A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: A cohort study

Background: Creating an easy-to-use instrument to identify predictors of short-term (30/60-day) mortality after an exacerbation of chronic obstructive pulmonary disease (eCOPD) could help clinicians choose specific measures of medical care to decrease mortality in these patients. The objective of this study was to develop and validate a classification and regression tree (CART) to predict short term mortality among patients evaluated in an emergency department (ED) for an eCOPD. Methods: We conducted a prospective cohort study including participants from 16 hospitals in Spain. COPD patients with an exacerbation attending the emergency department (ED) of any of the hospitals between June 2008 and September 2010 were recruited. Patients were randomly divided into derivation (50 %) and validation samples (50 %). A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample. Results: Two thousand four hundred eighty-seven patients, 1252 patients in the derivation sample and 1235 in the validation sample, were enrolled in the study. Based on the results of the univariate analysis, five variables (baseline dyspnea, cardiac disease, the presence of paradoxical breathing or use of accessory inspiratory muscles, age, and Glasgow Coma Scale score) were used to build the CART. Mortality rates 30 days after discharge ranged from 0 % to 55 % in the five CART classes. The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease. The highest mortality rate was in the branch with the highest baseline dyspnea level, use of accessory inspiratory muscles or paradoxical breathing upon ED arrival, and Glasgow score <15. The area under the receiver-operating curve (AUC) in the derivation sample was 0.835 (95 % CI: 0.783, 0.888) and 0.794 (95 % CI: 0.723, 0.865) in the validation sample. CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index, reaching an AUC in the derivation sample of 0.817 (95 % CI: 0.776, 0.859) and 0.770 (95 % CI: 0.716, 0.823) in the validation sample. Conclusions: We identified several easy-to-determine variables that allow clinicians to classify eCOPD patients by short term mortality risk, which can provide useful information for establishing appropriate clinical care. Trial registration: NCT02434536

The retina of Spalax ehrenbergi: Novel histologic features supportive of a modified photosensory role

FWN – Publicaties zonder aanstelling Universiteit Leide

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years

Purpose: To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Design: Observational and longitudinal study. Participants: One hundred patients with relapsing-remitting MS and 50 healthy controls. Methods: All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Main Outcome Measures: Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Results: Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Conclusions: Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL

Knowledge, attitudes and preventive practices of primary health care professionals towards alcohol use: A national, cross-sectional study

Introduction Primary care (PC) professionals' knowledge about alcohol use has been identified as one of the barriers PC providers face in their clinic. Both PC professionals' level of training and attitude are crucial in the clinical practice regarding alcohol use. Objective To evaluate the knowledge, attitude, and preventive practices of Spanish PC physicians and nurses towards alcohol use. Design An observational, descriptive, cross-sectional, multi-center study. Methodology Location: PC centers of the Spanish National Health System (NHS). Participants: PC physicians and nurses selected randomly from health care centers, and by sending an e-mail to semFYC and SEMERGEN members. Healthcare providers completed an online survey on knowledge, attitude, and follow-up recommendations for reducing alcohol intake. A descriptive, bivariate, and multivariate statistical analysis was conducted (p<0.05). Results Participants: 1, 760 healthcare providers completed the survey (75.6% [95% CI 73.5-77.6] family physicians; 11.4% [95% CI 9.9-12.9] medical residents; and 12.5% [95% CI 10.9-14.1] nurses), with a mean age of 44.7 (SD 11.24, range: 26-64, 95% CI: 47.2-48.2). Knowledge was higher in family physicians (p<0.001), older professionals (Spearman's r = 0.11, p<0.001), and resident trainers (p<0.001). The PC professional most likely to provide advice for reducing alcohol use was: a nurse (p<0.001), female (p = 0.010), between 46 and 55 years old (p <0.001). Conclusions PC providers' knowledge and preventive practices regarding alcohol use are scarce, hence specific training strategies to increase their knowledge and improve their attitude and skills with regard to this health problem should be considered a healthcare policy priority

