Multiple origins of extra electron diffractions in fcc metals.

Diffuse intensities in the electron diffraction patterns of concentrated face-centered cubic solid solutions have been widely attributed to chemical short-range order, although this connection has been recently questioned. This article explores the many nonordering origins of commonly reported features using a combination of experimental electron microscopy and multislice diffraction simulations, which suggest that diffuse intensities largely represent thermal and static displacement scattering. A number of observations may reflect additional contributions from planar defects, surface terminations incommensurate with bulk periodicity, or weaker dynamical effects.

Nacre-like surface nanolaminates enhance fatigue resistance of pure titanium.

Fatigue failure is invariably the most crucial failure mode for metallic structural components. Most microstructural strategies for enhancing fatigue resistance are effective in suppressing either crack initiation or propagation, but often do not work for both synergistically. Here, we demonstrate that this challenge can be overcome by architecting a gradient structure featuring a surface layer of nacre-like nanolaminates followed by multi-variant twinned structure in pure titanium. The polarized accommodation of highly regulated grain boundaries in the nanolaminated layer to cyclic loading enhances the structural stability against lamellar thickening and microstructure softening, thereby delaying surface roughening and thus crack nucleation. The decohesion of the nanolaminated grains along horizonal high-angle grain boundaries gives rise to an extraordinarily high frequency (≈1.7 × 103 times per mm) of fatigue crack deflection, effectively reducing fatigue crack propagation rate (by 2 orders of magnitude lower than the homogeneous coarse-grained counterpart). These intriguing features of the surface nanolaminates, along with the various toughening mechanisms activated in the subsurface twinned structure, result in a fatigue resistance that significantly exceeds those of the homogeneous and gradient structures with equiaxed grains. Our work on architecting the surface nanolaminates in gradient structure provides a scalable and sustainable strategy for designing more fatigue-resistant alloys.

Police Violence Exposure and Associated Health Outcomes Among Latinx Adults in the United States: An Integrative Review.

Police violence exposure among Latinx adults in the United States is increasingly concerning due to its prevalence and associated risks for adverse mental, behavioral, and physical health outcomes. This integrative review appraised studies published from 2003 to 2023 that examine the relationship between police violence exposure and negative health outcomes in Latinx adults. Using structured search terms, articles were identified in APA PsycInfo and PubMed databases, supplemented by a gray literature search and citation mining. Eleven studies met the inclusion criteria. Findings indicate a significant positive association between police violence exposure and adverse mental (n = 9), behavioral (n = 2), and physical (n = 1) health outcomes. The results underscore the mental, behavioral, and physical health consequences of police violence exposure for Latinx adults. Given the increasing Latinx population in the United States, further research is needed to better understand this relationship and inform interventions.

Comparing Analytical Methods for Composite Endpoints in Clinical Trials: Insights from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) Trial.

BACKGROUND AND AIMS: In the VICTORIA trial of participants with heart failure (HF) and reduced ejection fraction, vericiguat (V) reduced the primary composite outcome [time to first HF hospitalization (HFH) or cardiovascular death (CVD)] (897 events) compared to placebo (P) (972 events) (hazard ratio, 0.90; 95% confidence interval [CI], 0.82-0.98; p=0.02). In this prespecified secondary analysis, we applied the weighted composite endpoint (WCE) and the win ratio (WR) methods to provide complementary assessments of treatment effect. METHODS AND RESULTS: The WCE method estimated the mean HFH-adjusted survival based on prespecified weights from a Delphi panel of the VICTORIA executive committee and national leaders: mild (weight per event: 0.39), moderate (0.5) or severe (0.67) HFH, and CVD (1.0). The unmatched WR was estimated for the descending hierarchy of CVD, then recurrent HFH. The WCE used all 3412 primary clinical events: 875(V:416/P:459) severe HFH, 1614(767/847) moderate HFH and 68(38/30) mild HFH, 855(414/441) CVD. Improved HFH-adjusted survival occurred with vericiguat [mean 78.2% vs. 75.6%; difference (95% CI): 2.4% (1.7%-3.2%); p<0.0001]. Based on the comparison of 6,375,624 pairs, the WR of 1.13 (95% CI, 1.03-1.24, p=0.01) also indicated improved clinical outcomes with vericiguat. CONCLUSIONS: The results of the WCE and WR methods were consistent with the primary analysis of the time to first HFH or CVD. Whereas both WCE and WR assessed recurrent events, the WCE allowed inclusion of all recurrent events, insights on the severity of HFH events, and an absolute measure of the participant-treatment experience. This approach complements conventional assessment, better informing consumers of new therapeutics and future trial designs.

Current practices in the management of temporary mechanical circulatory support: A survey of CICU directors in North America.

INTRODUCTION: Despite the growing use of temporary mechanical circulatory support (tMCS), little data exists to inform management and weaning of these devices. METHODS: We performed an online survey among cardiac intensive care unit directors in North America to examine current practices in the management of patients treated with intraaortic balloon pump and Impella. RESULTS: We received responses from 84% of surveyed centers (n=37). Our survey focused on three key aspects of daily management: 1. Hemodynamic monitoring; 2. Hemocompatibility; and 3. Weaning and removal. We found substantial variability surrounding all three areas of care. CONCLUSION: Our findings highlight the need for consensus around practices associated with improved outcomes in patients treated with tMCS.

Foam fractionation studies of recombinant human apolipoprotein A-I.

Apolipoprotein A-I (apoA-I), the primary protein component of plasma high-density lipoproteins (HDL), is comprised of two structural regions, an N-terminal amphipathic α-helix bundle domain (residues 1-184) and a hydrophobic C-terminal domain (residues 185-243). When a recombinant fusion protein construct [bacterial pelB leader sequence - human apoA-I (1-243)] was expressed in Escherichia coli shaker flask cultures, apoA-I was recovered in the cell lysate. By contrast, when the C-terminal domain was deleted from the construct, large amounts of the truncated protein, apoA-I (1-184), were recovered in the culture medium. Consequently, following pelB leader sequence cleavage in the E. coli periplasmic space, apoA-I (1-184) was secreted from the bacteria. When the pelB-apoA-I (1-184) fusion construct was expressed in a 5 L bioreactor, substantial foam production (~30 L) occurred. Upon foam collection and collapse into a liquid foamate, SDS-PAGE revealed that apoA-I (1-184) was the sole major protein present. Incubation of apoA-I (1-184) with phospholipid vesicles yielded reconstituted HDL (rHDL) particles that were similar in size and cholesterol efflux capacity to those generated with full-length apoA-I. Mass spectrometry analysis confirmed that pelB leader sequence cleavage occurred and that foam fractionation did not result in unwanted protein modifications. The facile nature and scalability of bioreactor-based apolipoprotein foam fractionation provide a novel means to generate a versatile rHDL scaffold protein.

Postcrisis Follow-Up and Linkage to Community Services.

During the postcrisis period, many individuals struggle to transition to available care, often falling through the cracks. This article discusses effective postcrisis approaches that provide rapid access to transitional team-based care using critical time intervention strategies. It also highlights the development of state, county, and funder models for "care-traffic control" to ensure swift linkage to follow-up services, along with new funding models that support intensive community crisis stabilization during the postcrisis period. Emerging crisis systems can leverage these emerging services and approaches to facilitate successful transitions for individuals in need.

Associations between psychosocial stress, child's anxiety, and lung function in mid-childhood.

BACKGROUND: Reducing the risk of respiratory disease during the plastic stages of lung development could have long-term health impacts. Psychosocial stress has been previously linked to adverse childhood respiratory outcomes, but the influence of child's anxiety and sex differences has not been completely elucidated. AIM: To examine the association between maternal stress, child anxiety and lung function in children and to explore differences by sex. METHODS: Cross-sectional analyses included 294 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) birth cohort in Mexico City. Children's lung function was tested once at ages 8-13 years ofage, height and sex adjusted z-scores were estimated for forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75%). Maternal stress was assessed via the Crisis in Family Systems-Revised (CRISYS-R) survey, used toreport of negative life events experienced in the past 6 months and dichotomized at the median (<3 and ≥3). Child's self-reported anxiety was assessed using the Revised Children's Manifest Anxiety Scale short form and dichotomized at the clinically relevant cutoff (t-score≥60). The association between maternal stress, child anxiety and lung function outcomes was examined using linear models. Effect modification by sex was examined with interaction terms and in stratified analyses. RESULTS: We did not find any association between maternal stress and any lung function outcome. Clinically elevated child anxiety symptoms were associated with lower FEV1 (ß= -0.36, 95% CI -0.69, -0.02). We found no evidence of effect modification by sex. CONCLUSIONS: Results highlight the importance of considering childhood mental health in relation to lung function outcomes.

Achieving Equitable Cardiovascular Care for All: ACC Board of Trustees Health Equity Task Force Action Plan.

Advancements in cardiovascular (CV) disease management are notable, yet health inequities prevail, associated with increased morbidity and mortality noted among non-Hispanic African Americans in the United States. The 2002 Institute of Medicine Report revealed ongoing racial and ethnic health care disparities, spearheading a deeper understanding of the social determinants of health and systemic racism to develop strategies for CV health equity (HE). This article outlines the strategic HE approach of the American College of Cardiology, comprising 6 strategic equity domains: workforce pathway inclusivity, health care, data, science, and tools; education and training; membership, partnership, and collaboration; advocacy and policy; and clinical trial diversity. The American College of Cardiology's Health Equity Task Force champions the improvement of patients' lived experiences, population health, and clinician well-being while reducing health care costs-the Quadruple Aim of Health Equity. Thus, we examine multifaceted HE interventions and provide evidence for scalable real-world interventions to promote equitable CV care.

Functional dry powders of connexin-containing extracellular vesicles.

Extracellular vesicles (EVs) have emerged as a promising drug delivery system. Connectosomes are a specialized type of EVs that contain connexins in their membranes. Connexin is a surface transmembrane protein that forms connexin hemichannels. When a connexin hemichannel on a connectosome docks with another connexin hemichannel of a target cell, they form a gap junction that allows direct intracellular delivery of therapeutic cargos from within the connectosome to the cytoplasm of the recipient cell. In the present study, we tested the feasibility of converting connectosomes into dry powders by (thin-film) freeze-drying to enable their potential storage in temperatures higher than the recommended -80 °C, while maintaining their activity. Connectosomes were isolated from a genetically engineered HeLa cell line that overexpressing connexin-43 subunit protein tagged with red fluorescence protein. To facilitate the testing of the function of the connectosomes, they were loaded with calcein green dye. Calcein green-loaded connectosomes were thin-film freeze-dried with trehalose alone or trehalose and a polyvinylpyrrolidone polymer as lyoprotectant(s) to produce amorphous powders with high glass transition temperatures (>100 °C). Thin-film freeze-drying did not significantly change the morphology and structure of the connectosomes, nor their particle size distribution. Based on data from confocal microscopy, flow cytometry, and fluorescence spectrometry, the connexin hemichannels in the connectosomes reconstituted from the thin-film freeze-dried powder remained functional, allowing the passage of calcein green through the hemichannels and the release of the calcein green from the connectosomes when the channels were opened by chelating calcium in the reconstituted medium. The function of connectosomes was assessed after one month storage at different temperatures. The connexin hemichannels in connectosomes in liquid lost their function when stored at -19.5 ± 2.2 °C or 6.0 ± 0.5 °C for a month, while those in dry powder form remained functional under the same storage conditions. Finally, using doxorubicin-loaded connectosomes, we showed that the connectosomes reconstituted from thin-film freeze-dried powder remained pharmacologically active. These findings demonstrate that (thin-film) freeze-drying represents a viable method to prepare stable and functional powders of EVs that contain connexins in their membranes.

Open Capsular Repair with Dermal allograft and tarsal tunnel release in the treatment of Tarsal Tunnel Syndrome in a Young Collegiate Athlete: A Case Report.

Tarsal tunnel syndrome is an entrapment neuropathy of the posterior tibial nerve beneath the flexor retinaculum that can be precipitated by either intrinsic or extrinsic factors. We report a unique case of a posterior medial ankle joint capsular defect with localized fluid extravasation between the flexor digitorum longus and flexor hallucis longus leading to symptoms consistent with tarsal tunnel syndrome in a collegiate tennis player. This patient is a 19-year-old female with no past medical history who presented with symptoms consistent with tarsal tunnel syndrome. After confirmation with magnetic resonance imaging, the patient underwent capsular reconstruction with dermal allograft in combination with a tarsal tunnel release. The patient had improvement in pain and recovery of paresthesia 3 months postoperatively. At the latest follow-up of 1 year postoperatively, the patient has not had a recurrence of symptoms and has returned to the same level of competitive play. Many different causes of tarsal tunnel syndrome are described in the literature, but to our knowledge, there is no current literature that describes a defect in the tibiotalar joint capsule as a cause of tarsal tunnel syndrome.

Marine heatwave-driven mass mortality and microbial community reorganisation in an ecologically important temperate sponge.

Marine heatwaves (MHWs) are increasing in frequency, duration and intensity, disrupting global marine ecosystems. While most reported impacts have been in tropical areas, New Zealand experienced its strongest and longest MHW in 2022, profoundly affecting marine sponges. Sponges are vital to rocky benthic marine communities, with their abundance influencing ecosystem functioning. This study examines the impact of this MHW on the photosynthetic sponge Cymbastella lamellata in Fiordland, New Zealand. We describe the extent, physiological responses, mortality, microbial community changes and ecological impact of this MHW on C. lamellata. The Fiordland MHW reached a maximum temperature of 4.4°C above average, lasting for 259 days. Bleaching occurred in >90% of the C. lamellata Fiordland population. The population size exceeded 66 million from 5 to 25 m, making this the largest bleaching event of its kind ever recorded. We identified the photosynthetic symbiont as a diatom, and bleached sponges had reduced photosynthetic efficiency. Post-MHW surveys in 2023 found that over 50% of sponges at sampling sites had died but that the remaining sponges had mostly recovered from earlier bleaching. Using a simulated MHW experiment, we found that temperature stress was a driver of necrosis rather than bleaching, despite necrosis only rarely being observed in the field (<2% of sponges). This suggests that bleaching may not be the cause of the mortality directly. We also identified a microbial community shift in surviving sponges, which we propose represents a microbial-mediated adaptive response to MHWs. We also found that C. lamellata are key contributors of dissolved organic carbon to the water column, with their loss likely impacting ecosystem function. We demonstrate the potential for MHWs to disrupt key marine phyla in temperate regions, highlighting how susceptible temperate sponges globally might be to MHWs.

Longitudinal Changes in Youth Mental Health From Before to During the COVID-19 Pandemic.

Importance: Robust longitudinal studies of within-child changes in mental health associated with the COVID-19 pandemic are lacking, as are studies examining sources of heterogeneity in such changes. Objective: To investigate within-child changes, overall and between subgroups, in youth mental health from prepandemic to midpandemic. Design, Setting, and Participants: This cohort study used longitudinal prepandemic and midpandemic data from the Environmental influences on Child Health Outcomes (ECHO) Program, collected between January 1, 2015, and March 12, 2020 (prepandemic), and between March 13, 2020, and August 31, 2022 (midpandemic). Data were analyzed between December 1, 2022, and June 1, 2024. The sample included 9 US-based observational longitudinal pediatric ECHO cohorts. Cohorts were included if they collected the Child Behavior Checklist (CBCL) School Age version before and during the pandemic on more than 20 participants of normal birth weight aged 6 to 17 years. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: Prepandemic to midpandemic changes in CBCL internalizing, externalizing, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scores were estimated, and differences in outcome trajectories by child sociodemographic characteristics (age, sex, race, ethnicity, and poverty level) and prepandemic mental health problems were examined using established CBCL clinical score thresholds. Results: A total of 1229 participants (mean [SD] age during the pandemic, 10.68 [2.29] years; 625 girls [50.9%]) were included. The sample was socioeconomically diverse (197 of 1056 children [18.7%] lived at ≤130% of the Federal Poverty Level; 635 (51.7%) identified as White, 388 (31.6%) as Black, 147 (12.0%) as multiracial, 40 (3.3%) as another race, and 118 (9.6%) as Hispanic). Generalized linear mixed-effects models revealed minor decreases in externalizing problems (ß = -0.88; 95% CI, -1.16 to -0.60), anxiety (ß = -0.18; 95% CI, -0.31 to -0.05), and ADHD (ß = -0.36; 95% CI, -0.50 to -0.22), but a minor increase in depression (ß = 0.22; 95% CI, 0.10 to 0.35). Youth with borderline or clinically meaningful prepandemic scores experienced decreases across all outcomes, particularly externalizing problems (borderline, ß = -2.85; 95% CI, -3.92 to -1.78; clinical, ß = -4.88; 95% CI, -5.84 to -3.92). Low-income (ß = -0.76; 95% CI, -1.14 to -0.37) and Black (ß = -0.52; 95% CI, -0.83 to -0.20) youth experienced small decreases in ADHD compared with higher income and White youth, respectively. Conclusions and Relevance: In this longitudinal cohort study of economically and racially diverse US youth, there was evidence of differential susceptibility and resilience for mental health problems during the pandemic that was associated with prepandemic mental health and sociodemographic characteristics.

Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2.

