Kv7 channel opener retigabine reduces self-administration of cocaine but not sucrose in rats.

The increasing rates of drug misuse highlight the urgency of identifying improved therapeutics for treatment. Most drug-seeking behaviours that can be modelled in rodents utilize the repeated intravenous self-administration (SA) of drugs. Recent studies examining the mesolimbic pathway suggest that Kv7/KCNQ channels may contribute to the transition from recreational to chronic drug use. However, to date, all such studies used noncontingent, experimenter-delivered drug model systems, and the extent to which this effect generalizes to rats trained to self-administer drugs is not known. Here, we tested the ability of retigabine (ezogabine), a Kv7 channel opener, to regulate instrumental behaviour in male Sprague Dawley rats. We first validated the ability of retigabine to target experimenter-delivered cocaine in a conditioned place preference (CPP) assay and found that retigabine reduced the acquisition of place preference. Next, we trained rats for cocaine-SA under a fixed-ratio or progressive-ratio reinforcement schedule and found that retigabine pretreatment attenuated the SA of low to moderate doses of cocaine. This was not observed in parallel experiments, with rats self-administering sucrose, a natural reward. Compared with sucrose-SA, cocaine-SA was associated with reductions in the expression of the Kv7.5 subunit in the nucleus accumbens, without alterations in Kv7.2 and Kv7.3. Therefore, these studies reveal a reward-specific reduction in SA behaviour and support the notion that Kv7 is a potential therapeutic target for human psychiatric diseases with dysfunctional reward circuitry.

Cannabis Smoking and Storage within the Home: A Cross-Sectional Survey of Pregnant Women and Women with Young Children.

INTRODUCTION: Child cannabis exposure has increased in recent years - a trend that parallels changes to state cannabis legality. Yet, little is known about household cannabis practices. To address this gap, this study aimed to examine household cannabis practices among a geographically diverse sample of US women of reproductive age. We also examined variations in household cannabis practices across state cannabis policies. METHODS: The study sample (N = 114) included pregnant women and women with young children in their home. In Spring of 2021, 114 women completed a single cross-sectional online survey that included demographic information and asked about cannabis use, household cannabis practices (e.g., indoor smoking, cannabis storage), and cannabis use risk perceptions. We analyzed data using descriptive statistics and Fisher's exact tests. RESULTS: A total of 69.23% of women reported cannabis products were allowed in their home and 42.98% reported that smoking cannabis was permitted in one or more rooms. Self-reported cannabis use, as well as partner or family cannabis use were significantly associated with allowing cannabis products in the home (p < 0.001). There was no difference in cannabis smoking rules among women in states with legalized cannabis (47.73%) than those in states that had yet to legalize (40.00%), p = 0.339. CONCLUSIONS: Amid rapidly shifting cannabis policies, further examination of household cannabis practices is needed. Public heath efforts should focus on reducing in-home cannabis exposure and promote safe storage and smoking practices for families with children in the home.

Evidence for root adaptation to a spatially discontinuous water availability in the absence of external water potential gradients.

We hereby show that root systems adapt to a spatially discontinuous pattern of water availability even when the gradients of water potential across them are vanishingly small. A paper microfluidic approach allowed us to expose the entire root system of Brassica rapa plants to a square array of water sources, separated by dry areas. Gradients in the concentration of water vapor across the root system were as small as 10-4⋅mM⋅m-1 (∼4 orders of magnitude smaller than in conventional hydrotropism assays). Despite such minuscule gradients (which greatly limit the possible influence of the well-understood gradient-driven hydrotropic response), our results show that 1) individual roots as well as the root system as a whole adapt to the pattern of water availability to maximize access to water, and that 2) this adaptation increases as water sources become more rare. These results suggest that either plant roots are more sensitive to water gradients than humanmade water sensors by 3-5 orders of magnitude, or they might have developed, like other organisms, mechanisms for water foraging that allow them to find water in the absence of an external gradient in water potential.

Reducing CVD health disparities in Black women through addressing social determinants of health (SDOH): a scoping review.

