UCSF

Purpose

Patients and methods

Results

Conclusion

INTRODUCTION: Latinx individuals are disproportionately affected by alcohol use disorder (AUD). Understanding Latinx individuals barriers and facilitators to reach AUD-related goals can help implement culturally and linguistically concordant interventions to improve alcohol-related outcomes. METHODS: We conducted semi-structured qualitative interviews with Latinx, Spanish-speaking men with AUD within 20 weeks of hospital discharge who were seen by an addiction consult team during hospitalization in an urban, safety-net hospital in San Francisco. Interviews focused on the facilitators and barriers to participants AUD-related goals pre-, during, and post-hospitalization. We recorded and transcribed interviews and used a mixed deductive and inductive analytic approach until we reached thematic saturation (n = 10). RESULTS: We identified three major themes: 1. Hospitalization was an actionable moment for change; 2. Social factors were closely intertwined with AUD goals; and 3. Accessible addiction, physical health, and mental health services can help achieve AUD goals. CONCLUSIONS: Hospitalization may serve as a facilitator for Latinx individuals with AUD to achieve AUD goals. Addressing social determinants of health including housing, immigration status, and social support networks before, during, and after hospitalization, may help facilitate AUD goals. Providing language-concordant and accessible services may decrease barriers to achieving AUD goals.

Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how the TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism, while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as benchmarks for drug-induced immune activation in ex vivo models of the TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of the TIME underscores the significance of human patient-derived models in elucidating the complexities of anti-tumor immunity and therapeutic interventions.

Fetal growth restriction (FGR) is associated with perinatal death and adverse birth outcomes, as well as long-term complications, including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. Placental epigenetic reprogramming associated with FGR may mediate these long-term outcomes. Placental malaria (PM), characterized by sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous space, is the leading global cause of FGR, but its impact on placental epigenetics is unknown. We hypothesized that placental methylomic profiling would reveal common and distinct mechanistic pathways of non-malarial and PM-associated FGR. We analyzed placentas from a US cohort with no malaria exposure (n = 12) and a cohort from eastern Uganda, a region with a high prevalence of malaria (n = 12). From each site, 8 cases of FGR and 4 healthy controls were analyzed. PM was diagnosed by placental histopathology. We compared the methylation levels of over 850K CpGs of the placentas using Infinium MethylationEPIC v1 microarray. Non-malarial FGR was associated with 65 differentially methylated CpGs (DMCs), whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls without FGR. One DMC (cg16389901, located in the promoter region of BMP4) was commonly hypomethylated in both groups. We identified 522 DMCs between non-malarial FGR vs. PM-FGR placentas, independent of differing geographic location or cellular composition. Placentas with PM-associated FGR have distinct methylation profiles compared to placentas with non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. Larger cohort studies are needed to determine the distinct long-term health outcomes in PM-associated FGR pregnancies.

Healthcare-associated infections (HAI), particularly those involving multi-drug resistant organisms (MDRO), pose a significant public health threat. Understanding the transmission of these pathogens in short-term acute care hospitals (STACH) is crucial for effective control. Mathematical and computational models play a key role in studying transmission but often overlook the influence of long-term care facilities (LTCFs) and the broader community on transmission. In a systematic scoping review of 4,733 unique studies from 2016 to 2022, we explored the modeling landscape of the hospital-community interface in HAI-causing pathogen transmission. Among the 29 eligible studies, 28 % (n = 8) exclusively modeled LTCFs, 45 % (n = 13) focused on non-healthcare-related community settings, and 31 % (n = 9) considered both settings. Studies emphasizing screening and contact precautions were more likely to include LTCFs but tended to neglect the wider community. This review emphasizes the crucial need for comprehensive modeling that incorporates the communitys impact on both clinical and public health outcomes.

Intravital microscopy has enabled the study of immune dynamics in the pulmonary microvasculature, but many key events remain unseen because they occur in deeper lung regions. We therefore developed a technique for stabilized intravital imaging of bronchovascular cuffs and collecting lymphatics surrounding pulmonary veins in mice. Intravital imaging of pulmonary lymphatics revealed ventilation dependence of steady-state lung lymph flow and ventilation-independent lymph flow during inflammation. We imaged the rapid exodus of migratory dendritic cells through lung lymphatics following inflammation and measured effects of pharmacologic and genetic interventions targeting chemokine signaling. Intravital imaging also captured lymphatic immune surveillance of lung-metastatic cancers and lymphatic metastasis of cancer cells. To our knowledge, this is the first imaging of lymph flow and leukocyte migration through intact pulmonary lymphatics. This approach will enable studies of protective and maladaptive processes unfolding within the lungs and in other previously inaccessible locations.

