Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma

Eosinophils have been implicated as playing a major role in allergic airway responses. However, the importance of these cells to the development of this disease has remained ambiguous despite many studies, partly because of lack of appropriate model systems. In this study, using transgenic murine models, we more clearly delineate a role for eosinophils in asthma. We report that, in contrast to results obtained on a BALB/c background, eosinophil-deficient C57BL/6 ΔdblGATA mice (eosinophil-null mice via the ΔDblGATA1 mutation) have reduced airway hyperresponsiveness, and cytokine production of interleukin (IL)-4, -5, and -13 in ovalbumin-induced allergic airway inflammation. This was caused by reduced T cell recruitment into the lung, as these mouse lungs had reduced expression of CCL7/MCP-3, CC11/eotaxin-1, and CCL24/eotaxin-2. Transferring eosinophils into these eosinophil-deficient mice and, more importantly, delivery of CCL11/eotaxin-1 into the lung during the development of this disease rescued lung T cell infiltration and airway inflammation when delivered together with allergen. These studies indicate that on the C57BL/6 background, eosinophils are integral to the development of airway allergic responses by modulating chemokine and/or cytokine production in the lung, leading to T cell recruitment

Personality Predicts Mortality Risk: An Integrative Data Analysis of 15 International Longitudinal Studies

This study examined the Big Five personality traits as predictors of mortality risk, and smoking as a mediator of that association. Replication was built into the fabric of our design: we used a Coordinated Analysis with 15 international datasets, representing 44,094 participants. We found that high neuroticism and low conscientiousness, extraversion, and agreeableness were consistent predictors of mortality across studies. Smoking had a small mediating effect for neuroticism. Country and baseline age explained variation in effects: studies with older baseline age showed a pattern of protective effects (HR<1.00) for openness, and U.S. studies showed a pattern of protective effects for extraversion. This study demonstrated coordinated analysis as a powerful approach to enhance replicability and reproducibility, especially for aging-related longitudinal research.Funding support for this project was provided by the National Institute on Aging: P01-AG043362 (Integrative Analysis of Longitudinal Studies of Aging (IALSA), [Scott M. Hofer (PI)]), and Daniel K. Mroczek (CoInvestigator and Project Leader of the IALSA Personality & Health Project, as well as R01-AG018436 [Personality & Well-Being Trajectories in Adulthood, Daniel K. Mroczek, PI])

Measuring and forecasting progress in education: what about early childhood?

A recent Nature article modelled within-country inequalities in primary, secondary, and tertiary education and forecast progress towards Sustainable Development Goal (SDG) targets related to education (SDG 4). However, their paper entirely overlooks inequalities in achieving Target 4.2, which aims to achieve universal access to quality early childhood development, care and preschool education by 2030. This is an important omission because of the substantial brain, cognitive and socioemotional developments that occur in early life and because of increasing evidence of early-life learning's large impacts on subsequent education and lifetime wellbeing. We provide an overview of this evidence and use new analyses to illustrate medium- and longterm implications of early learning, first by presenting associations between pre-primary programme participation and adolescent mathematics and science test scores in 73 countries and secondly, by estimating the costs of inaction (not making pre-primary programmes universal) in terms of forgone lifetime earnings in 134 countries. We find considerable losses, comparable to or greater than current governmental expenditures on all education (as percentages of GDP), particularly in low- and lower-middle-income countries. In addition to improving primary, secondary and tertiary schooling, we conclude that to attain SDG 4 and reduce inequalities in a post-COVID era, it is essential to prioritize quality early childhood care and education, including adopting policies that support families to promote early learning and their children's education

Cognitively Stimulating Activities: Effects on Cognition across Four Studies with up to 21 Years of Longitudinal Data

Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases one&apos;s ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from one&apos;s previous level has at least a transitory association with cognitive performance measured at the same point in time

The effects of feeding low protein and low energy diets with microbial protease supplementation on growth performance, incidence of pododermatitis and immune response in broiler chickens stocked at different densities

A study was conducted to determine the effect of supplementing microbial protease to broiler chickens fed low protein and low energy (LPLE) diets on growth performance (GP), incidence of pododermatitis and antibody production against Newcastle disease (ND) vaccination under two stocking densities. Birds can be fed LPLE starter and low protein-normal energy (LPNE) finisher diet without any adverse effect on growth performance. Protease supplementation was of little benefit to broilers fed diets with lower energy and lower protein. High stocking density (HD) was detrimental to GP and stressful to birds. Low protein diets during the starter period and HD suppressed ND antibody production

The Gerontologist Physical, Cognitive, and Psychosocial Variables From the Disablement Process Model Predict Patterns of Independence and the Transition Into Disability for the Oldest-Old

Purpose: This study used the Disablement Process Model to predict whether a sample of the oldestold maintained their disability or disability-free status over a 2-and 4-year follow-up, or whether they transitioned into a state of disability during this time. Design and Methods: We followed a sample of 149 Swedish adults who were 86 years of age or older over a period of 4 years; we grouped them by ability in activities of daily living as being functional survivors (nondisabled over time), increasingly disabled (initially nondisabled but later disabled), chronically disabled (disabled at all waves), or deceased. We used variables from baseline to predict group membership into these four longitudinal outcome groups. Results: Results indicated that demographic factors, physical impairments, physical and cognitive limitations, and psychosocial variables at baseline predicted membership into the functional survivor group after 2 years and most continued to distinguish between functional survivors and other groups after 4 years. Implications: These findings indicate key variables that may be useful in predicting shorter term longitudinal changes in disability. By understanding the physical, cognitive, and psychological variables that predict whether a person develops a disability within the next 2 or 4 years, we may be better able to plan for care or implement appropriate interventions

Work-Related Stress May Increase the Risk of Vascular Dementia

Objectives: To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer\u27s disease (AD), and vascular dementia (VaD). Design: Cohort study. Setting: The population-based Study of Dementia in Swedish Twins. Participants: Two hundred fifty-seven people with dementia (167 AD, 46 VaD) and 9,849 without. Measurements: Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical examination. An established job exposure matrix was matched to main occupation categories to measure work characteristics. Results: In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.04–1.31) and VaD specifically (OR = 1.39, 95% CI = 1.07–1.81). Lower social support at work was associated with greater risk of dementia (OR = 1.15, 95% CI = 1.03–1.28), AD (OR = 1.14, 95% CI = 1.00–1.31), and VaD (OR = 1.28, 95% CI = 1.02–1.60). Greater job strain was associated with greater risk of VaD only (OR = 1.28, 95% CI = 1.02–1.60), especially in combination with low social support (OR = 1.35, 95% CI = 1.11–1.64). Age, sex, and education were controlled for. Work complexity, manual work, and vascular disease did not explain the results. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD. Conclusion: Work-related stress, including low job control and low social support at work, may increase the risk of dementia, particularly VaD. Modification to work environment, including attention to social context and provision of meaningful roles for employees, may contribute to efforts to promote cognitive health

Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of &#916;9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures

Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice

A history of allergies doubles the risk of vulvodynia&mdash;a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)&mdash;a biocide preservative ubiquitous in cosmetics and cleaners&mdash;dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of &Delta;9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain