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BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

BACKGROUND: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). OBJECTIVES: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. ANIMALS: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S. METHODS: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. RESULTS: Pre-supplementation blood vitamin E concentration was ≤2.0 μg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 μg/mL (range, 1.23-13.87 μg/mL), but only 12/23 (52%) were normal (≥3.0 μg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.

Abstract Background With access to and uptake of pre-exposure prophylaxis (PrEP), the United States can prevent new HIV infections. To end the HIV epidemic, health insurance plans must facilitate access to comprehensive preventive care benefits. Since plan benefit designs vary considerably by plan, it is difficult to systematically determine plans that facilitate and restrict preventive services for PrEP. Methods We applied an unsupervised machine learning method to cluster 17,061 Qualified Health Plans offered to individuals. We examined the clusters to draw conclusions about the types of benefits insurance companies tend to group together in plans. Then we analyzed the geographic distribution of those clusters across the United States to assess geographic inequities in access to HIV preventive care. Results Our method uncovered three cohesive clusters of plans. Plans in Cluster 1: the least restrictive cluster, facilitate access to preventive care using copays over coinsurance on almost all benefits; Cluster 2: the moderately restrictive cluster, plans cover HIV prevention benefits with copays but restrict access to general health benefits with coinsurance; and Cluster 3: the most restrictive cluster, plans cover almost all benefits using coinsurance. Overall, increased prior authorization requirements tend to accompany reductions in out-of-pocket costs. Examining the geographic plan distribution, states with at least one rating area where at least 75% of plans offered are in the most restrictive cluster included: Georgia, Illinois, Missouri, Oklahoma, Texas, Virginia, and Wyoming. Conclusions Insurance plan design is complex. To address the ambitious call to end the HIV epidemic in this country, plans should also take into account both public health and health equity factors to create plan designs that ensure access to critical preventive services for people who need them most. Addressing the growing disparities in PrEP access along racial and ethnic lines should be a national priority, and federal and state insurance regulators as well as insurance plans themselves should be part of the conversation about how to ensure people who would benefit from PrEP can access it. Better state/federal regulation of plan design to ensure access is consistent, equitable, and based on clinical recommendations will reduce the variability across plan designs.

Abstract The goal of designing safer, more effective drugs has led to tremendous interest in molecular mechanisms through which ligands can precisely manipulate the signaling of G-protein-coupled receptors (GPCRs), the largest class of drug targets. Decades of research have led to the widely accepted view that all agonists—ligands that trigger GPCR activation—function by causing rearrangement of the GPCR’s transmembrane helices, opening an intracellular pocket for binding of transducer proteins. Here we demonstrate that certain agonists instead trigger activation of free fatty acid receptor 1 by directly rearranging an intracellular loop that interacts with transducers. We validate the predictions of our atomic-level simulations by targeted mutagenesis; specific mutations that disrupt interactions with the intracellular loop convert these agonists into inverse agonists. Further analysis suggests that allosteric ligands could regulate the signaling of many other GPCRs via a similar mechanism, offering rich possibilities for precise control of pharmaceutically important targets.

The discovery that contracting skeletal muscle generates reactive oxygen species (ROS) was first reported over 40 years ago. The prevailing view in the 1980s was that exercise-induced ROS production promotes oxidation of proteins and lipids resulting in muscle damage. However, a paradigm shift occurred in the 1990s as growing research revealed that ROS are signaling molecules, capable of activating transcriptional activators/coactivators and promoting exercise-induced muscle adaptation. Growing evidence supports the notion that reduction-oxidation (redox) signaling pathways play an important role in the muscle remodeling that occurs in response to endurance exercise training. This review examines the specific role that redox signaling plays in this endurance exercise-induced skeletal muscle adaptation. We begin with a discussion of the primary sites of ROS production in contracting muscle fibers followed by a summary of the antioxidant enzymes involved in the regulation of ROS levels in the cell. We then discuss which redox-sensitive signaling pathways promote endurance exercise-induced muscle adaptation and debate the strength of the evidence supporting the notion that redox signaling plays an essential role in muscle adaptation to endurance exercise training. In hopes of stimulating future research, we highlight several important unanswered questions in this field.

Iminoiodinanes comprise a class of hypervalent iodine reagents that is often encountered in nitrogen-group transfer (NGT) catalysis. In general, transition metal catalysts are required to effect efficient NGT to unactivated olefins because iminoiodinanes are insufficiently electrophilic to engage in direct aziridination chemistry. Here, we demonstrate that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) activates N-arylsulfonamide-derived iminoiodinanes for the metal-free aziridination of unactivated olefins. 1H NMR and cyclic voltammetry (CV) studies indicate that hydrogen-bonding between HFIP and the iminoiodinane generates an oxidant capable of direct NGT to unactivated olefins. Stereochemical scrambling during aziridination of 1,2-disubstituted olefins is observed and interpreted as evidence that aziridination proceeds via a carbocation intermediate that subsequently cyclizes. These results demonstrate a simple method for activating iminoiodinane reagents, provide analysis of the extent of activation achieved by H-bonding, and indicate the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis.

Abstract Background Learning assistants (LAs) in undergraduate STEM lectures facilitate discussions between students in small groups. In this research study, we investigate the impact of LA facilitation on student learning as it occurs during LA–student interactions. To do so, our work builds on two sociocultural frameworks focused on LA facilitation and student in-the-moment learning. We conceptualize LA facilitation as either authoritative if it centers one perspective or dialogic if it centers multiple perspectives. Student in-the-moment learning is understood as the progression of student needs and the filling of those needs with LA and student ideas. Results Our analysis of 78 video recordings of LA–student interactions from 37 different chemistry and physics LAs revealed that LA facilitation had four major impacts on student in-the-moment learning: increasing grappling, reaching closure, sharing ideas and reasoning, and revisiting an earlier need. Rather than these impacts differing upon the use of authoritative and dialogic facilitation, all four impacts sometimes resulted from authoritative and sometimes from dialogic facilitation. However, authoritative facilitation was more often correlated with LA-centered manifestation of these impacts, while dialogic facilitation was more often correlated with student-centered manifestation. In addition to these conceptual impacts, we also found five socioemotional impacts: less participation, dominance continues, fostering participation, students choose not to participate, and lighthearted conversation. LAs added socioemotional components to both authoritative and dialogic facilitation, and actions aimed at bringing more students into the conversation indeed had this impact, while actions addressing specific students often continued to privilege the participation of the same students. Conclusion Our study expands theory on authoritativeness and dialogicity as it empirically validates that authoritative facilitation is more often correlated with LA-centered learning and dialogic facilitation is more often correlated with student-centered learning. Further, our work is the first to explore the socioemotional impact of LAs in the moment of interaction. Our findings can be used in LA trainings to teach LAs how to intentionally use authoritative and dialogic facilitation, how to incorporate socioemotional components to their facilitation, and how to adjust their practice to align with learning goals for students in their context.

Interactive teaching strategies provide opportunities for engaging children in discussing difficult concepts such as socio-emotional wellbeing and wide range of ideas about their social and personal lives. However, few studies have explored preschool teachers' efficacy of using coaching through 'Play and puppetry programs as approaches to developing children's emotional regulation, socio-emotional learning and wellbeing. This paper reports on a "Labyrinth Project" aimed to gain in-depth understandings of preschool teachers' experiences and perspectives pertaining to their efficacy of using play and puppetry as tools to promote children's emotional learning and development. The results showed that despite early challenges with the use of these two teaching strategies, coaching and professional development facilitated a progression from feelings of inadequacy to confidence to teach social emotional skills using play and puppetry. At the end of the second year of this three-year project, children demonstrated improved cognitive skills in managing their emotions. Suggestions are made on how to improve the project to achieve high quality outcomes.

In this reflective piece, representatives of the agencies that funded and managed the Early Learning Systems Research program -- the UK Foreign, Commonwealth and Development Office (FCDO) and the World Bank -- take stock of recent global developments in research, policy, and financing by donors for early childhood education (ECE). A rapid increase in research on early childhood interventions has secured a consensus that in vesting in early matters for later outcomes in life. In recent years, development finance institutions have taken unprecedented steps to incorporate ECE into their policies and approaches, have helped build research capacity, and fostered communities of practice on ECE. Despite these developments, however, the share of official development assistance (ODA) for ECE remains extremely low. Limited prioritization of ECE by donors may be reinforced by a persistence of low demand for ECE financing from governments and differences in delivery mechanisms between ECE and other levels of education. The authors conclude with considerations for researchers, practitioners, and policymakers interested in increasing donor finance for ECE.

In response to the global pandemic, we adapted a Jamaican early childhood, violence prevention, parenting program (the Irie Homes Toolbox (IHT)) for virtual delivery. The resultant virtual IHT (vIHT) is a 10-week program that consists of weekly, one-hour, virtual group parenting sessions and e-summary sent via WhatsApp, three SMS messages/week, and access to a data-free app. The vIHT was implemented with 557 Jamaican caregivers of 2- to 6-year-olds with virtual groups conducted by government officers. We conducted an ongoing process evaluation to identify enablers and barriers to implementation. Key enablers included high compliance by government officers in conducting virtual sessions, sessions were implemented with adequate levels of quality, 90% participants read the SMS/WhatsApp messages, and 79% attended at least one virtual group with 52% attending five or more. Barriers included poor internet connectivity, difficulty navigating the online environment, low usage of the app, and inconsistent caregiver attendance at virtual sessions.

As part of a 5-year study to develop and validate an instrument for measuring success in long-standing community-based participatory research (CBPR) partnerships, we utilized the Delphi method with a panel of 16 community and academic CBPR experts to assess face and content validity of the instrument's broad concepts of success and measurement items. In addition to incorporating quantitative and qualitative feedback from two online surveys, we included a 2-day face-to-face meeting with the Expert Panel to invite open discussion and diversity of opinion in line with the CBPR principles framing and guiding the study. The face-to-face meeting allowed experts to review the survey data (with maintained anonymity), convey their perspectives, and offer interpretations that were untapped in the online surveys. Using a CBPR approach facilitated a synergistic process that moved above and beyond the consensus achieved in the initial Delphi rounds, to enhance the Delphi technique and the development of items in the instrument.

Student affairs work is built on relationships, but these deep connections should not be devleoped too quickly. Each person should be allowed to choose what they disclose. Student affairs has drifted into the expectation of full disclosure as more valuable than safety and privacy. Student affairs professionals must examine and disrupt forced vulnerability practices. This article encourages the reader to examine these practices in their own workplaces.

Six distinct COI mitochondrial Haplotype Groups (HG) are morphologically, ecologically, and genetically characterized from the aquatic nematode family Tobrilidae. Collection locations included the extreme habitats of the Alkaline Lakes in the western Nebraska Sandhills and the contaminated stream, Johnson Creek, bordering the AltEn 2021 catastrophic pesticide release near the village of Mead in eastern Nebraska. Maximum likelihood and genetic distance metrics supported the genetic integrity of the haplotype groups. Discriminant function analysis of COI haplotype group datasets of combined morphological characters and soil chemistry attributes for both male and female Tobrilidae were classified correctly in all but one case. Scanning electron microscopy revealed new details about amphid apertures, male supplements, and spicules. Partial 18S gene phylogeny suggests that the genus Semitobrilus may not be a member of the subfamily Neotobrilinae, and three specimens in the 226 tobrilid dataset provide evidence of incongruence between COI and 18S derived phylogenies. Given the strong signal provided by the environmental chemistry data, tobrilid mitochondrial haplotypes may well have value as environmental indicators.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values