The Impact of Type 2 Diabetes on Peripheral and Cerebral Hemodynamic Responses to Active Stand.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM. METHODS: A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). RESULTS: Of 2 984 older adults (aged 64.3 ±â€…8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; p = .047). CONCLUSIONS: T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.

Slower speed of blood pressure recovery after standing is associated with accelerated brain aging: Evidence from The Irish Longitudinal Study on Ageing (TILDA).

Background: Impaired recovery of blood pressure (BP) in response to standing up is a prevalent condition in older individuals. We evaluated the relationship between the early recovery of hemodynamic responses to standing and brain health in adults over 50. Methods: Participants from The Irish Longitudinal Study on Ageing (TILDA) (n=411; age 67.6 ± 7.3 years; 53.4 % women) performed an active stand challenge while blood pressure and heart rate were continuously monitored. The recovery of these parameters was determined as the slope of the BP and HR response, following the initial drop/rise after standing. We have previously reported a novel and validated measure of brain ageing using MRI data, which measures the difference between biological brain age and chronological age, providing a brain-predicted age difference (brainPAD) score. Results: Slower recovery of systolic and diastolic BP was found to be significantly associated with higher brainPAD scores (i.e., biologically older brains), where a one-year increase in brainPAD was associated with a decrease of 0.02 mmHg/s and 0.01 mmHg/s in systolic and diastolic BP recovery, respectively, after standing. Heart rate (HR) recovery was not significantly associated with brainPAD score. Conclusion: These results demonstrate that slower systolic and diastolic BP recovery in the early phase after standing is associated with accelerated brain aging in older individuals. This suggests that the BP response to standing, measured using beat-to-beat monitoring, has the potential to be used as a marker of accelerated brain aging, relying on a simple procedure and devices that are easily accessible.

Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).

Anionic nanoplastic contaminants promote Parkinson's disease-associated α-synuclein aggregation.

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here, we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated α-synuclein. In mice, nanoplastics combine with α-synuclein fibrils to exacerbate the spread of α-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of α-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson's disease and related dementias.

Anionic Nanoplastic Contaminants Promote Parkinson's Disease-Associated α-Synuclein Aggregation.

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated α-synuclein. In mice, nanoplastics combine with α-synuclein fibrils to exacerbate the spread of α-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of α-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson's disease and related dementias.

Polarized Desmosome and Hemidesmosome Shedding via Exosomes is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of exosomes that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral exosomes from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of exosome release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in exosome content, including basal-side specific desmosome and hemidesmosome shedding via exosomes. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases, (e.g., AMD) and broadly from blood-CNS barriers in other neurodegenerative diseases.

School Parent Attitudes and Perceptions Relating to Animals, Animal-Assisted Interventions, and the Support of Children's Mental Health.

Growing awareness of the negative effects of trauma has led San Antonio, TX, school districts to expand efforts that can help mitigate these effects and support mental health. Given the literature around the psychological benefits of human-animal interactions, the concept of incorporating animals in treatments or interventions is not a new one. While schools have begun considering or utilizing animal-assisted interventions (AAIs), there have been limited efforts to understand existing perceptions relating to animals and AAIs among school parents in this Hispanic community. To address this gap, a cross-sectional study consisting of a 34-item survey was conducted to explore attitudes, knowledge, and perceptions relating to animals (i.e., pets), AAIs, and the need for supporting young children's mental health among parents. A total of 187 surveys from two school districts were completed and utilized for analysis. The study's findings demonstrate that parents acknowledged the importance of addressing mental health issues early on and were aware of the health benefits human-animal interactions can provide. Furthermore, parents had positive attitudes toward pets and positive perceptions toward AAIs in schools. Some implementation concerns were expressed relating to safety and well-being. Overall, these findings suggest there is existing parent support in using AAIs as a trauma-informed strategy and school innovation.

Susceptibility to the sound-induced flash illusion is associated with gait speed in a large sample of middle-aged and older adults.

BACKGROUND: Multisensory integration is the ability to appropriately merge information from different senses for the purpose of perceiving and acting in the environment. During walking, information from multiple senses must be integrated appropriately to coordinate effective movements. We tested the association between a well characterised multisensory task, the Sound-Induced Flash Illusion (SIFI), and gait speed in 3255 participants from The Irish Longitudinal Study on Ageing. High susceptibility to this illusion at longer stimulus onset asynchronies characterises older adults, and has been associated with cognitive and functional impairments, therefore it should be associated with slower gait speed. METHOD: Gait was measured under three conditions; usual pace, cognitive dual tasking, and maximal walking speed. A separate logistic mixed effects regression model was run for 1) gait at usual pace, 2) change in gait speed for the cognitive dual tasking relative to usual pace and 3) change in maximal walking speed relative to usual pace. In all cases a binary response indicating a correct/incorrect response to each SIFI trial was the dependent variable. The model controlled for covariates including age, sex, education, vision and hearing abilities, Body Mass Index, and cognitive function. RESULTS: Slower gait was associated with more illusions, particularly at longer temporal intervals between the flash-beep pair and the second beep, indicating that those who integrated incongruent sensory inputs over longer intervals, also walked slower. The relative changes in gait speed for cognitive dual tasking and maximal walking speed were also significantly associated with SIFI at longer SOAs. CONCLUSIONS: These findings support growing evidence that mobility, susceptibility to falling and balance control are associated with multisensory processing in ageing.

Economic Evaluation of an Intervention to Prevent Adolescent Dating Violence (Me & You).

Me & You: Building Healthy Relationships (Me & You) is a multilevel, technology-enhanced adolescent dating violence (DV) prevention program that aimed to reduce DV among ethnic-minority, early adolescent, urban youth. A group-randomized control trial of Me & You, conducted with 10 middle schools from a large urban school district in Southeast Texas in 2014-2015, found it to be effective in reducing DV perpetration and decreasing some forms of DV victimization. Economic evaluations of DV interventions are extremely limited, despite calls for more economic analyses to be incorporated in research. We help fill this gap by evaluating the cost-effectiveness from the payer and societal perspectives of implementing the Me & You program. Using cost data collected alongside the Me & You group-randomized trial, we computed incremental cost-effectiveness ratios. Our primary outcome was "any DV perpetrated" within 12 months of the intervention. We conducted a cost-benefit analysis beyond the intervention endpoint by using literature estimates of per-victim lifetime costs of DV. We performed sensitivity analyses to assess effects of uncertain parameters. Under the base-case scenario, the cost of the Me & You curriculum compared to the standard curriculum was $103.70 per-student from the societal perspective, and the effectiveness was 34.84 perpetrations averted, implying an incremental cost per perpetration averted of $2.98, which ranged from $0.48 to $73.24 in sensitivity analysis. Thus, we find the Me & You curriculum is cost-effective and cost-saving in most scenarios. Policymakers should carefully consider school-based DV prevention programs, and cost data should be regularly collected in adolescent prevention program evaluations.

Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4-year longitudinal study.

This was a longitudinal study utilising the Irish Longitudinal Study on Ageing (n 3849 aged ≥ 50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). A score ≥ 9 on the Center for Epidemiological Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. B12 status profiles (pmol/l) were defined as < 185, deficient low; 185 to < 258, low normal; > 258-601, normal and > 601 high. Folate status profiles (nmol/l) were defined as ≤ 10·0, deficient low; > 10-23·0, low normal; > 23·0-45·0, normal; >45·0, high. Logistic regression models were used to analyse the longitudinal associations. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms v. non-depressed (folate: 21·4 v. 25·1 nmol/l; P = 0·0003; B12:315·7 v. 335·9 pmol/l; P = 0·0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression 4 years later (OR 1·51, 95 % CI 1·01, 2·27, P = 0·043). This finding remained robust after controlling for relevant covariates. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51 % increased likelihood of developing depressive symptoms over 4 years. The findings highlight the need to further explore the low-cost benefits of optimising vitamin B12 status for depression in older adults.

Using Conditional Inference Forests to Examine Predictive Ability for Future Falls and Syncope in Older Adults: Results from The Irish Longitudinal Study on Ageing.