G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus

G protein-coupled estrogen receptor (GPER) in the amygdala and the dorsal hippocampus mediates actions of estradiol on anxiety, social recognition and spatial memory. In addition, GPER participates in the estrogenic regulation of synaptic function in the amygdala and in the process of adult neurogenesis in the dentate gyrus. While the distribution of the canonical estrogen receptors α and β in the amygdala and dorsal hippocampus are well characterized, little is known about the regional distribution of GPER in these brain regions and whether this distribution is affected by sex or the stages of the estrous cycle. In this study we performed a morphometric analysis of GPER immunoreactivity in the posterodorsal medial, anteroventral medial, basolateral, basomedial and central subdivisions of the amygdala and in all the histological layers of CA1 and the dentate gyrus of the dorsal hippocampal formation. The number of GPER immunoreactive cells was estimated in these different structures. GPER immunoreactivity was detected in all the assessed subdivisions of the amygdaloid nucleus and dorsal hippocampal formation. The number of GPER immunoreactive cells was higher in males than in estrus females in the central (P = 0.001) and the posterodorsal medial amygdala (P < 0.05); higher in males than in diestrus females in the strata orients (P < 0.01) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer of the dentate gyrus (P < 0.01); higher in diestrus females than in males in the basolateral amygdala (P < 0.05); higher in diestrus females than in estrus females in the central (P < 0.01), posterodorsal medial (P < 0.01) and basolateral amygdala (P < 0.01) and higher in estrus females than in diestrus females in the strata oriens (P < 0.05) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer (P < 0.05) and the hilus of the dentate gyrus (P < 0.05). The findings suggest that estrogenic regulation of the amygdala and hippocampus through GPER may be different in males and in females and may fluctuate during the estrous cycle.This study was supported by Ministero dell'Istruzione, dell'Università e della Ricerca, Italy (MIUR project Dipartimenti di Eccellenza 2018–2022) to Department of Neuroscience Rita Levi Montalcini, Agencia Estatal de Investigación, Spain (BFU2017-82754-R, PSI2017-86396-P), Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid and Fondos FEDER, GRUPOS UCM-BSCH 951579. MM fellowship was generously granted by Prof. G. C. Bergui

Nature of the spin-glass phase at experimental length scales

We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc. We demonstrate the relevance of equilibrium finite-size simulations to understand experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a time scale of one hour can be matched with equilibrium results on L=110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies to ensure equilibration in parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for publication in the Journal of Statistical Mechanic

Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis

Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis

Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug.

We attempt to identify the plasma membrane transporter involved in the uptake of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine. This novel oral fluoropyrimidine is used in cancer treatments and is a direct precursor of the cytostatic agent 5'-fluorouracil. We also examine the role of the transporter in 5'-DFUR cytotoxicity. The human concentrative nucleoside transporter (hCNT1) was cloned from human fetal liver and expressed in Xenopus laevis oocytes. The two-electrode voltage-clamp technique was used to demonstrate that 5'-DFUR, but not capecitabine or 5'-FU, is an hCNT1 substrate. Then, hCNT1 was heterologously expressed in the mammalian cell line Chinese hamster ovary-K1. Functional expression was demonstrated by monitoring transport of radiolabeled substrates and by using a monospecific polyclonal antibody generated against the transporter. hCNT1-expressing cells were more sensitive to 5'-DFUR than vector-transfected or wild-type cells. The sensitivity of the three cell types to other agents such as cisplatin or 5'-FU was identical. In conclusion, this study shows that 1) the pharmacological profile of a nucleoside transporter can be determined by an electrophysiological approach; 2) the hCNT1 transporter is involved in 5'-DFUR uptake; and 3) hCNT1 expression may increase cell sensitivity to 5'-DFUR treatment. This study also reports for the first time the generation of an antibody against hCNT1, which may be useful in the elucidation of the relationship between hCNT1 expression and tumor response to capecitabine treatmen