"Ripping Off the Band-Aid": uncovering future health care Professionals' "Fractured Knowledge" about sexual and reproductive health.

Background: Research has shown the role of identity on future health professionals' confidence and competence in addressing the sexual and reproductive health (SRH) needs of their patients. While there has been some work in increasing the sexual health literacy of future providers via various curricular approaches and comprehensive clinical-based training, there are research gaps on how social differences around identity impact future healthcare professionals' knowledge and practices around SRH. Objectives: This article presents research findings on the experiences of US undergraduate students attending a campus that provides training in the health sciences and health professions. Our study aims to understand the perspectives of these students as they pertain to their future career choices in healthcare, with a focus on how their past experiences learning about sex, sexuality, and reproduction impact their current and future professional trajectories. Methods: We present a qualitative analysis from 40 in-depth interviews with U.S. undergraduates. The interview questions were designed in collaboration with undergraduate researchers interested in sexual health education. These student researchers collected all the interview data and worked with senior researchers to analyze some of these data. Results: The themes that emerged from the interviews were around experiences with what students perceived as "fractured" sexual and reproductive health (SRH) knowledge they received as children and adolescents. This knowledge shaped essential aspects of their identity as young adults and future healers. Data indicated unique processes implicated in how past as well as present socialization experiences learning about sex, sexuality, and reproduction positions undergraduates in health professions to see young adulthood as a journey of "catching up" on sexual knowledge but also as an ongoing experience of anticipation and planning influencing their career-building journey. Conclusions: The importance of sexual health literacy among healthcare professionals cannot be overstated, as it is vital in providing patient-centered and non-judgmental sexual and reproductive health (SRH) care and services. To date, there is a shortage of studies looking at the impact of sexual health knowledge on healthcare professionals. More research is needed on educational strategies that could be implemented at the intra-personal level to assist college-aged young adults in healthcare career tracks to "catch up" or "fill in the gaps" in their sexual education journey.

A precision functional atlas of personalized network topography and probabilities.

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely.

Multi-level fMRI analysis applied to hemispheric specialization in the language network, functional areas, and their behavioral correlations in the ABCD sample.

Prior research suggests that the organization of the language network in the brain is left-dominant and becomes more lateralized with age and increasing language skill. The age at which specific components of the language network become adult-like varies depending on the abilities they subserve. So far, a large, developmental study has not included a language task paradigm, so we introduce a method to study resting-state laterality in the Adolescent Brain Cognitive Development (ABCD) study. Our approach mixes source timeseries between left and right homotopes of the (1) inferior frontal and (2) middle temporal gyri and (3) a region we term "Wernicke's area" near the supramarginal gyrus. Our large subset sample size of ABCD (n = 6153) allows improved reliability and validity compared to previous, smaller studies of brain-behavior associations. We show that behavioral metrics from the NIH Youth Toolbox and other resources are differentially related to tasks with a larger linguistic component over ones with less (e.g., executive function-dominant tasks). These baseline characteristics of hemispheric specialization in youth are critical for future work determining the correspondence of lateralization with language onset in earlier stages of development.

Just in case: undergraduate students identifying and mitigating barriers to their sexual and reproductive health needs.

BACKGROUND: Many U.S. colleges and universities offer access to a healthcare center that provides sexual and reproductive health (SRH) resources, services, and products. The importance of health centers in college and university settings in reducing sexual health disparities in student populations cannot be stressed enough. This article evaluates a student-led, mutual-aid, grassroots health promotion strategy for students with limited access to healthcare services, supplies, and tools via an anonymous and discrete distribution of SRH resources without charge. METHODS: In partnership with faculty, undergraduate students worked to address their school's unmet SRH needs by increasing on-campus access to comprehensive, evidence-based, and sex-positive resources. Referred to as Just in Case, this student-led, grassroots health promotion program provided students with supply kits containing contraceptives, sexual health wellness products, basic hygiene supplies, and education materials. Students were surveyed in a pre- (n = 95) post- (n = 73) pilot study to identify contraception acquisition barriers, discern perceptions of on-campus SRH resources, and elucidate trends in this program's use and impact. Chi-square tests of independence were used to compare survey group responses, and association rule mining was employed in tandem to identify SRH items that students requested. RESULTS: Students identified cost and privacy as significant barriers to acquiring sexual health products on campus. Of the 182 Just in Case supply kits requested by students during the 2022-2023 academic year, condoms were requested most frequently in 75% of fulfilled kits, while emergency contraception and pregnancy tests were asked most often in 61% of kits. 50% of students reported access to contraceptives on campus before this program's implementation, growing to 75% (p < 0.001) 1 year later post-implementation. Similar jumps were observed for reported access to sexual health education (30 to 73%, p < 0.001) and services (36 to 73%, p < 0.001). CONCLUSION: A student-led SRH supply and resource delivery strategy may immediately reduce SRH inequities and decrease barriers to contraceptive use for students with limited access to on-site SRH product availability.

Study design features that improve effect sizes in cross-sectional and longitudinal brain-wide association studies.

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behavior associations. Several recent studies showed that thousands of study participants are required to improve the replicability of BWAS because actual effect sizes are much smaller than those reported in smaller studies. Here, we perform analyses and meta-analyses of a robust effect size index (RESI) using 63 longitudinal and cross-sectional magnetic resonance imaging studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for improving standardized effect sizes and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger covariate variance have larger effect size estimates and that the longitudinal studies we examined have systematically larger standardized effect sizes than cross-sectional studies. We propose a cross-sectional RESI to adjust for the systematic difference in effect sizes between cross-sectional and longitudinal studies that allows investigators to quantify the benefit of conducting their study longitudinally. Analyzing age effects on global and regional brain measures from the United Kingdom Biobank and the Alzheimer's Disease Neuroimaging Initiative, we show that modifying longitudinal study design through sampling schemes to increase between-subject variability and adding a single additional longitudinal measurement per subject can improve effect sizes. However, evaluating these longitudinal sampling schemes on cognitive, psychopathology, and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset shows that commonly used longitudinal models can, counterintuitively, reduce effect sizes. We demonstrate that the benefit of conducting longitudinal studies depends on the strengths of the between- and within-subject associations of the brain and non-brain measures. Explicitly modeling between- and within-subject effects avoids conflating the effects and allows optimizing effect sizes for them separately. These findings underscore the importance of considering study design features to improve the replicability of BWAS.

Creating a sustainable action-oriented engagement infrastructure-a UMN-MIDB perspective.

Following the murder of George Floyd on May 25, 2020, Minneapolis represented the epicenter of protests that would reverberate internationally and re-instantiate a reckoning of the systemic and institutional racism that plagues American society. Also in the summer of 2020, and after several years of planning, the University of Minnesota (UMN) launched the Masonic Institute for the Developing Brain (MIDB), an interdisciplinary clinical and community research enterprise designed to create knowledge and engage all members of our community. In what follows, we describe the mission of the MIDB Community Engagement and Education (CEEd) Core and adjacent efforts within the UMN neuroscience and psychology community. Inherent to these efforts is the explicit attempt to de-center the dominant academic voice and affirm knowledge creation is augmented by diverse voices within and outside of traditional academic institutions. We describe several initiatives, including the Neuroscience Opportunities for Discovery and Equity (NODE) network, the NextGen Psych Scholars Program (NPSP), the Young Scientist Program, among others as exemplars of our approach. Developing and fortifying sustainable pathways for authentic community-academic partnerships are of central importance to enhance mutually beneficial scientific discovery. We posit that traditional academic approaches to community engagement to benefit the institution are severely constrained and perpetuate inherently exploitative power dynamics between academic institutions and communities.

Blood-Brain Barrier Dysfunction After Smoke Inhalation Injury, With and Without Skin Burn.

Only a handful of published reports exist today that describe neurological complications following smoke inhalation injury. In this study, we characterize acute pathophysiological changes in the brain of sheep exposed to smoke inhalation, with- and without third-degree skin burn that models the injuries sustained by human victims of fire accidents. Blood-brain barrier integrity and hemorrhage were analyzed throughout the brain using specific histological stains: Hematoxylin & Eosin, Luxol fast blue, Periodic acid-Schiff (PAS), and Martius, Scarlet and Blue (MSB). Our data show that, following smoke inhalation injury, alone and in combination with third-degree skin burn, there was a significant increase in the number of congested and dilated blood vessels in the frontal cortex, basal ganglia, amygdala, hippocampus, pons, cerebellum, and pituitary gland as compared to sham-injured controls. Positive PAS staining confirmed damage to the basement membrane of congested and dilated blood vessels throughout the brain. Severe rupturing of blood vessels, microvascular hemorrhaging and bleeding throughout the brain was also observed in the injured groups. No significant changes in hemodynamics and PaO2 were observed. Our data demonstrate for the first time that acute smoke inhalation alone results in diffuse blood-brain barrier dysfunction and massive bleeding in the brain in the absence of hypoxia and changes in hemodynamics. These findings provide critical information and prompt further mechanistic and interventional studies necessary to develop effective and novel treatments aimed at alleviating CNS dysfunction in patients with smoke and burn injuries.

Modulation of Peroxynitrite Reduces Norepinephrine Requirements in Ovine MRSA Septic Shock.

Vascular hypo-responsiveness to vasopressors during septic shock is a challenging problem. This study is to test the hypothesis that reactive nitrogen species (RNS), such as peroxynitrite, are major contributing factors to vascular hypo-responsiveness in septic shock. We hypothesized that adjunct therapy with peroxynitrite decomposition catalyst (PDC) would reduce norepinephrine requirements in sepsis resuscitation. Fourteen female Merino sheep were subjected to a "two-hit" injury (smoke inhalation and endobronchial instillation of live methicillin-resistant Staphylococcus aureus [1.6-2.5 × 10 CFUs]). The animals were randomly allocated to control: injured, fluid resuscitated, and titrated norepinephrine, n = 7; or PDC: injured, fluid resuscitated, titrated norepinephrine, and treated with PDC, n = 7. One-hour postinjury, an intravenous injection of PDC (0.1 mg/kg) was followed by a continuous infusion (0.04 mg/kg/h). Titration of norepinephrine started at 0.05 mcg/kg/min based on their mean arterial pressure. All animals were mechanically ventilated and monitored in the conscious state for 24 h. The mean arterial pressure was well maintained in the PDC with significantly less norepinephrine requirement from 7 to 23 h after injury compared with control. Total norepinephrine dose, the highest norepinephrine rate, and time on norepinephrine support were also significantly lower in PDC. Modified sheep organ failure assessment scores at 6 to 18 h postinjury were significantly lower in PDC compared with control. PDC improved survival rate at 24 h (71.4% vs. 28.6%). PDC treatment had no adverse effects. In conclusion, the modulation of RNS may be considered an effective adjunct therapy for septic shock, in the case of hypo-responsiveness to norepinephrine.

Adipose-derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation.

BACKGROUND: Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS. METHODS: Female sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer's solution, and cardiopulmonary hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein content in plasma and lung lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5. RESULTS: Lung lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the lung lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables. CONCLUSIONS: ASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.

The role of glial-specific Kir4.1 in normal and pathological states of the CNS.

Kir4.1 is an inwardly rectifying K(+) channel expressed exclusively in glial cells in the central nervous system. In glia, Kir4.1 is implicated in several functions including extracellular K(+) homeostasis, maintenance of astrocyte resting membrane potential, cell volume regulation, and facilitation of glutamate uptake. Knockout of Kir4.1 in rodent models leads to severe neurological deficits, including ataxia, seizures, sensorineural deafness, and early postnatal death. Accumulating evidence indicates that Kir4.1 plays an integral role in the central nervous system, prompting many laboratories to study the potential role that Kir4.1 plays in human disease. In this article, we review the growing evidence implicating Kir4.1 in a wide array of neurological disease. Recent literature suggests Kir4.1 dysfunction facilitates neuronal hyperexcitability and may contribute to epilepsy. Genetic screens demonstrate that mutations of KCNJ10, the gene encoding Kir4.1, causes SeSAME/EAST syndrome, which is characterized by early onset seizures, compromised verbal and motor skills, profound cognitive deficits, and salt-wasting. KCNJ10 has also been linked to developmental disorders including autism. Cerebral trauma, ischemia, and inflammation are all associated with decreased astrocytic Kir4.1 current amplitude and astrocytic dysfunction. Additionally, neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis demonstrate loss of Kir4.1. This is particularly exciting in the context of Huntington disease, another neurodegenerative disorder in which restoration of Kir4.1 ameliorated motor deficits, decreased medium spiny neuron hyperexcitability, and extended survival in mouse models. Understanding the expression and regulation of Kir4.1 will be critical in determining if this channel can be exploited for therapeutic benefit.