Time-related improvement of survival in resectable gastric cancer: the role of Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy

BACKGROUND: We investigated the change of prognosis in resected gastric cancer (RGC) patients and the role of radical surgery and adjuvant chemotherapy. METHODS: We retrospectively analyze the outcome of 426 consecutive patients from 1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207) and 1990 or after (TP2; n= 219). Partial gastrectomy and D1-lymphadenetomy was predominant in TP1 and total gastrectomy with D2-lymphadenectomy it was in TP2. Adjuvant chemotherapy consisted of mitomycin C (MMC), 10–20 mg/m2 iv 4 courses or MMC plus Tegafur 500 mg/m2 for 6 months. RESULTS: Positive nodes were similar in TP2/TP1 patients with 56%/59% respectively. Total gastrectomy was done in 56%/45% of TP2/TP1 respectively. Two-drug adjuvant chemotherapy was administered in 65%/18% of TP2/TP1 respectively. Survival at 5 years was 66% for TP2 versus 42% for TP1 patients (p < 0.0001). Survival by stages II, IIIA y IIIB for TP2 versus TP1 patients was 70 vs. 51% (p = 0.0132); 57 vs. 22% (p = 0.0008) y 30 vs. 15% (p = 0.2315) respectively. Multivariate analysis showed that age, stage of disease and period of treatment were independent variables. CONCLUSION: The global prognosis and that of some stages have improved in recent years with case RGC patients treated with surgery and adjuvant chemotherapy

Modulation of pain perception by transcranial magnetic stimulation of left prefrontal cortex

Evidence by functional imaging studies suggests the role of left dorsolateral prefrontal cortex (DLPFC) in the inhibitory control of nociceptive transmission system. Repetitive transcranial magnetic stimulation (rTMS) is able to modulate pain response to capsaicin. In the present study, we evaluated the effect of DLPFC activation (through rTMS) on nociceptive control in a model of capsaicin-induced pain. The study was performed on healthy subjects that underwent capsaicin application on right or left hand. Subjects judged the pain induced by capsaicin through a 0–100 VAS scale before and after 5 Hz rTMS over left and right DLPFC at 10 or 20 min after capsaicin application in two separate groups (8 subjects each). Left DLPFC-rTMS delivered either at 10 and 20 min after capsaicin application significantly decreased spontaneous pain in both hands. Right DLPFC rTMS showed no significant effect on pain measures. According to these results, stimulation of left DLPFC seems able to exert a bilateral control on pain system, supporting the critical antinociceptive role of such area. This could open new perspectives to non-invasive brain stimulation protocols of alternative target area for pain treatment

Physical Fitness and Telomere Length in Patients with Coronary Heart Disease: Findings from the Heart and Soul Study

Background: Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients. Methods: In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs). Results: 229 participants had low physical fitness (,5 METS), 334 had moderate physical fitness (5–7 METS), and 381 had high physical fitness (.7 METS). Mean6 T/S ratio ranged from 0.8660.21 (534963781 base pairs) in those with low physical fitness to 0.9560.23 (556663829 base pairs) in those with high physical fitness (p,.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds o

What Happens in Between? Human Oscillatory Brain Activity Related to Crossmodal Spatial Cueing

Previous studies investigated the effects of crossmodal spatial attention by comparing the responses to validly versus invalidly cued target stimuli. Dynamics of cortical rhythms in the time interval between cue and target might contribute to cue effects on performance. Here, we studied the influence of spatial attention on ongoing oscillatory brain activity in the interval between cue and target onset. In a first experiment, subjects underwent periods of tactile stimulation (cue) followed by visual stimulation (target) in a spatial cueing task as well as tactile stimulation as a control. In a second experiment, cue validity was modified to be 50%, 75%, or else 25%, to separate effects of exogenous shifts of attention caused by tactile stimuli from that of endogenous shifts. Tactile stimuli produced: 1) a stronger lateralization of the sensorimotor beta-rhythm rebound (15–22 Hz) after tactile stimuli serving as cues versus not serving as cues; 2) a suppression of the occipital alpha-rhythm (7–13 Hz) appearing only in the cueing task (this suppression was stronger contralateral to the endogenously attended side and was predictive of behavioral success); 3) an increase of prefrontal gamma-activity (25–35 Hz) specifically in the cueing task. We measured cue-related modulations of cortical rhythms which may accompany crossmodal spatial attention, expectation or decision, and therefore contribute to cue validity effects. The clearly lateralized alpha suppression after tactile cues in our data indicates its dependence on endogenous rather than exogenous shifts of visuo-spatial attention following a cue independent of its modality

Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium.

During aging, progenitor cells acquire mutations, which may generate clones that colonize the surrounding tissue. By middle age, normal human tissues, including the esophageal epithelium (EE), become a patchwork of mutant clones. Despite their relevance for understanding aging and cancer, the processes that underpin mutational selection in normal tissues remain poorly understood. Here, we investigated this issue in the esophageal epithelium of mutagen-treated mice. Deep sequencing identified numerous mutant clones with multiple genes under positive selection, including Notch1, Notch2 and Trp53, which are also selected in human esophageal epithelium. Transgenic lineage tracing revealed strong clonal competition that evolved over time. Clone dynamics were consistent with a simple model in which the proliferative advantage conferred by positively selected mutations depends on the nature of the neighboring cells. When clones with similar competitive fitness collide, mutant cell fate reverts towards homeostasis, a constraint that explains how selection operates in normal-appearing epithelium.This work was supported by grants from the Wellcome Trust to the Wellcome SangerInstitute (098051 and 296194) and Cancer Research UK Programme Grants to P.H.J.(C609/A17257 and C609/A27326). G.P. is supported by a Talento program fellowship from Comunidad de Madrid. B.A.H. and M.W.J.H. are supported by the MedicalResearch Council (Grant-in-Aid to the MRC Cancer unit grant no. MC_UU_12022/9 and NIRG to B.A.H. grant no. MR/S000216/1). M.W.J.H. acknowledges support fromthe Harrison Watson Fund at Clare College, Cambridge. B.A.H. acknowledges support from the Royal Society (grant no. UF130039). I.M. is funded by Cancer Research UK (C57387/A21777). S.D. benefited from the award of an ESPOD fellowship, 2018-21, from the Wellcome Sanger Institute and the European Bioinformatics Institute EMBL-EBI

Coronary revascularization treatment based on dual-source computed tomography

Therapy advice based on dual-source computed tomography (DSCT) in comparison with coronary angiography (CAG) was investigated and the results evaluated after 1-year follow-up. Thirty-three consecutive patients (mean age 61.9 years) underwent DSCT and CAG and were evaluated independently. In an expert reading (the “gold standard”), CAG and DSCT examinations were evaluated simultaneously by an experienced radiologist and cardiologist. Based on the presence of significant stenosis and current guidelines, therapy advice was given by all readers blinded from the results of other readings and clinical information. Patients were treated based on a multidisciplinary team evaluation including all clinical information. In comparison with the gold standard, CAG had a higher specificity (91%) and positive predictive value (PPV) (95%) compared with DSCT (82% and 91%, respectively). DSCT had a higher sensitivity (96%) and negative predictive value (NPV) (89%) compared with CAG (91% and 83%, respectively). The DSCT-based therapy advice did not lead to any patient being denied the revascularization they needed according to the multidisciplinary team evaluation. During follow-up, two patients needed additional revascularization. The high NPV for DSCT for revascularization assessment indicates that DSCT could be safely used to select patients benefiting from medical therapy only

Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection

The trials (NCT02604017, NCT02640157) were funded by AbbVie Inc

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente