Senescence and pathology in ageing.

The life expectancy of people living in the UK has been extended over the last century due to changes in the principal causes of death. Nowadays, people are more likely to die of diseases related to the ageing process rather than the infectious diseases which hitherto were more common causes of death in younger people. Ageing is associated with the degeneration of functional capacity in all parts of the body, and at all levels of organisation from molecules to complete organ systems. These functional changes are referred to as senescence. Both genetic and environmental factors govern senescence, although the precise mechanisms and the extent of their involvement are largely unknown. Senescence changes may themselves be responsible for certain diseases and disabilities associated with old age, or they may be a contributory factor and increase a person's susceptibility to particular diseases. The latter is the case with the most commonly encountered causes of morbidity and mortality today, namely atherosclerosis and cancer.     

Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico

ObjectiveWe analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes.Material and methodsRetrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival.ResultsWe included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (<pT2) in 36 patients (40%), positive surgical margins in 7 patients (8%), lymph node involvement (N1) in 16 patients (17.8%). A shorter time to progression was observed in the group of patients who did not achieve a complete pathological response (53 months vs. 83.1 in pT0 patients, P = 0.012), in patients with lymph node involvement compared to pN0 (65.4 vs. 28, 2 months, P = 0.014) and in those with positive surgical margins compared to those with tumor-free margins (63.5 vs. 8.5 months, P = 0.021).ConclusionThe adequate selection of patients with muscle-invasive bladder carcinoma has shown a good tolerance to NACT, with a high compliance rate prior to RC. The improvement in the complete response rate implies a greater survival in this group of patients, with lymph node involvement and positive surgical margins being important prognostic factors.     

EEG in ulcerative colitis.

Electroencephalographic tracings of 50 patients with ulcerative colitis (UC) were compared with those of 75 controls. In the UC patients a 24% incidence of abnormal tracings was found as compared with an 8% incidence in the controls. A higher incidence of abnormal electroencephalograms was found among active cases of UC than among those in remission. The meaning of these results is not yet clear.     

Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern

Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of alpha-chains of beta-integrins and their ligand ICAM-1. Survivin-induced expression of alpha-chains of beta 2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-kappaB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.     

Different characteristics of cardiac biomarkers to decide and predict the culprit lesions in patients with suspicious acute coronary syndrome

This multicenter prospective study was conducted to assess high-sensitivity troponin T (hs-TnT) and other biomarkers to decide and predict culprit lesions indicated for emergency percutaneous coronary intervention (PCI) in patients with suspicious acute coronary syndrome (ACS). We have reported Hs-TnT is the most sensitive biomarker for earlier diagnosis and decision making in patients with suspected ACS. In this study, we had conducted subanalysis investigating the usefulness for prediction of ACS culprit lesion. The patients with suspicious ACS and initially negative whole-blood rapid troponin T test, who underwent coronary angiogram (CAG), were enrolled (n = 74). Hs-TnT, quantitative assay for conventional troponin T (c-TnT), creatine kinase MB isozyme (CK-MB), and heart-type fatty acid-binding protein (H-FABP) were simultaneously measured. ACS culprit lesion was described as total occlusion, subtotal occlusion, and/or angiographical unstable lesion such as thrombosis, ulceration or irregularity. The CAG revealed that 49 cases had ACS lesions to be indicated for emergency PCI. The areas under the ROC curves and ROC-optimized cut-off of hs-TnT, c-TnT, CK-MB, and H-FABP were 0.75, 0.67, 0.68, and 0.75, respectively, and 18, 11, 2.0, and 4.6 ng/ml, respectively. In patients with total occlusion and 90–99 % of diameter stenosis (TIMI 2 or 3), hs-TnT could predict emergency PCI with significantly higher sensitivity compared with H-FABP (hs-TnT >14 ng/ml; 71 %, and H-FABP >6.2 ng/dl; 51 %, p = 0.021) and other biomarkers. Meanwhile, H-FABP displayed significant correlations with number of diseased vessels and presence of thrombotic lesion. The present study first revealed different characteristics of correlation between the angiographic culprit lesions and each cardiac biomarker. For prediction of ACS lesions requiring emergency PCI, hs-TnT had the highest sensitivity with satisfied analytical precision.     

Brain Stimulation Methods to Treat Tobacco Addiction

BackgroundTobacco smoking is the leading cause of preventable deaths worldwide, but many smokers are simply unable to quit. Psychosocial and pharmaceutical treatments have shown modest results on smoking cessation rates, but there is an urgent need to develop treatments with greater efficacy. Brain stimulation methods are gaining increasing interest as possible addiction therapeutics.ObjectivesThe purpose of this paper is to review the studies that have evaluated brain stimulation techniques on tobacco addiction, and discuss future directions for research in this novel area of addiction interventions.MethodsElectronic and manual literature searches identified fifteen studies that administered repetitive transcranial magnetic stimulation (rTMS), cranial electrostimulation (CES), transcranial direct current stimulation (tDCS) or deep brain stimulation (DBS).ResultsrTMS was found to be the most well studied method with respect to tobacco addiction. Results indicate that rTMS and tDCS targeted to the dorsolateral prefrontal cortex (DLPFC) were the most efficacious in reducing tobacco cravings, an effect that may be mediated through the brain reward system involved in tobacco addiction. While rTMS was shown to reduce consumption of cigarettes, as yet no brain stimulation technique has been shown to significantly increase abstinence rates. It is possible that the therapeutic effects of rTMS and tDCS may be improved by optimization of stimulation parameters and increasing the duration of treatment.ConclusionAlthough further studies are needed to confirm the ability of brain stimulation methods to treat tobacco addiction, this review indicates that rTMS and tDCS both represent potentially novel treatment modalities.     

Half Metallic Ferromagnetism and Transport Properties of Zinc Chalcogenides ZnX2Se4 (X = Ti,V, Cr) for Spintronic Applications

In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (T_c), spin polarization, half magnetic ferromagnetism and transport properties of ZnX₂Se₄ (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of T_c is perceived for ZnCr₂Se₄. The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) μ_B of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔE _crystal, exchange energies Δ _x(d), Δ _x (pd) and exchange constants (N_o α and N_o β ). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0–400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 10¹¹ W/mK²) among studied compounds.