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Exposure to environmental chemicals has been linked with endothelial dysfunction, which is a leading cause of human diseases, including atherosclerosis. Permethrin is a frequently used synthetic pyrethroid insecticide for which longer exposure may cause toxicity in several types of tissues and the development of metabolic diseases, including atherosclerosis, obesity and diabetes. The present study was designed to evaluate the potential adverse effect of permethrin on the function and activity of human endothelial cells.Permethrin was found to repress migration and tube formation by human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, as well as to significantly repress their viability after 24 and 48 h of treatment. Furthermore, increased reactive oxygen species (ROS) production was observed in cells treated with permethrin, and the permethrin-induced repression of cell viability was ROS-dependent. Permethrin did not influence apoptosis, necrosis or mitochondrial membrane potential in HUVECs.The results of the present study suggest that permethrin represses angiogenesis and viability through ROS-dependent and cell growth-, apoptosis- and necrosis-independent means. © 2022 Society of Chemical Industry.

Objectives:(1) To examine total quality of foods consumed on the day a home-delivered meal (HDM) of the Older Americans Act Nutrition Program (OAANSP) was served, and when a HDM was not served; and (2) to estimate proportion of HDM participants and non-participants meeting the daily average recommendations for guidance-based foods and nutrients.Design:Cross-sectional study.Setting:Data were obtained from the national 2015–2017 Outcomes Evaluation Study of HDM participants in the USA.Participants:Adults aged 67 years and older (n 1227), 620 HDM recipients and 607 matching non-participants examined in three groups: (1) meal recipients who received a HDM on the day of the 24-h dietary recall; (2) no-meal recipients who did not receive a HDM on the day of the recall and (3) matching HDM non-participants.Results:Healthy Eating Index (HEI)-2010 scores of HDM participants were significantly lower on the day the meal was not received compared with when a meal was received (52·5 v. 63·4, P < 0·0001). There was no significant difference in the total HEI-2010 scores of HDM meal recipients and HDM non-participants. Despite the meal, less than 20 % of HDM participants and non-participants met the 2010-Diet Guidelines for Americans recommended average daily intake for fruit, vegetables, dairy, protein foods and solid fats.Conclusion:HDM participants’ diet quality is poorer when they do not receive a meal putting them at increased risk of malnutrition. Expanding the OAANSP to offer meals on weekends and/or to include more than one meal/d is recommended to improve the diet of this vulnerable population.

Oxygenated water (OW) contains more oxygen than normal drinking water. It may induce oxygen enrichment in the blood and reduce oxidative stress. Hypoxia and oxidative stress could be involved in epilepsy. We aimed to examine the effects of OW-treated vs. control on four rodent models of epilepsy: (1) prenatal betamethasone priming with postnatal N-methyl-D-aspartate (NMDA)-triggered spasm, (2) no prenatal betamethasone, (3) repetitive kainate injection, and (4) intraperitoneal pilocarpine. We evaluated, in (1) and (2), the latency to onset and the total number of spasms; (3) the number of kainate injections required to induce epileptic seizures; (4) spontaneous recurrent seizures (SRS) (numbers and duration). In model (1), the OW-treated group showed significantly increased latency to onset and a decreased total number of spasms; in (2), OW completely inhibited spasms; in (3), the OW-treated group showed a significantly decreased number of injections required to induce epileptic seizures; and in (4), in the OW-treated group, the duration of a single SRS was significantly reduced. In summary, OW may increase the seizure threshold. Although the underlying mechanism remains unclear, OW may provide an adjunctive alternative for patients with refractory epilepsy.

Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. Triple-negative breast cancer (TNBC) accounts for about 10–15% of all breast cancers and is usually more aggressive and has a poorer prognosis. Sericite has been known to have antitumor and immune-stimulatory effects. Although the chemopreventive potential of sericite has been demonstrated in other cancers, its molecular pathways in TNBC still require investigation. Thus, in the present study, the antitumor mechanism of sericite against MDA-MB231 breast cancer cells was examined in vitro and in an in vivo xenograft mouse model. Sericite treatment reduced cell proliferation and cell proliferation marker proliferating cell nuclear antigen (PCNA) in MDA-MB231 cells. It also decreased the total cell number and arrested cells in the G0/G1 phase of the cell cycle with an increase in the phosphorylation of P53 and upregulation of cell cycle regulatory proteins P21 and P16. In addition, sericite treatment also induced apoptosis signaling, which was evident by the upregulation of apoptotic protein markers cleaved caspases 3 and 9. A reduction in reactive oxygen species (ROS), NADPH oxidase 4 (NOX4), p22phox, and heat shock proteins (HSPs) was also observed. Similar results were obtained in vivo with significantly reduced tumor volume in sericite-administered mice. Collectively, these findings suggest that sericite has antitumor potential based on its property to induce cell cycle arrest and apoptotic cell death and therefore could serve as a potential therapeutic agent and crucial candidate in anticancer drug development for TNBC.

