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Background Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node. Methods To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. To control for the contribution of exogenous metabolites in vivo, we conducted our T cell functional studies in vitro. T cells were differentiated into memory and effector T cells using standardized protocols. Cells were analyzed using stable isotopic tracing studies, metabolomics, RNAseq, ATACseq, ChIPseq and histone proteomics. Results Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. Due to depressed OXPHOS, TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis. Due to the block of PDC activity, histone acetylation was reduced, as were most other types of post translational modifications. Transcriptional and functional profiling revealed abnormal CD8+ memory T cell differentiation in vitro. Conclusions Collectively, our data indicate that PDC integrates the metabolome and epigenome in memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.

Background: Limited data exist regarding the impact of changes in physical activity (PA) over time on ischemic stroke risk. Exploring this understudied area could help improve stroke prevention strategies and promote PA during the lifespan. Methods: We evaluated 11,089 Atherosclerosis Risk in Communities (ARIC) participants recruited in 1987–1989 who completed Visit 3 (1993–1995). We classified PA as meeting recommendations, not meeting recommendations, or no PA. Categories of increased, decreased, stable high, and stable low PA and a continuous PA variable were also evaluated. Crude and adjusted Cox regression models were used to characterize the association of 6-year changes in PA and ischemic stroke risk. Results: Participants had a mean age of 60 years. During a median of 21 years, 762 ischemic stroke events occurred. Compared to the participants with recommended PA at both visits, those with no PA had 46% higher hazards of ischemic stroke (hazard ratio (HR) = 1.46 (95% confidence interval (CI) = 1.17, 1.82)), and those with recommended PA at Visit 1 and no PA at Visit 3 also had 37% higher hazards (HR = 1.37 (95% CI = 1.02, 1.83)). Participants who increased their PA from Visit 1 to Visit 3 had 23% lower hazard than those with stable low PA at both visits (HR = 0.77 (95% CI = 0.63, 0.94)), while those who decreased their PA had 25% higher hazards compared to those with stable high PA at both visits (HR = 1.25 (95% CI = 1.01, 1.54)). Conclusion: Physical inactivity during midlife increases ischemic stroke risk, while meeting PA recommendations reduces it.

BACKGROUND: The role of immunological disorders in the development of atopic dermatitis (AD) is currently beyond doubt. AIMS: Changes in the serum levels of IL-4, IL-10 and IL-13 in patients with atopic dermatitis (AD) after UV therapy combined with standard drug treatment have been studied. MATERIALS AND METHODS: The study included 80 patients with moderate to severe AD and 80 healthy volunteers. The patients with AD received a course of 311 nm UVB phototherapy combined with standard drug therapy. Serum IL-4, IL-10 and IL-13 levels were determined through enzyme-linked immunosorbent assay (ELISA). RESULTS: In the studied sample, patients with AD were found to have statistically significantly higher serum levels of IL-10 and IL-13 compared with healthy volunteers of the control group. Serum IL-10 level was 18.3 pg/ml in patients with AD and 13.2 pg/ml in those of the control group; the level of IL-13 was 15.8 pg/ml and 11.5 pg/ml, respectively; after the course of 311 nm UVB, serum IL-10 and IL-13 levels in patients with AD decreased (IL-10 by 27.8% and IL-13 by 12.5%). IL-4 values did not differ significantly in patients with AD and those in the control group, being 0.06 pg/ml and 0.05 pg/ml, respectively; after the course of phototherapy, serum IL-4 levels remained unchanged and were equal to 0.05 pg/ml. CONCLUSION: The results obtained confirm the assumptions about the significant role of IL-10 and IL-13 in the mechanisms of AD regulation and pathogenesis and demonstrate the anti-inflammatory efficacy of phototherapy (311 nm UVB) in patients with severe and moderate AD.

This article describes the clinical aspects and treatment of seborrheic keratosis. The authors report the highly effective use of destructive therapy, 1.5% zinc chloropropionate solution in 2-chloropropionic acid, in patients with seborrheic keratosis.

Skin cancer is the leading cancer type (12.6%) in both men and women in Russian Federation. Basal cell skin cancer is the most common non-melanoma, malignant epithelial skin tumor. The identification of skin tumors in the early stages is one of the priority purposes of modern medicine because it facilitates the radical treatment of these diseases. Notably, an examination by a dermatologist should be performed in conjunction with non-invasive diagnostic methods.

