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040), prevent overeating (adjR2 = .034), cope with body dissatisfaction (adjR2 = .046), and cope with nicotine withdrawal-related appetite increases (adjR2 = .030). CONCLUSION Distress intolerance may play an etiological role in maladaptive use of cigarettes to control appetite, weight, and body dissatisfaction among daily smokers, particularly those with weight- or shape-related concerns. Interventions aimed at increasing perceived ability to withstand distress could potentially reduce reliance on cigarettes for the aforementioned purposes.Human noroviruses are the major cause of non-bacterial acute gastroenteritis worldwide. Since no therapeutic agent has been proven to prevent human norovirus infection yet, preventive healthcare interventions to block the infection routes play an important role in infection control. One of the possible infection routes of human noroviruses are through contaminated hands, but no hand antiseptics have been proven effective. Olanexidine gluconate is a new biguanide compound that has already been approved for sale as an antiseptic for the surgical field in Japan. A new hand antiseptic was developed using olanexidine gluconate in this study, and its virucidal efficacy against human noroviruses was evaluated using modified RT-qPCR that can account for genome derived from intact viruses using RNase A and photo-reactive intercalators. We tested the virucidal efficacy of five materials; two olanexidine gluconate antiseptics (hand rub formulation and surgical field formulation), two kinds of ethanol solutions at different pH (approx. 3 or 7), and a base component of olanexidine gluconate hand rub formulation against 11 human norovirus genotypes by culture-independent methods. this website The infectivity of murine norovirus (MNV), a surrogate for human norovirus, was significantly reduced after use of the antiseptics. The olanexidine gluconate hand rub demonstrated the strongest virucidal efficacy against human norovirus among the five tested materials. This study showed that olanexidine gluconate has the potential to become a strong tool for the prevention of human norovirus infection.INTRODUCTION To assess treatment outcome and prognostic factors associated with prolonged survival in patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). METHODS/PATIENTS This study retrospectively reviewed 200 patients with 324 BM treated with one fraction (15-21 Gy) or 5-10 fractions (25-40 Gy) between January 2010 and August 2016. 26.5% of patients received whole brain radiotherapy (WBRT) and 25% initial surgery. Demographics, prognostic scales, systemic and local controls, patterns of relapse and rescue, toxicity, and cause of death were analyzed. A stratified analysis by primary tumor was done. RESULTS Median overall survival (OS) was 8 months from SRS/HFSRT. Breast cancer patients had a median OS of 17 months, followed by renal (11 months), lung (8 months), colorectal (5 months), and melanoma (4 months). The univariate analysis showed improved OS in females (p 0.004), RPA I-II (p  less then  0.001) initial surgery (p  less then  0.001), absence of extracranial disease (p 0.023), and good disease control (p 0.002). There were no differences in OS or local control between SRS and HFSRT or in patients receiving WBRT. Among 44% of brain recurrences, 11% were in field. 174 patients died, 10% from confirmed intracranial progression. CONCLUSIONS SRS and HSFRT are equally effective and safe for the treatment of BM, with no exceptions among different primary tumors. link2 Disease control, surgery, age, and prognostic scales correlated with OS. However, the lack of survival benefit regarding WBRT might become logical evidence for its omission in a subset of patients.BACKGROUND The role of DNA damage response (DDR) proteins is poorly understood in uveal melanoma. ATR belongs to one of those proteins that induce DDR by arresting the cell cycle which leads to DNA repair. ATR is localized at position 23 on the same chromosome 3 where BAP1 is located at position 21.1 which is a known poor prognostic marker of UM. The aim of our study is to detect the expression of ATR at the protein and RNA levels and determine its prognostic significance. METHODS Expression of nuclear ATR was investigated on sixty-nine UM patients. Formalin-fixed paraffin-embedded choroidal melanoma samples were taken to evaluate the expression of ATR. Fifty samples were also validated by real-time PCR. Results of both protein and mRNA were then correlated with clinicopathological parameters. To determine the prognostic significance, Kaplan-Meier and multivariate analyses were performed. RESULTS Loss of ATR protein was seen in 72% cases which was statistically significant with epithelioid cell type (p = 0.005), tumor thickness (p = 0.016), mitotic figures (p = 0.001) and BAP1 loss (p  less then  0.001). At the transcriptional level loss of ATR was seen in 76% cases which were statistically significant with metastasis (p = 0.046), staging (0.044) and loss of BAP1 (p = 0.022). On multivariate analysis loss of ATR and tumor staging came out to be independent prognostic parameters. CONCLUSION Our data suggest that ATR might serve as a potential prognostic marker in UM patients and could serve as a potential therapeutic target.Elucidation of the molecular mechanism underlying the metabolic adaptation is critical to understand homeostasis of life. This review provides the concept, experimental and computational methods, to deal with this issue using "trans-omics" approaches.Recent developments in the computational study of energy transport in proteins are reviewed, including advances in both methodology and applications. The concept of energy exchange network (EEN) is discussed, and a recent calculation of EENs for the allosteric protein FixL is reviewed, which illustrates how residues and protein regions involved in the allosteric transition can be identified. Recent work has examined relations between EENs and protein dynamics as well as structure. We review some of the computational studies carried out on several proteins that explore connections between energy conductivity across polar contacts in proteins and between proteins and water and equilibrium dynamics of the contacts, and we discuss some of the recent experimental work that addresses this topic.The anticancer drug dasatinib (Sprycel) is a BCR-ABL1-targeted tyrosine kinase inhibitor used in treating chronic myelogenous leukemia that has been shown in clinical trials to display cardiovascular toxicities. While dasatinib potently inhibits BCR-ABL1, it is not a highly selective kinase inhibitor and may have off-target effects. A neonatal rat cardiac myocyte model was used to investigate potential mechanisms by which dasatinib damaged myocytes. The anthracycline cardioprotective drug dexrazoxane was shown to be ineffective in preventing dasatinib-induced myocyte damage. Dasatinib treatment increased doxorubicin accumulation in myocytes and doxorubicin-induced myocyte damage, likely through its ability to bind to one or more ABC-type efflux transporters. Dasatinib induced myocyte damage either after a brief treatment that mimicked the clinical situation, or more potently after continuous treatment. Dasatinib slightly induced apoptosis in myocytes as evidenced by increases in caspase-3/7 activity. Dasatinib treatment reduced pERK levels in myocytes most likely through inhibition of RAF, which dasatinib strongly inhibits. Thus, inhibition of the RAF/MEK/ERK pro-survival pathway in the heart may be, in part, a mechanism by which dasatinib induces cardiovascular toxicity.Obsessive-compulsive disorder (OCD) is an important neuropsychiatric disorder worldwide. Common treatments of OCD include serotonergic antidepressants, which can cause potentially serious side effects. We assessed the effects of Lactobacillus casei (L. casei) Shirota consumption in an animal model of OCD. OCD-like symptoms were induced in rats by the chronic injection of the D2/D3 dopamine agonist quinpirole hydrochloride. Rats were classified into five groups of 6 rats. Four groups were injected chronically with quinpirole (0.5 mg/kg, twice weekly for 5 weeks). They were fed with L. casei Shirota (109 CF/g, daily for 4 weeks) (group 1), fluoxetine (10 mg/kg, daily for 4 weeks) (group 2), combination of L. casei Shirota and fluoxetine (group 3), and normal saline (positive control group). The last group did not receive dopamine agonist and was only injected with saline (negative control group). Expression levels of brain-derived neurotrophic factor (Bdnf), solute carrier family 6 member 4 (Slc6a4), and 5-hydroxytryptamine receptor type 2A (Htr2a) were assessed in orbitofrontal cortex tissues of all rats. Behavioral tests showed improvement of OCD signs in rats treated with L. casei Shirota, fluoxetine, and a combination of drugs. Quantitative PCR analysis showed a remarkable decrease in the expression of Bdnf and an increase in the expression of Htr2a in quinpirole-treated rats. After treatment with L. casei Shirota and fluoxetine, the expression level of Bdnf was increased remarkably, whereas Htr2a expression was decreased. The current study showed the effectiveness of L. casei Shirota in the treatment of OCD in a rat model. The beneficial effects of this probiotic are possibly exerted through the modulation of serotonin-related genes expression.PURPOSE Sleep disturbances have a negative impact on the prognosis of chronic kidney disease (CKD). However, information on the prevalence and predictors is limited. This study aimed to evaluate the prevalence and explore clinical factors affecting the quality of sleep in patients with non-dialysis CKD. METHODS Participants included 152 adult non-dialysis patients with stage 3-5 CKD. Demographic and clinical data were collected. Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), respectively. Sleep disturbances were defined as a PSQI score ≥ 5. Logistic regression was conducted to explore the independent factors of sleep disturbances. link3 Clinical parameters were correlated with BDI scores using linear regression models. RESULTS The total prevalence of patients with sleep disturbances was 66.4%. Older age, higher BDI scores, lower estimated glomerular filtration rate (eGFR) changes per month (△eGFR/m) before the study, and lower serum magnesium levels were found in patients with sleep disturbances. BDI scores (odds ratio [OR] 1.224, 95% confidence interval [CI] 1.091-1.373, p = 0.001) and age (OR 1.041, 95% CI 1.013-1.069, p = 0.003) were independent predictors of sleep disturbances. Serum uric acid levels (β - 0.629, 95% CI - 1.244 to - 0.013, p = 0.046), △eGFR/m before the study (β - 0.454, 95% CI - 0.885 to - 0.024, p = 0.039), and daily protein intake (β - 0.052, 95% CI - 0.102 to - 0.002, p = 0.043) were negatively associated with BDI scores. CONCLUSION A high overall prevalence of sleep disturbances was found in patients with non-dialysis stage 3-5 CKD. Depression, as a manageable predictor, should be managed, especially in elderly patients.