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Corn processing methods including finely ground (FGC), dry rolled (DRC), and crumbled corn (CRC) were evaluated to determine their effects on average daily gain (ADG), structural growth, starch digestibility, feeding behavior, and blood metabolites of young dairy heifers. In this study, 36 Holstein heifers [91 ± 4 d of age, 105 ± 6.5 kg of body weight (BW); mean ± standard deviation] housed in 9 pens (4 heifers per pen) were fed diets (dry matter basis) containing 20% forage (wheat straw) and 80% corn-based concentrate for 60 d. Pens were randomly assigned to 1 of 3 dietary treatments based on the type of corn grain used for the diets: (1) ground corn (FGC; fine: 1.11 ± 0.52 mm); (2) dry-rolled corn (DRC; 2.30 ± 0.68 mm); and (3) crumbled corn (CRC; 2.54 ± 0.70 mm). Heifers had ad libitum access to diets and water throughout the experiment and the feed intake was measured daily. Animals were weighed at the beginning (91 d of age) and end (151 d of age) of the study. The ADG (kg of BW/d) was calculated at the end of experiment at an individual level. Feeding behavior was recorded based on direct observation by monitoring each heifer every 5 min during a 22-h period at 150 d of age. The CRC and DRC tended to increase feed intake compared with FGC, whereas heifers fed CRC tended to have a greater withers height compared with other treatments. Feed efficiency was not affected; however, ADG and final BW increased in heifers fed the CRC diet compared with other diets. Feeding CRC increased total-tract starch digestibility compared with FGC and DRC diets (97.8 vs. 93.1 and 89.5%, respectively). Compared with FGC diet, feeding DRC and CRC tended to increase rumination time. The molar proportion of propionate was greater, and the molar proportion of acetate and acetate-to-propionate ratio were lower in heifers fed CRC than in those fed DRC. The blood glucose and insulin-like growth factor concentrations increased in heifers fed CRC compared with feeding DRC; however, blood urea concentrations decreased by CRC feeding. In conclusion, thermal processing (CRC diet) improved total-tract starch digestibility, ADG, feed intake, and skeletal growth, but had no effect on feed efficiency during the experimental period. Our results indicated that the thermal processing of corn grain improved growth performance of weaned heifers; however, the performance of heifers over a 60-d period did not differ between mechanical processing methods (grinding and dry rolling).
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Alimentación Animal , Zea mays , Alimentación Animal/análisis , Animales , Bovinos , Dieta/veterinaria , Digestión , Conducta Alimentaria , Femenino , Rumen/metabolismo , Almidón/metabolismo , Zea mays/metabolismoRESUMEN
Evidence from language, visual and sensorimotor learning suggests that training early in life is more effective. The present work explores the hypothesis that learning during sensitive periods involves distinct brain networks in addition to those involved when learning later in life. Expert pianists were tested who started their musical training early (<7 years of age; n = 21) or late (n = 15), but were matched for total lifetime practice. Motor timing expertise was assessed using a musical scale playing task. Brain activity at rest was measured using fMRI and compared with a control group of nonmusicians (n = 17). Functional connectivity from seeds in the striatum revealed a striatal-cortical-sensorimotor network that was observed only in the early-onset group. In this network, higher connectivity correlated with greater motor timing expertise, which resulted from early/late group differences in motor timing expertise. By contrast, networks that differentiated musicians and nonmusicians, namely a striatal-occipital-frontal-cerebellar network in which connectivity was higher in musicians, tended to not show differences between early and late musicians and not be correlated with motor timing expertise. These results parcel musical sensorimotor neuroplasticity into a set of musicianship-related networks and a distinct set of predominantly early-onset networks. The findings lend support to the possibility that we can learn skills more easily early in development because during sensitive periods we recruit distinct brain networks that are no longer implicated in learning later in life.
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Cuerpo Estriado/diagnóstico por imagen , Aprendizaje/fisiología , Red Nerviosa/diagnóstico por imagen , Plasticidad Neuronal/fisiología , Adulto , Factores de Edad , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Música , Adulto JovenRESUMEN
With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor T staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.
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OBJECTIVE: The diagnosis of primary SjÓ§gren's syndrome still relies upon a constellation of clinical, laboratory, imaging, and pathological findings. We aimed to evaluate the relation of the disease activity with the results of diagnostic tests for primary SjÓ§gren's syndrome. METHODS: A principal component with cluster analysis was performed to classify 69 patients with primary SjÓ§gren's syndrome based on the results of diagnostic evaluations. RESULTS: Anti-SSA autoantibody was the most represented feature on the principal components. The anti-SSA and ultrasound score were positively correlated (p=0.001). We identified two distinct clusters of low or high disease activity (p<0.001). Except for disease duration and serum beta2-microglobulin, the clusters were significantly different in salivary flow (p= 0.004), ultrasound findings (p<0.001), IgG (p= 0.001), and salivary beta2-microglobulin (p= 0.048). Also, positive findings were significantly different between the clusters in rheumatoid factor, antinuclear antibody, anti-SSA, and anti-SSB (all p≤0.013). CONCLUSION: Patients with higher syndrome activity were best recognized with serological and ultrasound assessments. However, patients with lower syndrome activity had a longer disease duration, higher stimulated salivary flow rate, and a positive biopsy of minor salivary glands (56%).
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Síndrome de Sjögren , Humanos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/patología , Autoanticuerpos , Anticuerpos Antinucleares , Factor Reumatoide , Análisis por ConglomeradosRESUMEN
AIMS/HYPOTHESIS: Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis. METHODS: We genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls. RESULTS: We found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 × 10â»4), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 × 10â»5). CONCLUSIONS/INTERPRETATION: Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants.
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Diabetes Mellitus Tipo 2/genética , Factor Nuclear 4 del Hepatocito/genética , Adulto , Anciano , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
AIMS/HYPOTHESIS: LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk. METHODS: We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we attempted replication of rs9825041 (a proxy for this group) and the previously identified H324Q variant in up to 35,715 participants of European descent. RESULTS: No association between the common SNPs in LARS2 and type 2 diabetes was found. Our replication studies for the two low-frequency variants, rs9825041 and H324Q, failed to confirm an association with type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95-1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715 respectively). CONCLUSIONS/INTERPRETATION: In this study, the largest study examining the role of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility.
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Aminoacil-ARNt Sintetasas/genética , Diabetes Mellitus Tipo 2/enzimología , Estudio de Asociación del Genoma Completo , Anciano , Sustitución de Aminoácidos , Aminoacil-ARNt Sintetasas/metabolismo , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Proteínas Mitocondriales/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Spoligotyping can help assess the transmission of Mycobacterium tuberculosis strains. We aimed to study the genotyping of M. tuberculosis isolated from patients with tuberculosis from the west of Iran by spoligotyping. Forty-seven M. tuberculosis isolates were collected from the west of Iran. All samples were cultured on Löwenstein-Jensen medium incubated at 37°C for 8 weeks. Bacterial isolates were identified as M. tuberculosis using standard biochemical tests. Drug resistance patterns of M. tuberculosis to rifampicin and isoniazid were determined, and multidrug-resistant (MDR) strains were isolated. After DNA extraction, spoligotyping was performed. We found new spoligotypes 4162 and 4163, which correlated with atypical lineage. Atypical and unknown lineages also had correlations with the MDR tuberculosis rate (4%). The most prevalent spoligointernational types were orphan (34%), 2669 (23.4%) and 127 (14.8%) types. The most prevalent clades were Ural-2 (NEW-1) (25.53%) and atypical (23.40%) lineages. The predominant clade was Ural-2 (NEW-1) and an atypical lineage restricted to Iran. The rate of MDR was low. Knowledge of the circulating isolates in the west of Iran will help implement control programmes, so knowledge of the dynamic transmission of local isolates is crucial.
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Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.
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Encéfalo/irrigación sanguínea , Imagen por Resonancia Magnética , Esquizofrenia/fisiopatología , Percepción del Habla/fisiología , Habla/fisiología , Estimulación Acústica/métodos , Adulto , Encéfalo/fisiopatología , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Estimulación Luminosa/métodos , Esquizofrenia/patologíaRESUMEN
OBJECTIVE: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition. METHODS: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 +/- 3.5 years. One hundred and sixty-three patients were treated with Dysport (mean dose, 389 +/- 144 U) and 44 with Botox (mean dose, 145 +/- 44 U). RESULTS: The mean clinical benefit, based on a 0-3 scale (0=no effect, 1=slight, 2=moderate and 3=marked improvement) was similar for Dysport (2.5 +/- 0.3) and Botox (2.2 +/- 0.4). Adverse events were mild and similar for both products. Fewer than 2% of the patients developed neutralizing antibodies. DISCUSSION: These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.
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Toxinas Botulínicas Tipo A/uso terapéutico , Tortícolis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.
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Enfermedad Crítica , Endotoxinas/toxicidad , Polineuropatías/etiología , Sepsis/complicaciones , Axones/patología , Estimulación Eléctrica , Electromiografía , Bacterias Gramnegativas/metabolismo , Humanos , Inflamación/patología , Neuronas Motoras/fisiología , Conducción Nerviosa/fisiología , Examen Neurológico , Neuronas Aferentes/fisiología , Nervios Periféricos/patología , Polineuropatías/patología , Receptores de Interleucina-2/efectos de los fármacos , Receptores de Interleucina-2/metabolismoRESUMEN
PURPOSE: To report on the efficacy and safety of combined phacoemulsification and an Ahmed valve glaucoma drainage implant with respect to visual acuity improvement, intraocular pressure (IOP) control, and requirement for antiglaucoma medication. METHODS: A retrospective chart review was conducted of 41 eyes (31 patients) with coexisting visually significant cataracts and uncontrolled glaucoma who had combined phacoemulsification and Ahmed valve implantation. The outcome measures were: visual acuity, IOP, antiglaucoma medication requirements, and intra- and post-operative complications. Success was categorized as absolute (IOP<21 mmHg without the need for antiglaucoma medication) and relative (IOP<21 mmHg with one or more antiglaucoma medications). Failure was considered to be an IOP<6 mmHg or IOP>21 mmHg on maximally tolerated medications or any devastating complication. RESULTS: The mean patient age was 67.3+/-5.9 years old. The mean visual acuity improved from 0.73+/-0.5 to 0.16+/-0.16 (p=0.000). The mean IOP decreased from 28.2+/-3.1 to 16.8+/-2.1 (p=0.000, 40.4%), while the number of antiglaucoma medication decreased from 2.6+/-0.66 to 1.2+/-1.4 (p=0.000). The absolute and relative success rates were 56.1% and 31.7%, respectively; 5 eyes (12.2%) were considered failures. There were no intraoperative complications; postoperative complications occurred in 8 eyes (19.5%). A hypertensive phase was detected in 12 (29.3%) eyes. CONCLUSIONS: Combined phacoemulsification and Ahmed valve glaucoma drainage implantation is a safe and effective alternative to phacotrabeculectomy in patients with coexisting cataract and refractory glaucoma.
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Catarata/complicaciones , Implantes de Drenaje de Glaucoma , Glaucoma/complicaciones , Facoemulsificación/métodos , Anciano , Catarata/fisiopatología , Catarata/terapia , Femenino , Glaucoma/fisiopatología , Glaucoma/cirugía , Humanos , Presión Intraocular/fisiología , Complicaciones Intraoperatorias , Masculino , Complicaciones Posoperatorias , Implantación de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
A methodology for non-invasive estimation of the pressure in internal carotid arteries is proposed. It uses data assimilation and Ensemble Kalman filters in order to identify unknown parameters in a mathematical description of the cerebral network. The approach uses patient specific blood flow rates extracted from Magnetic Resonance Angiography and Magnetic Resonance Imaging. This construction is necessary as the simulation of blood flows in complex arterial networks, such as the circle of Willis, is not straightforward because hemodynamic parameters are unknown as well as the boundary conditions necessary to close this complex system with many outlets. For instance, in clinical cases, the values of Windkessel model parameters or the Young's modulus and the thickness of the arteries are not available on per-patient cases. To make the approach computational efficient, a reduced order zero-dimensional compartment model is used for blood flow dynamics. Using this simplified model, the proof-of-concept study demonstrates how to use the EnKF as an optimization tool to find parameters and how to make the inverse hemodynamic problem tractable. The predicted blood flow rates in the internal carotid arteries and the predicted systolic and diastolic brachial blood pressures are found to be in good agreement with the clinical measurements.
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Arterias Cerebrales/fisiología , Modelos Cardiovasculares , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Arterias Cerebrales/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , IncertidumbreRESUMEN
Effects of the antiarrhythmic and antimyotonic drug mexiletine were studied on two sodium channel mutants causing paramyotonia congenita (R1448H) and an overlap paramyotonic and hyperkalemic paralytic syndrome (M1360V). Channels were expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. Compared to the wild-type, channel, both mutants showed alterations of inactivation, i.e. slower inactivation, left shift of steady-state inactivation and faster recovery from inactivation. Mexiletine caused a significantly larger use-dependent block of the R1448H mutant when compared to M1360V and wild-type channels. This can be explained by a prolonged recovery from mexiletine block as observed for R1448H channels, since the affinity of mexiletine for the inactivated state was similar for all three clones. The use-dependent block of sodium channels by mexiletine reduces repetitive series of action potentials and therefore improves muscle stiffness in myotonic patients. The enhanced use-dependent block as seen with R1448H may explain the extraordinary therapeutic efficacy of mexiletine in most patients with paramyotonia congenita.
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Mexiletine/farmacología , Mutación/efectos de los fármacos , Trastornos Miotónicos/genética , Parálisis Periódica Hiperpotasémica/genética , Canales de Sodio/genética , Línea Celular , Homeostasis , Humanos , Modelos Moleculares , Mutación/fisiología , Técnicas de Placa-Clamp , Bloqueadores de los Canales de Sodio , Canales de Sodio/fisiologíaRESUMEN
Riluzole is used as therapeutic agent in amyotrophic lateral sclerosis. We investigated the interaction of riluzole with recombinant GABA (gamma-aminobutyric acid)(A) receptor channels (alpha(1)beta(2)gamma(2)-subunits) and glycine receptor channels (alpha(1)beta-subunits) transiently expressed in HEK293 cells. For electrophysiological experiments, the patch-clamp technique in combination with tools for ultrafast solution exchange was used. Saturating concentrations of GABA or glycine were applied with different concentrations of riluzole to outside-out patches containing alpha(1)beta(2)gamma(2) GABA(A) receptor channels or alpha(1)beta-glycine receptor channels on their surface, respectively. The current declined after application of GABA or glycine with three time constants of desensitization to a steady-state current amplitude. Application of riluzole resulted in a shift to fast desensitized states at both receptors. The proportion of the time constants of fast desensitization increased and the time constants of slow desensitization and the steady-state current decreased whereas the maximal current amplitudes were not affected by riluzole. The data of the study demonstrate for the first time interaction of GABAergic and glycinergic currents with riluzole under physiological conditions.