Reactive oxygen species (ROS) exacerbate stroke-induced cell damage. We found that ShcA, a protein that regulates ROS, is highly expressed in a Rose Bengal photothrombosis model. We investigated whether ShcA is essential for mitophagy in ROS-induced cellular damage and determined whether ROS exacerbate mitochondrial dysfunction via ShcA protein expression. Ischemic stroke was generated by Rose Bengal photothrombosis in mice. To silence ShcA protein expression in the mouse brain, ShcA-targeting siRNA-encapsulated nanoparticles were intrathecally injected into the cisterna magna. Upon staining with antibodies against ShcA counterpart caspase-3 or NeuN, we found that the ShcA protein expression was increased in apoptotic neurons. In addition, mitochondrial dysfunction and excessive mitophagy were evident in photothrombotic stroke tissue. Infarct volumes were significantly reduced, and neurological deficits were diminished in the ShcA siRNA nanoparticle-treated group, compared with the negative control siRNA nanoparticle-treated group. We confirmed that the reduction of ShcA expression by nanoparticle treatment rescued the expression of genes, associated with mitochondrial dynamics and mitophagy mediation in a stroke model. This study suggests that the regulation of ShcA protein expression can be a therapeutic target for reducing brain damage with mitochondrial dysfunction caused by thrombotic infarction.

Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood. In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4. We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.

Objective: High plate waste in schools adds social, economic, and environmental burden and undermines child nutrition goals. In this study, we conducted formative research to examine potential for mindful-based approaches in reducing plate waste and improving fruit and vegetable intake. Methods: With a triangulation approach, research was conducted in 3 elementary schools using focus groups with students (N = 50), staff interviews (N = 15), and cafeteria observations (N = 9). Guided by Social Cognitive Theory, qualitative findings were analyzed using Constant Comparative Method. Results: Salient personal, behavioral, and environmental factors potentially contributing to student plate waste and eating behaviors were identified. School meal structure and regulations, cafeteria atmosphere, food quality perceptions, and food preferences were potential contributors to plate waste. Students had limited knowledge of mindfulness and were interested in reducing waste, particularly when others are food-insecure. Emphasizing mindfulness and sustainability in nutrition education, collaborating with parents and student leaders, and building on existing waste reduction initiatives could be considered to reduce plate waste and improve eating behaviors. Conclusions: Findings highlighted opportunities to design a program combining mindfulness and sustainable food system education and cafeteria environment changes to reduce plate waste and improve FV intake and sustainability of school meals.

Aims: We investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. Materials & methods: After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. Results: miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia. Conclusion: The anti-inflammatory effects of miR 146a-5p along with nanoparticle-based materials make miR NPs promising tools for treating neuropathic pain.

Schools are a recommended place for childhood obesity prevention. Local Wellness Policies (LWPs) establish guidelines for schools to provide opportunities for students to access nutritious foods and be physically active. Little is known about the impact of LWPs, when implemented, on students' behavior and body mass index (BMI). The Wellness Champions for Change trial assesses the student-level impact of providing theory-based training and technical assistance to help schools implement LWPs. This 3-arm, cluster randomized controlled trial will take place in 30 low- or middle-income schools (15 elementary and 15 middle) in five Maryland school districts. Ten schools will receive both Wellness Champions for Change (WCC), which involves training teacher-led wellness teams, and Wellness Champions for Change-Student (WCC-S), which engages students as wellness team members. Ten schools will receive WCC only, and ten control schools will receive a delayed intervention. The RE-AIM framework will guide evaluation. Student Effectiveness measures will include BMI z-scores, self-reported diet patterns, and objectively-measured physical activity. The sample size (1080 students across 30 schools, followed for 2.5 years) will enable power (>0.8) to detect BMI z-score differences. A three-level linear mixed model that accounts for clustering will be used to assess Effectiveness. A mixed methods approach will assess school- and district-level Reach, Adoption, and Implementation. If effective, this approach will represent a sustainable, multi-level, school-based strategy to prevent childhood obesity. The evaluation framework will allow for the description of factors necessary to broadly disseminate this approach for obesity prevention on a large scale.

Background Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates. Objectives This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography. Methods Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction–defined major bleeding during 2 years of follow-up. Results From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction–defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1). Conclusions PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxy-genation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical out-comes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thrombo-plastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin (IL)-1β levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anti-coagulation in ECMO.

AIMS AND OBJECTIVES To describe obesity-risk behaviours (diet, physical activity and sedentary behaviour) and examine the relationships of the obesity-risk behaviours with body mass index (BMI) in school-aged Korean American children. BACKGROUND Korean American children have a risk of becoming overweight or obese and developing obesity-related complications; however, there is limited research about obesity-risk behaviours in Korean American children. DESIGN A cross-sectional study. METHODS Obesity-risk behaviours of children were assessed with well-validated self-report questionnaires (i.e., Elementary-level School-based Nutrition Monitoring Questionnaire) from children and their mothers. Height and weight of children were measured. Data were analysed with bivariate and multivariate analyses using mixed effects models to incorporate the correlation within siblings. RESULTS A total of 170 Korean American children (mean age 10.9 [2.0] years; 52.4% girls; mean BMI 19.3 [3.2]; 28.7% ≥85 percentiles) participated in the study. Only 38.3% of Korean American children met established recommendations of five fruits/vegetables per day; 56.5% met recommendations for more than 3 days per week of vigorous physical activity; and 40.8% met recommendations for

Functional limitations in homebound older adults may cause difficulties with obtaining and preparing adequate healthy food. Services exist to help with these difficulties, however, not all individuals who could benefit receive them. This secondary analysis of observational data, obtained via questionnaires from homebound, recently hospital discharged older adults (n = 566), aimed to identify the prevalence and correlates of unmet need for such services, and to examine the disagreement between self-reported need for a service and functional limitation that could be addressed by that service. One-fifth of respondents reported unmet need for vision services and oral health services, and one-tenth reported unmet need for transportation services and physical therapy. There was a significant association between reported need and functional limitation (p 0.001) for all services, except mental health and grocery delivery. However, for each service there were participants who under-reported need, compared with functional ability indicators. More research is required to determine the best methods for measuring these needs to ensure that nutritional vulnerability is detected and addressed in those returning from hospital.

Background Diet and lifestyle are vital in maintaining good health and independence for older adults. Older adults living in rural areas are at risk for chronic disease, poor diet quality, and limited accessibility to healthy foods, compared to their urban counterparts. Objective To assess rural and urban older adults’ diet quality, food insecurity, and self-efficacy for overcoming barriers to making informed nutrition-related decisions. Study Design, Setting, Participants From April-August 2019, a cross-sectional design was used to administer a self-reported survey to adults ≥50 years, in Maryland, participating at senior/community sites. Using convenience sampling, 475 participants (Urban, n = 215; Rural n = 260) were recruited prior to a nutrition education program (44 sites, 19 counties). Measurable Outcome/Analysis Participants completed a self-administered survey (41 items). Measurable constructs included diet quality assessed by the validated Dietary Screening Tool (DST), which evaluates nutritional risk in older adults. Perceived self-efficacy for healthy eating behaviors, food insecurity, and sociodemographic factors were also measured. Data were analyzed using SPSS version 24.0 (t-test, chi-square, and multiple linear regression). Results Participants were predominantly women (83.6%), white (54.0%), who lived alone (53.6%), with a median age of 74.5 (SD ± 8.5), and reported their health as somewhat good/very good (53.1%). Those in rural areas had significantly lower DST scores (P = .024), higher average number of chronic diseases (P = .004), and lower self-efficacy for changing health behaviors (P = .001) compared to urban/suburban counterparts. After controlling for other variables, rural and urban dwelling was not a significant predictor of diet quality. However, DST scores were significant predictors of food insecurity (B = −3.097, P Conclusions Although previous research reported rural dwellers were more at risk for poor diet quality than urban dwellers, our findings did not support this. However, our results did support the need for nutrition interventions addressing food insecurity and barriers to self-efficacy for improving diet quality of all older adults.

Cartilage loss is a central event in the pathogenesis of osteoarthritis (OA), though other than mechanical loading, the biochemical mechanisms underlying OA pathology remain poorly elucidated. We investigated the role of Pink1-mediated mitophagy in mitochondrial fission, a crucial process in OA pathogenesis. We used a monosodium iodoacetate (MIA)-induced rodent model of OA, which inhibits the activity of articular chondrocytes, leading to disruption of glycolytic energy metabolism and eventual cell death. The OA rat cartilage exhibits significant induction of autophagy-related proteins LC3B and p62, similar to human osteoarthritic cartilage. Moreover, expression of Pink1 and Parkin proteins were also increased in OA. Here, we confirm that Pink1-mediated mitophagy leads to cell death in chondrocytes following MIA treatment, while deficiency in Pink1 expression was associated with decreased cartilage damage and pain behaviors in MIA-induced OA. Finally, we found that autophagy and mitophagy-related genes are highly expressed in human osteoarthritic cartilage. These results indicate that OA is a degenerative condition associated with mitophagy, and suggest that targeting the Pink1 pathway may provide a therapeutic avenue for OA treatment.

Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH4) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH4 synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH4-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague–Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH4 synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH4 storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH4 synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH4/NO pathway.

OBJECTIVES: This study aimed to quantify the amount of plate waste, by food category, generated in the university dining hall facility, and estimate the frequency patterns and resulting nutritional and environmental implications. METHODS: This study took place in a large, public university setting, and adopted a cross-sectional study design. A food waste audit was conducted during six intermittent days. Student plate waste was collected for the entire full-day service and weighed in hourly intervals. Food waste was categorized into seven food groups, determined based on nutritional value and environmental stress of food production. The average means of student plate waste was calculated, and frequency patterns of waste generation was determined. The university food services food production records were used to determine the proportion of food wasted, and the top food groups most wasted by students. The USDA National Nutrient Database for Standard Reference, Release 28 was used to contextualize the nutrient loss of food waste. Foods were coded and aggregated by food group, and nutrition was calculated per ounce of food wasted. The “Food Availability & Losses and Estimated Greenhouse Gas emissions,” table proposed by Heller & Keoleian, 2014, was used to estimate GHG emissions of wasted food. RESULTS: Food waste represented 18.65% of all food produced for consumption in the dining hall facility. The top three food groups most wasted by students were whole grains, dairy and fruits and vegetables, respectfully. An average of 257.44 lb of plate waste was collected per day, and an average 2026.33 meals were served per day yielding an average 0.13 lb (2.06 oz.) plate waste/meal. Frequency of plate waste generation mainly accumulated during traditional hours of meal time, between 12:30 to 2:30 PM and 6 to 8 PM. Food waste represented 102 kcal, 7 g protein, 1.9 g dietary fiber, 75.7 mg calcium, 0.35 µg vitamin D., and 0.37 kgCO2 eq/kg per meal, comparable to national estimates. CONCLUSIONS: This study confirmed that food waste in higher education institutions may be a significant issue with plate waste quantities comparable to national studies. It highlights that food waste reduction strategies may alleviate the amount of harmful greenhouse gas emissions and may provide more nutritious foods to vulnerable populations. FUNDING SOURCES: University of Maryland, Department of Nutrition and Food Science, University of Maryland Dining Services, University of Maryland, Office of Sustainability.

OBJECTIVES: The purpose of this formative study is to understand food waste behaviors of elementary school students and guide the development of a nutrition promotion program that emphasizes reducing food waste without compromising the goals of school meals through mindful selection and consumption. METHODS: Using a mixed method design, 3 elementary schools were recruited and 5 focus groups (n = 50) with 3(rd)-5(th) grade students, 15 in-depth interviews with staff, and 9 cafeteria observations were conducted across the schools to 1) explore students’ perceptions about and understanding of topics related to food waste and mindful eating in order to identify motivating factors and barriers related to reducing food waste while increase produce intake, 2) examine the feasibility of program logistics and potential for integration into the school wellness program, and 3) understand the cafeteria atmosphere and its possible influence on student behavior. RESULTS: Students and staff report that vegetables comprise the largest proportion of food waste during lunch. Focus group feedback indicated that students poor limited acceptance of vegetables caused by perceived limited autonomy in selection and that they are motivated to reduce waste when considering moral implications. Interviewees described efforts by schools to offer backpack pantries to increase access for food insecure students but staff expressed concerns regarding healthfulness of foods provided. Cafeteria observations highlighted an opportunity to update cafeteria menus, signage, and sharing tables to improve student intake and reduce waste. Targeted training for cafeteria monitors could encourage produce intake. Recovering uneaten foods to supplement school-based food pantries is an engaging strategy to address nutritional concerns and divert foods from landfills. Strategies can be coupled with mindfulness education to encourage vegetable consumption. CONCLUSIONS: Results are being used to plan a quasi-experimental controlled pilot intervention that seeks to increase elementary student vegetable consumption and reduce food waste through mindfulness-focused food system education. This program has the potential to increase the healthfulness of students’ diets, meet the needs of food insecure students, and reduce the environmental impact of school nutrition programs. FUNDING SOURCES: University of Maryland, Department of Nutrition and Food Science.

BACKGROUND High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS). METHODS This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs. RESULTS Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005–1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013–1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874–0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086–1.526); P = 0.004] were independently associated with NILs at follow-up. CONCLUSIONS High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful.

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

BACKGROUND The purpose of this study was to assess the effect of a school-based nutrition program using a cafeteria environment intervention and classroom nutrition education on self-reported fruit and vegetable (FV) consumption, self-efficacy to select FV, and preference for healthy foods. METHODS Using quasi-experimental pre-post design with 3 study conditions, a total of 665 fourth- and fifth-grade students participated in the study. The comprehensive intervention included a behavioral economics cafeteria intervention and weekly classroom nutrition education for 1 academic year. The intervention was designed and delivered by the extension system. RESULTS The comprehensive group showed significant improvement in some indicators including eating vegetables for lunch (p = .007), number of days eating vegetables (p < .001) and fruits (p < .001) in the last week, and self-efficacy in preparing FV at home (p = .034) compared to the control and cafeteria groups. Food preference of some food items, including oatmeal (p = .036 for cafeteria group, p < .001 for comprehensive group), whole grain noodles (p = .011 for comprehensive group), and vegetables (p = .003 for comprehensive group), significantly improved in the cafeteria and/or comprehensive group. CONCLUSIONS Classroom nutrition education combined with cafeteria improvement has the potential to improve diet-related behavior of elementary school children. Also, collaborative partnership between schools and extension can enhance program sustainability.

Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided. Stroke-induced microglia activation and neuroinflammation are believed to play a central role in the pathological progression of neonatal ischemic stroke. We induced a photothrombotic infarction with Rose Bengal in neonatal rats to investigate the effects of pre- and post-treatment with Aspirin (ASA), Clopidogrel (Clop), and Coenzyme Q10 (CoQ10), which are known for their neuroprotective effects in adult stroke. Pre-stroke medication ameliorates cerebral ischemic injury and reduces infarct volume by reducing microglia activation, cellular reactive oxygen species (ROS) production, and cytokine release. Post-stroke administration of ASA, Clop, and CoQ10 increased motor function and reduced the volume of infarction, and the statistical evidence was stronger than that seen in the pre-stroke treatment. In this study, we demonstrated that ASA, Clop, and CoQ10 treatment before and after the stroke reduced the scope of stroke lesions and increased behavioral activity. It suggests that ASA, Clop, and CoQ10 medication could significantly have neuroprotective effects in the neonates who have suffered strokes.

Neuroinflammation is one of the key mechanisms of neuropathic pain, which is primarily mediated by the Toll-like receptor 4 (TLR4) signaling pathways in microglia. Therefore, TLR4 may be a reasonable target for treatment of neuropathic pain. Here, we examined the analgesic effect of TLR4 antagonistic peptide 2 (TAP2) on neuropathic pain induced by spinal nerve ligation in rats. When lipopolysaccharide (LPS)-stimulated BV2 microglia cells were treated with TAP2 (10 µM), the mRNA levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS), were markedly decreased by 54–83% as determined by quantitative PCR (qPCR) analysis. Furthermore, when TAP2 (25 nmol in 20 µL PBS) was intrathecally administered to the spinal nerve ligation-induced rats on day 3 after surgery, the mechanical allodynia was markedly decreased for approximately 2 weeks in von Frey filament tests, with a reduction in microglial activation. On immunohistochemical and qPCR analyses, both the level of reactive oxygen species and the gene expression of the proinflammatory mediators, such as TNF-α, IL-1β, IL-6, COX-2, and iNOS, were significantly decreased in the ipsilateral spinal dorsal horn. Finally, the analgesic effect of TAP2 was reproduced in rats with monoiodoacetate-induced osteoarthritic pain. The findings of the present study suggest that TAP2 efficiently mitigates neuropathic pain behavior by suppressing microglial activation, followed by downregulation of neuropathic pain-related factors, such as reactive oxygen species and proinflammatory molecules. Therefore, it may be useful as a new analgesic for treatment of neuropathic pain., Graphical Abstract

Objective: Limited research is available examining community-based social support programs (SSPs) for individuals with type 1 diabetes (T1DM). The purpose of this study was to describe SSPs characteristics and the perceived benefits and barriers to attendance from the perspective of SSPs leaders. Research Design and Methods: This study used a qualitative study design. In-depth interviews were conducted with SSPs leaders (n = 9) in the Washington D.C. metro area. Individuals were recruited from community- and college-based programs. Using content analysis, interviews were analyzed for key themes. Results: Programs served different populations, leading to different discussion such as college-based groups discussing alcohol use while community-based groups discussing issues with their child’s diabetes. SSPs leaders described informational support, emotional support, and peer networking as benefits of program attendance while logistics, stigma, and avoidance of diabetes as barriers to program attendance. Conclusions : Exploring the characteristics of SSPs is essential to understanding their utilization and role in self-management and empowering individuals with T1DM. SSPs offer many benefits, and SSP attendance should be encouraged.

