State-Level Analysis of Intimate Partner Violence, Abortion Access, and Peripartum Homicide: Call for Screening and Violence Interventions for Pregnant Patients.

BACKGROUND: Despite representing 4% of the global population, the US has the fifth highest number of intentional homicides in the world. Peripartum people represent a unique and vulnerable subset of homicide victims. This study aimed to understand the risk factors for peripartum homicide. STUDY DESIGN: We used data from the 2018 to 2020 National Violent Death Reporting System to compare homicide rates of peripartum and nonperipartum people capable of becoming pregnant (12 to 50 years of age). Peripartum was defined as currently pregnant or within 1-year postpartum. We additionally compared state-level peripartum homicide rates between states categorized as restrictive, neutral, or protective of abortion. Pearson's chi-square and Wilcoxon rank-sum tests were used. RESULTS: There were 496 peripartum compared with 8,644 nonperipartum homicide victims. The peripartum group was younger (27.4 ± 71 vs 33.0 ± 9.6, p < 0.001). Intimate partner violence causing the homicide was more common in the peripartum group (39.9% vs 26.4%, p < 0.001). Firearms were used in 63.4% of homicides among the peripartum group compared with 49.5% in the comparison (p < 0.001). A significant difference was observed in peripartum homicide between states based on policies regarding abortion access (protective 0.37, neutral 0.45, restrictive 0.64; p < 0.01); the same trend was not seen with male homicides. CONCLUSIONS: Compared with nonperipartum peers, peripartum people are at increased risk for homicide due to intimate partner violence, specifically due to firearm violence. Increasing rates of peripartum homicide occur in states with policies that are restrictive to abortion access. There is a dire need for universal screening and interventions for peripartum patients. Research and policies to reduce violence against pregnant people must also consider the important role that abortion access plays in protecting safety.

Alterations in network robustness upon simultaneous temperature and pH perturbations.

Nervous systems have evolved to function consistently in the face of the normal environmental fluctuations experienced by animals. The stomatogastric nervous system (STNS) of the crab, Cancer borealis, produces a motor output that has been studied for its remarkable robustness in response to single global perturbations. Changes in environments, however, are often complex and multifactorial. Therefore, we studied the robustness of the pyloric network in the stomatogastric ganglion (STG) in response to simultaneous perturbations of temperature and pH. We compared the effects of elevated temperatures on the pyloric rhythm at control, acid, or base pHs. In each pH recordings were made at 11°C, and then the temperature was increased until the rhythms became disorganized ("crashed"). Pyloric burst frequencies and phase relationships showed minor differences between pH groups until reaching close to the crash temperatures. However, the temperatures at which the rhythms were disrupted were lower in the two extreme pH conditions. This indicates that one environmental stress can make an animal less resilient to a second stressor.NEW & NOTEWORTHY Resilience to environmental fluctuations is important for all animals. It is common that animals encounter multiple stressful events at the same time, the cumulative impacts of which are largely unknown. This study examines the effects of temperature and pH on the nervous system of crabs that live in the fluctuating environments of the Northern Atlantic Ocean. The ranges of tolerance to one perturbation, temperature, are reduced under the influence of a second, pH.

Trauma surgical skill sustainment at the University of Chicago AMEDD Military-Civilian Trauma Team Training Site: an observation report.

Background: The Army Medical Department (AMEDD) Military-Civilian Trauma Team Training (AMCT3) Program was developed to enhance the trauma competency and capability of the medical force by embedding providers at busy civilian trauma centers. Few reports have been published on the outcomes of this program since its implementation. Methods: The medical and billing records for the two AMCT3 embedded trauma surgeons at the single medical center were retrospectively reviewed for care provided during August 2021 through July 2022. Abstracted data included tasks met under the Army's Individual Critical Task List (ICTL) for general surgeons. The Knowledge, Skills, and Abilities (KSA) score was estimated based on previously reported point values for procedures. To assess for successful integration of the embedded surgeons, data were also abstracted for two newly hired civilian trauma surgeons. Results: The annual clinical activity for the first AMCT3 surgeon included 444 trauma evaluations and 185 operative cases. The operative cases included 80 laparotomies, 15 thoracotomies, and 15 vascular exposures. The operative volume resulted in a KSA score of 21 998 points. The annual clinical activity for the second AMCT3 surgeon included 424 trauma evaluations and 194 operative cases. The operative cases included 92 laparotomies, 8 thoracotomies, and 25 vascular exposures. The operative volume resulted in a KSA score of 22 799 points. The first civilian surgeon's annual clinical activity included 453 trauma evaluations and 151 operative cases, resulting in a KSA score of 16 738 points. The second civilian surgeon's annual clinical activity included 206 trauma evaluations and 96 operative cases, resulting in a KSA score of 11 156 points. Conclusion: The AMCT3 partnership at this single center greatly exceeds the minimum deployment readiness metrics established in the ICTLs and KSAs for deploying general surgeons. The AMEDD experience provided a deployment-relevant case mix with an emphasis on complex vascular injury repairs.

Trauma Surgeons Experience Compassion Fatigue - A Major Metropolitan Area Survey.

INTRODUCTION: Compassion Fatigue (CF), the physical, emotional, and psychological impact of helping others, is composed of three domains: Compassion Satisfaction (CS), Secondary Traumatic Stress (STS), and Burnout (BO). Trauma surgeons (TS) experience work-related stress resulting in high rates of CF which can manifest as physical and psychological disorders. We hypothesized that TS experience CF and there are potentially modifiable systemic factors to mitigate its symptoms. METHODS: All TS in a major metropolitan area were eligible. Personal and professional demographic information was obtained. Each participant completed six validated surveys: 1) Professional Quality of Life Scale (Pro-QOL), 2) Perceived Stress Scale (PSS), 3) Multidimensional Scale of Perceived Social Support (MSPSS), 4) Adverse Childhood Events (ACE) Questionnaire, 5) Brief Coping Inventory (BCI), and 6) Toronto Empathy Questionnaire (TEQ). CF subscale risk scores (low:<23, moderate:23-41, high:>41) were recorded. Linear regression analysis assessed the demographic and environmental factors association with BO, STS, and CS. Variables significant on univariate analysis were included in multivariate models to determine the independent influence on BO, STS, and CS. Significance was p ≤ 0.05. RESULTS: There were 57 TS (response rate:75.4% (n = 43); Caucasian: 65% (n = 28), male:67% (n = 29)). TS experienced CF (BO:26 (IQR: 21-32), STS:23 (IQR: 19-32), CS:39 (IQR: 34-45)). The PSS score was significantly associated with increased BO (Coef: 0.52, 95% CI: 0.28-0.77) and STS (Coef: 0.44. 95% CI: 0.15-0.73), and decreased CS (Coef: -0.51, 95% CI: -0.80- -0.23) (p < 0.01). Night shifts were associated with higher BO (Coef: 1.55, 95% CI: 0.07-3.03, p = 0.05), conversely day shifts were associated with higher STS (Coef: 1.94, 95% CI: 0.32-3.56, p = 0.03). Higher TEQ scores were associated with greater CS (Coef: 0.33, 95% CI: 0.12-0.55, p < 0.01). CONCLUSION: TS experience moderate BO and STS associated with modifiable system- and work-related stressors. Efforts to reduce CF should focus on addressing sources of workplace stress and promoting empathic care. LEVEL OF EVIDENCE: III, Prognostic and Epidemiological.

Increased Duration and Frequency of Lateral C-Arm Draping Does Not Increase Contamination Rates.

This study sought to quantify the rate of culture-positive drape contamination with varying degrees of drape manipulation for intra-operative fluoroscopic imaging. In this prospective cohort study, 30 patients with operatively closed lower extremity fractures were evaluated. The clip-drape technique was employed to cover the emitter. Swab samples were collected for bacterial growth. A t-test was applied for statistical comparison. Three of 30 cases (10% of operations) showed evidence of contamination. There was no statistically significant difference between duration of drape use or the amount of drape manipulations. None of the 30 patients in this study developed surgical site infection 90-days post-surgery. The clip drape technique for lateral fluoroscopy appears to be effective in maintaining surgical field sterility. Moreover, the number of drape manipulations and length of time the drape was in use was not related to drape contamination. Level of Evidence: Therapeutic Level II. (Journal of Surgical Orthopaedic Advances 32(2):107-110, 2023).

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.

Examining racial disparity in psychotic disorders related ambulatory care visits: an observational study using national ambulatory medical care survey 2010-2015.

BACKGROUND: One of the most consistent research findings related to race and mental health diseases is the disproportionately high rate of psychotic disorder diagnoses among people of color, specifically people of African descent. It is important to examine if a similar pattern exists among specific psychotic disorders. We aimed to examine the racial/ethnic differences in ambulatory care visits diagnosed with schizophrenia-spectrum disorders (SSDs). METHODS: We analyzed data from the National Ambulatory Medical Care Survey (NAMCS) 2010-2015. The study sample included physician office-based visits by individuals diagnosed with SSDs, including schizophrenia, schizoaffective, and unspecified psychotic disorder (n = 1155). We used descriptive and bivariate analysis by race/ethnicity and three multinomial logistic regression models to test the association between the SSDs and race/ethnicity, adjusting for age, gender, insurance, disposition, medication Rx, and co-morbidity, considering the design and weight. RESULT: Of the 1155 visits for SSDs, 44.8% had schizophrenia, 37.4% had schizoaffective disorder diagnosis, and 19.0% had unspecified psychosis disorder. We found significant racial disparities in the diagnosis of SSDs. Black patients were overrepresented in all three categories: schizophrenia (24%), schizoaffective disorder (17%), and unspecified psychosis disorder (26%). Also, a notable percentage of Black patients (20%) were referred to another physician in cases of schizophrenia compared to other ethnoracial groups (p < 0.0001). Moreover, we found a significant disparity in insurance coverage for schizoaffective disorder, with a higher percentage of Black patients (48%) having Medicaid insurance compared to patients from other ethnoracial groups (p < 0.0001). Black patients had nearly twice the odds of receiving a diagnosis of schizophrenia compared to White patients [AOR = 1.94; 95% CI: 1.28-2.95; P = 0.001]. However, they had significantly lower odds of being diagnosed with schizoaffective disorder [AOR = 0.42, 95% CI: 0.26-0.68; P = 0.003]. Race/ethnicity was not associated with receiving an unspecified psychosis disorder. CONCLUSIONS: Our results show that SSDs, more specifically schizophrenia, continue to burden the mental health of Black individuals. Validation of our findings requires rigorous research at the population level that reveals the epidemiological difference of SSDs diagnoses in different race/ethnicity groups. Also, advancing our understanding of the nature of disparity in SSDs diagnoses among the Black population requires disentangling etiologic and systemic factors in play. This could include psychological stress, the pathway to care, services use, provider diagnostic practice, and experiencing discrimination and institutional and structural racism.

Microfluidic device with reconfigurable spatial temporal gradients reveals plastic astrocyte response to stroke and reperfusion.

As a leading cause of mortality and morbidity, stroke constitutes a significant global health burden. Ischemic stroke accounts for 80% of cases and occurs due to an arterial thrombus, which impedes cerebral blood flow and rapidly leads to cell death. As the most abundant cell type within the central nervous system, astrocytes play a critical role within the injured brain. We developed a novel microphysiological platform that permits the induction of spatiotemporally controlled nutrient gradients, allowing us to study astrocytic response during and after transient nutrient deprivation. Within 24 h of inducing starvation in the platform, nutrient deprivation led to multiple changes in astrocyte response, from metabolic perturbations to gene expression changes, and cell viability. Furthermore, we observed that nutrient restoration did not reverse the functional changes in astrocyte metabolism, which mirrors reperfusion injury observed in vivo. We also identified alterations in numerous glucose metabolism-associated genes, many of which remained upregulated or downregulated even after restoration of the nutrient supply. Together, these findings suggest that astrocyte activation during and after nutrient starvation induces plastic changes that may underpin persistent stroke-induced functional impairment. Overall, our innovative device presents interesting potential to be used in the development of new therapies to improve tissue repair and even cognitive recovery after stroke.

Impact of educational and psychological interventions compared with standard care in college/university students with autism spectrum disorder: a systematic review protocol.

OBJECTIVE: This review will explore the impact of educational and psychological interventions on educational, social, behavioral, and mental health outcomes in students with autism spectrum disorder in tertiary education. INTRODUCTION: This systematic review will inform a new guideline on support for students with autism spectrum disorder in the tertiary education environment. These students face multiple educational, behavioral, social, and health-related problems that require effective interventions. INCLUSION CRITERIA: Participants are students with autism spectrum disorder in a tertiary education study program. Educational and psychological interventions will be included, such as accommodations, meta-cognitive and self-regulation training, psychological counseling, social skills training, and peer-mentoring/academic coaching. The comparator will be standard care. The study outcomes will include academic drop-out rates and evaluations, learning skills, social skills and social engagement, behavior, mental health (including anxiety, stress, and depression), and employment after graduation. This review will consider quantitative studies only. METHODS: A 3-step search strategy will be used to find both published and unpublished studies in MEDLINE, CINAHL, APA PsycINFO, SocINDEX, Web of Science, Clinical Trials, ProQuest Dissertations and Theses, Open Dissertations, ERIC, WHO ICRTP, and Google Scholar. There will be no date or language limitations. All stages of article screening, critical appraisal, and data extraction will be conducted by 2 independent reviewers with the resolution of any disagreements done via consensus or through a senior reviewer. If possible, the included studies will be pooled using meta-analysis. The degree of certainty of the evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022323554.

Rising Mortality in Pediatric Self-Inflicted Firearm Trauma Associated With Distinct Anatomic Injury.

INTRODUCTION: Self-inflicted injuries are the second leading cause of pediatric (10-18 y old) mortality. Self-inflicted firearm trauma (SIFT) was responsible for up to half of these deaths in certain age groups. We hypothesized that SIFT prevalence has increased and is associated with specific demographics, injury patterns, and outcomes. MATERIALS AND METHODS: Data were abstracted from the 2007-2018 American College of Surgeons (ACS) Trauma Quality Programs Participant Use Files (TQP-PUF). Pediatric (1-17 yold) victims of firearm violence were eligible. Age, race, gender, anatomic region, and intent were abstracted. Variables were analyzed using chi-squared tests, t-tests, and single-variate linear regression models. Temporal trends were analyzed using ANCOVA tests. Multivariate logistic regressions were conducted to identify factors influencing mortality. Significance was P < 0.05. RESULTS: There were 41,239 pediatric firearm trauma patients (SIFT: 5.5% [n = 2272]). SIFT incidence increased over the 12-y period (2007 (n = 67) versus 2018 (n = 232), P < 0.05). SIFT was significantly associated with Caucasian race, 67% (n = 1537), teenagers, 90% (n = 2056), male gender, 87% (n = 1978), and a higher median injury severity score (ISS) than other intents of injury (SIFT: 20.0 (IQR: 9.0, 25.0) versus other: 9.0 (IQR: 1.0-13.0), P < 0.001). The SIFT mortality rate was 44% (n = 1005). On multivariate regression head gunshot wounds (OR: 21.1, 95% C.I.: 9.9-45.2, P = 0.001), and ISS (OR:1.1, 95% C.I.: 1.1-1.1, P = 0.001) were significantly associated with mortality. Compared to other intents, SIFT mortality rates increased at a higher annual rate (P < 0.001). CONCLUSIONS: Comprehensive local and federal policy changes to reduce firearms access and increase pediatric mental health support may mitigate these injuries.

Quantifying Compassion Fatigue in Ancillary and Clinical Staff in an Adult Emergency Department.

