise as a research methodology.

3D Bioprinting of Spatially Heterogeneous Collagen Constructs for Cartilage Tissue Engineering.

3D printing of biological tissues has been of increasing interest to the biomaterials community in part because of its potential to produce spatially heterogeneous constructs. Such technology is particularly promising for orthopedic applications, which require the generation of complex geometries to match patient anatomy and complex microstructures to produce spatial heterogeneity and anisotropy. Prior research has demonstrated the capacity to create precisely shaped 3D printed constructs using biocompatible alginate hydrogels. However, alginate is extremely compliant and brittle, and high-density collagen hydrogels could be a preferable option for load-bearing applications. This research focused on developing and evaluating a method of printing soft tissue implants with high-density collagen hydrogels using a commercially available 3D printer, modified for tissue-engineering purposes. The tissue constructs, seeded with primary meniscal fibrochondrocytes, were evaluated using measures of geometric fidelity, cell viability, mechanical properties, and fiber microstructure. The constructs were found to be mechanically stable and were able to support and maintain cell growth. Furthermore, heterogeneous 3D-printed constructs were generated, consisting of discrete domains with distinct mechanical properties.