Cardiovascular disease (CVD) disparities among Black American women can be linked directly to social determinants of health (SDOH). This scoping review examines the breadth and depth of existing literature on CVD risk reduction interventions in young-to-middle-aged women that address SDOH. We searched PubMed, CINAHL, Scopus and Google Scholar for relevant peer-reviewed articles published in English. We included studies if they reported on the feasibility, acceptability, or findings of a CVD risk reduction intervention, addressed at least one SDOH domain, and included Black women 18-45 years of age. Of the 2,533 studies screened, 5 studies were eligible for inclusion. Specific SDOH domains addressed included: social and community context and health-care access and quality. All but one study reported culturally tailored intervention components. Feasibility and acceptability of culturally tailored interventions was high among included studies examining this outcome. Recommendations for future research focused on the need for additional interventions that were culturally tailored to young- and middle-aged Black women. Future research should work to address existing evidence gaps via development and implementation of culturally tailored, CVD risk reduction and disease prevention interventions for young-to-middle-aged Black women that focus addressing SDOH, as these types of interventions demonstrate promise for reducing CVD health disparities among Black women.

Negative disease-related stigma 3-months after hemorrhagic stroke is related to functional outcome and female sex.

OBJECTIVES: The objective of this study was to determine factors associated with negative disease-related stigma after hemorrhagic stroke. MATERIALS AND METHODS: Patients with non-traumatic hemorrhage (ICH or SAH) admitted between January 2015 and February 2021 were assessed by telephone 3-months after discharge using the Quality of Life in Neurological Disorders (Neuro-QoL) Negative Disease-Related Stigma Short Form inventory. We evaluated the relationship between disease-related stigma (T-score >50) and pre-stroke demographics, admission data, and poor functional outcome (3-month mRS score 3-5 and Barthel Index <100). RESULTS: We included 89 patients (56 ICH and 33 SAH). The median age was 63 (IQR 50-69), 43 % were female, and 67 % graduated college. Admission median GCS score was 15 (IQR 13-15) and APACHE II score was 12 (IQR 9-17). 31 % had disease-related stigma. On univariate analysis, disease-related stigma was associated with female sex, non-completion of college, GCS score, APACHE II score, and 3-month mRS score (all p < 0.05). On multivariate analysis, disease-related stigma was associated with female sex (OR = 3.72, 95 % CI = 1.23-11.25, p = 0.02) and 3-month Barthel Index <100 (OR = 3.46, 95 % CI = 1.13-10.64, p = 0.03) on one model, and female sex (OR = 3.75, 95 % CI = 1.21-11.58, p = 0.02) and 3-month mRS score 3-5 (OR = 4.23, 95 % CI = 1.21-14.75, p = 0.02) on a second model. CONCLUSION: Functional outcome and female sex are associated with disease-related stigma 3-months after hemorrhagic stroke. Because stigma may negatively affect recovery, there is a need to understand the relationship between these factors to mitigate stroke-related stigma.

The characteristics of users of an online screening tool for children and adolescents with intellectual disability and of those being screened.

Screening tools can help with the identification of intellectual disability, but little is known about who uses them. This study analysed anonymous information from 2691 users of an evidence-based, online, intellectual disability screening questionnaire for children and adolescents (CAIDS-Q) to explore the characteristics of the users and of those being screened. The users were split almost equally between parents/family members (48.6%) and professionals (49.9%), with the majority (63.8%) of the latter group being health staff. Significant differences in the characteristics of the children being screened were found, according to whether the user was a parent/family member or a professional, with the overall pattern suggesting that professionals screened children with greater complexity of needs, but about whom less was known. The screened children had a range of areas of difficulties that are common to those with intellectual disability. Implications for practice are discussed.

PHIP drives glioblastoma motility and invasion by regulating the focal adhesion complex.

The invasive behavior of glioblastoma is essential to its aggressive potential. Here, we show that pleckstrin homology domain interacting protein (PHIP), acting through effects on the force transduction layer of the focal adhesion complex, drives glioblastoma motility and invasion. Immunofluorescence analysis localized PHIP to the leading edge of glioblastoma cells, together with several focal adhesion proteins: vinculin (VCL), talin 1 (TLN1), integrin beta 1 (ITGB1), as well as phosphorylated forms of paxillin (pPXN) and focal adhesion kinase (pFAK). Confocal microscopy specifically localized PHIP to the force transduction layer, together with TLN1 and VCL. Immunoprecipitation revealed a physical interaction between PHIP and VCL. Targeted suppression of PHIP resulted in significant down-regulation of these focal adhesion proteins, along with zyxin (ZYX), and produced profoundly disorganized stress fibers. Live-cell imaging of glioblastoma cells overexpressing a ZYX-GFP construct demonstrated a role for PHIP in regulating focal adhesion dynamics. PHIP silencing significantly suppressed the migratory and invasive capacity of glioblastoma cells, partially restored following TLN1 or ZYX cDNA overexpression. PHIP knockdown produced substantial suppression of tumor growth upon intracranial implantation, as well as significantly reduced microvessel density and secreted VEGF levels. PHIP copy number was elevated in the classical glioblastoma subtype and correlated with elevated EGFR levels. These results demonstrate PHIP's role in regulating the actin cytoskeleton, focal adhesion dynamics, and tumor cell motility, and identify PHIP as a key driver of glioblastoma migration and invasion.