PURPOSE: To develop and validate a 3D turbo spin-echo (TSE)-compatible approach to enhancing black-blood (BB) effects while preserving T1 weighting and overall SNR. METHODS: Following the excitation RF pulse, a 180° RF pulse sandwiched by a pair of flow-sensitive dephasing (FSD) gradient pulses in the phase- (y) and partition-encoding (z) directions, respectively, is added. The polarity of FSD gradients in z direction is toggled every TR, achieving an interleaved FSD (iFSD) configuration in y-z plane. The technique was optimized and evaluated in 18 healthy volunteers and 32 patients with neurovascular disease or brain metastases. Comparisons were made among TSE with and without one of BB preparations: iFSD, delay alternating with nutation for tailored excitation, and motion-sensitized driven equilibrium. RESULTS: iFSD-TSE achieved the best blood flow suppression indicated by venous sinus SNR and parenchyma-to-sinus contrast-to-noise ratio (CNR). iFSD-TSE yielded slightly lower white matter SNR (106.6 ± 32.9) and white-to-gray matter CNR (27.3 ± 8.1) compared to TSE (111.4 ± 31.5 and 28.6 ± 8.8), which were significantly higher than those of delay alternating with nutation for tailored excitation-prepared TSE (84.3 ± 25.0 and 16.8 ± 4.8) and motion-sensitized driven equilibrium-prepared TSE (77.3 ± 26.6 and 15.9 ± 5.3). At the neurovascular wall lesions, iFSD-TSE yielded the highest wall-to-lumen CNR among the three sequences with a BB preparation, all of which significantly outperformed TSE. iFSD-TSE effectively suppressed slow-flow artifacts that otherwise mimicked an atherosclerotic lesion or strongly contrast-enhancing vessel wall. In diagnosing brain metastases, iFSD allowed for highest inter-reader agreement (κ 0.75) and shortest reading time. CONCLUSION: iFSD is a promising approach compatible with 3D TSE for robust blood flow suppression and preserved T1 weighting and overall SNR.

AIM(S): To assess barriers and facilitators to seeking inpatient psychiatric treatment among transgender and nonbinary people. DESIGN: Qualitative interview study. METHODS: Semi-structured interviews were conducted from March 2019 to June 2022 with transgender and nonbinary people admitted to an inpatient psychiatric hospital in the United States during the past 5 years. Data were analysed using thematic analysis and constructed within a modified social-ecological model of stigma. Standards for Reporting Qualitative Research were used for this study. RESULTS: Participants (N = 15) described barriers and facilitators across all three social-ecological levels. i) Individual themes included distrust of the mental healthcare system, feeling unsafe, loss of autonomy, minimizing ones own mental health needs, and feelings of accountability to others. ii) Interpersonal themes included: lack of support for transgender/nonbinary identity, limited transgender/nonbinary knowledge among mental healthcare professionals, and allyship. iii) Structural themes included: carceral setting, financial costs, and availability of non-profit treatment options. CONCLUSION: Multi-level themes were identified as barriers and facilitators to seeking inpatient psychiatric care for transgender and nonbinary people, providing opportunities among inpatient settings to improve care delivery and engagement. Greater health equity can be achieved by addressing barriers to care. IMPLICATIONS: Incorporating inclusive and affirming practices in inpatient psychiatric services presents an opportunity to reduce barriers to seeking care. IMPACT: The present study describes the experiences of transgender and nonbinary people as they determine whether to voluntarily seek inpatient psychiatric treatment. This perspective allows nurses, health systems, and policymakers to integrate transgender and nonbinary peoples needs to improve healthcare delivery. PATIENT/PUBLIC CONTRIBUTION: Transgender and nonbinary participants were recruited in collaboration with community organizations. Members of the transgender and nonbinary community participated in study design development and analysis and were part of the study team.

Despite ongoing efforts to increase the number of women in science, technology, engineering, and mathematics (STEM) and in medicine, Hispanic women remain severely underrepresented in these fields. This disparity not only hinders scientific innovation and the delivery of culturally competent medical care but also perpetuates a systemic exclusion. Research specifically addressing the challenges faced by Hispanic women, the extent of underrepresentation in these disciplines, and strategies to mitigate these issues is sparce. The authors conducted a systematic analysis of peer-reviewed articles to address this gap. The findings reveal a stark underrepresentation of Hispanic women across all examined fields, particularly compared with White women. In addition, the underrepresentation persists when compared with Hispanic men, although the disparity is less pronounced. The authors identify ongoing disparities in promotion, compensation, and retention rates for Hispanic women; present data for barriers to entry and retention; and highlight existing programs and strategies aimed at addressing this underrepresentation. Finally, a framework is presented for future studies and actionable initiatives, and the broader implications of these findings for the field of oncology are highlighted.