Incidence, predictors, and evolution of conduction disorders and atrial arrhythmias after contemporary mitral valve repair

Background: Conduction disorders (CD) and atrial arrhythmias (AA) in the postoperative period of cardiac surgery impede prompt clinical recovery and prolong hospitalization. Mitral valve repair (MVR) has become the treatment of choice for patients with significant valvular regurgitation, but information on CD and AA in this population is scarce.Methods: Records of consecutive patients undergoing MVR at a single center were reviewed. Patients with a preoperative pacemaker, CD, prior cardiac surgery or concomitant MVR were excluded. A total of 290 patients were included in the final analysis. Electrocardiograms pre andpost-operatively were analyzed for CD and AA.Results: CD occurred in 69 (23.7%) patients: 47 (16.2%) had first degree atrio-ventricular block (AVB), 10 (3.4%) had Mobitz I, 3 (1.03%) had Mobitz II, and 9 (3.1%) complete AVB. Only 6 (2.0%) patients required pacemakers. Univariate predictors of AVB were age, preexisting right bundle branch block (RBBB), mitral valve ring size, and bypass time. The only multivariate predictors of AVB were bypass time and preexisting RBBB (OR 3.23 and 1.98, respectively). The most common AA was atrial fibrillation 13.1% (38 patients) followed by atrial flutter 2.7% (8 patients). Multivariate predictors of AA were age and left atrial size (OR 1.85 and 4.2, respectively). Length of stay in patients with CD or AA was prolonged 2.2 ± 2 days compared to controls (p < 0.05).Conclusions: In this large sample of patients undergoing MVR, we found that bypass time and preexisting RBBB were independent predictors of CD; age and left atrial size were independent predictors of AA.

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

BACKGROUND: Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of (18)F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. METHODS: Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. RESULTS: Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. CONCLUSION: PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion

Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.

Congenital disorders of glycosylation (CDG) are a heterogeneous and rapidly growing group of diseases caused by abnormal glycosylation of proteins and/or lipids. Mutations in genes involved in the homeostasis of the endoplasmic reticulum (ER), the Golgi apparatus (GA), and the vesicular trafficking from the ER to the ER-Golgi intermediate compartment (ERGIC) have been found to be associated with CDG. Here, we report a patient with defects in both N- and O-glycosylation combined with a delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex. TRAPPIII is implicated in the anterograde transport from the ER to the ERGIC as well as in the vesicle export from the GA. This report expands the spectrum of genetic alterations associated with CDG, providing new insights for the diagnosis and the understanding of the physiopathological mechanisms underlying glycosylation disorders

Substance P autocrine signaling contributes to persistent HER2 activation that drives malignant progression and drug resistance in breast cancer.

ERBB receptor transmodulation by heterologous G-protein-coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2(+) primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored

Multi-technical approach for the characterization of polychrome decorative surfaces at Spanish Mission Churches in Nueva Vizcaya (Chihuahua, Mexico)

An interdisciplinary and multi-institutional group of science and art conservation specialists has provided new insight into the painting materials used in the polychrome walls and wooden ceilings in four seventeenth century Spanish colonial churches of Nueva Vizcaya (Chihuahua, Mexico). A multi-analytical study of the decorative surfaces was performed in situ using spectroscopic approaches (XRF, FORS), False Colour Infrared Reflectography–IRFC, as well as micro sampling (ATR-FTIR, LM, GC/MS). A survey of natural resources and study (ATR-FTIR, LM) was carried out to elucidate the natural occurrence of a select number of materials in the surrounding areas of the churches. The present paper presents a multi-analytical study and characterization of green, red-orange and black colour pigments and binders selected from the decorative surfaces. The aim of this study is to highlight relationships between local materials and those from the original polychrome ceilings, in order to understand the material and technological influences that converged in the Spanish colonial architecture of northern Mexico

Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis.

OBJECTIVE Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown. RESEARCH DESIGN AND METHODS 821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9-53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles. RESULTS One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P < 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P < 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P < 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P < 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P < 0.001) increase in myocardial uptake. CONCLUSIONS Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.The PESA study is funded by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Santander Bank. B.I. is supported by the European Commission (grant numbers 819775 and 945118), by the Spanish Ministry of Science and Innovation (PID2019- 110369RB-I00), and by the Red Madrilena de ~ Nanomedicina en Imagen Molecular-Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). A.D. is an Alfonso Martin Escudero fellow and is scientifically supported by La Caixa Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/ 10.13039/501100011033).S

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex

[Background] The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression.[Research Question] What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?[Study Design and Methods] We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.[Results] The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).[Interpretation] Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.[Trial Registry] ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.govThis study was funded in part by an unrestricted grant from AstraZeneca, and also by the COPD Research Program of the Spanish Respiratory Society (PII de EPOC of SEPAR).Peer reviewe

Search for charginos in e+e- interactions at sqrt(s) = 189 GeV

An update of the searches for charginos and gravitinos is presented, based on a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by combining the chargino searches with neutralino searches at the Z resonance implies a limit on the mass of the lightest neutralino which, for a heavy sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure