Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

Performance evaluation of Trichoderma reseei in tolerance and biodegradation of diuron herbicide in agar plate, liquid culture and solid-state fermentation.

The present study evaluated the performance of the fungus Trichoderma reesei to tolerate and biodegrade the herbicide diuron in its agrochemical presentation in agar plates, liquid culture, and solid-state fermentation. The tolerance of T. reesei to diuron was characterized through a non-competitive inhibition model of the fungal radial growth on the PDA agar plate and growth in liquid culture with glucose and ammonium nitrate, showing a higher tolerance to diuron on the PDA agar plate (inhibition constant 98.63 mg L-1) than in liquid culture (inhibition constant 39.4 mg L-1). Diuron biodegradation by T. reesei was characterized through model inhibition by the substrate on agar plate and liquid culture. In liquid culture, the fungus biotransformed diuron into 3,4-dichloroaniline using the amide group from the diuron structure as a carbon and nitrogen source, yielding 0.154 mg of biomass per mg of diuron. A mixture of barley straw and agrolite was used as the support and substrate for solid-state fermentation. The diuron removal percentage in solid-state fermentation was fitted by non-multiple linear regression to a parabolic surface response model and reached the higher removal (97.26%) with a specific aeration rate of 1.0 vkgm and inoculum of 2.6 × 108 spores g-1. The diuron removal in solid-state fermentation by sorption on barley straw and agrolite was discarded compared to the removal magnitude of the biosorption and biodegradation mechanisms of Trichoderma reesei. The findings in this work about the tolerance and capability of Trichoderma reesei to remove diuron in liquid and solid culture media demonstrate the potential of the fungus to be implemented in bioremediation technologies of herbicide-polluted sites.

Uncovering Surface Penetration by Enterococci From Urinary Tract Infection Patients.

IMPORTANCE: The relationship between Enterococcus faecalis vaginal colonization and urinary tract infections (UTIs) remains uncertain. OBJECTIVE: We aimed to evaluate the surface invasion capability of E faecalis isolates from patients with and without UTIs as a potential readout of pathogenicity. STUDY DESIGN: Participants were females from urogynecology clinics, comprising symptomatic UTI and asymptomatic non-UTI patients, categorized by the presence or absence of E faecalis-positive cultures identified via standard urine culture techniques. Vaginal and urine samples from patients were plated on enterococci selective medium, and E faecalis isolates detected in both cohorts were species specific identified using 16S rRNA sequencing. Clinical isolates were inoculated on semisolid media, and both external colonies and underneath colony prints formed by agar-penetrating enterococci were imaged. External growth and invasiveness were quantified by determining colony-forming units of the noninvading and agar-penetrating cells and compared with the E faecalis OG1RF. RESULTS: We selected E faecalis isolates from urine and vaginal samples of 4 patients with and 4 patients without UTIs. Assays demonstrated that most isolates formed similarly sized external colonies with comparable colony-forming unit. Surface invasion differed across patients and isolation sites compared with OG1RF. The vaginal isolate from UTI patient 1, who had the most recurrences, exhibited significantly greater agar-invading capacity compared with OG1RF. CONCLUSIONS: Our pilot study indicates that ex vivo invasion assays may unveil virulence traits in E faecalis from UTI patients. Enhanced enterococcal surface penetration could increase urogenital invasion risk. Further research is needed to correlate penetration with disease severity in a larger patient group.

Vértigo posicional paroxístico benigno primario y secundario a neuritis vestibular. Estudio de casos y controles / Primary and Secondary Benign Paroxysmal Positional Vertigo due to Peripheral Acute Vestibular Syndrome: A Case-Control Study

Introducción y objetivo: El objetivo de nuestro estudio fue demostrar las diferencias clínicas entre el vértigo posicional paroxístico benigno (VPPB) idiopático y secundario a síndrome vestibular agudo periférico (SVA). Método: Estudio de casos y controles, retrospectivo. La recolección de datos fue tomada de historias clínicas de nuestro hospital. Datos demográficos y clínicos de pacientes con diagnóstico de VPPB idiopático y secundario a SVA, fueron recogidos para el análisis. Además, en el grupo de los casos, se realizó una correlación entre el déficit vestibular periférico, medido a través del video head impulse test (vHIT), y el número de maniobras y tiempo hasta la resolución del VPPB. Resultados: Se incluyeron 72 pacientes, 64% mujeres. En el grupo control se incluyeron 50 pacientes con VPPB idiopático y 22 con VPPB secundario a SVA en el grupo de los casos. En el VPPB secundario, el canal semicircular posterior estuvo afectado en el 100% (OR: 1.2; IC 95% [1,088 - 1,436]). Ambos grupos mostraron una resolución del vértigo del 90% y 89%, respectivamente. El grupo de VPPB secundario tuvo 4 veces más riesgo de recurrencia (OR: 4.18; IC 95% [1.410 - 12.406]); necesitaron más maniobras (3.32 ± 2.2 vs. 1.7 ± 1.3, p = 0.004) y tiempo (61.9 días ± 73.1 vs. 12.9 días ± 9.6, p = 0.007) para la resolución del VPPB. Se encontraron correlaciones significativas entre la diferencia de ganancia media del reflejo vestíbulo-ocular (RVO) y el número de maniobras (r = 0.462, p = 0.030) y el tiempo hasta la resolución (r = 0.577, p = 0.008). Discusión: Existen diferencias clínicas entre el VPPB idiopático y secundario a SVA, principalmente en términos de canal semicircular afecto, mayor número de maniobras y tiempo en días hasta la resolución del VPPB. Además, de determinar que a mayor déficit vestibular en un paciente con VPPB secundario a SVA, necesitará un mayor número de maniobras y un tiempo prolongado hasta la resolución del VPPB. Conclusiones: ... (AU)

Introduction and Objective: The aim of our study was to demonstrate the clinical differences between idiopathic benign paroxysmal positional vertigo (BPPV) and BPPV secondary to acute peripheral vestibular syndrome (APVS). Method: Retrospective case-control study. Data collection was obtained from medical records at our hospital. Demographic and clinical data of patients diagnosed with idiopathic BPPV and BPPV secondary to APVS were collected for analysis. Additionally, in the case group, a correlation was performed between peripheral vestibular deficit, measured through the video head impulse test (vHIT), and the number of maneuvers and time until resolution of BPPV. Results: Seventy-two patients were included, with 64% being women. The control group included 50 patients with idiopathic BPPV and 22 with BPPV secondary to APVS in the case group. In secondary BPPV, the posterior semicircular canal was affected in 100% of cases (OR: 1.2; 95% CI [1.088 - 1.436]). Both groups showed a vertigo resolution rate of 90% and 89%, respectively. The secondary BPPV group had a 4-fold higher recurrence risk (OR: 4.18; 95% CI [1.410 - 12.406]); they required more maneuvers (3.32 ± 2.2 vs. 1.7 ± 1.3, p = 0.004) and more time (61.9 days ± 73.1 vs. 12.9 days ± 9.6, p = 0.007) for BPPV resolution. Significant correlations were found between the difference in mean gain of the vestibulo-ocular reflex (VOR) and the number of maneuvers (r = 0.462, p = 0.030) and the time until resolution (r = 0.577, p = 0.008). Discussion: Clinical differences exist between idiopathic BPPV and BPPV secondary to APVS, primarily in terms of the affected semicircular canal, a higher number of maneuvers, and a longer time in days until BPPV resolution. Furthermore, it was determined that a greater vestibular deficit in a patient with secondary BPPV to APVS requires a higher number of maneuvers and an extended time until BPPV resolution. Conclusions: ... (AU)

Isotemporal Substitution of Sedentary Time With Physical Activity Among Middle-Aged and Older Latinos: Effects on Episodic Memory.

