Promoting TIA Awareness: Decreasing Stroke Mortality in Vermont

The death rate from stroke in Washington County, VT was nearly twice that of the state in 2015. Risk of death from stroke can be decreased by timely intervention, however many patients are unaware as to signs and symptoms of stroke, and when to seek medical attention. A brochure was developed and distributed, aiming to shorten the time between experiencing TIA symptoms and point of contact with medical professionals.https://scholarworks.uvm.edu/fmclerk/1497/thumbnail.jp

Farm to Early Care and Education in Vermont

Introduction. Farm to Early Care and Education (ECE) is a program of the Nation- al Farm to School Network that aims to extend the core elements of Farm to School into ECE settings with the goal of improving the health of children ages zero to five and enhancing their educational experience with food and nutrition. The purpose of this project was to gather baseline Farm to ECE data for Vermont. Methods. The 2015 National Survey of Early Care and Education Provider was used to create a 23-question survey. The survey was built with SurveyMonkey and distribut- ed through the Child Development Division. Results. 600 providers received the survey with 73 respondents. Minimum one meal is served daily at 93% of programs surveyed, and most serve local foods (84%). Most food is purchased from grocery stores (97%), followed by wholesale provid- ers (64%) and farmers markets (43%). Cost and food quality were the most important factors when determining where to buy food. 80% respondents reported they don’t currently engage in Farm to ECE activities; however, when polled on activities at their center 96% of participants who originally answered no, marked at least one activity that qualifies as a Farm to ECE event. Discussion/Recommendations. Vermont would like to extend the Farm to School Program to 75% of Vermont schools by 2025. Based on the results of this project, we suggest that a similar goal be established for Vermont-based early care programs targeting improved nutrition for Vermont’s youngest children and while supporting local farms and markets.https://scholarworks.uvm.edu/comphp_gallery/1262/thumbnail.jp

Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model

Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by somatic mutations in JAK2, leading to increased red blood cell (RBC) production uncoupled from mechanisms that regulate physiological erythropoiesis. At steady-state, bone marrow macrophages promote erythroid maturation, whereas splenic macrophages phagocytose aged or damaged RBCs. The binding of the anti-phagocytic ("don't eat me") CD47 ligand expressed on RBCs to the SIRPα receptor on macrophages inhibits phagocytic activity protecting RBCs from phagocytosis. In this study, we explore the role of the CD47-SIRPα interaction on the PV RBC life cycle. Our results show that blocking CD47-SIRPα in a PV mouse model due to either anti-CD47 treatment or loss of the inhibitory SIRPα-signal corrects the polycythemia phenotype. Anti-CD47 treatment marginally impacted PV RBC production while not influencing erythroid maturation. However, upon anti-CD47 treatment, high-parametric single-cell cytometry identified an increase of MerTK+ splenic monocyte-derived effector cells, which differentiate from Ly6C$^{hi}$ monocytes during inflammatory conditions, acquire an inflammatory phagocytic state. Furthermore, in vitro, functional assays showed that splenic JAK2 mutant macrophages were more "pro-phagocytic," suggesting that PV RBCs exploit the CD47-SIRPα interaction to escape innate immune attacks by clonal JAK2 mutant macrophages

Pocket depth and bleeding on probing and their associations with dental, lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter feasibility study of the German National Cohort

Background: To investigate the periodontal disease status in a multi-center cross-sectional study in Germany. Associations of dental, socio-economic, blood and biomedical variables with periodontal outcome parameters were evaluated. Methods: From 4 different centers N = 311 persons were included, drawn randomly from the registration offices. Maximal pocket depth (PD) was used as primary indicator for periodontitis. It was classified as: no/mild ≤3 mm, moderate 4-5 mm, severe ≥6 mm. Associations between socioeconomic (household income, education), lifestyle, and biomedical factors and PD or bleeding on probing (BOP) per site (“Yes”/”No”) was analyzed with logistic regression analysis. Results: Mean age of subjects was 46.4 (range 20–77) years. A significantly higher risk of deeper pockets for smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR = 1.6, BMI increase by 5) was found. Severity of periodontitis was significantly associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p < .0001), leukocytes (p = 0.04), HbA1c (p &lt; .0001) and MCV (p = 0.04). PD was positively correlated with BOP. No significant associations with BOP were found in regression analysis. Conclusions: Earlier findings for BMI and smoking with severity of PD were confirmed. Dental variables might be influenced by potential confounding factors e.g. dental hygiene. For blood parameters interactions with unknown systemic diseases may exist

