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1.
Emergencias (Sant Vicenç dels Horts) ; 32(1): 9-18, feb. 2020. graf, tab
Artigo em Espanhol | IBECS-Express | ID: ibc-ET2-3431

RESUMO

Objetivos. Analizar qué características clínicas y del ECG de la primera valoración de pacientes con dolor torácico no traumático (DNT) se asocian con una clasificación inicial de sospecha de síndrome coronario agudo (SCA) y con el diagnóstico final de SCA, e identificar cuáles resultan sobre o infravaloradas durante la clasificación inicial. Método. Se incluyeron las consultas consecutivas por DTNT en una unidad de dolor torácico durante 10 años (2008-2017) en las que se disponía de los diagnósticos inicial de sospecha (SCA/no SCA) y final de alta de urgencias (SCA/no SCA). Se incluyeron 33 variables independientes (2 demográficas, 5 comorbilidad cardiovascular, 22 dolor torácico, 4 datos ECG). Se calcularon las odds ratio (OR) para la clasificación (inicial y final) como SCA para cada variable independiente, crudas y ajustadas en modelos globales que incluían todas ellas. En estos modelos ajustados se comparó si las OR para la clasificación inicial y final como SCA eran significativamente diferentes. Resultados. Se incluyeron 34.552 visitas. Las 33 variables analizadas mostraron asociación significativa para la clasificación inicial y final del DTNT como SCA, y en muchos casos esta asociación se mantuvo en el modelo ajustado. Diecinueve variables mostraron OR significativamente diferentes para la sospecha inicial de SCA que para el diagnóstico final de SCA: 10 sobrestimaban la asociación final y 9 la subestimaban. Conclusión. Los datos clínicos iniciales clásicamente utilizados para sospechar SCA pacientes con DTNT en urgencias identifican todos ellos individualmente a pacientes con riesgo incrementado de ser clasificado inicial y finalmente como SCA; sin embargo, algunos de ellos sobreestiman y otros subestiman inicialmente el riesgo final. Los urgenciólogos debieran sensibilizarse más con estos datos subestimados


Objectives. To analyze clinical data and electrocardiographic (ECG) findings obtained during the initial evaluation of patients with nontraumatic chest pain (NTCP). To explore associations between these findings and the initial and final diagnoses of acute coronary syndrome (ACS). To assess which variables initially over- or underestimate risk ACS. Methods. Consecutive patients with NTCP attended in a chest pain unit during the 10-year period of 2008–2017 were included if the suspected and discharge diagnoses of interest (ACS or non-ACS) had been recorded. Thirtythree independent variables (demographic, 2; cardiovascular, 5; chest pain, 22; ECG, 4). We included all variables in models to calculate crude and adjusted odds ratios (ORs) between each independent variable and the initial and final diagnoses. The adjusted ORs were compared to determine whether the initial and final diagnoses of ACS differed significantly in relation to the variables. Results. A total of 34 552 patient visits were attended. The ORs for the 33 variables were significantly associated with initial and final NTCP classification as ACS or non-ACS, and in many cases the association was confirmed by the adjusted ORs. The adjusted ORs for 19 variables were significantly different in their relation to the initial and final diagnoses of ACS: 10 overpredicted the probability of the diagnosis and 9 underpredicted it. Conclusions. The variables traditionally used to warn of ACS in emergency patients with NTCP identify individuals likely to be initially and finally diagnosed with ACS. However, some of these variables overestimate or underestimate the risk of a final ACS diagnosis. Emergency medicine physicians should be aware of variables associated with underestimation of risk

2.
J Neurochem ; : e14959, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943210

RESUMO

Psychostimulants are widely abused drugs that may cause addiction in vulnerable individuals. While the reward circuitry of the brain is involved in addiction establishment, various pathways in the brain may provide protection at the molecular level that limits the acute and chronic effects of drugs. These targets may be used for strategies designed to prevent and treat addiction. Swiprosin-1/EFhd2 is a Ca2+ -binding cytoskeletal adaptor protein involved in sensation seeking behaviour, anxiety and alcohol addiction. Here, we tested how EFhd2 contributes to the physiological and behavioural effects of the psychostimulant drugs methamphetamine (METH) and cocaine. An in-vivo microdialysis study in EFhd2 knock out (KO) mice revealed that EFhd2 controls METH- and cocaine-induced changes in extracellular dopamine (DA), serotonin and noradrenaline levels through different mechanisms in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Electrophysiological recordings in a slice preparation showed that a lack of EFhd2 increases dopaminergic neuronal activity in the ventral tegmental area and increases the sensitivity of neurons to stimulation. We report a role of EFhd2 in METH-induced locomotor activation and in the conditioned locomotor effects. No role, however, was observed in the establishment of METH- or cocaine-induced conditioned place preference. These findings may suggest that EFhd2 modulates the activity of the dopaminergic system and the neurochemical effects of METH and cocaine, which translate into a modulation of the behavioural effects of these drugs at the level of the acute and conditioned locomotor activity.

3.
Emergencias ; 32(1): 9-18, 2020 Feb.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-31909907

RESUMO

OBJECTIVES: To analyze clinical data and electrocardiographic (ECG) findings obtained during the initial evaluation of patients with nontraumatic chest pain (NTCP). To explore associations between these findings and the initial and final diagnoses of acute coronary syndrome (ACS). To assess which variables initially over- or underestimate risk ACS. MATERIAL AND METHODS: Consecutive patients with NTCP attended in a chest pain unit during the 10-year period of 2008-2017 were included if the suspected and discharge diagnoses of interest (ACS or non-ACS) had been recorded. Thirtythree independent variables (demographic, 2; cardiovascular, 5; chest pain, 22; ECG, 4). We included all variables in models to calculate crude and adjusted odds ratios (ORs) between each independent variable and the initial and final diagnoses. The adjusted ORs were compared to determine whether the initial and final diagnoses of ACS differed significantly in relation to the variables. RESULTS: A total of 34 552 patient visits were attended. The ORs for the 33 variables were significantly associated with initial and final NTCP classification as ACS or non-ACS, and in many cases the association was confirmed by the adjusted ORs. The adjusted ORs for 19 variables were significantly different in their relation to the initial and final diagnoses of ACS: 10 overpredicted the probability of the diagnosis and 9 underpredicted it. CONCLUSION: The variables traditionally used to warn of ACS in emergency patients with NTCP identify individuals likely to be initially and finally diagnosed with ACS. However, some of these variables overestimate or underestimate the risk of a final ACS diagnosis. Emergency medicine physicians should be aware of variables associated with underestimation of risk.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31977016

RESUMO

AIMS: Atrial fibrillation (AF) and frailty are common, and the prevalence is expected to rise further. We aimed to investigate the prevalence of frailty and the ability of a frailty index (FI) to predict unplanned hospitalizations, stroke, bleeding and death in patients with AF. METHODS AND RESULTS: Patients with known AF were enrolled in a prospective cohort study in Switzerland. Information on medical history, lifestyle-factors and clinical measurements were obtained. The primary outcome was unplanned hospitalization; secondary outcomes were all-cause mortality, bleeding and stroke. The FI was measured using a cumulative deficit approach, constructed according to previously published criteria and divided into three groups (non-frail, pre-frail, frail). The association between frailty and outcomes was assessed using multivariable adjusted Cox regression models. Of the 2369 included patients, prevalence of pre-frailty and frailty was 60.7% and 10.6%, respectively. Pre-frailty and frailty were associated with a higher risk of unplanned hospitalizations (adjusted hazard ratio [aHR] 1.82; 95% confidence interval [CI], 1.49-2.22, p < 0.001; and aHR 3.59; 95%CI 2.78-4.63, p < 0.001), all-cause mortality (aHR 5.07; 95%CI 2.43-10.59, p < 0.001; and aHR 16.72; 95%CI 7.75-36.05, p < 0.001), and bleeding (aHR 1.53; 95%CI 1.11-2.13, p = 0.01; and aHR 2.46; 95%CI 1.61-3.77, p < 0.001). Frailty, but not pre-frailty was associated with a higher risk of stroke (aHR 3.29; 95%CI 1.29-8.39, p = 0.01). CONCLUSION: Over two thirds of patients with AF are pre-frail or frail. These patients have a high risk for unplanned hospitalizations and other adverse events. These findings emphasize the need to carefully evaluate these patients. However, whether screening for pre-frailty and frailty and targeted prevention strategies improve outcomes needs to be shown in future studies.

5.
J Neurochem ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792978

RESUMO

Behavioral neuroscience has taken a long time to finally recognize that the largely distinct behavioral repertoires of males and females may arise from differences in brain function. This may in particular apply for the neurochemistry of the dopamine systems and their roles in the organization of emotion, learning, and reinforcement in health and in pathological conditions. The current Editorial highlights a study by Egenrieder and colleagues published in the current issue of the Journal of Neurochemistry, in which the authors have analyzed extracellular dopamine neurochemistry from females and males in a meta-analysis. Largely surprising, they report that after detailed control of methodological differences between studies, no major differences in basal or drug-induced extracellular dopamine activity emerged between sexes in rodents. The locally dissociating effects of ovariectomy in females reported in the Egenrieder et al. study, may furthermore suggest that there may be different sex effects in the distinct dopaminergic projections of the mesolimbic and nigrostriatal dopamine system. However, this may only be the beginning of a system's analysis of dopaminergic sex differences that calls for further meta-analyses of the existing studies.

7.
Nanomaterials (Basel) ; 9(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835842

RESUMO

Graphene-based materials are a family of carbonaceous structures that can be produced using a variety of processes either from graphite or other precursors. These materials are typically a few layered sheets of graphene in the form of platelets and maintain some of the properties of pristine graphene (such as two-dimensional platelet shape, aspect ratio, and graphitic bonding). In this work we present melt mixed graphene-based polypropylene systems with significantly reduced percolation threshold. Traditionally melt-mixed systems suffer from poor dispersion that leads to high electrical percolation values. In contrast in our work, graphene was added into an isotactic polypropylene matrix, achieving an electrical percolation threshold of ~1 wt.%. This indicates that the filler dispersion process has been highly efficient, something that leads to the suppression of the ß phase that have a strong influence on the crystallization behavior and subsequent thermal and mechanical performance. The electrical percolation values obtained are comparable with reported solution mixed systems, despite the use of simple melt mixing protocols and the lack of any pre or post-treatment of the final compositions. The latter is of particular importance as the preparation method used in this work is industrially relevant and is readily scalable.

8.
Addict Biol ; : e12847, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828921

RESUMO

Depression and alcohol dependence are associated with increased plasma ceramide concentrations in humans. Pharmacological increase in C16 ceramide concentrations in the dorsal hippocampus (DH) induced a depressive-like phenotype in naïve mice. However, the effects of C16 ceramide on alcohol consumption and anxiety-like behavior as well as the behavioral effects of other ceramide species are yet unknown. Therefore, we investigated whether repeated infusion of ceramides with different fatty acid chain lengths (C8, C16, and C20) into the DH and the basolateral amygdala (BLA) alter alcohol consumption, emotional behavior, and tissue monoamine levels. Our results revealed that C16, but not C8 and C20, ceramide altered alcohol drinking and emotional behavior in a brain region-specific way without altering tissue noradrenaline, dopamine, and serotonin levels in the prefrontal cortex, ventral striatum, and dorsal mesencephalon. In more detail, C16 ceramide increased alcohol consumption when infused into the BLA, but not when infused into the DH. Furthermore, C16 ceramide induced a depressive-like phenotype when infused into the DH, but a predominantly anxiogenic-like phenotype (in a non-social, but not a social context) when infused into the BLA. In turn, alcohol drinking normalized C16 ceramide-induced depressive-like and anxiogenic-like phenotypes. This study demonstrates a complex ceramide species-specific and brain region-specific modulation of alcohol consumption and emotional behavior in mice and provides the framework for future studies investigating the involvement of distinct ceramide species in the regulation of emotional behavior.

9.
Disabil Rehabil ; : 1-11, 2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31868030

RESUMO

Purpose: This study was conducted in a home-based context where trained occupational therapists delivered progressive physical exercise training and home modification intervention for preventing falls, namely the FIT-at-Home intervention. We assessed the feasibility of the intervention's content and mode of delivery from the occupational therapists' perspective as well as the feasibility of study procedures.Methods: We used a mixed-methods approach, which generated qualitative data from 14 OTs' after delivering the intervention via interviews and quantitative data of the study procedures via questionnaires and documentation sheets.Results: In total, 16 of the 17 older people completed the intervention. Of 9 recorded falls, no serious physical problems occurred. Qualitative data suggested that the intervention content and mode was feasible. Only minor adaptations to the program are needed based on the users' feedback. The main benefit was seen in the fact that simple exercises can be integrated into everyday life for older people with restricted mobility.Conclusion: The FIT-at-Home intervention comprising lifestyle-integrated balance and strength exercises and home safety is feasible for occupational therapists to deliver. The findings will help to further refine the intervention and study procedures.Implications for rehabilitationFalling is a frequent and serious health problem for many community-living older people, and the incidence of injurious falls increases with advancing age.Home visiting programs comprising physical exercise training and home modification appear to be beneficial for older people with poor health, functional limitations, and limited mobility.This study indicates that it is feasible to introduce lifestyle-integrated balance and strength exercises, performed as part of daily routine for older people at risk of falling.Behavioural self-management strategies have the potential to improve the implementation of exercises during the course of rehabilitation treatment and afterward.