In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level and organization associated with CLL-cell birth rate and the type and consequences of BCR signaling in humans and mice. The latter IgM-driven effects were abrogated when BCR signaling was inhibited. Collectively, these studies demonstrated a critical, selective role for IgM in BCR signaling and B cell fate decisions, possibly opening new avenues for CLL therapy., publishedVersion

Explored from the viewpoint of the faculty member, nonprofit director, and service-learning staff, this chapter provides insight into the complexity of the service-learning relationship in rural communities. Specifically, it provides perspectives that highlight the cultivation and maintenance of a relationship with a local nonprofit, challenges of incorporating and implementing a e-service-learning project in a hybrid format, and the outcome of the e-service-learning project between a graduate level public health course and a free medical clinic that serves the medically uninsured. These highlights will be discussed through sections detailing the geographical location of the area, through an overview of the local nonprofit community partner, which is a free medical clinic, a review of the community partners various university partnerships, an overview of e-service-learning within the graduate level course, the faculty member perspective, the community partner perspective, and the service-learning staff member perspective.

A comprehensive study is made of the properties of samples of BiFe1−xMnxO3 (0.05 ≤ x ≤ 0.15) solid solutions synthesized using the sol-gel technique. Stabilization of the main phase, a reduction in the average granule size, and an increase in the dielectric constant are observed upon an increase in concentration x. The presence of Mn ions in BiFe1−xMnxO3 solid solutions results in semiconductor-type conductivity and the emergence of magnetic ordering at 605 K (х = 0.05) and 550 K (х = 0.15).

Numerous investigations implicate pronounced changes in the functioning of T-type Ca2+ channels localized on the somata of primary nociceptor units in the development and maintenance of painful diabetic neuropathy. This review highlights the role of T-type Ca2+ channels of nociceptive afferents in the processing of pain signals under diabetic conditions, as well as suggests a promising therapeutic strategy to treat painful diabetic neuropathy.

Objectives To better understand the disproportionate burdens from cancer, cardiovascular disease, diabetes mellitus, stroke, and other chronic conditions related to energy balance, we studied diet and physical activity patterns in younger and older adults in rural Appalachia by using a nonclinical, cross-sectional, community-based sampling approach. Methods A total of 651 younger (ages 18-59) and 254 older (ages ≥60) Appalachians were recruited from 43 churches or community organizations. Participants answered questions about fruit and vegetable intake and physical activity. Analyses were adjusted for clustering within churches. Results Compared with older Appalachians, younger Appalachians consumed significantly fewer fruits and vegetables (P = 0.01) and reported significantly more moderate-to-vigorous physical activity (P = 0.01). Regardless of age, engagement in healthy behaviors was suboptimal and well below national averages. Conclusions This community-based sample demonstrated elevated behavioral risk factors that likely contribute to some of the nation's highest rates of premature mortality. Despite suboptimal dietary intake and physical activity, results indicate some potential leverage points between the generations that may be used to improve health. For example, the older generation could benefit from engaging with their younger relatives in physical activities while advocating for a better-rounded diet. Given traditions of intergenerational connectedness, mutual aid, and self-reliance, transmission of healthier behaviors across the generations may be beneficial in the rural Appalachian context.

PURPOSE The Centers for Disease Control and Prevention identified rural mothers as a priority population for targeted breastfeeding promotion programs. In Georgia, breastfeeding rates lag behind the national ones. This study examines rural-urban differences and trends over time in breastfeeding initiation and continuation (breastfeeding for at least 8 weeks) among women with a live birth from 2004 to 2013 in Georgia. METHODS This observational study is based on the Pregnancy Risk Assessment Monitoring System data. The National Center for Health Statistics urban-rural continuum codes were used to operationalize mother's county of residence. Prevalence of breastfeeding was estimated from the logistic regression models, unadjusted and adjusted for sociodemographic and health-related characteristics. FINDINGS In both unadjusted and adjusted analyses, significantly fewer rural (60.2%, 95% CI: 57.5-62.9 and 64.5%, 95% CI: 61.3-67.6, respectively) than urban (74.9%, 95% CI: 73.4-76.4 and 72.9%, 95% CI: 71.1-74.6, respectively) mothers initiated breastfeeding (P

A slowly decaying anomaly of magnetic susceptibility (characteristic time τ ~ 103 s) is revealed in studying the ferromagnetic–paramagnetic phase transition in polycrystalline cobaltite GdBaCo2O5.53 that occurs due to the remaining short-range magnetic order at temperatures above the Curie point (TC = 275 K). High hydrostatic pressures (up to 1.48 GPa) are found to have a weak effect on TC with baric coefficient dTC/dP = 2.1 K/GPa.

