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Background: In an American society where a majority of students are from minoritized backgrounds, a better understanding of the relationship between psychosocial factors and school climate across racial groups is needed to assist schools in providing a supportive and positive learning environment for all students. Objective: The relationship between school climate and five psychosocial factors--motivation, academic self-concept, goal valuation, attitude towards teachers, and attitude towards school--is explored and a better understanding of how these psychosocial factors predict one's experience of their school's climate, both in general and across racial groups is further investigated. Method: Data was collected through a school-administered survey focused on improving school climate. A diverse sample of 2524 high school students completed the survey, which was administered by school teachers during a school-wide free period with students. Results: All five psychosocial factors predict students' having a positive perception of their school's climate, with medium to large effect sizes. Further, results from a series of stepwise multiple regressions indicate that (a) student attitudes toward their teachers were the most significant predictor of their perceptions about their school's climate, and (b) the combination of psychosocial factors that best predict student perceptions of their school climate varied across racial groups. Conclusion: The findings highlight an important first step in exploring how psychosocial perceptions can be leveraged to improve students' perceptions of their school climate, in addition to considering the importance of teachers and racial considerations within school climate.

Abstract The only cure of HIV has been achieved in a small number of people who received a hematopoietic stem cell transplant (HSCT) comprising allogeneic cells carrying a rare, naturally occurring, homozygous deletion in the CCR5 gene. The rarity of the mutation and the significant morbidity and mortality of such allogeneic transplants precludes widespread adoption of this HIV cure. Here, we show the application of CRISPR/Cas9 to achieve >90% CCR5 editing in human, mobilized hematopoietic stem progenitor cells (HSPC), resulting in a transplant that undergoes normal hematopoiesis, produces CCR5 null T cells, and renders xenograft mice refractory to HIV infection. Titration studies transplanting decreasing frequencies of CCR5 edited HSPCs demonstrate that

The outgrowth and stabilization of nascent dendritic spines are crucial processes underlying learning and memory. Most new spines retract shortly after growth; only a small subset is stabilized and integrated into the new circuit connections that support learning. New spine stabilization has been shown to rely upon activity-dependent molecular mechanisms that also contribute to long-term potentiation (LTP) of synaptic strength. Indeed, disruption of the activity-dependent targeting of the kinase CaMKIIα to the GluN2B subunit of the NMDA-type glutamate receptor disrupts both LTP and activity-dependent stabilization of new spines. Yet it is not known which of CaMKIIα's many enzymatic and structural functions are important for new spine stabilization. Here, we used two-photon imaging and photolysis of caged glutamate to monitor the activity-dependent stabilization of new dendritic spines on hippocampal CA1 neurons from mice of both sexes in conditions where CaMKIIα functional and structural interactions were altered. Surprisingly, we found that inhibiting CaMKIIα kinase activity either genetically or pharmacologically did not impair activity-dependent new spine stabilization. In contrast, shRNA knockdown of CaMKIIα abolished activity-dependent new spine stabilization, which was rescued by co-expressing shRNA-resistant full-length CaMKIIα, but not by a truncated monomeric CaMKIIα. Notably, overexpression of phospho-mimetic CaMKIIα-T286D, which exhibits activity-independent targeting to GluN2B, enhanced basal new spine survivorship in the absence of additional glutamatergic stimulation, even when kinase activity was disrupted. Together, our results support a model in which nascent dendritic spine stabilization requires structural and scaffolding interactions mediated by dodecameric CaMKIIα that are independent of its enzymatic activities.

Conventional letter- or number-based grading systems, though ubiquitous at all levels of education, do not optimize the learning experience. The philosophy of "ungrading" includes a variety of approaches that decenter or even remove numeric or letter scoring of student work in favor of descriptive feedback, opportunities for revision, self-assessment and reflection, and assessment toward mastery. This paper presents one of the few published descriptions of the use of ungrading approaches in geoscience courses at the undergraduate and graduate level. We showcase four approaches, detailing the courses and ungrading structures used, positive outcomes and challenges, and tools that might allow others to apply these methods. We describe (a) mastery and specifications grading, chosen to promote mastery of course materials in mid- and upper-level courses for college majors; (b) labor-based grading used to promote depth of student learning by focusing on revision; (c) collaborative grading utilizing self-assessment and reflection chosen to promote meta-cognition and growth mindset; and, (d) partial ungrading as a means to begin the ungrading process. Importantly, our experiences have led us to recognize the equity that ungrading approaches create, enabling students from different backgrounds, including students of color and disabled students, to find stronger support and build greater competence and confidence in geoscience classes.

High teacher attrition rates suggest the need for new methods of STEM teacher education to prepare teachers for fulfilling professional and personal lives. This design research study explores an approach to teacher learning within a US university-based teacher education course which centres projective agency as a key aspect of teacher learning, specifically to imagine transformative educational futures. Using thematic narrative analysis, this study presents evidence suggesting teachers can articulate their educational values by creating aligned possible futures. Drawing upon their experiences, these teachers envision futures that sometimes reimagine the constraints of the current educational system. By fostering projective agency, these envisioned pathways facilitate expansive action beyond teachers' past experiences and present circumstances, fostering sustainable flourishing for both teachers and students.

Abstract Non‐pharmaceutical interventions are needed to target the growing intergenerational cycle of obesity. We aimed to determine whether in utero exposure to different exercise doses during pregnancy directly reduces infant cellular and whole‐body adiposity. Pregnant women completed ~24 weeks of supervised exercise training; for standardization of exercise analysis (frequency, intensity, time, and volume‐FIT‐V), metrics were assessed from 16 to 36 weeks. Mesenchymal stem cells (MSC) collected from the umbilical cord at delivery underwent 21 days of adipogenic differentiation, then Oil Red O staining for lipid content. Infant body composition was measured at 1 month of age. ANCOVA and Pearson correlations determined the influence of prenatal exercise on infant adiposity. Exercise decreased infant MSC lipid content (p = 0.01) and body fat percentage (p = 0.009) irrespective of dose. Total exercise volume throughout pregnancy was negatively correlated with infant body fat % (R2 = 0.31, p = 0.02) due to lower subscapular skinfolds (R2 = 0.30, p = 0.02), while weekly exercise duration influenced adipogenic MSC lipid accumulation (R2 = −0.23, p = 0.03) and BF% (R2 = −0.15, p = 0.01). In utero exposure to exercise reduced cellular and whole‐body infant adiposity in a dose‐dependent manner.

BackgroundThe aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk.MethodsThis was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively.ResultsData from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613.ConclusionsIn this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.

The integration of behavioral health services in primary care has become increasingly popular in pediatric settings in recent years. While there are various models of integrated behavioral health (IBH), the aim is constant: to increase access to behavioral and mental health care through collaboration between behavioral health providers and physicians. Prior to the pandemic, only 20%-50% of children and adolescents received mental health care from a professional. Since COVID-19, access to care has only worsened. Given this reality, the use of IBH has promising benefits, including: (1) positive outcomes for patients and providers; (2) improved screening, identification, and intervention; (3) improved mental health outcomes; and (4) reduction of provider burnout. Given these aims and outcomes, a major opportunity exists for school psychologists to bring unique, but highly transferable, knowledge and skills to an emerging field. In this article, the authors share the real-life experiences of a licensed school psychologist and advanced practicum student to highlight how the comprehensive training of school psychologists prepares us to perform well in an integrated setting. The authors also call attention to the numerous possibilities available for those looking for an alternative setting or expansion of their current practice.

Collaborative problem-solving research approaches have the potential to support improvement in educational policy and practice beyond instruction, by facilitating the development of a shared understanding of complex problems and creating social structures where district, community, and research partners can work together to solve them. This study investigates how findings from a developmental evaluation of a district attendance initiative were incorporated into the initiation process of a networked improvement community to create a shared narrative about how members conceptualized the problem of absenteeism and how they should adapt their levers to better align to that problem. The developmental learning process created an infrastructure within which district leaders and community partners could develop a partnership culture that facilitated change in policy. This study suggests the need to revisit the assumptions that have driven non-instructional improvement efforts and highlights the potential of collaborative problem-solving to strengthen the implementation of district reforms.

Background Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta‐analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90‐day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. Methods and Results Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90‐day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random‐effects meta‐analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90‐day stroke recurrence was 8.6% (95% CI, 6.5–10.7), reducing by 0.60% (95% CI, 0.09–1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5–8.0) when compared with non‐dual antiplatelet trial arms (7.2%, 95% CI, 4.7–9.6) and observational studies 10.6% (95% CI, 7.0–14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference – score ≤3: 8.6% (95% CI, 6.0–11.1), score ≤4: 8.4% (95% CI, 6.1–10.6), as did excluding studies with n

Abstract Maternal exercise (ME) has been established as a useful non‐pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. We found that infants from exercising mothers have improvements in MSC insulin signaling related to higher MSC respiration and fat oxidation, and expression and activation of energy‐sensing and redox‐sensitive proteins. Further, we found that infants exposed to exercise in utero were leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. These data suggest that infants from exercising mothers are relatively leaner, and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.

Delivery to the correct membrane domain in polarized epithelial cells is a critical regulatory mechanism for transmembrane proteins. The trafficking of these proteins is directed by short amino acid sequences known as sorting motifs. In six basolaterally-localized proteins lacking the canonical tyrosine- and dileucine-based basolateral sorting motifs, a monoleucine-based sorting motif has been identified. This review will discuss these proteins with an identified monoleucine-based sorting motif, their conserved structural features, as well as the future directions of study for this non-canonical basolateral sorting motif.

Background Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence. Methods and Results We conducted a nested case–control study using a hospital‐based cohort from the Third China National Stroke Registry selecting 214 age‐ and sex‐matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data‐independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large‐artery atherosclerosis (Causative Classification of Ischemic Stroke [CCS]1), 16 in small‐artery occlusion (CCS3), and 25 in undetermined causes (CCS5) among patients with recurrent stroke. In the CCS1 and CCS3 subgroups, differentially expressed proteins were associated with platelet aggregation, neuronal death/cerebroprotection, and immune response, whereas differentially expressed proteins in the CCS5 subgroup were linked to altered metabolic functions. Validated recurrence predictors included proteins associated with neutrophil activity and vascular inflammation (TAGLN2 [transgelin 2], ITGAM [integrin subunit α M]/TAGLN2 ratio, ITGAM/MYL9 [myosin light chain 9] ratio, TAGLN2/RSU1 [Ras suppressor protein 1] ratio) in the CCS3 subgroup and proteins associated with endothelial plasticity and blood–brain barrier integrity (ITGAM/MYL9 ratio and COL1A2 [collagen type I α 2 chain]/MYL9 ratio) in the CCS3 and CCS5 subgroups, respectively. Conclusions These findings provide a foundation for developing a blood‐based biomarker panel, using causative classifications, which may be used in routine clinical practice to predict stroke recurrence.

Background and purposeRandomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis.MethodsThis is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis.ResultsAmong 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68-3.57], P

Background Atrial fibrillation/flutter (AF) after transient ischemic attack (TIA) has not been well studied. We compared the likelihood of new AF diagnosis after ischemic stroke versus TIA. Methods and Results The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled adults within 12 hours of minor ischemic stroke or high-risk TIA. Our exposure was index event type (ischemic stroke versus TIA). The primary analysis used the original trial definition of TIA (resolution of symptoms/signs). In secondary analyses, TIA cases with infarction on neuroimaging were reclassified as strokes. Our primary outcome was a new AF diagnosis, ascertained from adverse event and treatment interruption/discontinuation reports. We calculated C-statistics for variables associated with newly diagnosed AF. We used Kaplan-Meier survival statistics and Cox models adjusted for demographics and vascular risk factors. Excluding 49 subjects with baseline AF, 2746 patients had index stroke and 2086 patients had index TIA. During the 90-day follow-up, 106 patients had newly diagnosed AF. Cumulative risks of AF were 2.7% (95% CI, 2.1%-3.4%) after stroke and 2.0% (95% CI, 1.5%-2.7%) after TIA (P=0.15). After reclassifying index events by neuroimaging, cumulative AF risk was higher after stroke (2.7%; 95% CI, 2.2%-3.4%) than TIA (1.8%; 95% CI, 1.3%-2.5%) (P=0.04). Index event type had negligible predictive utility (C-statistic, 0.54). Conclusions Among patients with cerebral ischemia, the distinction between TIA versus minor stroke did not stratify the risk of subsequent AF diagnosis, implying that patients with TIA should undergo similar heart-rhythm monitoring strategies as patients with ischemic stroke.