Purpose: Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation. Design: A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester. Subjects: We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital. Methods: Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants' ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively. Main Outcome Measures: Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants' retinal maturity indicators between the 2 study groups. Results: Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (P < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (P = 0.242) and more mature foveal parameters compared with those in the Control Group. Conclusion: Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants' ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Sex-specific associations of a ferroalloy metal mixture with motor function in Italian adolescents.

Background: Motor function is critical for children's health, yet remains an understudied neurodevelopmental domain. Exposure to metals has been linked with motor function, but no study has examined the joint effects of metal mixtures. Methods: We evaluated cross-sectional associations between a metal mixture and motor function among 569 adolescents (10-14 years old) living near the ferroalloy industry. Concentrations of blood lead, hair manganese, hair copper, and hair chromium were quantified using inductively coupled plasma mass spectrometry. Neuropsychologists administered multiple fine motor function assessments: pursuit aiming, finger tapping, visual reaction time (VRT), and subtests from the Luria Nebraska battery. We estimated associations between motor function and the metal mixture using quantile-based g-computation and multivariable linear regression, adjusting for child age, sex, and socioeconomic status. We explored sex-specific associations in stratified models. Results: Associations between the metal mixture and motor function were mostly null but were modified by sex. We observed a beneficial association among females: a quartile increase in all metals in the mixture was associated with a 2.6% faster average response time on the VRT (95% confidence interval [CI] = -4.7%, -0.5%), driven by Cu and Cr. In contrast, this association was adverse among males (ß = 1.5% slower response time [95% CI = -0.7%, 3.9%]), driven by Cu and Mn. Conclusions: Results suggest that males may be more susceptible to the adverse effects of metal exposure on motor function during adolescence than females. Future studies, particularly prospective study designs, are warranted to further understand the associations of metal mixtures with motor function.

Heparin-Binding Protein Stratifies Mortality Risk Among Ugandan Children Hospitalized With Respiratory Distress.

Background: Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis. Methods: We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores. Results: Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41-150]) compared to children who survived (median, 31 ng/mL [IQR, 18-57]) (P < .001). Children with HBP >41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9-9.5]; P < .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66-.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score (P = .0026). Conclusions: Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death.

Evaluating and mitigating unfairness in multimodal remote mental health assessments.

Research on automated mental health assessment tools has been growing in recent years, often aiming to address the subjectivity and bias that existed in the current clinical practice of the psychiatric evaluation process. Despite the substantial health and economic ramifications, the potential unfairness of those automated tools was understudied and required more attention. In this work, we systematically evaluated the fairness level in a multimodal remote mental health dataset and an assessment system, where we compared the fairness level in race, gender, education level, and age. Demographic parity ratio (DPR) and equalized odds ratio (EOR) of classifiers using different modalities were compared, along with the F1 scores in different demographic groups. Post-training classifier threshold optimization was employed to mitigate the unfairness. No statistically significant unfairness was found in the composition of the dataset. Varying degrees of unfairness were identified among modalities, with no single modality consistently demonstrating better fairness across all demographic variables. Post-training mitigation effectively improved both DPR and EOR metrics at the expense of a decrease in F1 scores. Addressing and mitigating unfairness in these automated tools are essential steps in fostering trust among clinicians, gaining deeper insights into their use cases, and facilitating their appropriate utilization.

LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.

Mounting evidence supports a critical role for central nervous system (CNS) glial cells in neuroinflammation and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), as well as neurovascular ischemic stroke. Previously, we found that loss of the PD-associated gene leucine-rich repeat kinase 2 (Lrrk2) in macrophages, peripheral innate immune cells, induced mitochondrial stress and elevated basal expression of type I interferon (IFN) stimulated genes (ISGs) due to chronic mitochondrial DNA engagement with the cGAS/STING DNA sensing pathway. Here, we report that loss of LRRK2 results in a paradoxical response in microglial cells, a CNS-specific macrophage population. In primary murine microglia and microglial cell lines, loss of Lrrk2 reduces tonic IFN signaling leading to a reduction in ISG expression. Consistent with reduced type I IFN, mitochondria from Lrrk2 KO microglia are protected from stress and have elevated metabolism. These protective phenotypes involve upregulation of NRF2, an important transcription factor in the response to oxidative stress and are restricted by LRRK2 kinase activity. Collectively, these findings illustrate a dichotomous role for LRRK2 within different immune cell populations and give insight into the fundamental differences between immune regulation in the CNS and the periphery.