Mitochondrial metabolism regulation and epigenetics in hypoxia.

The complex and dynamic interaction between cellular energy control and gene expression modulation is shown by the intersection between mitochondrial metabolism and epigenetics in hypoxic environments. Poor oxygen delivery to tissues, or hypoxia, is a basic physiological stressor that sets off a series of reactions in cells to adapt and endure oxygen-starved environments. Often called the "powerhouse of the cell," mitochondria are essential to cellular metabolism, especially regarding producing energy through oxidative phosphorylation. The cellular response to hypoxia entails a change in mitochondrial metabolism to improve survival, including epigenetic modifications that control gene expression without altering the underlying genome. By altering the expression of genes involved in angiogenesis, cell survival, and metabolism, these epigenetic modifications help cells adapt to hypoxia. The sophisticated interplay between mitochondrial metabolism and epigenetics in hypoxia is highlighted by several important points, which have been summarized in the current article. Deciphering the relationship between mitochondrial metabolism and epigenetics during hypoxia is essential to understanding the molecular processes that regulate cellular adaptation to reduced oxygen concentrations.

Heat stress and host-parasitoid interactions: lessons and opportunities in a changing climate.

Ongoing climate change is increasing the frequency and magnitude of high-temperature events (HTEs), causing heat stress in parasitoids and their hosts. We argue that HTEs and heat stress should be viewed in terms of the intersecting life cycles of host and parasitoid. Recent studies illustrate how the biological consequences of a given HTE may vary dramatically depending on its timing within these lifecycles. The temperature sensitivity of host manipulation by parasitoids, and by viral endosymbionts of many parasitoids, can contribute to differing responses of hosts and parasitoids to HTEs. In some cases, these effects can result in reduced parasitoid success and increased host herbivory and may disrupt the ecological interactions between hosts and parasitoids. Because most studies to date involve endoparasitoids of aphid or lepidopteran hosts in agricultural systems, our understanding of heat responses of host-parasitoid interactions in natural systems is quite limited.

Patient and Caregiver Satisfaction With the Brain Injury Rehabilitation: Improving the Transition Experience (BRITE) Intervention.

OBJECTIVE: To ascertain patient and caregiver satisfaction with an individualized case management intervention to improve transition from inpatient rehabilitation care to the community after traumatic brain injury (TBI). SETTING: Participants from 6 National Institute on Disability, Independent Living, and Rehabilitation Research-funded TBI Model Systems sites in the United States. PARTICIPANTS: Adult, English-speaking patients with TBI who had moderate-to-severe TBI and were discharged from a TBI Model Systems site and who were in the intervention arm of the Brain Injury Rehabilitation: Improving the Transition Experience pragmatic clinical trial, as well as their caregivers. DESIGN: A survey of participants in the intervention arm, which included an individualized case management program administered by a TBI Care Manager (TCM) who facilitated resource connection, education, and support. MAIN MEASURES: Satisfaction with intervention was measured through Likert-scaled and open-ended questions. The survey was administered verbally through telephone, audio-recorded, and transcribed. Descriptive statistics were calculated for categorical variables, and content analysis was conducted for open-ended responses. RESULTS: Patient and caregiver participants were satisfied with the intervention and highlighted the benefits of the interpersonal and practical support provided by the TCM. Participants identified the need for a more intensive intervention and clear expectations of the TCM role, as well as gaps in available medical and rehabilitation services in the community, as areas for improvement. CONCLUSION: Patients with TBI and their caregivers reported satisfaction with the individualized case management program in supporting their transition from inpatient rehabilitation to the community. Further research is needed to understand the impact on outcomes.

Improving Post-Injury Follow-up Survey Response: Incorporating Automated Modalities.