INTRODUCTION: Emergency department (ED) staff are at a high risk for compassion fatigue (CF) due to a work environment that combines high patient acuity, violence, and other workplace stressors. This multifaceted syndrome has wide-ranging impacts which, if left untreated, can lead to adverse mental health conditions including depression, anxiety, and substance use disorders. However, the majority of studies examining CF look solely at clinicians; as a result, there is little information on the impact of CF across other roles involved in supporting patient care. We conducted this study to establish the prevalence of CF across both clinical and non-clinical roles in the adult ED setting. METHODS: For this single institution, cross-sectional study, all full- and part-time ED staff members who worked at least 50% of their shifts in the ED or within the adult trauma service line were eligible to participate. Using the Professional Quality of Life Scale, which measures CF via compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS), we assessed for group differences between roles using non-parametric one-way ANOVA. RESULTS: A total of 152 participants (response rate = 38.0%) completed the survey. This included attending physicians (n = 15, 9.7%), resident/fellow physicians (n = 23, 15.1%), staff nurses (n = 54, 35.5%), emergency technicians (n = 21, 13.8%), supportive clinical staff (n = 28, 18.4%), and supportive ancillary staff (n = 11, 7.2%). Across all roles, the majority of respondents had average levels of BO (median = 25.0, interquartile range [IQR] 20.0-29.0) and STS (median = 23.0, IQR 18.0-27.0) coupled with high levels of CS (median = 38.0, IQR 33.0-43.0). There was a difference in CS by role (P = .01), with nurses reporting lower CS than attending physicians. Secondary traumatic stress also differed by role (P = .01), with attending physicians reporting lower STS than both emergency technicians and nurses. Group differences were not seen in BO. CONCLUSIONS: Rates of compassion fatigue subcomponents were similar across all ED team members, including non-clinical staff. Programs to identify and mitigate CF should be implemented and extended to all roles within the ED.

Derivation and validation of an improved pediatric shock index for predicting need for early intervention and outcomes in pediatric trauma.

BACKGROUND: Shock index, pediatric age adjusted (SIPA), has been widely applied in pediatric trauma but has limited precision because of the reference ranges used in its derivation. We hypothesized that a pediatric shock index (PSI) equation based on age-based vital signs would outperform SIPA. METHODS: A retrospective cohort of trauma patients aged 1 to 18 years from Trauma Quality Programs - Participant Use File 2010 to 2018 was performed. A random 70% training subset was used to derive Youden index-optimizing shock index (SI) cutoffs by age for blood transfusion within 4 hours. We used linear regression to derive equations representing the PSI cutoff for children 12 years or younger and 13 years or older. For children 13 years or older, the well-established SI of 0.9 remained optimal, consistent with SIPA and other indices. For children 12 years or younger in the 30% validation subset, we compared our age-based PSI to SIPA as predictors of early transfusion, mortality, pediatric intensive care unit admission, and injury severity score of ≥25. For bedside use, a simplified "rapid" pediatric shock index (rPSI) equation was also derived and compared with SIPA. RESULTS: A total of 439,699 patients aged 1 to 12 years met the inclusion criteria with 2,718 (1.3% of those with available outcome data) requiring transfusion within 4 hours of presentation. In the validation set, positive predictive values for early transfusion were higher for PSI (8.3%; 95% confidence interval [CI], 7.5-9.1%) and rPSI (6.3%; 95% CI, 5.7-6.9%) than SIPA (4.3%; 95% CI, 3.9-4.7%). For early transfusion, negative predictive values for both PSI (99.3%; 95% CI, 99.2-99.3%) and rPSI (99.3%; 95% CI, 99.2-99.4%) were similar to SIPA (99.4%; 95% CI, 99.3-99.4%). CONCLUSION: We derived the PSI and rPSI for use in pediatric trauma using empiric, age-based SI cutoffs. The PSI and rPSI achieved higher positive predictive values and similar negative predictive values to SIPA in predicting the need for early blood transfusion and mortality. LEVEL OF EVIDENCE: Prognostic/Epidemiological; level III.

Demographic and Regional Factors Associated With Reporting Homicides of Transgender People in the United States.

INTRODUCTION: The American Medical Association recently declared homicides of transgender individuals an epidemic. However, transgender homicide victims are often classified as nontransgender. Our objective was to describe existing data and coding of trans (i.e., transgender) victims and to examine the risk factors for homicides of trans people relative to nontrans people across the United States. METHODS: A retrospective review of the Centers for Disease Control and Prevention's National Violent Death Reporting System for the years 2003-2018 identified victims defined as transgender either through the "transgender" variable or narrative reports. Fisher's exact tests and logistic regression models were run to compare the demographics of trans victims to those not identified as trans. RESULTS: Of the 147 transgender victims identified, 14.4% were incorrectly coded as nontrans despite clear indication of trans status in the narrative description, and 6% were coded as hate crimes. Relative to nontrans victims, trans victims were more frequently Black (54.4% versus 40.7%, P = 0.001), had a mental health condition (26.5% versus 11.3%, P < 0.001), or reported being a sex worker (9.5% versus 0.2%, P < 0.001). There were disproportionately few homicides of transgender people in the South (13.6% of trans victims versus 29.1% of nontrans victims, P < 0.001). Conversely, the West and Midwest accounted for a higher-than-expected proportion of trans victims relative to nontrans victims (23.1% of trans victims versus 16.2% of nontrans victims, P = 0.03; 24.5% of trans victims versus 16.8% of nontrans victims, P = 0.02, respectively). CONCLUSIONS: Though the murder of transgender individuals is a known public health crisis, inconsistencies still exist in the assessment and reporting of transgender status. Further, these individuals were more likely to have multiple distinct vulnerabilities. These findings provide important information for injury and violence prevention researchers to improve reporting of transgender status in the medical record and local trauma registries.

Alternative shock index cutoffs for pediatric patients outperform the Shock Index Pediatric Age-adjusted (SIPA) on strength of association with adverse outcomes in pediatric trauma patients.

BACKGROUND: The shock index is a tool for evaluating critically ill patients that is defined as the ratio of their heart rate divided by systolic blood pressure. The SI is associated with outcomes in adult trauma patients. The Shock Index Pediatric Age-adjusted was developed as a pediatric-specific tool to account for the physiologic differences of children of varying ages. There is growing interest in Shock Index Pediatric Age-adjusted, which is associated with adverse outcomes in pediatric trauma. We hypothesized that alternative shock index cutoffs based on the Advanced Trauma Life Support or the Pediatric Advanced Life Support vital sign reference ranges would outperform Shock Index Pediatric Age-adjusted. METHODS: We analyzed a retrospective cohort of pediatric trauma patients (age 1 to 16 years old) in the American College of Surgeons Trauma Quality Programs Participant Use File from 2010 to 2018. The primary outcome measure was in-hospital mortality. The Shock Index Pediatric Age-adjusted was compared to an Advanced Trauma Life Support-based and a Pediatric Advanced Life Support-based shock index cutoff system. Our findings were subsequently confirmed with a separate, internal validation data set. RESULTS: A total of 598,830 Trauma Quality Programs Participant Use File patients were included, 0.9% (n = 5,471) of whom died. For mortality, the Advanced Trauma Life Support-based system yielded the highest positive predictive value (15.8%; 95% confidence interval 15.0%-16.7%) compared with the Pediatric Advanced Life Support-based system (4.3%; 95% confidence interval 4.1%-4.5%). Both the Advanced Trauma Life Support-based and Pediatric Advanced Life Support-based systems achieved higher positive predictive values compared to Shock Index Pediatric Age-adjusted (2.6%; 95% confidence interval 2.5%-2.7%). The negative predictive values were not clinically different. Our findings were validated using a separate internal trauma database, in which the positive predictive value for mortality of the Advanced Trauma Life Support-based system was significantly higher than Shock Index Pediatric Age-adjusted (18.2% [95% confidence interval: 8.2%-32.7%] vs 2.9% [95% confidence interval: 1.6%-5.0%], P < .05). CONCLUSION: Advanced Trauma Life Support and Pediatric Advanced Life Support-based shock index cutoffs achieved higher positive predictive values and similar negative predictive values compared to Shock Index Pediatric Age-adjusted for adverse outcomes in pediatric trauma.

Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology.

Alzheimer's disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPTP301S tauopathy mice revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression.

The tight rope act: A multicenter regional experience of tourniquets in acute trauma resuscitation.