PURPOSE: To examine the estimated effects of substituting 30 min of sedentary time with low-light physical activity (LLPA) and high-light physical activity (HLPA) on episodic memory, executive functioning, and working memory among middle-aged and older Latinos. DESIGN: A cross-sectional study. SETTING: Chicago and Chicagoland suburbs. SUBJECTS: Middle-aged and older Latinos (n = 61). MEASURES: Accelerometer-assessed physical activity. A cognitive battery was administered to assess episodic memory, executive function, and working memory. ANALYSIS: Isotemporal substitution analyses were conducted, where unstandardized coefficients from linear regression models were used to examine the substitution effect of replacing sedentary time with LLPA and HLPA. RESULTS: Substitution of sedentary time with LLPA was associated with better episodic memory (Immediate recall, B = .947, P = .008; Delayed recall, B = .857, P = .013). No other significant substitution effects were present. CONCLUSION: Middle-aged and older Latinos who replace sedentary time with LLPA may have better episodic memory. Future studies may target light physical activity to address cognition disparities and can inform the development of physical activity interventions that are appealing and accessible for Latinos.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

Cold platelet transfusion: The effects of a fluid warmer on platelet function.

BACKGROUND: Recently the US Food and Drug Administration has granted variances to select blood centers to supply cold-stored platelet components (CSP). In hemorrhage resuscitation warming of blood components with approved fluid warming devices is common. STUDY DESIGN AND METHODS: Pathogen-reduced apheresis platelet units were collected and stored in one of two ways: (1) CSP-I, (2) CSP-D. CSP-I were collected and immediately stored at 1-6°C until used. CSP-D were collected and stored at 20-24°C for 5 days and transferred to storage at 1-6°C until use. Aggregometry using arachidonic acid (AA), adenosine diphosphate (ADP) and collagen as agonists was performed on the unit samples before and after the units were infused through a Ranger blood-warming device. RESULTS: CSP-I, 23 units, had very high aggregation responses to all agonists (all ≥47.6 ± 20.7). There was a statistically significant reduction in ADP-induced aggregometry results from 55.1 ± 23.2 before compared to 33.5 ± 14.6 following infusion of the PLT through the blood warmer (p < .001). There were no differences in AA and collagen aggregometry results before and after the infusion of the platelets through the blood warmer. CSP-D had 5 of the 15 units with visible clotting in the bag. The 10 CSP-Ds studied had lower aggregation than all agonists before and after infusion through the blood-warming device (all ≤49.9 ± 35.9). CONCLUSION: We detected a statistically significant reduction in ADP-induced aggregometry in CSP-I run through a Ranger blood-warming device with no change with AA or collagen agonist aggregometry.

Influence of Age and Cardiovascular Risk Factors in Vestibular Neuritis: Retrospective Cohort Study.

To analyze the influence of age and cardiovascular risk factors (CVRFs) in the evolution of vestibular neuritis (VN). METHODS: Retrospective cohort study. VN-diagnosed patients were included and divided into two groups: those with and without CVRFs. We analyzed the mean vestibular-ocular reflex (VOR) gain, measured through the video head impulse test (vHIT) at the diagnosis and one-year follow-up. We conducted a factorial analysis of variance (ANOVA) to evaluate the effect of age, sex, and CVRFs in the mean VOR gain. RESULTS: Sixty-three VN-diagnosed patients were included. There were no statistically significant differences in the mean VOR gain between both groups. However, in the subgroup analysis, there were statistically significant differences when comparing the mean VOR gain at the one-year follow-up between the group over 55 years of age 0.77 ± 0.20 and the group under 55 years 0.87 ± 0.15 (p = 0.036). Additionally, the factorial ANOVA demonstrated a significant main effect of age group on the mean VOR gain at the one-year follow-up (p = 0.018), and it also found a significant interaction between the factors of gender, age group, HTN (p = 0.043). CONCLUSIONS: CVRFs do not independently affect the mean VOR gain in VN patients' follow-ups. However, age significantly impacts VOR gain in VN and could be modulated by gender and hypertension.