Background: Incorporating post-discharge data into trauma registries would allow for better research on patient outcomes, including disparities in outcomes. This pilot study tested a follow-up data collection process to be incorporated into existing trauma care systems, prioritizing low-cost automated response modalities. Methods: This investigation was part of a larger study that consisted of two protocols with two distinct cohorts of participants who experienced traumatic injury. Participants in both protocols were asked to provide phone, email, text, and mail contact information to complete follow-up surveys assessing patient-reported outcomes six months after injury. To increase follow-up response rates between protocol 1 and protocol 2, the study team modified the contact procedures for the protocol 2 cohort. Frequency distributions were utilized to report the frequency of follow-up response modalities and overall response rates in both protocols. Results: A total of 178 individuals responded to the 6-month follow-up survey: 88 in protocol 1 and 90 in protocol 2. After implementing new follow-up contact procedures in protocol 2 that relied more heavily on the use of automated modalities (e.g., email and text messages), the response rate increased by 17.9 percentage points. The primary response modality shifted from phone (72.7%) in protocol 1 to the combination of email (47.8%) and text (14.4%) in protocol 2. Conclusions: Results from this investigation suggest that follow-up data can feasibly be collected from trauma patients. Use of automated follow-up methods holds promise to expand longitudinal data in the national trauma registry and broaden the understanding of disparities in patient experiences.

Identifying Common Data Elements to Achieve Injury-related Health Equity Across the Lifespan: A Consensus-Driven Approach.

Background: Limited availability and poor quality of data in medical records and trauma registries impede progress to achieve injury-related health equity across the lifespan. Methods: We used a Nominal Group Technique (NGT) in-person workgroup and a national web-based Delphi process to identify common data elements (CDE) that should be collected. Results: The 12 participants in the NGT workgroup and 23 participants in the national Delphi process identified 10 equity-related CDE and guiding lessons for research on collection of these data. Conclusions: These high-priority CDE define a detailed, equity-oriented approach to guide research to achieve injury-related health equity across the lifespan.

Transverse Myelitis as a Presenting Symptom of Celiac Disease.

Celiac disease (CD) is associated with several neurological diseases. We report a case of a 25-year-old man with CD that was discovered during hospitalization for acute transverse myelitis. The diagnosis of CD was suspected after positive serological tests and was confirmed with duodenal biopsy. Steroid pulse therapy and plasma exchange stabilized the patient's condition. The patient started a gluten-free diet and rituximab therapy before discharge. Although the association of CD with various neurological diseases is well established, this case report describes a less explored association between CD and transverse myelitis.

Association of Client and Provider Race with Approaches Pursued by Social Workers for Reducing Firearm Access.

Social workers assess and intervene to prevent harm among clients at risk of harm to self (HTS) and harm to others (HTO) with a firearm. This study sought to assess the impact of client race on social workers' approaches to reduce firearm access when they weighed voluntary (e.g., store out-of-home) and involuntary (e.g., extreme risk protection order) removal methods. We considered the role of social workers' self-identified race as a moderator of this relationship, comparing white (single race) and Black, Indigenous, and People of Color (BIPOC) social workers. A survey was distributed to Washington state social workers (n = 9073) who were presented with two case vignettes, each randomized to view the client's race as Black or white. Logistic regression was used to assess the association between the client's race and the pursuit of voluntary or involuntary methods, stratified by social workers' race. Among the participants (n = 1306), 26% pursued at least one involuntary care plan option for the HTS client, and 59% for the HTO client. The Black client at risk of HTS had lower odds of an involuntary care plan option compared to the white client (OR = 0.69, 95% CI 0.54-0.88), while the Black client at risk of HTO had higher odds of an involuntary care plan options (OR = 1.13, 95% CI 1.07-1.66). These associations were not statistically significantly different between white (single race selected) and BIPOC social workers. This study contributes to the growing understanding of potential racial disparities in social workers' decision-making regarding firearm access reduction strategies.

Transgender Patient Preferences When Discussing Gender in Health Care Settings.