BACKGROUND: As tourniquets have become more prevalent, device use has been questioned. This study sought to characterize the incidence, indication, and efficacy of tourniquet placement in acute trauma resuscitation. METHODS: Nine regional level 1 trauma centers prospectively enrolled for 12 months adult patients (18 years or older) who had a tourniquet placed. Age, sex, mechanism, tourniquet type, indication, applying personnel, location placed, level of occlusion, and degree of hemostasis were collected. Major vascular injury, imaging and operations performed, and outcomes were assessed. Analyses were performed with significance at p < 0.05. RESULTS: A total of 216 tourniquet applications were reported on 209 patients. There were significantly more male patients (183 [88%]) and penetrating injuries (186 [89%]) with gunshots being most common (127 [61%]). Commercial tourniquets were most often used (205 [95%]). Ninety-two percent were placed in the prehospital setting (by fire/paramedics, 56%; police, 33%; bystanders, 2%). The most common indications were pooling (47%) and pulsatile (32%) hemorrhage. Only 2% were for amputation. The most frequent location was high proximal extremity (70%). Four percent were placed over the wound, and 0.5% were distal to the wound. Only 61% of applications were arterial occlusive. Median application time was 30 minutes (interquartile range, 20-40 minutes). Imaging was performed in 54% of patients. Overall, 36% had a named arterial injury. Tourniquet application failed to achieve hemostasis in 22% of patients with a named vascular injury. There was no difference in hemostasis between those with and without vascular injury (p = 0.12) or between who placed the tourniquet (p = 0.07). Seventy patients (34%) required vascular operations. Thirty-four percent of patients were discharged home without admission. CONCLUSION: Discerning which injuries require tourniquets over pressure dressings remains elusive. Trained responders had high rates of superfluous and inadequate deployments. As tourniquets continue to be disseminated, emphasis should be placed on improving education, device development, and quality control. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level III.

Ipsilateral and Simultaneous Comparison of Responses from Acceleromyography- and Electromyography-based Neuromuscular Monitors.

BACKGROUND: The paucity of easy-to-use, reliable objective neuromuscular monitors is an obstacle to universal adoption of routine neuromuscular monitoring. Electromyography (EMG) has been proposed as the optimal neuromuscular monitoring technology since it addresses several acceleromyography limitations. This clinical study compared simultaneous neuromuscular responses recorded from induction of neuromuscular block until recovery using the acceleromyography-based TOF-Watch SX and EMG-based TetraGraph. METHODS: Fifty consenting patients participated. The acceleromyography and EMG devices analyzed simultaneous contractions (acceleromyography) and muscle action potentials (EMG) from the adductor pollicis muscle by synchronization via fiber optic cable link. Bland-Altman analysis described the agreement between devices during distinct phases of neuromuscular block. The primary endpoint was agreement of acceleromyography- and EMG-derived normalized train-of-four ratios greater than or equal to 80%. Secondary endpoints were agreement in the recovery train-of-four ratio range less than 80% and agreement of baseline train-of-four ratios between the devices. RESULTS: Acceleromyography showed normalized train-of-four ratio greater than or equal to 80% earlier than EMG. When acceleromyography showed train-of-four ratio greater than or equal to 80% (n = 2,929), the bias was 1.3 toward acceleromyography (limits of agreement, -14.0 to 16.6). When EMG showed train-of-four ratio greater than or equal to 80% (n = 2,284), the bias was -0.5 toward EMG (-14.7 to 13.6). In the acceleromyography range train-of-four ratio less than 80% (n = 2,802), the bias was 2.1 (-16.1 to 20.2), and in the EMG range train-of-four ratio less than 80% (n = 3,447), it was 2.6 (-14.4 to 19.6). Baseline train-of-four ratios were higher and more variable with acceleromyography than with EMG. CONCLUSIONS: Bias was lower than in previous studies. Limits of agreement were wider than expected because acceleromyography readings varied more than EMG both at baseline and during recovery. The EMG-based monitor had higher precision and greater repeatability than acceleromyography. This difference between monitors was even greater when EMG data were compared to raw (nonnormalized) acceleromyography measurements. The EMG monitor is a better indicator of adequate recovery from neuromuscular block and readiness for safe tracheal extubation than the acceleromyography monitor.