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Introduction: Emergency departments (ED) provide trauma-informed care to sexual assault (SA) survivors and connect them with comprehensive services. Through surveying SA survivor advocates, we aimed to 1) document updated trends in the quality of care and resources offered to SA survivors and 2) identify potential disparities according to geographic regions in the US, urban vs rural clinic locations, and the availability of sexual assault nurse examiners (SANE).Methods: We conducted a cross-sectional study between June-August 2021, surveying SA advocates who were dispatched from rape crisis centers to support survivors during ED care. Survey questions addressed two major themes in quality of care: staff preparedness to provide trauma-response care; and available resources. Staff preparedness to provide trauma-informed care was assessed through observations of staff behaviors. We used Wilcoxon rank-sum and Kruskal-Wallis tests to analyze differences in responses according to geographic regions and SANE presence.Results: A total of 315 advocates from 99 crisis centers completed the survey. The survey had a participation rate of 88.7% and a completion rate of 87.9%. Advocates who indicated that a higher proportion of their cases were attended by SANEs were more likely to report higher rates of trauma-informed staff behaviors. For example, the recalled rate of staff asking patients for consent at every step of the exam was significantly associated with SANE presence (P < 0.001). With respect to access to resources, 66.7% of advocates reported that hospitals often or always have evidence collection kits available; 30.6% reported that resources such as transportation and housing are often or always available, and 55.3% reported that SANEs are often or always part of the care team. The SANEs were reported to be more frequently available in the Southwest than in other US regions (P < 0.001) and in urban as opposed to rural areas (P < 0.001).Conclusion: Our study indicates that support from sexual assault nurse examiners is highly associated with trauma-informed staff behaviors and comprehensive resources. Urban-rural and regional disparities exist regarding access to SANEs, suggesting that elevating nationwide quality and equity in care of survivors of sexual assault requires increased investments in SANE training and coverage.

CD45 is a receptor-like tyrosine phosphatase that positively regulates BCR signaling by dephosphorylating the inhibitory tyrosine of the Src family kinases. We showed previously that a single point mutation, E613R, introduced into the cytoplasmic membrane-proximal "wedge" domain of CD45 is sufficient to drive a lupus-like autoimmune disease on a susceptible genetic background. To clarify the molecular mechanism of this disease, we took advantage of a unique allelic series of mice in which the expression of CD45 is varied across a broad range. Although both E613R B cells and those with supraphysiologic CD45 expression exhibited hyperresponsive BCR signaling, they did so by opposite regulation of the Src family kinase Lyn. We demonstrated that the E613R allele of CD45 does not function as a hyper- or hypomorphic allele but rather alters the substrate specificity of CD45 for Lyn. Despite similarly enhancing BCR signaling, only B cells with supraphysiologic CD45 expression became anergic, whereas only mice harboring the E613R mutation developed frank autoimmunity on a susceptible genetic background. We showed that selective impairment of a Lyn-dependent negative-regulatory circuit in E613R B cells drove autoimmunity in E613R mice. This demonstrates that relaxing negative regulation of BCR signaling, rather than enhancing positive regulation, is critical for driving autoimmunity in this system.

The Src and Syk families of kinases are two distinct sets of kinases that play critical roles in initiating membrane-proximal B cell receptor (BCR) signaling. However, unlike in other lymphocytes, such as T cells, the "division of labor" between Src family kinases (SFKs) and Syk in B cells is not well separated because both Syk and SFKs can phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) present in proteins comprising the BCR. To understand why B cells require both SFKs and Syk for activation, we investigated the roles of both families of kinases in BCR signaling with computational modeling and in vitro experiments. Our computational model suggested that positive feedback enabled Syk to substantially compensate for the absence of SFKs when spatial clustering of BCRs was induced by multimeric ligands. We confirmed this prediction experimentally. In contrast, when B cells were stimulated by monomeric ligands that failed to produce BCR clustering, both Syk and SFKs were required for complete and rapid BCR activation. Our data suggest that SFKs could play a pivotal role in increasing BCR sensitivity to monomeric antigens of pathogens and in mediating a rapid response to soluble multimeric antigens of pathogens that can induce spatial BCR clustering.