Importance: Transgender (trans) patients report frequent discriminatory and harmful experiences in health care settings; gender-affirming, competent health care improves trans individuals' health and well-being. Objective: To identify factors influencing trans patients' decision-making regarding sharing gender-related information with providers (clinicians, health care organizations, health care systems) and trans patient preferences for gender-related questions, as well as the subsequent impact on health care experiences. Design, Setting, and Participants: A qualitative, interpretivist phenomenological study was conducted via telephone or video (using Zoom) in English and Spanish from August 10 to September 11, 2020. Participants were recruited via trans-specific social media groups and email listservs. Interviews were transcribed verbatim and analyzed from October 2020 to January 2022 using thematic analysis by a majority trans research team. Main Outcomes and Measures: Semistructured interviews explored patient health care experiences and preferences. Results: Participants included 27 trans and/or nonbinary adults (mean [SD] age, 30.9 [10.4] years; range, 21-69 years) from 13 US states. Four themes were identified: (1) impact of provider behaviors, (2) engaging in relational risk assessment, (3) receiving affirming vs medically competent care, and (4) "how are you going to fit [me] into your system?" The first theme reflected the impact of provider actions, including level of flexibility in care and interpersonal interactions, ability to explain medical relevance of gender-related questions, and preparedness to work with trans patients. Second, respondents weighed a variety of implicit or explicit safety cues when deciding whether and how to share information with providers. Third, participants spoke at length about affirming and medically competent care, noting that they have had to prioritize one over the other. Last, participants reported their needs often being at odds with health care system norms and standards of care. Conclusion and Relevance: In this qualitative study of trans patient preferences when discussing gender-related information with providers, it was found that equitable, gender-affirming, and competent health care requires flexibility and responsiveness to patient preferences. It requires provider humility and engagement, as well as institutional policies that support competent and gender-affirming spaces. Future research could identify additional roles that providers, administrators, and systems can play in ensuring competent care for trans patients.

Language access research for community health: provider perspectives on language access techniques and the role of communication technology.

BACKGROUND: In the United States, 66 million people speak a language other than English at home. Patients with diverse language needs often face significant health disparities. Information and communication technologies have expanded the realm of modalities for patient-provider communication. However, the extent to which digital language access tools are utilized by healthcare providers is unknown. This research examines provider perspectives on language assistance techniques and the role of communication technology when serving patients with non-English language preference (NELP). METHODS: Between April and July 2019, an online survey was administered to 3,033 healthcare providers (doctors, nurse practitioners, pharmacists, and dentists) in Washington State. Providers reported on their language access practices and perspectives on communication technology. RESULTS: Most providers reported using ad hoc language access techniques when engaging patients with NELP, such as a patient's family member or friend (75.8%), a patient's child specifically (61.9%), or a bilingual staff member (64.3%). Professional techniques, such as in-person interpretation (53.5%), phone interpretation (57%), and video remote interpretation (38.8%), were used less often. Dissatisfaction with the language access processes of healthcare providers' place of work was associated with a higher reliance on a patient's family or friend for language interpretation. CONCLUSIONS: Findings suggest that providers might be under-utilizing professional and digital interpreter services while relying on ad hoc techniques. Such practices reveal systemic constraints on language access that might make it difficult for providers to access timely and reliable options for professional language interpretation, despite federal regulations that mandate such services for patients with NELP.

Characterization of Propofol Use For Non-Procedural Sedation in a Pediatric Intensive Care Unit.