The work is devoted to the design of a spraying device for the combustion chamber GTE-65.1 on liquid fuel. The paper presents the following results: 1) The 3D calculations of the air channels characteristics for two burners types — pilot and main — were carried out. Data were obtained on the flow and pressure fields inside and at the burners outlet, and also the volumes of the reverse flow zones. 2) The main and pilot nozzles have been designed for the two spraying devices types. The values of droplet dispersity and spray angle were obtained, depending on the fuel injection pressure. 3) Based on the calculations carried out, the models of two spraying liquid fuel devices were designed and manufactured, the design of which is based on the design of the single-fuel combustion chamber (CC) on natural gas burners for GTE-65.1. At the next stage of the work, it is planned to carry out experimental studies of the two devices models aimed at obtaining an aerosol mixture with the desired properties to ensure uninterrupted operation of the GTE-65.1 on liquid fuel. Some preliminary experimental data are presented in this paper.

In the production technology of non-autoclaved cellular concrete, there are a number of technological changes, the possibility of intensifying which is possible by inserting chemical and mineral additives-stabilizers of the foam matrix. These additives can simultaneously act as accelerators of hardening and setting, as well as stabilize the foam matrix at the initial stage. For the research, the foam matrix mineralizers—fine-ground sulfates were selected for the purpose of possible intensification of the injection molding technology of cellular concrete. The solution to this problem lies in the assessment of the main mixing parameters, the choice of raw materials, the availability of additives and the overall manufacturability of the production process. The paper clarifies the effect of foam matrix mineralizers together with additives that accelerate setting, and also evaluates the effect of a complex of additives on the main properties of foams: durability, multiplicity and syneresis. The influence of the pH environment on the primary characteristics of foams obtained on the basis of foaming agents of various nature is considered separately. The regularities of the influence of the hydrolysis constants of additive on the multiplicity of the resulting foam were identified; the possibility of changing the pH value of the environment on the stability of the foam matrix and initial syneresis was evaluated. Recommendations on the use of some sulfates together with foam thickeners in the technology of non-autoclaved foam concrete are given.

Tobacco use delivers nicotine, tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs), which are metabolized and excreted in urine offering useful biomarkers of exposure. Previous studies compared individual toxicants across tobacco users. Based on a group of biomarkers, cluster analysis was used to define tobacco toxicant exposure profiles. Clusters with distinct exposure profiles, were determined and described, based on levels of urinary biomarkers of exposure to nicotine, TSNAs, VOCs, and PAHs among a national sample of current, established, adult tobacco users, and examine the association of use behavior and cluster membership. The PATH Biomarker Wave 1 data were analyzed. Current established tobacco users with complete urinary biomarker data were included (N = 6724). User groups included cigarette smokers, users of electronic cigarette (ECIG), smokeless tobacco (SLT), and dual and poly tobacco users. Cluster analysis, pairwise comparisons, and multinomial logistic regression were conducted. Cigarette smokers were primarily in clusters with high biomarker concentrations across all groups, but actual concentrations were associated with smoking quantity. A cluster with high TSNAs but low levels of PAHs and VOCs was heavily populated by SLT users. Exclusive ECIG users, depending on use frequency, were predominantly in clusters with low biomarker concentrations, except for one cluster that had relatively high TSNAs. Clusters heavily populated by dual and poly tobacco users were the same as those heavily populated by cigarette smokers. Ten exposure profiles (clusters) were determined and linked to tobacco use behavior. Findings could inform future research and policy initiatives.

While earlier studies on men having sex with men (MSM) tended to examine infection-related cancers, an increasing number of studies have been focusing on effects of sexual orientation on other cancers and social and cultural causes for cancer disparities. As a type of tertiary research, this umbrella review (UR) aims to synthesize findings from existing review studies on the effects of sexual orientation on cancer. Relevant peer-reviewed systematic reviews (SRs) will be identified without date or language restrictions using MEDLINE, Cochrane Database of Systematic Reviews, and the International Prospective Register for Systematic Reviews, among others. The research team members will prepare the data extraction forms. Two reviewers will independently assess extracted SRs using the Assessment of Methodological Quality of Systematic Reviews. A third reviewer will weigh in to resolve discrepancies. The reviewers will be blinded to publisher, journal, and authors, making their judgements on the title, year, and abstract. The Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist will guide data synthesis. By collating evidence from multiple reviews into one accessible and usable document, our first UR on global epidemiology of malignancies among MSM would serve as an evidence-based decision-making tool for the public health community.

Introduction: Engagement in leisure-time physical activity (PA) levels recommended by the American Heart Association (AHA) is inversely associated with both ischemic and hemorrhagic stroke risk. PA levels fluctuate over the lifecourse, but the association between changes in PA from mid- to late-life and stroke risk is unknown. Hypothesis: Participants who maintained ideal levels of PA or increased their PA across 6 years will have lower ischemic and hemorrhagic stroke risk relative to those who had persistently poor PA. Methods: We included 11,658 participants of the Atherosclerosis Risk in Communities study without a history of CHD or stroke at visit 3 (1993-1995). Leisure-time PA was assessed using the modified Baecke questionnaire at visits 1 and 3 and categorized according to the AHA guidelines for PA (ideal, intermediate, or poor). All adjudicated definite and probable incident ischemic and hemorrhagic strokes between visit 3 and end of year 2013 were included. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ischemic and hemorrhagic stroke by categories of PA at visits 1 and 3. Those with poor PA at both visits were the referent group. We adjusted for age, sex, race/center, smoking, alcohol consumption, hypertension, diabetes mellitus, LDL, HDL, triglycerides, and body mass index. Results: During a median of 18.7 years of follow-up, 640 incident ischemic strokes and 76 hemorrhagic strokes occurred. In adjusted analyses, participants with ideal PA at both visits had a significantly lower ischemic stroke risk (HR=0.75 (0.59, 0.96)) but not significantly lower hemorrhagic stroke risk (HR=1.27 (0.65, 2.48)). Those whose PA levels increased from poor to ideal also had lower ischemic stroke risk (HR=0.74 (0.54, 1.03)) but not hemorrhagic stroke risk (HR=0.74 (0.28, 2.02)). Conclusion: Increasing PA between visit 1 and visit 3 was associated with lower ischemic stroke risk. Increasing PA may be an important component of stroke prevention.

Despite judicious monitoring and care, patients with fatty acid oxidation disorders may experience metabolic decompensation due to infection which may result in rhabdomyolysis, cardiomyopathy, hypoglycemia and liver dysfunction and failure. Since clinical studies on metabolic decompensation are dangerous, we employed a preclinical model of metabolic decompensation due to infection. By infecting mice with mouse adapted influenza and using a pair-feeding strategy in a mouse model of long-chain fatty acid oxidation (Acadvl(−/−)), our goals were to isolate the effects of infection on tissue acylcarnitines and determine how they relate to their plasma counterparts. Applying statistical data reduction techniques (Partial Least Squares-Discriminant Analysis, PLS-DA), we were able to identify critical acylcarnitines that were driving differentiation of our experimental groups for all the tissues studied. While plasma displayed increases in metabolites directly related to mouse VLCAD deficiency (e.g. C16 and C18), organs like the heart, muscle and liver also showed involvement of alternative pathways (e.g. medium chain FAO and ketogenesis), suggesting adaptive measures. Matched correlation analyses showed strong correlations (r > 0.7) between plasma and tissue levels for a small number of metabolites. Overall, our results demonstrate that infection as a stress produces perturbations in metabolism in Acadvl(−/−) that differ greatly from WT infected and Acadvl(−/−) pair-fed controls. This model system will be useful for studying the effects of infection on tissue metabolism as well as evaluating interventions aimed at modulating the effects of metabolic decompensation.

Purpose The purpose of this study was to examine the importance of rural location in the likelihood of adolescent drunk driving and riding in a vehicle with a driver under the influence while controlling for a variety of student-, school-, and county-level factors. Methods Data from the 2013 Georgia Student Health Survey (GSHS) II (a statewide assessment of student health in public school students in Georgia) were analyzed using multilevel binary regressions to examine rural-urban differences in prevalence of driving under the influence (11th and 12th graders only; n = 114,907) and riding with a driver under the influence (9th -12th graders; n = 258,610), controlling for school-level race, gender, and income, in addition to county-level education level, unemployment, alcohol use, and smoking. Findings Across geographies, students were twice as likely to report riding with a driver under the influence (10.32%) as driving under the influence (4.16%). While both outcomes were more likely among rural adolescents in unadjusted analyses, in adjusted analyses, rural adolescents were not significantly more likely to drive under the influence (ORadj = 1.19; P = .055), but they were significantly more likely to ride with a driver under the influence (ORadj = 1.18; P = .002). Conclusions Our findings suggest that riding with a driver under the influence rather than driving under the influence may be a more pressing public health issue for adolescents in rural areas. Future research focused on the formative work necessary to build novel, culturally tailored interventions should be conducted to minimize the associated substantial burden of motor vehicle deaths within rural adolescents.

The effect of hydrogen additives on the working process of a piston-type gasoline engine is studied. The indicator diagram has been built, and the operation of the piston engine on gasoline-air mixtures enriched with hydrogen in the amount of 0…20 % of the volume of air entering the engine has been analyzed. The possibility of obtaining satisfactory parameters when the engine works on gasoline with hydrogen additives is shown. The dynamics of the engine performance is studied depending on the oxidant excess coefficient. It has been established that the oxidizer excess ratio at which the maximum indicator pressure is reached is moved to the zone of poor mixtures. When the mixture is enriched with hydrogen in the amount of 20 % of the air volume, the maximum of indicator pressure pimax = 5.3...5.8 MPa is reached at α = 1.15...1.25, while for 10 % hydrogen addition the maximum pimax = 4.9...5.2 MPa takes place at α = 1.05...1.10 against pimax = 4.7...5.1 MPa at α = 0.90...0.95 for pure gasoline. According to the indicator diagram, the dynamics of intra-cylinder parameters is studied when the mixture is enriched with hydrogen. Thus, with a 20 % hydrogen addition the mean indicator pressure decreases by 12...19 %, despite a slight increase in the maximum cycle pressure (3...18 %), compared with gasoline operation, which leads to a proportional decrease in both the engine indicator power, and the indicator efficiency.

Complex magnetic, resistive, and dielectric studies of Pr1–xCaxMnO3 (х = 0.15–0.30) manganites reveal multiferroic properties at T≫TC in these solid solutions. States with local magnetization in the form of ferromagnetic clusters (nucleation temperature T* ≈ 700 K) and high dielectric constants coexist in the temperature window TC ≤ T ≤ T*. There is a correlation between the temperature dependences of specific resistance and specific magnetization.

The concentration of 16 polycyclic aromatic hydrocarbons (PAHs) in the gasoline combustion products emitted into the atmosphere by internal combustion engines (ICE) has been measured using the gas chromatography method. The concentrations of PAHs in the exhaust gases sampled behind a catalytic converter has been determined when the ICE operates in five modes: idle mode, high speed mode, load mode, ICE cold start mode (engine warm-up) and transient mode. Using 92 RON, 95 RON and 98 RON gasoline the effect of the octane number of gasoline on the PAHs content in the exhaust gases has been revealed. The concentration of the most carcinogenic component (benzo(α)pyrene) in the exhaust gases behind a catalytic converter significantly exceeds a reference value of benzo(α)pyrene in the atmospheric air established by the WHO and the EU for ICE in the load mode.

This study examined the association between adherence to American College of Sports Medicine and American Cancer Society guidelines on aerobic and muscle-strengthening activities and mortality risks among 3+ year cancer survivors in the U.S.The observational study was based on 1999-2009 National Health Interview Survey Linked Mortality Files with follow-up through 2011. After applying exclusion criteria, there were 13,997 observations. The hazard ratios (HRs) for meeting recommendations on muscle-strengthening activities only, on aerobic activities only, and on both types of physical activity (i.e., adhering to complete guidelines) were calculated using a reference group of cancer survivors engaging in neither. Unadjusted and adjusted HRs of all-cause, cancer-specific, and cardiovascular disease-specific mortalities were estimated using Cox proportional hazards models.In all models, compared to the reference group, cancer survivors adhering to complete guidelines had significantly decreased all-cause, cancer-specific, and cardiovascular disease-specific mortalities (HRs ranged from 0.37 to 0.64, p's 0.05). There were no statistically significant differences between hazard rates of cancer survivors engaging in recommended levels of muscle-strengthening activities only and the reference group (HRs ranged from 0.76 to 0.94, p's 0.05). Wald test statistics suggested a significant dose-response relationship between levels of adherence to complete guidelines and cancer-specific mortality.While muscle-strengthening activities by themselves do not appear to reduce mortality risks, such activities may provide added cancer-specific survival benefits to 3+ year cancer survivors who are already aerobically active.

Background Over the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking. Objectives To examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992–2013. Methods The disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models. Results The 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the “Other” Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P Conclusions OC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research.