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage.

BACKGROUND: The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS: We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS: Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS: More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

An Improved Framework for Estimating Organic Carbon Content of Mangrove Soils Using loss-on-ignition and Coastal Environmental Setting.

The use of loss on ignition (LOI) measurements of soil organic matter (SOM) to estimate soil organic carbon (OC) content is a decades-old practice. While there are limitations and uncertainties to this approach, it continues to be necessary for many coastal wetlands researchers and conservation practitioners without access to an elemental analyzer. Multiple measurement, reporting, and verification (MRV) standards recognize the need (and uncertainty) for using this method. However, no framework exists to explain the substantial differences among equations that relate SOM to OC; consequently, equation selection can be a haphazard process leading to widely divergent and inaccurate estimates. To address this lack of clarity, we used a dataset of 1,246 soil samples from 17 mangrove regions in North, Central, and South America, and calculated SOM to OC conversion equations for six unique types of coastal environmental setting. A framework is provided for understanding differences and selecting an equation based on a study region's SOM content and whether mineral sediments are primarily terrigenous or carbonate in origin. This approach identifies the positive dependence of conversion equation slopes on regional mean SOM content and indicates a distinction between carbonate settings with mean (± 1 S.E.) OC:SOM of 0.47 (0.002) and terrigenous settings with mean OC:SOM of 0.32 (0.018). This framework, focusing on unique coastal environmental settings, is a reminder of the global variability in mangrove soil OC content and encourages continued investigation of broadscale factors that contribute to soil formation and change in blue carbon settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-023-01698-z.

Stroke epidemiology and outcomes in the modern era of left ventricular assist devices.

The care for the patients with end-stage heart failure has been revolutionized by the introduction of durable left ventricular assist devices, providing a substantial improvement in patient survival and quality of life and an alternative to heart transplantation. The newest devices have lower instances of mechanical dysfunction and associated pump thrombosis. Despite these improvements in complications, the use of continuous flow assist devices is still associated with high rates of thrombotic and hemorrhagic complications, most notably stroke in approximately 10% of continuous flow assist devices patients per year. With the newest HeartMate 3 devices, there have been lower observed rates of stroke, which has in part been achieved by both improvements in pump technology and knowledge of the risk factors for stroke and neurological complications. The therapeutic options available to clinicians to reduce the risk of stroke, including management of hypertension and antithrombotics, will be reviewed in this manuscript.

Antigen Receptor T Cells (CAR-T) Effectively Control Tumor Growth in a Colorectal Liver Metastasis Model.

BACKGROUND: Effective treatment of solid tumors requires multi-modality approaches. In many patients with stage IV liver disease, current treatments are not curative. Chimeric antigen receptor T cells (CAR-T) are an intriguing option following success in hematological malignancies, but this has not been translated to solid tumors. Limitations include sub-optimal delivery and elevated interstitial fluid pressures. We developed a murine model to test the impact of high-pressure regional delivery (HPRD) on trafficking to liver metastases (LM) and tumor response. MATERIALS AND METHODS: CAR-T were generated from CD45.1 mice and adoptively transferred into LM-bearing CD45.2 mice via regional or systemic delivery (RD, SD). Trafficking, tumor growth, and toxicity were evaluated with flow cytometry, tumor bioluminescence (TB, photons/sec log2-foldover baseline), and liver function tests (LFTs). RESULTS: RD of CAR-T was more effective at controlling tumor growth versus SD from post-treatment days (PTD) 2-7 (P = 0.002). HPRD resulted in increased CAR-T penetration versus low-pressure RD (LPRD, P = 0.004), suppression of tumor proliferation (P = 0.03), and trended toward improved long-term control at PTD17 (TB=3.7 versus 6.1, P = 0.47). No LFT increase was noted utilizing HPRD versus LPRD (AST/ALT P = 0.65/0.84) while improved LFTs in RD versus SD groups suggested better tumor control (HPRD AST/ALT P = 0.04/0.04, LPRD AST/ALT P = 0.02/0.02). CONCLUSIONS: Cellular immunotherapy is an emerging option for solid tumors. Our model suggests RD and HPRD improved CAR-T penetration into solid tumors with improved short-term tumor control. Barriers associated with SD can be overcome using RD techniques to maximize therapeutic delivery and HPRD may further augment efficacy without increased toxicity.

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke.

In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use and both radiographic and functional outcome is not well understood. We sought to explore the relationship between pre-admission antithrombotic use in patients who underwent thrombectomy for acute ischemic stroke at two medical centers in New York City between December 2018 and November 2020. Analyses were performed using analysis of variance and Pearson's chi-squared tests. Of 234 patients in the analysis cohort, 65 (28%) were on anticoagulation, 64 (27%) were on antiplatelet, and 105 (45%) with no antithrombotic use pre-admission. 3-month Modified Rankin Scale (mRS) score of 3-6 was associated with pre-admission antithrombotic use (71% anticoagulation vs. 77% antiplatelet vs. 56% no antithrombotic, p = 0.04). There was no relationship between pre-admission antithrombotic use and Thrombolysis in Cerebral Iinfarction (TICI) score, post-procedure Alberta Stroke Program Early CT Score (ASPECTS) score, rate of hemorrhagic conversion, length of hospital admission, discharge NIH Stroke Scale (NIHSS), discharge mRS score, or mortality. When initial NIHSS score, post-procedure ASPECTS score, and age at admission were included in multivariate analysis, pre-admission antithrombotic use was still significantly associated with a 3-month mRS score of 3-6 (OR 2.36, 95% CI 1.03-5.54, p = 0.04). In this cohort of patients with acute ischemic stroke who underwent thrombectomy, pre-admission antithrombotic use was associated with 3-month mRS score, but no other measures of radiographic or functional outcome. Further research is needed on the relationship between use of specific anticoagulation or antiplatelet agents and outcome after acute ischemic stroke, but moreover, improve stroke prevention.

Validity of self-report measures of cannabis use compared to biological samples among women of reproductive age: a scoping review.

BACKGROUND: Most existing evidence about the prevalence of prenatal cannabis use relies on self-reported measures, which is limited by social desirability bias and recall bias. To date, several studies have examined the validity of self-reported measures of prenatal cannabis use, but this evidence has yet to be synthesized. To address this gap, we performed a scoping review to systematically identify and synthesize existing evidence on the validity of self-reported measures of cannabis use among pregnant women. METHODS: We searched PubMed, PyschINFO, CINAHL, Cochrane/CENTRAL, and Google Scholar for peer-reviewed studies published in English between January 2010 and June 2021. We included studies that compared self-reported measures of cannabis use to a biochemical measure of cannabis (e.g., urine, hair, meconium) in pregnant women. We excluded studies reporting solely on prenatal cannabis use prevalence as well as those that examined self-reported drug use in which cannabis use was not a distinct category. RESULTS: We found 12 unique studies (11 primary studies and one systematic review) that examined the validity of self-reported prenatal cannabis use, compared to a biochemical sample. Most studies were conducted in the US and conducted in either a hospital or clinical setting. We found that self-report was more valid in populations with a current or prior history of drug use. Self-report was also more valid when assessed via interviews by research team members than health care provider screenings or self-administered surveys. The most commonly used biochemical measure used was urine drug testing, which was found to have the highest level of concordance with self-report. CONCLUSIONS: This scoping review systematically mapped existing evidence on the validity of self-reported prenatal cannabis use. Although much remains unknown in this area, an important next step is a systematic review that would provide robust evidence on clinical utilization of self-reported use in conjunction with biochemical samples. Further research is needed to examine validity by type of measure and mode of administration. Additionally, future studies could assess factors associated with disclosure of use across different critical maternal health periods beyond pregnancy.

Measuring cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age: a scoping review.

BACKGROUND: Cannabis use among women of reproductive age has increased substantially in recent decades. Understanding reasons for cannabis use in this population is critical for cannabis use prevention efforts. Thus, this scoping review aimed to identify and synthesize current measures on reasons for cannabis use in women of reproductive age. METHODS: We searched PubMed, PyschINFO, CINAHL, and Google Scholar for relevant studies published in English between January 2010 and April 2021. Peer-reviewed, quantitative studies reporting on measures of cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age were eligible for inclusion. We excluded studies not focused on women of reproductive age and studies reporting cannabis use prevalence data only. RESULTS: We included 11 studies (10 primary studies and 1 review) with varying subpopulation samples of women, including non-pregnant women (n = 2), women experiencing infertility (n = 1), pregnant women (n = 4), postpartum women (n = 3), and women in the perinatal period (n = 1). Measurement topic areas included information received from health care professionals, attitudes, perceptions and experiences about cannabis use, knowledge of potential harms, and motivations for cannabis use. Most studies including measures of risk perceptions were conducted among pregnant or postpartum women (n = 4). A single study measured influences of cannabis use; no studies measured social or peer influences of use. Most studies (n = 7) created their own measures, with 2 studies using secondary data via measures from population-based surveillance systems in the United States, and one using a previously validated instrument. Recommendations for future research were centered around addressing knowledge gaps of health effects of cannabis use across different time periods, and etiology of cannabis use. CONCLUSIONS: We found vast measurement gaps in current measures of antecedents of cannabis use among women of reproductive age, providing clear direction for future research in this area. Findings necessitate psychometric evaluation of existing measures to ascertain validity and reliability, as well as development of additional measures of women's cannabis-related attitudes, perceptions, motivations, and influences. This work is critical to guide not only epidemiologic studies, but cannabis-related prevention work as well.

Hydrogel-based transparent soils for root phenotyping in vivo.

Root phenotypes are increasingly explored as predictors of crop performance but are still challenging to characterize. Media that mimic field conditions (e.g., soil, sand) are opaque to most forms of radiation, while transparent media do not provide field-relevant growing conditions and phenotypes. We describe here a "transparent soil" formed by the spherification of hydrogels of biopolymers. It is specifically designed to support root growth in the presence of air, water, and nutrients, and allows the time-resolved phenotyping of roots in vivo by both photography and microscopy. The roots developed by soybean plants in this medium are significantly more similar to those developed in real soil than those developed in hydroponic conditions and do not show signs of hypoxia. Lastly, we show that the granular nature and tunable properties of these hydrogel beads can be leveraged to investigate the response of roots to gradients in water availability and soil stiffness.

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS: We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS: We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS: The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

Beyond Ethnicity: Applying Helms's White Racial Identity Development Model Among White Youth.

Research on racial identity among Youth of Color has expanded considerably in recent years, but a parallel examination of racial identity among white youth has not occurred, reiterating whiteness as normative. We applied Janet Helms's White Racial Identity Development (WRID) model among white U.S. youth (8-14 years old) to address this research gap. WRID centers racism and white supremacy, offering a framework to analyze white racial identity in the context of systemic inequity. Using longitudinal, qualitative analysis, we found age-related change over time, with some evidence of increasing resistance to racism. There was high participant variability, however, indicating that socio-cognitive abilities alone cannot predict anti-racist white identity development. We discuss implications for racial identity research and social justice-orientated developmental science.

Tachycardia is associated with mortality and functional outcome after thrombectomy for acute ischemic stroke.

BACKGROUND: The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS: We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS: Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS: Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.

The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague.

Yersinia pestis is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with Y. pestis is nearly 100% lethal within 4 to 7 days without antibiotic intervention. Pneumonic plague progresses in two phases, beginning with extensive bacterial replication in the lung with minimal host responsiveness, followed by the abrupt onset of a lethal proinflammatory response. The precise mechanisms by which Y. pestis is able to colonize the lung and survive two very distinct disease phases remain largely unknown. To date, a few bacterial virulence factors, including the Ysc type 3 secretion system, are known to contribute to the pathogenesis of primary pneumonic plague. The bacterial GTPase BipA has been shown to regulate expression of virulence factors in a number of Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhi. However, the role of BipA in Y. pestis has yet to be investigated. Here, we show that BipA is a Y. pestis virulence factor that promotes defense against early neutrophil-mediated bacterial killing in the lung. This work identifies a novel Y. pestis virulence factor and highlights the importance of early bacterial/neutrophil interactions in the lung during primary pneumonic plague.

Contemporary Clinical Isolates of Staphylococcus aureus from Pediatric Osteomyelitis Patients Display Unique Characteristics in a Mouse Model of Hematogenous Osteomyelitis.

Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.