We report our initial experience of using a microcatheter for contact aspiration of acute distal occlusions for recanalization. Endovascular technique and a case using Excelsior XT-27 microcatheter are presented. After manual suction within distal middle cerebral artery segments using a 50-ml syringe, instant and complete recanalization was obtained. Microcatheter suction thrombectomy using a 50-ml syringe can be considered a feasible treatment option for acute distal small artery occlusions.

Isocitrate dehydrogenase 2 (IDH2) is an essential enzyme in the mitochondrial antioxidant system, which produces nicotinamide adenine dinucleotide phosphate, and thereby defends against oxidative stress. We have shown that IDH2 downregulation results in mitochondrial dysfunction and reactive oxygen species (ROS) generation in mouse endothelial cells. The redox enzyme p66shc is a key factor in regulating the level of ROS in endothelial cells. In this study, we hypothesized that IDH2 knockdown-induced mitochondrial dysfunction stimulates endothelial inflammation, which might be regulated by p66shc-mediated oxidative stress. Our results showed that IDH2 downregulation led to mitochondrial dysfunction by decreasing the expression of mitochondrial oxidative phosphorylation complexes I, II, and IV, reducing oxygen consumption, and depolarizing mitochondrial membrane potential in human umbilical vein endothelial cells (HUVECs). The dysfunction not only increased mitochondrial ROS levels but also activated p66shc expression in HUVECs and IDH2 knockout mice. IDH2 deficiency increased intercellular adhesion molecule (ICAM)-1 expression and mRNA levels of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, and interleukin [IL]-1β) in HUVECs. The mRNA expression of ICAM-1 in endothelial cells and plasma levels of TNF-α and IL-1β were also markedly elevated in IDH2 knockout mice. However, p66shc knockdown rescued IDH2 deficiency-induced mitochondrial ROS levels, monocyte adhesion, ICAM-1, TNF-α, and IL-1β expression in HUVECs. These findings suggest that IDH2 deficiency induced endothelial inflammation via p66shc-mediated mitochondrial oxidative stress.

There is limited understanding about the obesity-related behaviors of diet, physical activity, and sedentary behavior in Korean American women. The purpose of this study was to cluster obesity-related behavior patterns of Korean American women and to examine group differences in acculturation, socioeconomic status (SES), and body mass index (BMI). A secondary analysis from a cross-sectional study was conducted using two-step cluster analysis for clustering groups. A total of 137 Korean American women ( M age = 42.7 years, SD = 3.9 years; M BMI = 23.1 kg/m2, SD = 3.1 kg/m2; 47.7% BMI ⩾ 23 kg/m2) participated. Three clusters were identified: healthy lifestyle, unhealthy lifestyle, and low physical activity but healthy diet group. The unhealthy lifestyle group was more likely to have high acculturation compared with other groups ( p = .03). SES and BMI were not significantly different between groups. Further intervention is needed to improve obesity-related behaviors of acculturated Korean American women.

Current guideline recommends intensive blood pressure (BP) control in hypertensive patients, but the appropriate target BP level after ischemic stroke due to intracranial atherosclerotic stenosis remains uncertain.In this randomized, single-blinded trial, patients with symptomatic internal carotid or middle cerebral artery steno-occlusion (50%) within 7-42 days after index stroke received intensive (target SBP 120 mmHg) or modest (target SBP 140 mmHg) BP control from April 2010 to December 2012. The primary outcome was the change in ischemic lesion volume in white matter lesions at the whole forebrain between baseline and 24 weeks as measured from fluid attenuation inversion recovery (FLAIR) images, which was tested in noninferiority test (noninferiority margin of 3 cm).Among 132 patients, follow-up FLAIR images were available in 111 (59 in the intensive and 52 in the moderate BP control groups). After 24 weeks, the SBP in the intensive group was significantly lower (124.6 ± 10.5 mmHg) than in the modest group (132.3 ± 10.6 mmHg). The ischemic lesion volume increased more in the intensive group (4.9 ± 18.3 cm) than the modest group (2.2 ± 8.2 cm), which failed to prove noninferiority. The frequency of new ischemic lesions on 24-week FLAIR images was nonsignificantly higher in the intensive group than the modest group [10 (16.9%) vs. 5 (9.6%), respectively; P = 0.26)]. Only one recurrent stroke developed during the study period in each group.Intensive BP control in intracranial atherosclerotic stenosis patients failed to prove noninferiority compared with modest BP control, and may increase ischemic lesion volume in the subacute stage.

CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation. Plasma levels and mRNA expression of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were markedly elevated in endothelium-specific CRIF1-knockout mice and CRIF1-silenced endothelial cells, respectively. Moreover, CRIF1 deficiency-induced vascular adhesion molecule-1 (VCAM-1) expression was consistently attenuated by the antioxidant N-acetyl-cysteine and NF-κB inhibitor (BAY11). We next showed that siRNA-mediated CRIF1 downregulation markedly activated NF-κB. SIRT1 overexpression not only rescued CRIF1 deficiency-induced NF-κB activation but also decreased inflammatory cytokines (TNF-α, IL-1β, and IL-6) and VCAM-1 expression levels in endothelial cells. These results strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-κB, all of which were inhibited by SIRT1 overexpression.

Objective “Wellness Champions for Change” (WCC) aims to create health-promoting school environments by training teachers and student leaders (5th or 8th graders) to promote Local Wellness Policy (LWP) implementation. LWPs are school district documents outlining food/physical activity (PA) policies. This abstract describes data collection/intervention implementation at the mid-point of the funding period and plans for dissemination. Description Twenty-one schools (12 elementary/9 middle) serving low-income families in three school districts and 572 students (evaluation cohort) were recruited in grades 3/4 or 6/7 to be followed for 2 years. Schools were block randomized to: WCC-teachers+student leaders, WCC-teachers only, control. Student-level impact is assessed via measures of height/weight (BMI-for-age calculated), PA (accelerometry), and diet (Perceptions of Diet at School screener). Implementation of teacher/student leader curricula is tracked through attendance/activity logs, fidelity checklists, and participant interviews. Local, state, and national dissemination planning is led by a partnership of extension agents, state department of education representatives, eXtension COP members, and WCC wellness specialists/investigators. Evaluation Students were 43% male, 56.5% in elementary school, 45.8% overweight/obese, and averaged 15 minutes/day of moderate-vigorous PA at school (30 minutes/day overall). Most lunches were from the school cafeteria (50%) or home (34%). During lunch, 60% reported consuming a fruit and 37% a vegetable. Six schools completed the intervention year and are in a sustainability-planning year. Of these, all WCC-teachers schools (n = 4) attended training, three built active wellness teams, two focused on PA opportunities and two on promoting school meals/smart snacks. Student leaders (n = 2 schools) focused on included advocating for PA time/promoting healthy eating through social marketing. Fifteen schools are in the intervention year with implementation tracking ongoing. Conclusion and Implications At the mid-point of a five-year project, schools and students within three districts have been recruited/evaluated, with intervention implementation ongoing. Two additional districts will participate in future years. Dissemination plans include train-the-trainer modules, an online professional credit course for teachers, and distributing the manualized student leader curricula to schools with active teacher wellness teams. Funding 2016-68001-24927.

Background: To investigate the effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on motor symptoms especially freezing of gait (FoG), and nonmotor symptoms in Parkinson disease (PD). Methods: In this randomized, double-blind, sham-controlled study, fifteen PD patients were enrolled. For 10 days, 5 Hz, both motor cortices and dorsolateral prefrontal cortex (DLPFC) were stimulated. The motor symptoms and FoG were evaluated by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, FoG questionnaire (FoG-Q), variable parameters of FoG, and kinematic gait analysis. Nonmotor symptoms were evaluated by the Korean version of non-Motor Symptoms Scale (K-NMSS), 39-item Parkinson disease questionnaire (K-PDQ39), Mini-Mental Status examination (K-MMSE), Montreal Cognitive Assessment (K-MoCA), and Frontal assessment battery (FAB). Results: Finally, 12 patients (real:8, sham:4) data were analyzed. FoG-Q and UPDRS part III were improved (p=0.002, 0.022) and variable parameters of FoG was improved after 10 days stimulation in real treatment group. In addition, their effects maintained until 6 weeks from the baseline. In nonmotor symptoms, K-NMSS and K-PDQ 39 were improved until 6 weeks in real treatment group (p=0.002, 0.002), however no changes were shown in cognitive function test. Conclusions: The high frequency rTMS was effective for FoG, in addition to motor and a few nonmotor symptoms in PD. J Korean Neurol Assoc 33(4):297-305, 2015