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP).

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

Neuroelectric indices of attention are related to academic skills in preschool-aged children.

PURPOSE: This study assessed the relationship between neuroelectric indices of attention and inhibition and academic skills in children 4-6 years-old. We hypothesized that modulation of the P3 and N2 components would be related to academic skills. METHODS: Participants (N = 27, 16 female) completed The Woodcock Johnson Early Cognitive and Academic Development Test to assess general intellectual abilities (GIA) and early academic skills (EAS). Electroencephalography was recorded during an auditory oddball task to elicit P3 and N2 components. Two-step linear regressions including age, sex, income, and GIA assessed relationships between P3 and N2 modulations and EAS. RESULTS: P3 peak amplitude (R2=0.765, ß=0.379, p = 0.030) and N2 mean (R2=0.759, ß=0.302, p = 0.039) and peak (R2=0.759, ß=0.303, p = 0.038) amplitude modulation were positively related to EAS. CONCLUSION: Upregulation of P3 and N2 components was associated with EAS independent of GIA. Therefore, neuroelectric assessments of attention and inhibition may a biomarker of academic achievement in early childhood.

Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis.

Recognition of pathogen-associated molecular patterns can trigger the inositol-requiring enzyme 1 α (IRE1α) arm of the endoplasmic reticulum (ER) stress response in innate immune cells. This process maintains ER homeostasis and also coordinates diverse immunomodulatory programs during bacterial and viral infections. However, the role of innate IRE1α signaling in response to fungal pathogens remains elusive. Here, we report that systemic infection with the human opportunistic fungal pathogen Candida albicans induced proinflammatory IRE1α hyperactivation in myeloid cells that led to fatal kidney immunopathology. Mechanistically, simultaneous activation of the TLR/IL-1R adaptor protein MyD88 and the C-type lectin receptor dectin-1 by C. albicans induced NADPH oxidase-driven generation of ROS, which caused ER stress and IRE1α-dependent overexpression of key inflammatory mediators such as IL-1ß, IL-6, chemokine (C-C motif) ligand 5 (CCL5), prostaglandin E2 (PGE2), and TNF-α. Selective ablation of IRE1α in leukocytes, or treatment with an IRE1α pharmacological inhibitor, mitigated kidney inflammation and prolonged the survival of mice with systemic C. albicans infection. Therefore, controlling IRE1α hyperactivation may be useful for impeding the immunopathogenic progression of disseminated candidiasis.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

Association of Blood Pressure Variability with Delirium in Patients with Critical Illness.

BACKGROUND: The objective was to examine the association of blood pressure variability (BPV) during the first 24 h after intensive care unit admission with the likelihood of delirium and depressed alertness without delirium ("depressed alertness"). METHODS: This retrospective, observational, cohort study included all consecutive adult patients admitted to an intensive care unit at Mayo Clinic, Rochester, Minnesota, from July 1, 2004, through October 31, 2015. The primary outcomes were delirium and delirium-free days, and the secondary outcomes included depressed alertness and depressed alertness-free days. Logistic regression was performed to determine the association of BPV with delirium and depressed alertness. Proportional odds regression was used to assess the association of BPV with delirium-free days and depressed alertness-free days. RESULTS: Among 66,549 intensive care unit admissions, delirium was documented in 20.2% and depressed alertness was documented in 24.4%. Preserved cognition was documented in 55.4% of intensive care unit admissions. Increased systolic and diastolic BPV was associated with an increased odds of delirium and depressed alertness. The magnitude of the association per 5-mm Hg increase in systolic average real variability (the average of absolute value of changes between consecutive systolic blood pressure readings) was greater for delirium (odds ratio 1.34; 95% confidence interval 1.29-1.40; P < 0.001) than for depressed alertness (odds ratio 1.06; 95% confidence interval 1.02-1.10; P = 0.004). Increased systolic and diastolic BPV was associated with fewer delirium-free days but not with depressed alertness-free days. CONCLUSIONS: BPV in the first 24 h after intensive care unit admission is associated with an increased likelihood of delirium and fewer delirium-free days.

A mixed methods study of perceptions of bias among neonatal intensive care unit staff.

BACKGROUND: Inequity in neonatology may be potentiated within neonatal intensive care units (NICUs) by the effects of bias. Addressing bias can lead to improved, more equitable care. Understanding perceptions of bias can inform targeted interventions to reduce the impact of bias. We conducted a mixed methods study to characterize the perceptions of bias among NICU staff. METHODS: Surveys were distributed to all staff (N = 245) in a single academic Level IV NICU. Respondents rated the impact of bias on their own and others' behaviors on 5-point Likert scales and answered one open-ended question. Kruskal-Wallis test (KWT) and Levene's test were used for quantitative analysis and thematic analysis was used for qualitative analysis. RESULTS: We received 178 responses. More respondents agreed that bias had a greater impact on others' vs. their own behaviors (KWT p < 0.05). Respondents agreed that behaviors were influenced more by implicit than explicit biases (KWT p < 0.05). Qualitative analysis resulted in nine unique themes. CONCLUSIONS: Staff perceive a high impact of bias across different domains with increased perceived impact of implicit vs. explicit bias. Staff perceive a greater impact of others' biases vs. their own. Mixed methods studies can help identify unique, unit-responsive approaches to reduce bias. IMPACT: Healthcare staff have awareness of bias and its impact on their behaviors with patients, families, and staff. Healthcare staff believe that implicit bias impacts their behaviors more than explicit bias, and that they have less bias than others. Healthcare staff have ideas for strategies and approaches to mitigate the impact of bias. Mixed method studies are effective ways of understanding environment-specific perceptions of bias, and contextual assets and barriers when creating interventions to reduce bias and improve equity. Generating interventions to reduce the impact of bias in healthcare requires a context-specific understanding of perceptions of bias among staff.

Association of Indication for Hospitalization With Subsequent Amyloid Positron Emission Tomography and Magnetic Resonance Imaging Biomarkers.

BACKGROUND: Hospitalization in older age is associated with accelerated cognitive decline, typically preceded by neuropathologic changes. We assess the association between indication for hospitalization and brain neurodegeneration. METHODS: Included were participants from the Mayo Clinic Study of Aging, a population-based longitudinal study, with ≥1 brain imaging available in those older than 60 years of age between 2004 and 2017. Primary analyses used linear mixed-effects models to assess association of hospitalization with changes in longitudinal trajectory of cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH). Additional analyses were performed with imaging outcomes dichotomized (normal vs abnormal) using Cox proportional hazards regression. RESULTS: Of 2 480 participants, 1 966 had no hospitalization and 514 had ≥1 admission. Hospitalization was associated with accelerated cortical thinning (annual slope change -0.003 mm [95% confidence interval (CI) -0.005 to -0.001], p = .002), but not amyloid accumulation (0.003 [95% CI -0.001 to 0.006], p = .107), or WMH increase (0.011 cm3 [95% CI -0.001 to 0.023], p = .062). Interaction analyses assessing whether trajectory changes are dependent on admission type (medical vs surgical) found interactions for all outcomes. While surgical hospitalizations were not, medical hospitalizations were associated with accelerated cortical thinning (-0.004 mm [95% CI -0.008 to -0.001, p = .014); amyloid accumulation (0.010, [95% CI 0.002 to 0.017, p = .011), and WMH increase (0.035 cm3 [95% CI 0.012 to 0.058, p = .006). Hospitalization was not associated with developing abnormal cortical thinning (p = .407), amyloid accumulation (p = .596), or WMH/infarctions score (p = .565). CONCLUSIONS: Medical hospitalizations were associated with accelerated cortical thinning, amyloid accumulation, and WMH increases. These changes were modest and did not translate to increased risk for crossing the abnormality threshold.