BACKGROUND: The extent to which gait and mobility measures predict falls relative to other risk factors is unclear. This study examined the predictive accuracy of over 70 baseline risk factors, including gait and mobility, for future falls and syncope using conditional inference forest models. METHODS: Data from 3 waves of The Irish Longitudinal Study on Ageing (TILDA), a population-based study of community-dwelling adults aged ≥50 years were used (n = 4 706). Outcome variables were recurrent falls, injurious falls, unexplained falls, and syncope occurring over 4-year follow-up. The predictive accuracy was calculated using 5-fold cross-validation; as there was a class imbalance, the algorithm was trained using undersampling of the larger class. Classification rate, the area under the receiver operating characteristic curve (AUROC), and area under the precision recall curve (PRAUC) assessed predictive accuracy. RESULTS: Highest overall accuracy was 69.7% for recurrent falls in 50-64-year olds. AUROC and PRAUC were ≤0.69 and ≤0.39, respectively, for all outcomes indicating low predictive accuracy. History of falls, unsteadiness while walking, fear of falling, mobility, medications, mental health, and cardiovascular health and function were the most important predictors for most outcomes. CONCLUSIONS: Conditional inference forest models using over 70 risk factors resulted in low predictive accuracy for future recurrent, injurious and unexplained falls, and syncope in community-dwelling adults. Gait and mobility impairments were important predictors of most outcomes but did not discriminate well between fallers and non-fallers. Results highlight the importance of multifactorial risk assessment and intervention and validate key modifiable risk factors for future falls and syncope.

The Healthy Native Youth Implementation Toolbox: Using Implementation Mapping to adapt an online decision support system to promote culturally-relevant sexual health education for American Indian and Alaska Native youth.

Background: American Indian and Alaska Native (AI/AN) youth experience serious disparities in sexual and reproductive health, including the highest teen birth rate among racial/ethnic groups, and disproportionate rates of sexually transmitted infections (STI), including HIV. A growing number of evidence-based programs (EBPs) that integrate the strengths and cultural teachings of Native communities exist. Yet, multiple factors, including lack of trained personnel, limited resources, and geographic isolation, may hinder their adoption and implementation. Innovative implementation strategies that facilitate the adoption and implementation of sexual health EBPs in Native communities may help reduce these disparities. Methods: We applied Implementation Mapping, a systematic planning framework that utilizes theory, empirical evidence, and community input, to adapt a theory-based, online decision support system, iCHAMPSS (CHoosing And Maintaining Effective Programs for Sex Education in Schools), to support underlying dissemination and implementation processes unique to Native communities. We used an iterative design process, incorporating input from Native practitioners and academicians, to ensure that the adapted decision support system reflects cultural identification, community values, and experiences. Results: Grounded in diffusion of innovations, organizational stage theory, and social cognitive theory, the Healthy Native Youth Implementation Toolbox supports Native practitioners through five phases (Gather, Choose, Prepare, Implement, and Grow) to adopt, implement, and maintain a culturally-relevant, age-appropriate sexual health EBP. The Toolbox provides tools, ready-to-use templates, and guidance to plan, implement, and grow a culturally-relevant adolescent health program with their Tribe or community. Hosted within the Healthy Native Youth website (www.healthynativeyouth.org), the Toolbox comprises: (1) a curriculum portal with access to 15 culturally-relevant, age-appropriate evidence-based health promotion programs for AI/AN youth; (2) a "resource library" comprising 20+ support tools, templates, and links to external resources, and (3) "stories from the field" comprising testimonials from experienced Native educators, who have implemented sexual health programs. Conclusion: There is a continued need to design, test, and evaluate D&I strategies that are relevant to Native communities. The Healthy Native Youth Implementation Toolbox contributes to the dissemination and implementation of evidence-based, culturally-relevant sexual health education programs in diverse Native communities. Implementation Mapping provided a systematic approach to guide the adaptation process and integrate community voice with the ultimate goal of enhancing sexual health equity among AI/AN youth.

Investigation of the role of sleep and physical activity for chronic disease prevalence and incidence in older Irish adults.

BACKGROUND: Chronic diseases are the leading cause of death worldwide. Many of these diseases have modifiable risk factors, including physical activity and sleep, and may be preventable. This study investigated independent associations of physical activity and sleep with eight common chronic illnesses. METHODS: Data were from waves 1, 3 and 5 of The Irish Longitudinal Study on Ageing (n = 5,680). Inverse probability weighted general estimating equations were used to examine longitudinal lifetime prevalence and cumulative incidence of self-reported conditions. RESULTS: Sleep problems were significantly associated with increased odds of incident and prevalent arthritis and angina. Additionally sleep problems were associated with higher odds of lifetime prevalence of hypertension and diabetes. Physical activity was negatively associated incident osteoporosis and respiratory diseases and negatively associated with lifetime prevalence of hypertension, high cholesterol and diabetes. CONCLUSIONS: Worse sleep quality and lower physical activity were associated with higher odds of chronic diseases. Interventions to improve sleep and physical activity may improve health outcomes.

