Activity

Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p less then 0.01 and false discovery rate less then 0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.Farmland management and irrigation scheduling are vital to a productive agricultural economy. A multistage stochastic programming model is proposed to maximize farmers’ annual profit under uncertainty. The uncertainties considered include crop prices, irrigation water availability, and precipitation. During the first stage, pre-season decisions including seed type and plant density are made, while determinations of when to irrigate and how much water to be used for each irrigation are made in the later stages. The presented case study, based on a farm in Nebraska, U.S.A., showed that a 10% profit increase could be achieved by taking the corn price and irrigation water availability uncertainties into consideration using two-stage stochastic programming. An additional 13% profit increase could be achieved by taking precipitation uncertainty into consideration using multistage stochastic programming. The stochastic model outperforms the deterministic model, especially when there are limited water supplies. These results indicate that multistage stochastic programming is a promising method for farm-scale irrigation management and can increase farm profitability.Objectives miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients. The aims of our study were to evaluate miR-155 levels in plasma, to investigate its gene methylation level, and to correlate these levels with RA disease activity. Methods One hundred and twenty-five patients with RA, and 30 age and sex-matched healthy controls (HC) were enrolled. Whole blood and plasma samples were collected and stored at -80°C until analysis. DAS28 score at the time of the blood draw was used to assess RA disease activity. The methylation status of miR-155 host gene was determined in whole blood by quantitative real-time methylation-specific PCR (qPCR). miR-155 expression levels were evaluated by quantitative reverse transcription PCR. Results We found significantly lower circulating miR155 levels in RA patients compared to HC. Interestingly, the miR-155 gene methylation level was significantly higher in RA patients than in HC. miR-155 levels did not correlate with ACPA or RF positivity or disease activity. Conclusions We show here higher miR-155 methylation in whole blood and lower plasma miR155 expression in RA patients in comparison to HC. The evaluation of miR-155 host gene methylation status or miR155 plasma level might be a potentially useful marker in RA determination.Cognitive control and incentive sensitivity are related to overeating and obesity. Optimal white matter integrity is relevant for an efficient interaction among reward-related brain regions. However, its relationship with sensitivity to incentives remains controversial. selleck inhibitor The aim of this study was to assess the incentive sensitivity and its relationship to white matter integrity in normal-weight and overweight groups. Seventy-six young adults participated in this study 31 were normal-weight (body mass index [BMI] 18.5 to less then 25.0 kg/m2, 14 females) and 45 were overweight (BMI ≥ 25.0 kg/m2, 22 females). Incentive sensitivity was assessed using an antisaccade task that evaluates the effect of incentives (neutral, reward, and loss avoidance) on cognitive control performance. Diffusion tensor imaging studies were performed to assess white matter integrity. The relationship between white matter microstructure and incentive sensitivity was investigated through tract-based spatial statistics. Behavioral antisaccade results showed that normal-weight participants presented higher accuracy (78.0 vs. 66.7%, p = 0.01) for loss avoidance incentive compared to overweight participants. Diffusion tensor imaging analysis revealed a positive relationship between fractional anisotropy and loss avoidance accuracy in the normal-weight group (p less then 0.05). No relationship reached significance in the overweight group. These results support the hypothesis that white matter integrity is relevant for performance in an incentivized antisaccade task.Background Laypersons’ efforts to initiate basic life support (BLS) in witnessed Out-of-Hospital Cardiac Arrest (OHCA) remain comparably low within western society. Therefore, in order to shorten no-flow times in cardiac arrest, several police-based first responder systems equipped with automated external defibrillators (Pol-AED) were established in urban areas, which subsequently allow early BLS and AED administration by police officers. However, data on the quality of BLS and AED use in such a system and its impact on patient outcome remain scarce and inconclusive. Methods A total of 85 Pol-AED cases were randomly assigned to a gender, age and first rhythm matched non-Pol-AED control group (n = 170) in a 12 ratio. Data on quality of BLS were extracted via trans-thoracic impedance tracings of used AED devices. Results Comparing Pol-AED cases and the control group, we observed a similar compression rate per minute (p = 0.677) and compression ratio (p = 0.651), mirroring an overall high quality of BLS administered by police officers. Time to the first shock was significantly shorter in Pol-AED cases (6 minutes [IQR 2-10] vs. 12 minutes [IQR 8-17]; p less then 0.001). While Pol-AED was not associated with increased sustained return of spontaneous circulation (p = 0.564), a strong and independent impact on survival until hospital discharge (adj. OR 1.85 [95%CI 1.06-3.23; p = 0.030]) and a borderline significance for the association with favorable neurological outcome (adj. OR 1.58 [95%CI 0.96-2.89; p = 0.052) were observed. Conclusion We were able to demonstrate an early start and a high quality of BLS and AED use in Pol-AED assessed OHCA cases. Moreover, the presence of Pol-AED care was associated with better patient survival and borderline significance for favorable neurological outcome.Objective Lifestyle is considered as a key factor that affects one’s health and quality of life, and it has become the focus of increasing research interest worldwide. Research has shown that lifestyle is an important health determinant in preventive health care. However, lifestyle is a multifaceted construct and there is limited evidence regarding lifestyle assessment, which evaluates individuals’ multi-domain lifestyle factors. This study developed evaluation items for measuring the multifaceted lifestyle profile of community-dwelling older adult to prevent chronic disease and improve their health and quality of life. Methods Opinions from 21 experts with experience in older adults and lifestyle research were collected from December 2019 to January 2020. Three Delphi surveys were carried out, based on previous research. The first survey gathered opinions using a mix of open- and closed-ended questions regarding items of the older adults’ multifaceted lifestyle profile. The second was conducted after adding and modifying several items based on the first Delphi survey. In the third survey, after the results of the second one were presented to the expert panels, final opinions from the experts were converged. Results In total, 59 items were selected as the first Delphi results; 62 items were selected as the second results after adding and modifying the values below a content validity ratio of .42; and 62 items were selected as the third Delphi results. The average content validity ratio of the final Delphi survey was .92, the stability was .18, and the consensus was .80, which were all high. Conclusions This study verified the content validity of the evaluation items for community-dwelling older adults’ multifaceted lifestyle profile. In the future, it is expected that after verifying the validity and reliability, this will be used as a standardized assessment tool in clinical environments.Background Children living with HIV remain undiagnosed due to missed opportunities along the prevention of mother-to-child HIV transmission cascade. This study addresses programmatic gaps in the cascade by describing pregnancy and HIV-related services received by mothers of children newly identified as HIV-positive through active case finding. Methods This was a prospective observational cohort (2017-2018) of HIV-positive children less then 15 years of age newly diagnosed at study facilities and/or surrounding communities in Kenya and Uganda. At enrollment, caregivers were interviewed about maternal and child health and HIV history. Child medical and laboratory information was abstracted at two months post-diagnosis. Descriptive summary statistics were calculated; associations between selected factors and child age at HIV diagnosis were evaluated using generalized estimating equations. Results 174 HIV-positive children (median age 2.4 years) were enrolled. Among maternal caregivers, 110/132 (83.3%) attended systems and interventions to ensure HIV-positive women receive lifelong antiretroviral therapy throughout the cascade, and broader implementation of community case finding so children not engaged in care receive testing services.The perishable nature of fresh agricultural products and their vulnerability to environmental impacts make fresh agricultural product supplies susceptible to more complex social risks and unpredictable natural risks. This study identifies 13 social and natural risk factors that could adversely affect the fresh agricultural product supply and uses ISM and MICMAC to develop a hierarchical structure of the risks to analyze the correlation of these risk factors. The results showed that these risk factors have a strong positive correlation, a reasonable risk-sharing mechanism should be established for the fresh agricultural product supply and the improvement in the supervision error correction system should be strengthened.