"I realized I was not alone": A mixed-methods investigation of the implementation of Ubuntu groups to reduce burnout and social isolation in an allopathic medical School in the Southeastern United States.

PURPOSE/BACKGROUND: Healthcare providers experience higher rates of workplace burnout, a reality highlighted by the COVID-19 pandemic. In response, small groups, inspired by South African philosophy, Ubuntu, were introduced to decrease burnout and social isolation and build community and belonging. This study examines how participation in these groups can impact these measures. METHODS: In this mixed-methods study, trained facilitators led small groups that utilized story-sharing to foster connections within the group and broader community. Quantitative and qualitative data were analyzed separately and merged to identify convergence. RESULTS: Three main qualitative themes emerged: 1) seeking and building connections and community, 2) curiosity, learning, and growing, and 3) open-hearted and thriving. These themes were linked to quantitative outcomes, showing a statistically significant decrease in social isolation among staff/faculty and students. Furthermore, faculty/staff exhibited reduced burnout compared to students, while students reported increased feelings of belonging. CONCLUSION: Participation in Ubuntu groups positively influenced students' sense of belonging, reduced faculty/staff burnout, and alleviated social isolation for all participants. Future research should explore the potential of this intervention to further promote wellness on medical campuses. Programs emphasizing the well-being of individuals, including faculty, staff, and students, are crucial for supporting the overall health of medical communities and the wider society.

Loss of Brca1 and Trp53 in adult mouse mammary ductal epithelium results in development of hormone receptor-positive or hormone receptor-negative tumors, depending on inactivation of Rb family proteins.

BACKGROUND: Breast cancer is a heterogenous disease with several histological and molecular subtypes. Models that represent these subtypes are essential for translational research aimed at improving clinical strategy for targeted therapeutics. METHODS: Different combinations of genetic aberrations (Brca1 and Trp53 loss, and inhibition of proteins of the Rb family) were induced in the mammary gland by injection of adenovirus expressing Cre recombinase into the mammary ducts of adult genetically engineered mice. Mammary tumors with different genetic aberrations were classified into molecular subtypes based on expression of molecular markers and RNAseq analysis. In vitro potency assays and Western blots were used to examine their drug sensitivities. RESULTS: Induction of Brca1 and Trp53 loss in mammary ductal epithelium resulted in development of basal-like hormone receptor (HR)-negative mammary tumors. Inhibition of Rb and Trp53 loss or the combination of Rb, Trp53 and Brca1 aberrations resulted in development of luminal ductal carcinoma positive for ER, PR, and Her2 expression. HR positivity in tumors with Rb, Trp53 and Brca1 aberrations indicated that functionality of the Rb pathway rather than Brca1 status affected HR status in these models. Mammary tumor gene expression profiles recapitulated human basal-like or luminal B breast cancer signatures, but HR-positive luminal cancer models were endocrine resistant and exhibited upregulation of PI3K signaling and sensitivity to this pathway inhibition. Furthermore, both tumor subtypes were resistant to CDK4/6 inhibition. CONCLUSIONS: Examination of molecular expression profiles and drug sensitivities of tumors indicate that these breast cancer models can be utilized as a translational platform for evaluation of targeted combinations to improve chemotherapeutic response in patients that no longer respond to hormone therapy or that are resistant to CDK4/6 inhibition.

SARS-CoV-2 Infection Inducing Immune Thrombocytopenic Purpura: Case Series.

Background: Immune thrombocytopenic purpura (ITP) refers to immune-mediated destruction of platelets. Viral infections have been proposed as an etiology of ITP; antibodies developed in response to infection may cross-react with normal platelets and result in their destruction. Case Series: We report 2 cases in which coronavirus disease 2019 (COVID-19) likely induced severe ITP. Conclusion: ITP may also play a role in the thrombocytopenia observed in some patients with COVID-19. ITP in this patient population may be more prevalent than currently documented.

The Indenoisoquinoline TOP1 Inhibitors Selectively Target Homologous Recombination-Deficient and Schlafen 11-Positive Cancer Cells and Synergize with Olaparib.

PURPOSE: Irinotecan and topotecan are used to treat a variety of different cancers. However, they have limitations, including chemical instability and severe side effects. To overcome these limitations, we developed the clinical indenoisoquinolines: LMP400 (indotecan), LMP776 (indimitecan), and LMP744. The purpose of the study is to build the molecular rationale for phase II clinical trials. EXPERIMENTAL DESIGN: CellMinerCDB (http://discover.nci.nih.gov/cellminercdb) was used to mine the cancer cell lines genomic databases. The causality of Schlafen11 (SLFN11) was validated in isogenic cell lines. Because topoisomerase I (TOP1)-mediated replication DNA damage is repaired by homologous recombination (HR), we tested the "synthetic lethality" of HR-deficient (HRD) cells. Survival and cell-cycle alterations were performed after drug treatments in isogenic DT40, DLD1, and OVCAR cell lines with BRCA1, BRCA2, or PALB2 deficiencies and in organoids cultured from prostate cancer patient-derived xenografts with BRCA2 loss. We also used an ovarian orthotopic allograft model with BRCA1 loss to validate the efficacy of LMP400 and olaparib combination. RESULTS: CellMinerCDB reveals that SLFN11, which kills cells undergoing replicative stress, is a dominant drug determinant to the clinical indenoisoquinolines. In addition, BRCA1-, BRCA2-, and PALB2-deficient cells were hypersensitive to the indenoisoquinolines. All 3 clinical indenoisoquinolines were also synergistic with olaparib, especially in the HRD cells. The synergy between LMP400 and olaparib was confirmed in the orthotopic allograft model harboring BRCA1 loss. CONCLUSIONS: Our results provide a rationale for molecularly designed clinical trials with the indenoisoquinolines as single agents and in combination with PARP inhibitors in HRD cancers expressing SLFN11.

A Transplantable Syngeneic Allograft Mouse Model for Nongestational Choriocarcinoma of the Ovary.

Nongestational choriocarcinoma is a rare malignancy in humans with poor prognosis. Naturally occurring choriocarcinoma is also rare in laboratory mice, and no genetic mouse model accurately recapitulates the features of this cancer. Here we report development of a genetically engineered mouse (GEM) model with alterations in Brca2, Trp53, and RB that develops ovarian tumors. Most of the ovarian tumors displayed histological characteristics of nongestational choriocarcinoma of the ovary (NGCO) (47%) with abundant syncytiotrophoblasts and cytotrophoblasts, positive immunolabeling for human chorionic gonadotropin, and positive periodic acid-Schiff reaction. The rest of the ovarian tumors were serous epithelial ovarian carcinoma (SEOC) (26%) or mixed tumors consisting of NGCO and SEOC (26%). We further established syngeneic orthotopic mouse models for NGCO by in vivo passaging of GEM tumors. These metastatic models provide a platform for evaluating new treatment strategies in preclinical studies aimed at improving outcomes in choriocarcinoma patients.

The Use of Lifestyle and Behavioral Modification Approaches in Obesity Interventions for Black Women: A Literature Review.

The alarming obesity prevalence in Black women is well documented yet poorly understood. Obesity interventions for Black women have failed to produce long-term reductions in weight. Recommendations to incorporate a lifestyle and behavioral modification approach have been made to address obesity in this population. The purpose of this article was to provide a comprehensive review of the literature to identify lifestyle and behavioral modification obesity intervention studies for Black women. We included articles published between February 1992 and January 2013. This search identified 28 articles from the PsycInfo, MEDLINE, CINAHL, and SPORTDiscus databases. Results of these studies were summarized primarily into six categories. The importance of modest improvements in health outcomes that result from adapting healthier behaviors was highlighted. Future research is required for identifying the most salient intervention component or combination of components that lead to the best outcomes for ensuring intervention success and minimizing weight regain postintervention.

Computerized physician order entry- based hyperglycemia inpatient protocol and glycemic outcomes: The CPOE-HIP study.

OBJECTIVE: To evaluate the impact of implementing a computerized physician order entry (CPOE)-based hyperglycemia inpatient protocol (HIP) on glycemic outcomes. METHODS: This retrospective, cross-sectional study compared blood glucose values, hemoglobin A(1c) values, diabetes medication profles, and demographic data of diabetic patients admitted to medicine services between March 15, 2006, and April 11, 2006 (before CPOE-HIP protocol was adopted), with data of diabetic patients admitted between October 3, 2007, and October 30, 2007 (1 year after CPOE-HIP protocol was implemented). RESULTS: A total of 241 diabetic patients comprised the pre-CPOE-HIP group and 197 patients comprised the post-CPOE-HIP group. After the protocol was adopted, there was a decrease of 10.8 mg/dL in the mean glucose concentration per patient-day (175.5 +/- 81.2 mg/dL vs 164.7 +/- 82 mg/dL, P<.001). Additional glycemic control improvements included a 5% increase in patient-days with serum glucose concentrations between 70 and 150 mg/dL (41.1% vs 46.1%, P = .008) and a 3.1% decrease in patient-days with glucose concentrations above 299 mg/dL (16.9% vs 13.8%, P = .023). The percentage of patient-days with glucose concentrations less than or equal to 50 mg/dL was not significantly different (0.95% vs 1.27%,P = .15). Compliance with the American Diabetes Association recommendation for hemoglobin A1c inpatient testing frequency increased from 37.3% to 64.5% (P<.001). The length of stay did not differ between the groups. CONCLUSIONS: Implementation of a hospital-wide, CPOE-based, hyperglycemia management protocol had a favorable impact on glucose targets, decreasing excessively high glucose levels without increasing clinically meaningful hypoglycemic events. Compliance with hemoglobin A(1c) testing recommendations also improved.

Migraine care among different ethnicities: do disparities exist?

OBJECTIVE: Evaluate whether, in a primary care setting, Caucasians (C) and African Americans (AA) with moderately to severely disabling migraines differed in regards to: utilizing the health-care system for migraine care, migraine diagnosis and treatment, level of mistrust in the health-care system, perceived communication with their physician, and perceived migraine triggers. BACKGROUND: Research has documented ethnic disparities in pain management. However, almost no research has been published concerning potential disparities in utilization, diagnosis, and/or treatment of migraine. It is also important to consider whether ethnic differences exist for trust and communication between patients and physicians, as these are essential when diagnosing and treating migraine. METHODS: Adult patients with headache (n = 313) were recruited from primary care waiting rooms. Of these, 131 (AA = 77; C = 54) had migraine, moderate to severe headache-related disability, and provided socioeconomic status (SES) data. Participants completed measures of migraine disability (MIDAS), migraine health-care utilization, diagnosis and treatment history, mistrust of the medical community, patient-physician communication (PPC), and migraine triggers. Analysis of covariance (controlling for SES and recruitment site), chi-square, and Pearson product moment correlations were conducted. RESULTS: African Americans were less likely to utilize the health-care setting for migraine treatment (AA = 46% vs. C = 72%, P < .001), to have been given a headache diagnosis (AA = 47% vs. C = 70%, P < .001), and to have been prescribed acute migraine medication (AA = 14% vs. C = 37%, P < .001). Migraine diagnosis was low for both groups, and <15% of all participants had been prescribed a migraine-specific medication or a migraine preventive medication despite suffering moderate to severe levels of migraine disability. African Americans had less trust in the medical community (P < .001, eta2 = 0.26) and less positive PPC (P < .001, eta2 = 0.11). Also, the lower the trust and communication, the less likely they were to have ever seen (or currently be seeing) a doctor for migraine care or to have been prescribed medication. CONCLUSIONS: Migraine utilization, diagnosis, and treatment were low for both groups. However, this was especially true for African Americans, who also reported lower levels of trust and communication with doctors relative to Caucasians. The findings highlight the need for improved physician and patient education about migraine diagnosis and treatment, the importance of cultural variation in pain presentation, and the importance of communication when diagnosing and treating migraine.