OBJECTIVE: Given the limited literature describing propofol use in pediatric patients, this study aimed to describe the dosing and duration of propofol infusions for non-procedural sedation in the pediatric intensive care unit (PICU). The secondary objectives were to describe the change in concomitant sedative requirements from the 24-hour period before propofol initiation to the 24-hour period after discontinuation of propofol and to review the frequency of adverse events. METHODS: This retrospective descriptive cohort study evaluated children 1 month to less than 18 years old who received a continuous infusion of propofol for non-procedural sedation in the PICU between May 2018 and August 2020. RESULTS: One hundred thirty propofol infusions representing 127 unique patients (median age, 2.9 years) were included. The median (IQR) propofol infusion duration was 18 (10-28) hours, and the median (IQR) average dose was 4.1 (2.9-5.6) mg/kg/hr. Extubation was attempted in 96 patients (74%) within 24 hours of propofol infusion discontinuation. For patients that remained intubated with continuous sedation, concomitant continuous opioid and midazolam requirements decreased by 20% (p = 0.865) and 43% (p = 0.011), respectively. Patients receiving propofol for over 24 hours experienced the largest percent decrease in concomitant sedation with midazolam. There were no confirmed cases of propofol-related infusion syndrome (PRIS). CONCLUSIONS: Durations and doses of propofol infusions for non-procedural sedation vary widely at our institution. Propofol may be beneficial as an adjunct sedative, but prospective studies are needed to further explore the effect of propofol on decreasing the requirements of concomitant opioids and benzodiazepines.

Integration of extreme risk protection orders into the clinical workflow: Qualitative comparison of clinician perspectives.

Extreme risk protection orders (ERPO) seek to temporarily reduce access to firearms for individuals at imminent risk of harming themselves and/or others. Clinicians, including physicians, nurse practitioners, and social workers regularly assess circumstances related to patients' risk of firearm-related harm in the context of providing routine and acute clinical care. While clinicians cannot independently file ERPOs in most states, they can counsel patients or contact law enforcement about filing ERPOs. This study sought to understand clinicians' perspectives about integrating ERPO counseling and contacting law enforcement about ERPOs into their clinical workflow. We analyzed responses to open-ended questions from an online survey distributed May-July of 2021 to all licensed physicians (n = 23,051), nurse practitioners (n = 8,049), and social workers (n = 6,910) in Washington state. Of the 4,242 survey participants, 1,126 (26.5%) responded to at least one of ten open-ended questions. Two coders conducted content analysis. Clinicians identified barriers and facilitators to integrating ERPOs into the clinical workflow; these influenced their preferences on who should counsel or contact law enforcement about ERPOs. Barriers included perceptions of professional scope, knowledge gaps, institutional barriers, perceived ERPO effectiveness and constitutionality, concern for safety (clinician and patient), and potential for damaging provider-patient therapeutic relationship. Facilitators to address these barriers included trainings and resources, dedicated time for counseling and remuneration for time spent counseling, education on voluntary removal options, and ability to refer patients to another clinician. Participants who were hesitant to be the primary clinician to counsel patients or contact law enforcement about ERPOs requested the ability to refer patients to a specialist, such as social workers or a designated ERPO specialist. Results highlight the complex perspectives across clinician types regarding the integration of ERPO counseling into the clinical workflow. We highlight areas to be addressed for clinicians to engage with ERPOs.

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

OBJECTIVE: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli. METHODS: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22). All three groups were stained for MPO immunohistochemically, and the MPO expressions in the endothelium of PTC and glomeruli were evaluated and correlated with serum creatinine (SCr). In addition, the ultrastructural layers of the PTC (an index for chronic allograft rejection) were correlated with MPO indices in PTC. RESULTS: The negative control group and the transplant controls showed no MPO expression in the endothelium of glomeruli and PTC. However, in the biopsies with ABMR, there were MPO-positive stains in the endothelial cells of glomeruli (15/21 cases, 71.4 %) and PTC (16/22 cases, 72.7 %). There were significant correlations between the peritubular MPO staining versus SCr (r=0.355 and p=0.0106) and glomerular MPO staining versus SCr (r=0.365 and p=0.0092). Furthermore, the layers of PTC by electron microscopy were significantly correlated with MPO scores in PTC (r=0.696, p=0.0001). CONCLUSION: Our data suggest that the MPO-positive endothelial injuries are most likely the cause leading to renal graft dysfunction following ABMR.

