COVID-19 Vaccines: Moderna And Pfizer-BioNTech Use Varied By Urban, Rural Counties.

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.

The FAM13A Long Isoform Regulates Cilia Movement and Co-ordination in Airway Mucociliary Transport.

SNPs in the FAM13A locus are amongst the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases, however the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the FAM13A locus: 'long' and 'short', but their functions remain unknown, partly due to a lack of isoform conservation in mice. We performed in-depth characterisation of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase activating protein (RhoGAP) domain. Using purified proteins, we directly demonstrate RhoGAP activity of this domain. In Xenopus laevis, which conserve the long isoform, Fam13a-deficiency impaired cilia-dependent embryo motility. In human primary epithelial cells, long isoform deficiency did not affect multiciliogenesis but reduced cilia co-ordination in mucociliary transport assays. This is the first demonstration that FAM13A isoforms are differentially expressed within the airway epithelium, with implications for the assessment and interpretation of SNP effects on FAM13A expression levels. We also show that the long FAM13A isoform co-ordinates cilia-driven movement, suggesting that FAM13A risk alleles may affect susceptibility to respiratory diseases through deficiencies in mucociliary clearance. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Pharmacists as clinical care partners: How a pharmacist-led intervention is associated with improved medication adherence in older adults with common chronic conditions.

BACKGROUND: Hypertension, hyperlipidemia, and type 2 diabetes (T2D) are 3 of the most common chronic conditions, but related medication adherence rates are far below 80%. Consequences of poor adherence include high health care utilization/costs and increased mortality. There is accumulating evidence in support of the benefits of affording pharmacists the opportunity to practice at the full scope of their licensure by engaging in patients' clinical care. OBJECTIVE: To examine the impact of a large national pharmacy chain's pharmacist-led interventions to improve medication adherence among older adults with hypertension, hyperlipidemia, or T2D. A secondary objective was to estimate the potential cost savings associated with improved adherence. METHODS: Participants were Medicare patients aged 18 years or older who had 2 or more prescription fills in at least 1 of the 3 therapeutic classes. The primary outcome, optimal adherence, was defined as proportion of days covered (PDC) of 80% or higher. A difference-in-differences (DID) design with a generalized linear model analytical approach was applied to examine differences between intervention participants and controls. The study period spanned from 2020 to 2022. RESULTS: Intervention participants (n = 317,613, age 70.1 years, female sex 57.0%) had lower baseline optimal adherence than controls (n = 943,389, age 73.3, female sex 56.1%) for diabetes (76.9% vs 79.8%), hypertension (79.0% vs 83.0%), and cholesterol (78.6% vs 82.1%). The DID results showed that between 2020 and 2022, optimal adherence had significant absolute increases for intervention participants (diabetes: +4.0%, hypertension: +6.3%, cholesterol: +6.1%) vs controls who declined in adherence (diabetes: -1.6%, hypertension: -0.4%, cholesterol: -1.4%). All DID models were significant at P < 0.0001. Total cost of care was projected based on improvements in adherence. Based on PDC improvements for the test population, we estimate that the pharmacist consultations were associated with annual total health care cost savings of $10,329,284 ($109 per capita), $31,640,660 ($122 per capita), and $21,589,875 ($75 per capita) for test population patients with diabetes, hypertension, and hyperlipidemia, respectively. CONCLUSIONS: The study found that the pharmacist-led interventions were significantly associated with increased optimal adherence over 2 years. These findings demonstrate the potential of pharmacist-led interventions to improve medication adherence among older adults with chronic conditions. Strategies to expand pharmacist-provided care must be further examined.

Examining birth preparedness and complication readiness: a systematic review and meta-analysis of pregnant and recently delivered women in India.

BACKGROUND: Birth preparedness and complication readiness (BPCR) is an essential component of safe motherhood programs. This study aims to systematically identify and synthesize available evidence on birth preparedness and complication readiness among pregnant and recently delivered women in India. METHODS: The study followed PRISMA guidelines and used databases such as PubMed, Cochrane Library, and ProQuest. Joanna Briggs Institute [JBI] Tool was used for critical appraisal of studies. The meta-analysis was conducted using Comprehensive Meta-Analysis [CMA] tool and R studio software. Statistical heterogeneity was evaluated using visual inspection of the forest plot, Cochran's Q test, and the I2 statistic results. Funnel plot and Egger's tests were applied to explore the possibility of the publication bias in the studies [PROSPERO: CRD42023396109]. RESULT: Thirty-five cross-sectional studies reported knowledge on one or more components of birth preparedness [BP], whilst knowledge on complication readiness [CR] or danger signs was reported in 34 included studies. Utilizing the random effect model, the pooled result showed that only about half of the women [49%; 95% CI: 44%, 53%] were aware on BPCR components. This result ranged between 15% [95% CI: 12%, 19%] to 79% [95% CI: 72%, 84%] in Maharashtra and Karnataka respectively [I2 = 94%, p = < 0.01]. High heterogeneity [> 90%] is observed across all components [p < 0.01]. The result of subgroup analysis indicated no significant difference in the proportion on BPCR among pregnant women [50%; 95% CI: 45%, 55%] and recently delivered women [54%; 95% CI: 46%, 62%]. However, the southern region of India indicates relatively better [56%; 95% CI: 45%, 67%] prevalence. CONCLUSION: Our study highlights the low prevalence of BPCR in India and the factors associated with it. Scaling up cost-effective interventions like BPCR that have a positive overall effect is necessary. Authors strongly suggests that birth preparedness and complication readiness should be given utmost importance to reduce maternal morbidity and mortality to achieve the Sustainable Development Goals. Consideration should be given to fortifying existing resources, such as frontline workers and primary healthcare, as a strategic approach to augmenting the effectiveness of awareness initiatives.

Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner.

Oncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress.

Paenibacillus lentimorbus alleviates nutrient deficiency-induced stress in Zea mays by modulating root system architecture, auxin signaling, and metabolic pathways.

KEY MESSAGE: Paenibacillus lentimorbus reprograms auxin signaling and metabolic pathways for modulating root system architecture to mitigate nutrient deficiency in maize crops. The arable land across the world is having deficiency and disproportionate nutrients, limiting crop productivity. In this study, the potential of plant growth-promoting rhizobacteria (PGPR) viz., Pseudomonas putida, Paenibacillus lentimorbus, and their consortium was explored for growth promotion in maize (Zea mays) under nutrient-deficient conditions. PGPR inoculation improved the overall health of plants under nutrient-deficient conditions. The PGPR inoculation significantly improved the root system architecture and also induced changes in root cortical aerenchyma. Based on plant growth and physiological parameters inoculation with P. lentimorbus performed better as compared to P. putida, consortium, and uninoculated control. Furthermore, expression of auxin signaling (rum1, rul1, lrp1, rtcs, rtcl) and root hair development (rth)-related genes modulated the root development process to improve nutrient acquisition and tolerance to nutrient-deficient conditions in P. lentimorbus inoculated maize plants. Further, GC-MS analysis indicated the involvement of metabolites including carbohydrates and organic acids due to the interaction between maize roots and P. lentimorbus under nutrient-deficient conditions. These findings affirm that P. lentimorbus enhance overall plant growth by modulating the root system of maize to provide better tolerance to nutrient-deficient condition.

Accuracy of Surgical Outcome Using Computer-Aided Surgical Simulation in Fronto-Orbital Advancement for Craniosynostosis: A Pilot Study.

BACKGROUND AND OBJECTIVE: Computer-aided surgical simulation (CASS) can be used to virtually plan ideal outcomes of craniosynostosis surgery. Our purpose was to create a workflow analyzing the accuracy of surgical outcomes relative to virtually planned fronto-orbital advancement (FOA). METHODS: Patients who underwent FOA using CASS between October 1, 2017, and February 28, 2022, at our center and had postoperative computed tomography within 6 months of surgery were included. Virtual 3-dimensional (3D) models were created and coregistered using each patient's preoperative and postoperative computed tomography data. Three points on each bony segment were used to define the object in 3D space. Each planned bony segment was manipulated to match the actual postoperative outcome. The change in position of the 3D object was measured in translational (X, Y, Z) and rotational (roll, pitch, yaw) aspects to represent differences between planned and actual postoperative positions. The difference in the translational position of several bony landmarks was also recorded. Wilcoxon signed-rank tests were performed to measure significance of these differences from the ideal value of 0, which would indicate no difference between preoperative plan and postoperative outcome. RESULTS: Data for 63 bony segments were analyzed from 8 patients who met the inclusion criteria. Median differences between planned and actual outcomes of the segment groups ranged from -0.3 to -1.3 mm in the X plane; 1.4 to 5.6 mm in the Y plane; 0.9 to 2.7 mm in the Z plane; -1.2° to -4.5° in pitch; -0.1° to 1.0° in roll; and -2.8° to 1.0° in yaw. No significant difference from 0 was found in 21 of 24 segment region/side combinations. Translational differences of bony landmarks ranged from -2.7 to 3.6 mm. CONCLUSION: A high degree of accuracy was observed relative to the CASS plan. Virtual analysis of surgical accuracy in FOA using CASS was feasible.

Effectiveness of BNT162b2 BA.4/5 Bivalent mRNA Vaccine Against Symptomatic COVID-19 Among Immunocompetent Individuals Testing at a Large US Retail Pharmacy.

BACKGROUND: Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking. METHODS: This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (15 September 2022 to 31 January 2023) at a large national retail pharmacy chain. The exposure was receipt of 2-4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs unvaccinated) and relative (vs 2-4 wild-type doses) vaccine effectiveness (VE) were calculated as (1 - adjusted odds ratio from logistic regression) × 100. VE was stratified by age and self-reported prior infection. RESULTS: Overall, 307 885 SARS-CoV-2 tests were included (7916 aged 5-11, 16 329 aged 12-17, and 283 640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2-4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1-2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE was 22%-60% and was significantly higher among those reporting prior infection (range, 55%-79%) than not (range, no protection to 50%). Relative VE was 31%-64%. CONCLUSIONS: BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection.

Immunogenicity of cancer cells: An overview.

The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes. One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death. These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as "eat me" signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis. Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation. Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.

The hidden harmony: Exploring ROS-phytohormone nexus for shaping plant root architecture in response to environmental cues.

Root system architecture, encompassing lateral roots and root hairs, plays a vital in overall plant growth and stress tolerance. Reactive oxygen species (ROS) and plant hormones intricately regulate root growth and development, serving as signaling molecules that govern processes such as cell proliferation and differentiation. Manipulating the interplay between ROS and hormones has the potential to enhance nutrient absorption, stress tolerance, and agricultural productivity. In this review, we delve into how studying these processes provides insights into how plants respond to environmental changes and optimize growth patterns to better control cellular processes and stress responses in crops. We discuss various factors and complex signaling networks that may exist among ROS and phytohormones during root development. Additionally, the review highlights possible role of reactive nitrogen species (RNS) in ROS-phytohormone interactions and in shaping root system architecture according to environmental cues.

Acute air pollution and temperature exposure as independent and joint triggers of spontaneous preterm birth in New South Wales, Australia: a time-to-event analysis.

Introduction: Exposure to high ambient temperatures and air pollution has been shown to increase the risk of spontaneous preterm birth (sPTB). Less clear are the effects of cold and the joint effects of air pollution and temperature. Methods: Using a Cox proportional hazard regression model, we assessed the risk of independent and combined short-term exposure to ambient daily mean temperature and PM2.5 associated with sPTB in the last week before delivery on overall sPTB (weeks 23-36) and three subtypes: extremely sPTB, very sPTB, and moderate-to-late sPTB for a birth cohort of 1,318,570 births from Australia (Jan 2001-Dec 2019), while controlling for chronic exposure (i.e., throughout pregnancy except the last week before delivery) to PM2.5 and temperature. The temperature was modeled as a natural cubic spline, PM2.5 as a linear term, and the interaction effect was estimated using a multiplicative term. For short-term exposure to temperature hazard ratios reported are relative to the median temperature (18.1°C). Results: Hazard ratios at low temperature [5th percentile(11.5°C)] were 0.95 (95% CI: 0.90, 1.00), 1.08 (95% CI: 0.84, 1.4), 0.87 (95% CI: 0.71, 1.06), and 1.00 (95% CI: 0.94, 1.06) and greater for high temperature [95th percentile (24.5°C)]: 1.22 (95% CI: 1.16, 1.28), 1.27 (95% CI: 1.03, 1.57), and 1.26 (95% CI: 1.05, 1.5) and 1.05 (1.00, 1.11), respectively, for overall, extremely, very, and moderate-to-late sPTBs. While chronic exposure to PM2.5 had adverse effects on sPTB, short-term exposure to PM2.5 appeared to have a negative association with all types of sPTB, with hazard ratios ranging from 0.86 (95th CI: 0.80, 0.94) to 0.98 (95th CI: 0.97, 1.00) per 5 µg/m3 increase in PM2.5. Discussion: The risk of sPTB was found to increase following acute exposure to hot and cold ambient temperatures. Earlier sPTB subtypes seemed to be the most vulnerable. This study adds to the evidence that short-term exposure to ambient cold and heat and longer term gestational exposure to ambient PM2.5 are associated with an elevated risk of sPTB.

Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design.

Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial.

BACKGROUND: Kligman's trio (KT), combining hydroquinone, retinoic acid and corticosteroid, is considered as the gold standard treatment of melasma. Its efficacy has never been matched before, but it is tempered by frequent adverse effects. OBJECTIVE: To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. METHODS: We conducted a 24-week monocentric trial, randomized, double-blind, controlled versus KT, with 40 melasma patients. NT and KT were applied for 12 weeks and associated with the same sunscreen applied for 24 weeks. The primary endpoint was the modified Melasma Area Severity Index (mMASI) at 12 weeks. Patient quality of life was investigated using MelasQoL. RESULTS: After 12 weeks, KT and NT groups both demonstrated a significant improvement in mMASI, respectively -2.84 (SE 0.69, p < 0.0002) and -4.33 (SE 0.71, p < 0.0001). The mean difference between the two groups was -1.49 (IC 95% -3.52 to 0.54, p = 0.14). MelasQoL improvement was -6.66 (SE 3.29, p = 0.0515) with KT and -12.57 (SE 3.29, p = 0.0006) with NT. CONCLUSION: The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.

Racial and ethnic disparities in COVID-19 booster vaccination among U.S. older adults differ by geographic region and Medicare enrollment.

Introduction: COVID-19 booster vaccines are highly effective at reducing severe illness and death from COVID-19. Research is needed to identify whether racial and ethnic disparities observed for the primary series of the COVID-19 vaccines persist for booster vaccinations and how those disparities may vary by other characteristics. We aimed to measure racial and ethnic differences in booster vaccine receipt among U.S. Medicare beneficiaries and characterize potential variation by demographic characteristics. Methods: We conducted a cohort study using CVS Health and Walgreens pharmacy data linked to Medicare claims. We included community-dwelling Medicare beneficiaries aged ≥66 years who received two mRNA vaccine doses (BNT162b2 and mRNA-1273) as of 8/1/2021. We followed beneficiaries from 8/1/2021 until booster vaccine receipt, death, Medicare disenrollment, or end of follow-up (12/31/2021). Adjusted Poisson regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) comparing vaccine uptake between groups. Results: We identified 11,339,103 eligible beneficiaries (mean age 76 years, 60% female, 78% White). Overall, 67% received a booster vaccine (White = 68.5%; Asian = 67.0%; Black = 57.0%; Hispanic = 53.3%). Compared to White individuals, Black (RR = 0.78 [95%CI = 0.78-0.78]) and Hispanic individuals (RR = 0.72 [95% = CI 0.72-0.72]) had lower rates of booster vaccination. Disparities varied by geographic region, urbanicity, and Medicare plan/Medicaid eligibility. The relative magnitude of disparities was lesser in areas where vaccine uptake was lower in White individuals. Discussion: Racial and ethnic disparities in COVID-19 vaccination have persisted for booster vaccines. These findings highlight that interventions to improve vaccine uptake should be designed at the intersection of race and ethnicity and geographic location.

Factors associated with receipt of mRNA-1273 vaccine at a United States national retail pharmacy during the COVID-19 pandemic.

INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted accelerated vaccine development of novel messenger RNA (mRNA)-based vaccines by Moderna and Pfizer, which received FDA Emergency Use Authorization in December 2020. The purpose of this study was to examine trends in primary series administration and multi-dose completion rates with Moderna's mRNA-1273 vaccine administered at a United States retail pharmacy. METHODS: Walgreens pharmacy data were joined to publicly available data sets to examine trends in mRNA-1273 primary series and multi-dose completion across patient race/ethnicity, age, gender, distance to first vaccination, and community characteristics. Eligible patients received their first dose of mRNA-1273 administered by Walgreens between December 18, 2020 and February 28, 2022. Variables significantly associated with on-time second dose (all patients) and third dose (immunocompromised patients) in univariate analyses were included in linear regression models. A subset of patients in selected states were studied to identify differences in early and late vaccine adoption. RESULTS: Patients (N = 4,870,915) who received ≥ 1 dose of mRNA-1273 were 57.0% White, 52.6% female, and averaged 49.4 years old. Approximately 85% of patients received a second dose during the study period. Factors associated with on-time second dose administration included older age, race/ethnicity, traveling ≤ 10 miles for the first dose, higher community-level health insurance, and residing in areas with low social vulnerability. Only 51.0% of immunocompromised patients received the third dose as recommended. Factors associated with third dose administration included older age, race/ethnicity, and small-town residence. Early adopters accounted for 60.6% of patients. Factors associated with early adoption included older age, race/ethnicity, and metropolitan residence. CONCLUSION: Over 80% of patients received their on-time second dose of mRNA-1273 vaccine per CDC recommendations. Patient demographics and community characteristics were associated with vaccine receipt and series completion. Novel approaches to facilitate series completion during a pandemic should be further studied.

Separate and combined effects of elevated pCO2 and temperature on the branching reef corals Acropora digitifera and Montipora digitata.

Ocean acidification (OA) and warming (OW) are major global threats to coral reef ecosystems; however, studies on their combined effects (OA + OW) are scarce. Therefore, we evaluated the effects of OA, OW, and OA + OW in the branching reef corals Acropora digitifera and Montipora digitata, which have been found to respond differently to environmental changes. Our results indicate that OW has a greater impact on A. digitifera and M. digitata than OA and that the former species is more vulnerable to OW than the latter. OW was the main stressor for increased mortality and decreased calcification in the OA + OW group, and the effect of OA + OW was additive in both species. Our findings suggest that the relative abundance and cover of M. digitata are expected to increase whereas those of A. digitifera may decrease in the near future in Okinawa.

Modeling the Inflammatory Response of Traumatic Brain Injury Using Human Induced Pluripotent Stem Cell Derived Microglia.

The neuroinflammatory response after traumatic brain injury (TBI) is implicated as a key mediator of secondary injury in both the acute and chronic periods after primary injury. Microglia are the key innate immune cell in the central nervous system, responding to injury with the release of cytokines and chemokines. In this context, we aimed to characterize the downstream cytokine response of human induced pluripotent stem cell (iPSC)-derived microglia when stimulated with five separate cytokines identified after human TBI. The iPSC-derived microglia were exposed to interleukin (IL)-1ß, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF) in the concentration ranges identified in clinical TBI studies. The downstream cytokine response was measured against a panel of 37 separate cytokines over a 72h time-course. The secretome revealed concentration-, time- and combined concentration and time-dependent downstream responses. TNF appeared to be the strongest inducer of downstream cytokine changes (51), followed by IL-1ß (26) and IL-4 (19). IL-10 (11) and IL-6 (10) produced fewer responses. We also compare these responses with our previous studies of iPSC-derived neuronal and astrocyte cultures and the in vivo human TBI cytokine response. Notably, we found microglial culture to induce both a wider range of downstream cytokine responses and a greater fold change in concentration for those downstream responses, compared with astrocyte and neuronal cultures. In summary, we present a dataset for human microglial cytokine responses specific to the secretome found in the clinical context of TBI. This reductionist approach complements our previous datasets for astrocyte and neuronal responses and will provide a platform to enable future studies to unravel the complex neuroinflammatory network activated after TBI.

Analysis of Need for Intervention in Low-Grade Traumatic Splenic Injury.

BACKGROUND: Blunt splenic injuries are common traumatic injuries. Severe injuries may require blood transfusion, procedural, or operative intervention. Conversely, patients with low-grade injuries and normal vital signs frequently do not require intervention. The level and duration of monitoring required to safely manage these patients are unclear. We hypothesize that low-grade splenic trauma has a low rate of intervention and may not require acute hospitalization. METHODS: This retrospective descriptive analysis included patients admitted to a level I trauma center with low injury burden (injury severity score <15) and The American Association for the Surgery of Trauma (AAST) grade 1 (G1) and 2 (G2) splenic injuries between January 2017 and December 2019 using the Trauma Registry of the American College of Surgeons (TRACS). The primary outcome was the need for any intervention. Secondary outcomes included time to intervention and length of stay. RESULTS: 107 patients met inclusion criteria. 87.9% required no intervention . 9.4% required blood products, with a median time to transfusion of 7.4 hours from arrival. All patients receiving blood products had extenuating circumstances such as bleeding from other injuries, anticoagulant use, or medical comorbidities. 2 patients required splenic artery embolization, one presenting with return precautions 9 days post-injury and 1 with significant comorbidities. One patient with concomitant bowel injury required splenectomy. CONCLUSIONS: Low-grade blunt splenic trauma has a low rate of intervention, which typically occurs within the first 12 hours of presentation. This suggests that outpatient management with return precautions may be appropriate for select patients after a short interval of observation.