10.
FEBS Lett ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733150

RESUMO

The hirudin-like factor 1 (HLF1) of Hirudo medicinalis belongs to a new class of leech-derived factors. In previous investigations, HLF1 did not exhibit anticoagulatory activities. Here, we describe the analysis of natural and synthetic variants of HLF1 and HLF-Hyb, a yet uncharacterized member of the HLF family. Modifications within the N terminus of HLF1 have a strong impact on its activity. Some variants of HLF1 exhibit thrombin-inhibiting activity comparable to hirudins, whereas others have reduced or no activity. The analyses of HLF-Hyb variants revealed a strong impact of the central globular domain on activity. Our results indicate a comparable mode of action of hirudins and thrombin-inhibiting HLF variants. Finally, we propose and discuss criteria for classifying hirudins and HLFs.

11.
Disabil Rehabil ; : 1-13, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31760814

RESUMO

Purpose: In this paper, we report on the development and refinement of a progressive physical exercise training and home modification intervention for older people with a risk of falling located in Germany by using the United Kingdom's Medical Research Council framework.Methods: The process was iterative and six phases of development emerged: (1) establishing an intervention development group, (2) identifying the evidence on interventions, (3) identifying a theory to underpin the intervention, (4) designing the intervention components, (5) drafting the intervention manual and training course, and (6) piloting and refining of intervention components.Results: The result was an evidence-based, theory-informed, and user-endorsed intervention: FIT-at-Home. This intervention comprised nine individual sessions over 12 weeks and two follow-up booster sessions delivered by trained occupational therapists. A feasibility study demonstrated the acceptance and feasibility of intervention delivery. Users responses were generally favorable and included recommendations about the intervention manual, mode of delivery of the home hazard assessment, and producing a manual for older people.Conclusions: We developed a feasible home-based lifestyle-integrated physical exercise training and home modification intervention for older people with a risk of falling by using a systematic approach. Implications include how this intervention could enrich occupational therapy fall prevention strategy in older people living at home.IMPLICATIONS FOR REHABILITATIONFalls in older people represent a major public health concern and occupational therapists in rehabilitation practice are encouraged to apply evidence-based interventions that reduce the risk of falls in older people living in a community.Many physical and environmental fall risks are modifiable by lifestyle changes such as physical exercise training, home safety assessment, and home modification. We developed a home-based balance and strength exercise training and home modification intervention that aims to improve strength, balance, and home safety.This study indicates that older people, at risk of falling, with functional limitations, and limited mobility, who participated in the FIT-at-Home intervention, felt that exercising at home suited them best.

12.
Neurosignals ; 27(S1): 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31742960

RESUMO

BACKGROUND/AIMS: Swiprosin-1/ EF-hand domain 2 (EFhd2) is a Ca2+ sensor protein that plays an important role in the immune system. Its abundant expression in the brain, however, suggested also a role in neuronal circuits and behavior. METHODS: Here we review recent discoveries on the structure and molecular function, its role in immunity and its function in the brain regarding behavioral control and pathologies. RESULTS: While EFhd2 did not emerge as a vital protein for brain development, changes in its expression may nevertheless shape the adult behavioral repertoire significantly and contribute to adult personality traits. A defective function of EFhd2 may also render individuals more prone to the development of psychiatric disorders. Most prominently, EFhd2 proved to be a resilience factor protecting from fast establishment of drug addiction. Moreover, EFhd2 is critical for adult neurogenesis and as a modulator of monoaminergic systems. CONCLUSION: Dysregulated activity of EFhd2 is increasingly considered as a contributing factor for the development of numerous neurodegenerative disorders. Whether EFhd2 can be used as biomarker or in therapeutic approaches has to be addressed in future research.