Adapting forensic case reporting to account for marginalization and vulnerability.

Scholarship of forensic sciences has shown politicalization of human remains and potential biases in criminal investigations. Specifically, concerns have been raised regarding how forensic anthropology analysis and documentation may hinder identification processes or obfuscate other data. As part of this scholarship, some have suggested that forensic anthropologists expand their reporting to include broader public health and safety information as well as reconsider who should be included in reports of anthropological findings. In response to these burgeoning discussions, this piece provides examples of ways anthropologists may formulate reports that capture evidence of marginalization or structural vulnerability. Documentation of findings can occur in myriad formats, including, but not limited to, individual case reports, reports on population analyses from cases, collaborative end-of-year reporting conducted with other medicolegal professionals, and collaborative databasing. This piece provides various templates and suggestions for reporting this kind of data while encouraging further discussion on related merits and concerns.

Disparities in Misclassification of Race and Ethnicity in Electronic Medical Records Among Patients with Traumatic Injury.

Systems-level barriers to self-reporting of race and ethnicity reduce the integrity of data entered into the medical record and trauma registry among patients with injuries, limiting research assessing the burden of racial disparities. We sought to characterize misclassification of self-identified versus hospital-recorded racial and ethnic identity data among 10,513 patients with traumatic injuries. American Indian/Alaska Native patients (59.9%) and Native Hawaiian/Pacific Islander patients (52.4%) were most likely to be misclassified. Most Hispanic/Latin(x) patients preferred to only be identified as Hispanic/Latin(x) (73.2%) rather than a separate race category (e.g., White). Incorrect identification of race/ethnicity also has substantial implications for the perceived demographics of patient population; according to the medical record, 82.3% of the population were White, although only 70.6% were self-identified as White. The frequency of misclassification of race and ethnicity for persons of color limits research validity on racial and ethnic injury disparities.

Extreme Risk Protection Orders in Washington State: Understanding the Role of Health Professionals.

Objective: Extreme Risk Protection Orders (ERPO) allow a petitioner to file a civil order to temporarily restrict access to firearms among individuals ("respondents") deemed to be at extreme risk of harming themselves, others, or both. Although unable to file ERPOs for their clients in most states, health professionals may play a pivotal role in the ERPO process by recommending an eligible petitioner initiate the process. We describe the process of filing an ERPO when a healthcare, mental health, or social service professional contacted an ERPO petitioner. Method: Court documents of ERPOs involving health professionals in Washington State between December 8th, 2016 and May 10th, 2019 were qualitatively analyzed (n=24). We constructed pen portraits from the documents and analyzed them using an inductive qualitative thematic approach. Results: Themes included factors influencing the process by which each professional evaluated respondent behaviors, factors considered during assessment, factors influencing interpretation of respondent behaviors and subsequent provider response during a crisis. These influenced the outcome of the crisis event that led to ERPO filing. Conclusions: Each professional group differed in their approach to risk assessment of respondent behaviors. Strategies to better coordinate and align approaches may improve the ERPO process.

Defining the Culture of Surgery.

BACKGROUND: Surgical culture is often referenced but not well defined. Recent research and changing policies in graduate medical education have influenced the training paradigm and expectations of surgical trainees. It is unclear how these changes impact surgeons' understanding of surgical culture today and how those views impact surgical training. We sought to understand surgical culture and its impact on training from the perspective of a diverse group of surgeons with varied amounts of experience. STUDY DESIGN: A series of semi-structured, qualitative interviews were conducted with 21 surgeons and trainees in a single academic institution. Interviews were transcribed, coded, and analyzed using directed content analysis. RESULTS: We identified 7 major themes that impact surgical culture. Cohorts were separated by those who had been promoted to at least associate professor (late-career surgeons) and assistant professors, fellows, residents, and students (early-career surgeons). Both cohorts similarly emphasized patient-centered care, hierarchy, high standards, and meaningful work. Late- and early-career surgeons highlighted themes differently: late-career surgeons' perceptions were informed by experience and focused on challenges, complications, humility, and work ethic, while perceptions of early-career surgeons were more individually focused and referenced being goal-oriented and self-sacrificing, and focus on education and work-life balance. CONCLUSIONS: Late- and early-career surgeons both emphasize that patient-centered care is core to surgical culture. Early-career surgeons expressed more themes related to personal well-being, while late-career surgeons emphasized themes related to professional accomplishment. Differences in the perceived culture can lead to strained interactions between generations of surgeons and trainees, and a better understanding of these differences would lead to improved communication and interactions between these groups, as well as better management of expectations for surgeons in their training and career.

