UCSF

A growing body of research has documented disrespectful, abusive, and neglectful treatment of women in facilities during childbirth, as well as the drivers of such mistreatment. Yet, little research exists on effective interventions to improve Person-Centred Maternal Care (PCMC)-care that is respectful and responsive to individual women's preferences, needs, and values. We sought to extend knowledge on interventions to improve PCMC, with a focus on two factors - provider stress and implicit bias - that are driving poor PCMC and contributing to disparities in PCMC. In this paper we describe the process towards the development of the intervention. The intervention design was an iterative process informed by existing literature, behaviour change theory, formative research, and continuous feedback in consultation with key stakeholders. The intervention strategies were informed by the Social Cognitive Theory, Trauma Informed System framework, and the Ecological Perspective. This process resulted in the 'Caring for Providers to Improve Patient Experience (CPIPE)' intervention, which has 5 components: provider training, peer support, mentorship, embedded champions, and leadership engagement. The training includes didactic and interactive content on PCMC, stress, burnout, dealing with difficult situations, and bias, with some content integrated into emergency obstetric and neonatal care (EmONC) simulations to enable providers apply concepts in the context of managing an emergency. The other components create an enabling environment for ongoing individual behavior and facility culture change. The pilot study is being implemented in Migori County, Kenya. The CPIPE intervention is an innovative theory and evidence-based intervention that addresses key drivers of poor PCMC and centers the unique needs of vulnerable women as well as that of providers. This intervention will advance the evidence base for interventions to improve PCMC and has great potential to improve equity in PCMC and maternal and neonatal health.

Latinx physician rates are lower than non-Latinx white physicians. Many pathway programs to careers in medicine have been established for underrepresented students, yet few focus on premedical college education or undergraduate pathway programs, which marks a critical junction in the commitment to and preparation for application to medical school. Moreover, little is known about the program components which prepare and support learners. Framed by Swail's Model for Persistence and Achievement, we characterize how a given program's components impact support and growth for participating students. Using the process step of the Context, Input, Process, and Product evaluation model, we conducted focus groups at the end of the program, with four cohorts of student participants between 2019 and 2022. Focus groups identified strengths and limitations in content and delivery to improve program effectiveness and plan for the future of a program. We used thematic analysis, following an inductive approach, to analyze data from transcribed focus groups. A total of 66 of 81 (81.5%) students participated in focus groups. Students described that supportive program components include long-term mentorship and advising that builds trust, academic preparation for medical school, early exposure to clinical career exploration, tools to articulate students' personal narrative, methods to recognize and address challenging situations in the professional environment, community leadership development, and leveraging health policy and advocacy to empower students to create systems change within communities. Our findings affirm and provide a needed account of program components known to be contributors to student success in undergraduate pathway programs. Our evaluation also characterizes additional supportive processes not discussed elsewhere. Our findings contribute to knowledge about development and implementation of undergraduate pathway programs and the components by which these programs create opportunities for success among underrepresented students aspiring to careers in medicine.

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Significance: Leakage in the interfaces between restorative materials and tooth structure allows for fluid and bacterial acid infiltration, causing restoration failure due to secondary caries. Dentists spend more time replacing composite restorations than placing new ones. Previous in vitro and in vivo studies on enamel and root surfaces using shortwave-infrared (SWIR) and thermal imaging during dehydration with forced air have been promising for assessing lesion activity. Aim: We hypothesized that SWIR reflectance and thermal imaging methods can be used to monitor the activity of secondary caries lesions around composite restorations. The objective of this study was to employ these methods to measure the rate of fluid loss from lesions during dehydration with forced air to assess lesion activity. Approach: Sixty-three extracted human teeth with total of 109 suspected secondary lesions were examined using SWIR and thermal imaging during dehydration. The thickness of the highly mineralized transparent surface layer (TSL) at lesion interfaces indicative of lesion activity was measured by optical coherence tomography (OCT). Micro-computed tomography (MicroCT) was used to further confirm lesion severity and structure. OCT and MicroCT measurements of lesion structure, depth, and severity were correlated with fluid loss rates measured with SWIR reflectance and thermal imaging. Results: TSL thickness measured with OCT correlated with both SWIR reflectance and thermal measurements of rates of fluid loss ( p<0.05 ). Increasing TSL thickness led to decreased permeability of lesions, potentially indicating full lesion arrest at TSL≥70  μm . SWIR performed better than thermal imaging for secondary lesion activity assessment, although both methods performed best on smooth surface lesions. Conclusions: Nondestructive SWIR reflectance and OCT imaging methods are promising for clinically monitoring the activity of secondary caries lesions.

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.

Distinct CD4+ T cell epitopes have been associated with spontaneous control of HIV-1 replication, but analysis of antigen-dependent factors that influence epitope selection is lacking. To examine these factors, we used a cell-free antigen processing system that incorporates soluble HLA-DR (DR1), HLA-DM (DM), cathepsins, and full-length protein antigens for epitope identification by LC-MS/MS. HIV-1 Gag, Pol, Env, Vif, Tat, Rev, and Nef were examined using this system. We identified 35 novel epitopes, including glycopeptides. Epitopes from smaller HIV-1 proteins mapped to regions of low protein stability and higher solvent accessibility. HIV-1 antigens associated with limited CD4+ T cell responses were processed efficiently, while some protective epitopes were inefficiently processed. 55% of epitopes obtained from cell-free processing induced memory CD4+ T cell responses in HIV-1+ donors, including eight of 19 novel epitopes tested. Thus, an in vitro processing system utilizing the components of Class II processing reveals factors influencing epitope selection of HIV-1 and represents an approach to understanding epitope selection from non-HIV-1 antigens.