13.
JCI Insight ; 4(23)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31600170

RESUMO

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

14.
Chem Commun (Camb) ; 55(92): 13812-13815, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612181

RESUMO

A hitherto unknown triphosphatricyclo[3.2.1.02,7]oct-3-ene was obtained in high yield by a total of four consecutive pericyclic reactions from di-2-pyrone and excess TMS-C[triple bond, length as m-dash]P. DFT calculations gave insight into the reaction mechanism. The chiral phosphorus cage readily forms coordination compounds with Au(i) and Cu(i).

17.
Swiss Med Wkly ; 149: w20125, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31656035

RESUMO

Biomarkers are noninvasive, inexpensive, highly reproducible tools that allow clinicians to quantify pathophysiological processes relevant to a specific disease. Although the concept of biomarker-guided precision medicine is still in its infancy once a specific cardiovascular diagnosis is established, biomarker guidance has become the standard of care in the early diagnosis of acute cardiovascular disease in patients presenting to the emergency department with common symptoms such as acute chest pain or acute dyspnoea. This review highlights recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers, namely high-sensitivity cardiac troponin and natriuretic peptides in established indications such as the early diagnosis of acute myocardial infarction and heart failure. In addition, we address emerging indications such as the screening for perioperative myocardial infarction.

18.
Nat Neurosci ; 22(11): 1834-1843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31636447

RESUMO

Learning drives behavioral adaptations necessary for survival. While plasticity of excitatory projection neurons during associative learning has been extensively studied, little is known about the contributions of local interneurons. Using fear conditioning as a model for associative learning, we found that behaviorally relevant, salient stimuli cause learning by tapping into a local microcircuit consisting of precisely connected subtypes of inhibitory interneurons. By employing deep-brain calcium imaging and optogenetics, we demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in the basolateral amygdala are activated by aversive events and provide a mandatory disinhibitory signal for associative learning. Notably, VIP interneuron responses during learning are strongly modulated by expectations. Our findings indicate that VIP interneurons are a central component of a dynamic circuit motif that mediates adaptive disinhibitory gating to specifically learn about unexpected, salient events, thereby ensuring appropriate behavioral adaptations.

19.
Biomacromolecules ; 20(10): 3924-3932, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31525970

RESUMO

Many polymers, including polyethylene, feature a relatively low melting point and hence must be cross-linked to make them viable for applications that demand a high stiffness and creep resistance at elevated temperatures. The resulting thermoset plastics cannot be recycled, and therefore alternative materials with a reconfigurable internal network structure are in high demand. Here, we establish that such a thermoset-like yet recyclable material can be realized through the addition of a nanocellulose reinforcing agent. A network consisting of cellulose nanocrystals, nano- or microfibrils imparts many of the characteristics that are usually achieved through chemical cross-linking. For instance, the addition of only 7.5 wt % of either nanocellulose material significantly enhances the melt stiffness of an otherwise molten ethylene-acrylate copolymer by at least 1 order of magnitude. At the same time, the nanocellulose network reduces the melt creep elongation to less than 10%, whereas the neat molten matrix would rupture. At high shear rates, however, the molten composites do not display a significantly higher viscosity than the copolymer matrix, and therefore retain the processability of a thermoplastic material. Repeated re-extrusion at 140 °C does not compromise the thermomechanical properties, which indicates a high degree of recyclability. The versatility of dynamic nanocellulose networks is illustrated by 3D printing of a cellulose composite, where the high melt stiffness improves the printability of the resin.

20.
Organometallics ; 38(16): 3187-3196, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31474784

RESUMO

The catalytic asymmetric transfer hydrogenation (ATH) of ketones is a powerful methodology for the practical and efficient installation of chiral centers. Herein, we describe the synthesis, characterization, and catalytic application of a series of manganese complexes bearing simple chiral diamine ligands. We performed an extensive experimental and computational mechanistic study and present the first detailed experimental kinetic study of Mn-catalyzed ATH. We demonstrate that conventional mechanistic approaches toward catalyst optimization fail and how apparently different precatalysts lead to identical intermediates and thus catalytic performance. Ultimately, the Mn-N,N complexes under study enable quantitative ATH of acetophenones to the corresponding chiral alcohols with 75-87% ee.

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