In humans, up to 75% of newly generated B cells and about 30% of mature B cells show some degree of autoreactivity. Yet, how B cells establish and maintain tolerance in the face of autoantigen exposure during and after development is not certain. Studies of model B-cell antigen receptor (BCR) transgenic systems have highlighted the critical role of functional unresponsiveness or ‘anergy’. Unlike T cells, evidence suggests that receptor editing and anergy, rather than deletion, account for much of B-cell tolerance. However, it remains unclear whether the mature diverse B-cell repertoire of mice contains anergic autoreactive B cells, and if so, whether antigen was encountered during or after their development. By taking advantage of a reporter mouse in which BCR signalling rapidly and robustly induces green fluorescent protein expression under the control of the Nur77 regulatory region, antigen-dependent and antigen-independent BCR signalling events in vivo during B-cell maturation were visualized. Here we show that B cells encounter antigen during development in the spleen, and that this antigen exposure, in turn, tunes the responsiveness of BCR signalling in B cells at least partly by downmodulating expression of surface IgM but not IgD BCRs, and by modifying basal calcium levels. By contrast, no analogous process occurs in naive mature T cells. Our data demonstrate not only that autoreactive B cells persist in the mature repertoire, but that functional unresponsiveness or anergy exists in the mature B-cell repertoire along a continuum, a fact that has long been suspected, but never yet shown. These results have important implications for understanding how tolerance in T and B cells is differently imposed, and how these processes might go awry in disease.

Interactions between emergency department (ED) staff and sexual assault (SA) survivors can be a source of retraumatization for survivors, increasing their risk of posttraumatic stress and decreasing utilization of longitudinal medical care. Little is known about nationwide trends in ED staff attitudes and behaviors toward survivors, including the impact of survivor identity. We conducted a survey to determine if survivor identity influenced ED staff behaviors. A nationwide survey of SA patient advocates was conducted between June and August 2021. Advocates are volunteers or staff dispatched from rape crisis centers to support survivors during ED care. Advocates participated in an online survey to determine the frequency of observing six potentially retraumatizing provider attitudes and behaviors. Adaptive questioning was used to explore the impact of survivor identity on each attitude or behavior and which identity groups were more likely to be affected. Three hundred fifteen advocates responded to the survey. Less than 10% indicated that ED staff often or always convey disbelief or blame to survivors. Almost 75% of advocates indicated that they often or always observe ED staff showing empathy to survivors. Disparities were found in provider attitudes. Over 75% of advocates observed that survivors' mental health status or substance use impacted conveyed belief from providers. Patients who were intoxicated when assaulted, had psychiatric disorders, were Black, Hispanic/LatinX, or indigenous, or were not cis-females were more likely to experience disbelief. Patients who were white and/or cis-gender females were more likely to be pressured by ED staff to complete the forensic exam and/or report to the police. Our study documents disparities in ED staff behavior towards SA survivors according to survivor identity. Given that post-assault ED interactions are critical turning points in survivors' future medical processes, disparities in ED care may be linked to larger disparities in healing from trauma. [ABSTRACT FROM AUTHOR]

Emergency departments (EDs) providing care and forensic examinations for sexual assault (SA) survivors are often supported by SA patient advocates. This study explored advocates' perspectives regarding problems and potential solutions in SA patient care through a focus group with 12 advocates. Thematic analysis identified two major themes: provider–patient interactions and ED–hospital systems. Challenging aspects of provider–patient interactions included (a) provider attitudes and (b) disempowering behaviors. Within ED–hospital systems, themes included time constraints, efficiencies, and hospital preparation. Advocates surveyed were optimistic about an increased presence of SA nurse examiners and enhanced protocols and provider training to improve survivors' experiences. [ABSTRACT FROM AUTHOR]

Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue-device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer-silicon nanowire composite mesh can be used to convert fast moving, lowradiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency. [ABSTRACT FROM AUTHOR]

Scales are rooted in soft tissues, and are regenerated by specialized cells. The realization of dynamic synthetic analogues with inorganic materials has been a significant challenge, because the abiological regeneration sites that could yield deterministic growth behavior are hard to form. Here we overcome this fundamental hurdle by constructing a mutable and deformable array of three-dimensional calcite heterostructures that are partially locked in silicone. Individual calcite crystals exhibit asymmetrical dumbbell shapes and are prepared by a parallel tectonic approach under ambient conditions. The silicone matrix immobilizes the epitaxial nucleation sites through self-templated cavities, which enables symmetry breaking in reaction dynamics and scalable manipulation of the mineral ensembles. With this platform, we devise several mineral-enabled dynamic surfaces and interfaces. For example, we show that the induced growth of minerals yields localized inorganic adhesion for biological tissue and reversible focal encapsulation for sensitive components in flexible electronics. [ABSTRACT FROM AUTHOR]