a cross-sectional, multicenter feasibility study of the German National Cohort

Background To investigate the periodontal disease status in a multi-center cross-sectional study in Germany. Associations of dental, socio-economic, blood and biomedical variables with periodontal outcome parameters were evaluated. Methods From 4 different centers N = 311 persons were included, drawn randomly from the registration offices. Maximal pocket depth (PD) was used as primary indicator for periodontitis. It was classified as: no/mild ≤3 mm, moderate 4-5 mm, severe ≥6 mm. Associations between socioeconomic (household income, education), lifestyle, and biomedical factors and PD or bleeding on probing (BOP) per site (“Yes”/”No”) was analyzed with logistic regression analysis. Results Mean age of subjects was 46.4 (range 20–77) years. A significantly higher risk of deeper pockets for smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR = 1.6, BMI increase by 5) was found. Severity of periodontitis was significantly associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p < .0001), leukocytes (p = 0.04), HbA1c (p < .0001) and MCV (p = 0.04). PD was positively correlated with BOP. No significant associations with BOP were found in regression analysis. Conclusions Earlier findings for BMI and smoking with severity of PD were confirmed. Dental variables might be influenced by potential confounding factors e.g. dental hygiene. For blood parameters interactions with unknown systemic diseases may exist

Superior Ventriculo-Arterial Coupling with Decellularized Allografts Compared with Conventional Prostheses

Background To date, no experimental or clinical study provides detailed analysis of vascular impedance changes after total aortic arch replacement. This study investigated ventriculoarterial coupling and vascular impedance after replacement of the aortic arch with conventional prostheses vs. decellularized allografts. Methods After preparing decellularized aortic arch allografts, their mechanical, histological and biochemical properties were evaluated and compared to native aortic arches and conventional prostheses in vitro. In open-chest dogs, total aortic arch replacement was performed with conventional prostheses and compared to decellularized allografts (n = 5/group). Aortic flow and pressure were recorded continuously, left ventricular pressure-volume relations were measured by using a pressure- conductance catheter. From the hemodynamic variables end-systolic elastance (Ees), arterial elastance (Ea) and ventriculoarterial coupling were calculated. Characteristic impedance (Z) was assessed by Fourier analysis. Results While Ees did not differ between the groups and over time (4.1±1.19 vs. 4.58±1.39 mmHg/mL and 3.21±0.97 vs. 3.96±1.16 mmHg/mL), Ea showed a higher increase in the prosthesis group (4.01±0.67 vs. 6.18±0.20 mmHg/mL, P<0.05) in comparison to decellularized allografts (5.03±0.35 vs. 5.99±1.09 mmHg/mL). This led to impaired ventriculoarterial coupling in the prosthesis group, while it remained unchanged in the allograft group (62.5±50.9 vs. 3.9±23.4%). Z showed a strong increasing tendency in the prosthesis group and it was markedly higher after replacement when compared to decellularized allografts (44.6±8.3dyn·sec·cm−5 vs. 32.4±2.0dyn·sec·cm−5, P<0.05). Conclusions Total aortic arch replacement leads to contractility-afterload mismatch by means of increased impedance and invert ventriculoarterial coupling ratio after implantation of conventional prostheses. Implantation of decellularized allografts preserves vascular impedance thereby improving ventriculoarterial mechanoenergetics after aortic arch replacement

Lactation-associated macrophages exist in murine mammary tissue and human milk

Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11c$^{+}$CX3CR1$^{+}$Dectin-1$^{+}$ macrophage population (liMac) that was distinct from the two resident F4/80$^{hi}$ and F4/80$^{lo}$ macrophage subsets present pregestationally. LiMacs were predominantly monocyte-derived and expanded by proliferation in situ concomitant with nursing. LiMacs developed independently of IL-34, but required CSF-1 signaling and were partly microbiota-dependent. Locally, they resided adjacent to the basal cells of the alveoli and extravasated into the milk. We found several macrophage subsets in human milk that resembled liMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation

IL-12 protects from psoriasiform skin inflammation

Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional programme that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis

Establishing performance standards for child development: learnings from the ECDI2030

Background: Standards of early childhood development (ECD) are needed to determine whether children living in different contexts are developmentally on track. The Early Childhood Development Index 2030 (ECDI2030) is a population-level measure intended to be used in household surveys to collect globally comparable data on one of the indicators chosen to monitor progress toward target 4.2 of the Sustainable Development Goals: The proportion of children aged 24–59 months who are developmentally on track in health, learning and psychosocial well-being. Methods: To define performance cut-scores for the ECDI2030 we followed a criterion-referenced standard setting exercise using the modified Angoff method. The exercise gauged the expectations from 15 global experts in ECD and was informed by representative population data collected in Mexico and the State of Palestine. The final calibrated age-specific performance cut-scores were applied to these data to estimate the proportion of children developmentally on track, disaggregated by background characteristics, including the child's sex and attendance to early childhood education. Results: Through a process of standard setting, we generated robust performance standards for the ECDI2030 by establishing five age-specific cut-scores to identify children as developmentally on track. Conclusions: This paper demonstrated how the standard setting methodology, typically applied to measures in the health and education fields, could be applied to a measure of child development. By creating robust criterion-referenced standards, we have been able to ensure that the cut-scores related to age for the ECDI2030 are based on performance standards set by global experts in the ECD field for defining on and off track development