Association between vitamin D deficiency and the risk of prevalent type 2 diabetes and incident prediabetes: A prospective cohort study using data from The Irish Longitudinal Study on Ageing (TILDA).

Background: It is hypothesized that vitamin D contributes to the aetiology of type 2 diabetes mellitus (diabetes). This study's objective was to examine the relationships between baseline vitamin D status (as measured by plasma 25-hydroxyvitamin D concentration) and both prevalent diabetes and prospective risk of developing diabetes, including prediabetes, in a population with historically low levels of vitamin D. Methods: In this prospective cohort study, data from The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of adults aged ≥50 years residing in Ireland were analysed, including wave 1 (October 2009-June 2011) (n = 5272) and wave 3 (March 2014-October 2015) (n = 3828). Those aged <50 years at baseline or who did not complete the health assessment were excluded. Logistic regression models examined the associations between baseline vitamin D concentration (nmol/L) with prevalent diabetes status and incident diabetes/prediabetes collected at a 4-year follow-up. Models were adjusted for age, sex, education, body mass index, smoking history, physical activity, use of statins, and the season in which the vitamin D concentration was sampled. Findings: Deficient baseline vitamin D concentration was cross-sectionally associated with an increased likelihood of having prevalent diabetes (Relative Risk Ratio [RRR] 1·5, 95% CI: 1·03, 2·18; p = 0·037). In longitudinal analyses evaluating diabetes status 4 years later, there was a 62% increased likelihood (RRR: 1·62, 95% CI: 1·12, 2·35; p = 0·011) of developing prediabetes for those with vitamin D <30 nmol/L compared to those with ≥75 nmol/L. The rate of progression from prediabetes to diabetes between wave 1 and 3 was observed to be 32·5%. Interpretation: Those with lower concentrations of vitamin D, as measured by 25-hydroxyvitamin D, may have different risk profiles with regards to their glycaemic status. Our study had limited power due to the low incidence of diabetes but showed strong associations with incident prediabetes, so further research is required. Optimising vitamin D status at a population level may significantly reduce diabetes. Funding: TILDA is funded by Atlantic Philanthropies, the Irish Department of Health, and Irish Life, while additional funding was provided by the Irish Department of Agriculture, Food and the Marine (13F492) to cover the cost of 25-hydroxyvitamin D analysis.

Evaluación neurológica durante el primer año en niños muy bajo peso al nacer con infección por citomegalovirus / Neurological evaluation during the first year in very low birth weight children with cytomegalovirus infection

Introducción: La infección congénita por citomegalovirus es causa de pérdida auditiva y alteraciones cognitivas. La infección perinatal por este virus es más frecuente en neonatos< 1500 g y produce menos secuelas neurológicas. Objetivo: Describir la evaluación neurológica en el primer año de vida en niños muy bajo peso al nacer con infección por citomegalovirus. Métodos: Estudio descriptivo y longitudinal en el que se incuyeron 14 neonatos< 1500 g, con diagnóstico de infección congénita o perinatal por citomegalovirus; a los cuales se les realizó evaluación del neurodesarrollo, ultrasonido craneal, potenciales evocados auditivos de tallo cerebral y potenciales visuales a las 40 semanas, a los seis meses y al año de edad gestacional corregida. En la primera evaluación se realizó además, electroencefalograma. Resultados: El 43 por ciento tuvo infección congénita y 57 por ciento infección perinatal. A las 40 semanas se evaluaron completamente 79 % de los casos, a los seis meses 64 por ciento y al año 36 por ciento. No se observaron anormalidades en el ultrasonido craneal, ni en el electroencefalograma. Al año de edad corregida, se detectaron alteraciones ligeras del neurodesarrolo en 33,3 por ciento del total de casos (2/6) y con igual porcentaje en los niños con infección congénita (1/3) y perinatal (1/3). En ningún paciente evaluado se detectó sordera neurosensorial, ni daño del nervio visual. Conclusiones: Las alteraciones del neurodesarrollo encontradas al año de edad corregida pueden estar relacionadas con la prematuridad o la infección por citomegalovirus. El seguimiento a mediano y largo plazo es necesario para detectar otras secuelas neurológicas de debut tardío(AU)

Introduction: Congenital cytomegalovirus infection is a cause of hearing loss and cognitive impairments. Perinatal infection by this virus is more frequent in neonates< 1500 g and produces fewer neurological sequelae. Objective: To describe neurological evaluation in the first year of life in very low birth weight children with cytomegalovirus infection. Methods: A descriptive and longitudinal study involving 14 neonates< 1500 g, with a diagnosis of congenital or perinatal cytomegalovirus infection; to which neurodevelopmental evaluation, cranial ultrasound, auditory brain stem evoked potentials and visual potentials were performed at 40 weeks, six months and one year of corrected gestational age. In the first evaluation, electroencephalogram was also performed. Results: 43 percent had congenital infection and 57 percent perinatal infection. At 40 weeks, 79 percent of cases were fully evaluated, at six months 64 percent and at one year 36 percent. No abnormalities were observed on the cranial ultrasound or electroencephalogram. At one year of corrected age, slight alterations in neurodevelopment were detected in 33.3 percent of all cases (2/6) and with the same percentage in children with congenital (1/3) and perinatal (1/3) infection. In no patient evaluated, sensorineural deafness or visual nerve damage was detected. Conclusions: The neurodevelopmental alterations found at one year of corrected age may be related to prematurity or cytomegalovirus infection. Medium- and long-term follow-up is necessary to detect other late-onset neurological sequelae(AU)

Structural Correlates of Overt Sentence Reading in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

BACKGROUND: Overt sentence reading in mild cognitive impairment (MCI) and mild-tomoderate Alzheimer's disease (AD) has been associated with slowness of speech, characterized by a higher number of pauses, shorter speech units and slower speech rate and attributed to reduced working memory/ attention and language capacity. OBJECTIVE: This preliminary case-control study investigates whether the temporal organization of speech is associated with the volume of brain regions involved in overt sentence reading and explores the discriminative ability of temporal speech parameters and standard volumetric MRI measures for the classification of MCI and AD. METHODS: Individuals with MCI, mild-to-moderate AD, and healthy controls (HC) had a structural MRI scan and read aloud sentences varying in cognitive-linguistic demand (length). The association between speech features and regional brain volumes was examined by linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of temporal and MRI features. RESULTS: Longer sentences, slower speech rate, and a higher number of pauses and shorter interpausal units were associated with reduced volumes of the reading network. Speech-based classifiers performed similarly to the MRI-based classifiers for MCI-HC (67% vs. 68%) and slightly better for AD-HC (80% vs. 64%) and AD-MCI (82% vs. 59%). Adding the speech features to the MRI features slightly improved the performance of MRI-based classification for AD-HC and MCI-HC but not HC-MCI. CONCLUSION: The temporal organization of speech in overt sentence reading reflects underlying volume reductions. It may represent a sensitive marker for early assessment of structural changes and cognitive- linguistic deficits associated with healthy aging, MCI, and AD.

Exploring School Staff Perceptions Relating to Animals and Their Involvement in Interventions to Support Mental Health.

Given the growing awareness of the health benefits of human-animal interactions, the use of animal-assisted interventions (AAIs) in educational settings has increased over the years. While many school districts are now considering or utilizing AAIs, the literature investigating AAI-related perceptions among school stakeholders is limited with previous studies focusing on evaluating specific programs. To address this gap, a qualitative exploratory study was conducted using semi-structured interviews with school staff in the San Antonio, TX community. A total of 11 interviews were completed with staff serving preschool and elementary school age children. Data collected from interviews were analyzed using thematic analysis. Findings demonstrated that participating staff had some knowledge of the potential benefits of human-animal interactions and perceived the involvement of animals in interventions to be beneficial to children's emotions and social-emotional skills. While perceptions of AAIs were generally positive, concerns around children's safety and well-being were expressed as potential barriers in the adoption of AAIs in schools. These findings are preliminary and provide a segue to future research that can help expand our understanding of how school staff perceive AAIs, their impact on children's mental health, their compatibility with school values, and their advantage relative to other interventions.

Using Implementation Mapping to Build Organizational Readiness.

Organizational readiness is essential for high-quality implementation of innovations (programs, policies, practices, or processes). The R = MC2 heuristic describes three readiness components necessary for implementation-the general functioning of the organization (general capacities), the ability to deliver a particular innovation (innovation-specific capacities), and the motivation to implement the innovation. In this article, we describe how we used the Readiness Building System (RBS) for assessing, prioritizing, and improving readiness and Implementation Mapping (IM), a systematic process for planning implementation strategies, to build organizational readiness for implementation of sexual assault prevention evidence-based interventions (EBIs). While RBS provides an overarching approach for assessing and prioritizing readiness constructs (according to the R = MC2 heuristic; Readiness = Motivation x general Capacity × innovation specific Capacity), it does not provide specific guidance on the development and/or selection and tailoring of strategies to improve readiness. We used the five IM tasks to identify and prioritize specific readiness goals and develop readiness-building strategies to improve subcomponents described in the R = MC2 heuristic. This article illustrates how IM can be used synergistically with the RBS in applied contexts to plan implementation strategies that will improve organizational readiness and implementation outcomes. Specifically, we provide an example of using these two frameworks as part of the process of building organizational readiness for implementation of sexual assault prevention EBIs.

Intermediary Role of Lung Alveolar Type 1 Cells in Epithelial Repair upon Sendai Virus Infection.

The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+ (Sry-box 2+) clusters without differentiating into AT1 or AT2 cells. Large AT2 cell-depleted areas remain covered by AT1 cells, which we name "AT2-less regions", and are replaced by SOX2+ clusters spreading both basally and luminally. AT2 cell proliferation and differentiation are largely confined to topologically distal regions and form de novo alveolar surface, with limited contribution to in situ repairs of AT2-less regions. Time-course single-cell RNA sequencing profiling and RNAscope validation suggest enhanced immune responses and altered growth signals in AT1 cells. Our comprehensive spatiotemporal and genomewide study highlights the hitherto unappreciated role of AT1 cells in lung injury-repair.

The Impact of COVID-19 on the Delivery of Educational Programs in Native American Communities: Qualitative Study.

BACKGROUND: Despite the availability of culturally responsive sexual health educational programs for American Indian and Alaska Native (AI/AN) youth, barriers to their uptake and utilization persist in tribal communities. These challenges were exacerbated by the COVID-19 pandemic, which required flexible program delivery using both in-person and virtual classrooms. OBJECTIVE: This exploratory study provides a preliminary understanding of the extent to which pre-existing challenges impact the delivery of culturally responsive sexual health education programs in Native communities and to what extent they were exacerbated by the COVID-19 pandemic. It also highlights the challenges faced by adolescent health advocates when adapting culturally responsive health curricula to online platforms. Finally, this study discloses major socioeconomic, health, and mental challenges experienced by AI/AN youth during the pandemic. METHODS: An exploratory, descriptive, qualitative design approach was adopted to carry out 5 individual and 1 collective in-depth key informant interviews. A total of 8 Native and non-Native sexual health educators served as key informants and shared their personal experiences with the delivery of sexual health education programs for youth during the COVID-19 pandemic. The interviews were conducted virtually from October to November 2020 using Zoom to reach participants dispersed across different regions of the United States. We followed the consolidated criteria for reporting qualitative research (COREQ) as a reference for the study methodology. We also used the Braun and Clarke framework (2006) to conduct a thematic analysis. RESULTS: Experts' opinions were structured according to 5 main themes: (1) competing community priorities during COVID-19; (2) moving to web-based programming: skills, training, support; (3) recruiting youth; and (4) challenges for implementation in a household environment; and (5) recommendations to overcome implementation challenges. These themes are complementary, connected, and should be considered holistically for the development, dissemination, and implementation of online sexual health programs for AI/AN youth, specifically during the COVID-19 pandemic. The results raised the following points for discussion: (1) Building partnerships with schools and community organizations facilitates program adaptation and implementation, (2) there is a need to adopt a holistic approach when addressing youth sexual health in AI/AN communities, (3) a systematic and culturally responsive adaptation approach ensures effective virtual program delivery, and (4) community and youth engagement is essential for the success of virtual sexual health programs. CONCLUSIONS: Findings can provide recommendations on actions to be taken by sexual health educators and guidelines to follow to ensure cultural sensitivity, effective adaptation, and successful implementation when setting out to advocate for online sexual health programs for AI/AN youth.