Nafamostat mesilate (NM), a serine protease inhibitor, has a broad range of clinical applications that include use as an anticoagulant during hemodialysis in cerebral hemorrhage patients, as a hemoperfusion anticoagulant for patients with intravascular coagulation, hemorrhagic lesions, and hemorrhagic tendencies, and for the improvement of acute pancreatitis. However, the effects of NM on acute cerebral ischemia have yet to be investigated. Thus, the present study utilized a rat model in which transient middle cerebral artery occlusion (MCAO) was used to induce ischemic injury to investigate the effects of NM on infarct volume and histological and biological changes. NM (1mg/kg) was intravenously administered prior to and after the MCAO procedure. Compared to control rats, the administration of NM significantly decreased infarct size and the extent of brain edema after the induction of focal ischemia via MCAO. Additionally, NM treatment attenuated MCAO-induced neuronal degeneration and activation of microglia and astrocytes. NM treatment also inhibited the MCAO-induced expression levels of glucose-regulated protein 78 (GRP78), CATT/EBP homologous protein (CHOP), and p-eukaryotic initiation factor 2α (eIF2α), which are endoplasmic reticulum (ER) stress markers, in the cerebral cortex. The present findings demonstrate that NM exerts neuroprotective effects in the brain following focal ischemia via, at least in part, the inhibition of ER stress.

Background Stroke is the number one cause of adulthood disability in Korea. Rehabilitation after stroke can minimize functional disability, enhance recovery toward independence, and optimize community reintegration. The inter-departmental stroke meeting (IDSM) is a potential method to improve rehabilitation outcomes in patients with stroke. We aimed to analyze the effect of IDSM on rehabilitation after acute ischemic stroke management. Methods Medical records of 753 patients with acute ischemic stroke admitted to the neurology department of our medical center between January and December 2014 were reviewed retrospectively. In May 2014, weekly IDSMs were initiated. All physicians responsible for the patient's care reviewed patient treatment, methods of secondary prevention, and future rehabilitation plans. Results The transfer rate significantly increased after initiation of IDSM (phase 2, 3) and the length of stay (LOS) before transfer to the rehabilitation department decreased significantly from 9.68 ± 8.50 days to 5.75 ± 2.12 days. There was a reduction in the total LOS from 52 ± 28.57 days to 35 ± 27.21 days after IDSMs were introduced. In non-transferred patients also, the total LOS reduced significantly. The transfer rate increased significantly and the LOS before transfer to the rehabilitation department decreased significantly after implementation of IDSM in a subgroup of patients with moderate to severe stroke. Conclusion The introduction of IDSM was significantly correlated with improvements in transfer rates and reduction of LOS in hospital. This finding shows that IDSMs are an important intervention to improve therapeutic progress and outcomes for patients with stroke., Graphical Abstract

Objective To develop and pilot-test Wellness Champions for Change (WCC) to enhance local wellness policy (LWP) implementation by forming wellness teams. Design Randomized, controlled school-level pilot study. Setting Five Maryland school districts. Participants A total of 63 elementary, middle, or high schools. Intervention(s) Developed from stakeholder interviews, focus groups, and existing programs. Schools were randomized within district to (1) WCC training (6-hour, single-day teacher training), (2) WCC training plus technical assistance (TA), or (3) delayed training (control). Main Outcome Measure(s) Online teacher/administrator survey pre-post (spring, 1 year apart) that examined the direct effect of the intervention on active wellness team formation (postintervention, 8-item sum score) and LWP implementation (29 items, not implemented to fully implemented)/indirect effect of intervention on LWP implementation via active wellness team formation. Analysis Adjusted linear or logistic regression and mediation modeling. Results Postintervention, WCC plus TA and WCC had more active wellness teams (vs control, β = 1.49, P = .02 and β = 1.42, P = .03, respectively). No direct effect of intervention on LWP implementation was found. Formation of active wellness teams mediated the association between both WCC plus TA and WCC and LWP implementation (WCC plus TA confidence interval [CI], 1.22–16.25; WCC CI, 10.98–15.61 [CI was significant without 0]). Conclusions and Implications The WCC intervention approaches indirectly affected LWP implementation through the formation of active wellness teams. These results support building and school-level wellness teams.

Background. Young adults living with type 1 diabetes (T1DM) often encounter poor health outcomes, such as uncontrolled blood glucose levels. Social support programs can be a helpful method to support T1DM self-management. Effectively planning and tailoring social support programs for young adults living with T1DM are crucial for improving these programs and associated outcomes. Objectives. This study convened an expert panel primarily composed of young adults living with T1DM to generate ideas and key components for sequential inclusion in social support programs prioritizing them. Method. Exploratory expert panel meetings consisting of four individuals living with T1DM were held where Nominal Group Technique and Ideawriting exercises were used to develop themes and discussion points. Results. Six themes emerged from the meetings representing areas of difficulty for young adults living with T1DM. Topics such as following self-care recommendations, nutrition, handling stress, coping with social situations, and navigating the health care system were identified as important issues facing young adults. Conclusions. By incorporating this approach into new or existing support group improved program discussions for young adults can be achieved and pertinent issues addressed, thus leading to improved health care outcomes.