Jedinstveni obrazac djelovanja bisfenola A na ekspresiju gena čimbenika rasta živca embrionske mišje stanične linije N-44 dobivene iz hipotalamusa

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf) in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 μmol L-1 the Ngf mRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.U istraživanju toksičnosti bisfenola A (BPA) utvrđena je ekspresija gena čimbenika rasta živca (eng. nerve growth factor - NGF) embrionske mišje stanične linije mHypoE-N44 dobivene iz hipotalamusa nakon trosatnog izlaganja BPA-u u rasponu doza od 0,02 do 200 μmol L-1. Razine Ngf mRNA snizile su se ovisno o dozi, a značajne razlike od kontrolne skupine zamijećene su za raspon od 2 do 50 μmol L-1. Međutim, počevši od doze od 100 do 200 μmol L-1, razine Ngf mRNA značajno su se povećale u odnosu na kontrolu, a ekspresija gena kaspaze 3 i transformacijskog proteina 73 značajno snizila. Ti rezultati upućuju na to da visoke doze BPA u embrionskoj hipotalamičkoj staničnoj liniji stvaraju jedinstveni obrazac ekspresije gena Ngf te da BPA može suprimirati apoptozu koja je nužna za rani razvoj mozga

Efficacy of Dietary Behavior Modification for Preserving Cardiovascular Health and Longevity

Cardiovascular disease (CVD) and its predisposing risk factors are major lifestyle and behavioral determinants of longevity. Dietary lifestyle choices such as a heart healthy diet, regular exercise, a lean weight, moderate alcohol consumption, and smoking cessation have been shown to substantially reduce CVD and increase longevity. Recent research has shown that men and women who adhere to this lifestyle can substantially reduce their risk of coronary heart disease (CHD). The preventive benefits of maintaining a healthy lifestyle exceed those reported for using medication and procedures. Among the modifiable preventive measures, diet is of paramount importance, and recent data suggest some misconceptions and uncertainties that require reconsideration. These include commonly accepted recommendations about polyunsaturated fat intake, processed meat consumption, fish choices and preparation, transfatty acids, low carbohydrate diets, egg consumption, coffee, added sugar, soft drink beverages, glycemic load, chocolate, orange juice, nut consumption, vitamin D supplements, food portion size, and alcohol

Impact of catheter ablation for atrial fibrillation on cardiac disorders in patients with coexisting heart failure

AIMS: We sought to investigate the time course of cardiac disorders after catheter ablation for atrial fibrillation (AF) in patients with coexisting heart failure (HF) during long-term follow-up. METHODS AND RESULTS: We analysed consecutive 280 patients undergoing first-time catheter ablation for AF who had coexisting HF, which was defined as prior HF hospitalization, estimated right ventricular systolic pressure ≥45 mmHg, or B-type natriuretic peptide (BNP) ≥200 pg/dL before the procedure. The primary endpoints were improvements in left ventricular ejection fraction (LVEF), E/e', BNP, left atrial dimension (LAD), and mitral regurgitation (MR) at 1 year. The secondary endpoints were serial changes of LVEF, E/e', BNP, LAD, and MR at 6 months, 1 year, and 5 years and cumulative incidence of HF hospitalization. During the mean follow-up of 5.1 ± 3.0 years, 70.7% of patients were free from recurrent AF. Among patients with LVEF < 50%, E/e' ≥ 15, BNP ≥ 200 pg/dL, LAD ≥ 40 mm, and moderate-to-severe MR, changes in those parameters from baseline to 1 year were 34.5 ± 9.9% to 43.2 ± 14.4% (P < 0.001), 19.7 ± 3.9 to 12.5 ± 6.6 (P < 0.001), 290 to 85 pg/dL (P < 0.001), and 100% to 37.8% (P < 0.001), respectively. The improvements in the cardiac disorders were maintained up to 5 years except for E/e'. In patients with LVEF < 40%, significant delayed improvement of LVEF beyond 1 year was observed (ΔLVEF = 10.5 ± 18.5, P = 0.001), but not in patients with LVEF of 40-49%. The cumulative incidence of HF hospitalization was 12.6% at 5 years. Baseline diastolic dysfunction was the only independent predictor for subsequent HF hospitalization. CONCLUSIONS: In patients undergoing AF ablation with coexisting HF, all cardiac disorders significantly improved after the procedure, which was mostly maintained during 5 year follow-up

Effect of Configuration of Micro-/Nanoscale Structure on Sliding Surface on Molecular Gas-Film Lubrication

Abstract. Nakamori et al. found experimentally that the friction between a partly polished diamond coating and a metal surface was drastically reduced to zero as relative speed increased to a few m/s [Diamond Relat. Mater. 14, (2005), 2122]. It seems that diamond coating took off the counter surface because sliding was noiseless in their experiment. However, the mechanism of this phenomenon was unknown. In the previous work, we performed the numerical simulation of micro-/nanoscale gas flow between two sliding surfaces, i. e., the slider surface with microscale surface roughness like partly polished diamond coating and the flat counter surface. And then, we successfully reproduced lift force large enough to suspend the slider used in the experiment and found that this effect became notable only for micro-/nanoscale gas flow. In the present paper, we investigate the effect of configuration of micro-/nanoscale structure on sliding surface on molecular gas-film lubrication. Since micro-/nanoscale gas flows between two sliding surfaces cannot be treated as a continuum, we use the direct simulation Monte Carlo (DSMC) method

Effect of Configuration of Micro-/Nanoscale Structure on Sliding Surface on Molecular Gas-Film Lubrication

Abstract. Nakamori et al. found experimentally that the friction between a partly polished diamond coating and a metal surface was drastically reduced to zero as relative speed increased to a few m/s [Diamond Relat. Mater. 14, (2005), 2122]. It seems that diamond coating took off the counter surface because sliding was noiseless in their experiment. However, the mechanism of this phenomenon was unknown. In the previous work, we performed the numerical simulation of micro-/nanoscale gas flow between two sliding surfaces, i. e., the slider surface with microscale surface roughness like partly polished diamond coating and the flat counter surface. And then, we successfully reproduced lift force large enough to suspend the slider used in the experiment and found that this effect became notable only for micro-/nanoscale gas flow. In the present paper, we investigate the effect of configuration of micro-/nanoscale structure on sliding surface on molecular gas-film lubrication. Since micro-/nanoscale gas flows between two sliding surfaces cannot be treated as a continuum, we use the direct simulation Monte Carlo (DSMC) method

Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation

CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status

Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.</p> <p>Results</p> <p>To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.</p> <p>Conclusions</p> <p>This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.</p

Impact of a learning health system on acute care and medical complications after intracerebral hemorrhage

Introduction: Patients with stroke often experience pneumonia during the acute stage after stroke onset. Oral care may be effective in reducing the risk of stroke‐associated pneumonia (SAP). We aimed to determine the changes in oral care, as well as the incidence of SAP, in patients with intracerebral hemorrhage, following implementation of a learning health system in our hospital. Methods: We retrospectively analyzed the data of 1716 patients with intracerebral hemorrhage who were hospitalized at a single stroke center in Japan between January 2012 and December 2018. Data were stratified on the basis of three periods of evolving oral care: period A, during which conventional, empirically driven oral care was provided (n = 725); period B, during which standardized oral care was introduced, with SAP prophylaxis based on known risk factors (n = 469); and period C, during which oral care was risk‐appropriate based on learning health system data (n = 522). Logistic regression analysis was performed to evaluate associations between each of the three treatment approaches and the risk of SAP. Results: Among the included patients, the mean age was 71.3 ± 13.6 years; 52.6% of patients were men. During the course of each period, the frequency of oral care within 24 hours of admission increased (P < .001), as did the adherence rate to oral care ≥3 times per day (P < .001). After adjustment for confounding factors, a change in the risk of SAP was not observed in period B; however, the risk significantly decreased in period C (odds ratio 0.61; 95% confidence interval 0.43‐0.87) compared with period A. These associations were maintained for SAP diagnosed using strict clinical criteria or after exclusion of 174 patients who underwent neurosurgical treatment. Conclusions: Risk‐appropriate care informed by the use of learning health system data could improve care and potentially reduce the risk of SAP in patients with intracerebral hemorrhage in the acute stage

An Optically Dark GRB Observed by HETE-2: GRB 051022

GRB 051022 was detected at 13:07:58 on 22 October 2005 by HETE-2. The location of GRB 051022 was determined immediately by the flight localization system. This burst contains multiple pulses and has a rather long duration of about 190 seconds. The detections of candidate X-ray and radio afterglows were reported, whereas no optical afterglow was found. The optical spectroscopic observations of the host galaxy revealed the redshift z = 0.8. Using the data derived by HETE-2 observation of the prompt emission, we found the absorption N_H = 8.8 -2.9/+3.1 x 10^22 cm^-2 and the visual extinction A_V = 49 -16/+17 mag in the host galaxy. If this is the case, no detection of any optical transient would be quite reasonable. The absorption derived by the Swift XRT observations of the afterglow is fully consistent with those obtained from the early HETE-2 observation of the prompt emission. Our analysis implies an interpretation that the absorbing medium could be outside external shock at R ~ 10^16 cm, which may be a dusty molecular cloud.Comment: 6 pages, 2 figures, accepted for publication in PASJ lette