Centering patient perspectives to achieve injury-related health equity in trauma care systems: Improving trauma registry data.

BACKGROUND: Limitations in current data collection systems for patients who experience traumatic injury limit researchers' ability to identify and address disparities in injury and outcomes. We sought to develop and test a patient-centered data-collection system for equity-related data indicators that was acceptable to racially and ethnically diverse patients being treated for traumatic injuries. METHODS: Health equity indicators included in this study were race and ethnicity, language, education, employment, housing, and injury address. We conducted interviews with 245 racially and ethnically diverse trauma patients who were treated at a level-1 trauma center in the US in 2019-2020. We first interviewed 136 patients to develop a culturally resonant process and options for the health equity indicators to be added to a revised data collection system for the electronic medical record. English and Spanish interviews were audio-recorded and transcribed verbatim; qualitative analysis was used to assess patient preferences. We then pilot tested the revised data collection system with an additional 109 trauma patients to assess acceptability. Acceptability was defined as having more than 95% of participants self-identify with one of the proposed options for race/ethnicity, language, education, employment, and housing. Injury address (to identify geographic disparities) was pre-defined as acceptable if at least 85% of participants could identify exact address, cross streets, a landmark or business, or zip code of injury. RESULTS: A revised data collection system, including culturally resonant indicators and a process to be used by patient registrars to collect health equity data, was pilot tested, refined, and considered acceptable. Culturally resonant question phrasing/answer options for race/ethnicity, language, education, employment, housing status, and injury address were identified as acceptable. CONCLUSIONS: We identified a patient-centered data collection system for health equity measures with racially and ethnically diverse patients who have experienced traumatic injury. This system has the potential to increase data quality and accuracy, which is critical to quality improvement efforts and for researchers seeking to identify groups most impacted by racism and other structural barriers to equitable health outcomes and effective intervention points.

Effect of RISE Bundle implementation on school adoption of a student-centered return-to-learn program in Washington state.

BACKGROUND: Appropriate concussion care in school is vital for full recovery, but school return-to-learn (RTL) programs are lacking and vary in quality. Establishing student-centered RTL programs may reduce disparities in RTL care. OBJECTIVE: To examine the effect of RISE Bundle (Return to Learn Implementation Bundle for Schools) implementation on high school adoption of a student-centered RTL program. METHODS: A convenience sample of fourteen (4 rural and 10 urban) small and large Washington (WA) State public high schools were enrolled in a stepped-wedge study with baseline, end of study, and monthly measures over the 2021-2022 academic year. Schools identified an RTL champion who led RISE Bundle implementation in 6-week steps. Concussion knowledge and impact of RTL program on concussion care were examined. RESULTS: Ten schools (71.4%) successfully completed RISE Bundle implementation and established a functional RTL program. Self-reported concussion knowledge from RTL Champions increased post intervention. Establishing RTL programs facilitated provision of tailored accommodations, and perceived variation and inequities in RTL care were reduced. CONCLUSION: RISE Bundle implementation proved feasible, supported the establishment of a functional RTL program, and perceived to reduce disparities in concussion care in rural and urban WA State public high schools of varying sizes.