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Fármacos Neuroprotectores/farmacología , Receptores de GABA-A/efectos de los fármacos , Receptores de Glicina/efectos de los fármacos , Riluzol/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Glicina/farmacología , Humanos , Riñón/citología , Técnicas de Placa-Clamp , Receptores de GABA-A/fisiología , Receptores de Glicina/fisiología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Propofol directly activates gamma-aminobutyric acid (GABA(A)) receptors in the absence of the natural agonist. This mechanism is supposed to contribute to its sedative-hypnotic actions. We studied the effects of seven structurally related phenol derivatives on chloride inward currents via rat alpha1beta2gamma2 GABA(A) receptors, heterologously expressed in HEK 293 cells in order to find structural determinants for this direct agonistic action. Only compounds with the phenolic hydroxyl attached directly to the benzene ring and with aliphatic substituents in ortho position to the phenolic hydroxyl activated chloride currents in the absence of GABA. Concentrations required for half-maximum effect were 980 microM for 2-methylphenol, 230 microM for 2,6-dimethylphenol, 200 microM for thymol, and 23 microM for propofol. Drug-induced chloride currents showed no desensitisation during the 2-s application. These results show that the position of the aliphatic substituents with respect to the phenolic hydroxyl group is the crucial structural feature for direct GABA(A) activation by phenol derivatives.
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Canales de Cloruro/fisiología , Potenciales de la Membrana/efectos de los fármacos , Fenol/farmacología , Receptores de GABA-A/fisiología , Animales , Línea Celular , Cresoles/farmacología , Relación Dosis-Respuesta a Droga , GABAérgicos/farmacología , Humanos , Fenol/química , Propofol/farmacología , Ratas , Receptores de GABA-A/genética , Relación Estructura-Actividad , Timol/farmacología , Xilenos/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Recombinant nicotinic acetylcholine receptor (nAChR) channels transiently expressed in HEK293 cells were investigated using the patch-clamp technique in the cell-attached and outside-out modes for single-channel analysis and ultra-fast agonist application to multiple channels. Deactivation (current decay after removal of agonist) and desensitization (current decay in the presence of agonist) were analyzed at embryonic- (gamma) and adult-type (epsilon) nAChR channels. Time constants of desensitization were similar for both receptor types (epsilon: 53.1+/-16.9 ms; gamma: 49.2+/-15.7 ms) and corresponded to the mean duration of clusters of single channel openings activated by pulses of 1 mM ACh. Deactivation showed distinct characteristics. Time constants were 1.76+/-0.16 ms for epsilon- and 3.19+/-0.18 ms for gamma-nAChR channels, corresponding to mean burst duration analyzed from single channels in the same preparation (epsilon: 1.85+/-1.2 ms, gamma: 3.85+/-2.1 ms). It is assumed that differences in deactivation are of functional relevance at the muscle endplate.
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Canales Iónicos/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/embriología , Receptores Nicotínicos/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Acetilcolina/farmacología , Factores de Edad , Animales , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Feto , Humanos , Canales Iónicos/metabolismo , Potenciales de la Membrana/fisiología , Ratones , Unión Neuromuscular/metabolismo , Agonistas Nicotínicos/farmacología , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Transmisión Sináptica/fisiología , TransfecciónRESUMEN
BACKGROUND: Cytokines and co-stimulatory molecules are important factors determining the outcome of transplantation. OBJECTIVE: To investigate the effect of IL-18 and CD40 gene polymorphisms on the outcome of liver transplantation. METHODS: 150 liver transplant recipients were included in this study. Alleles and genotypes frequencies for IL-18 (rs1946519) and CD40 (rs1883832) were determined in 28 acutely rejected (AR group) and 122 non-acutely rejected (non-AR group) liver transplant recipients. IL-18 and CD40 gene polymorphisms were evaluated by PCR-RFLP methods. RESULTS: There were no significant associations between IL-18 and CD40 polymorphism with acute rejection in liver transplant patients. IL-18TT and TG genotypes had a significant association with rejection in women compared to men. After grouping the liver recipients according to living vs cadaver donors, a significant association was found between CC genotype of CD40 and rejection in male living donor recipients. IL-18 TG genotype had a significant association with rejection in female cadaver donor recipients. CONCLUSION: There is no correlation between all genotype and alleles of IL-80 and CD40 polymorphism and the outcome of liver transplantation. However, gender and type of donor affect the correlation between all genotype and alleles of IL-18 and CD40, and the outcome of liver transplantation.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Neoplasias Esofágicas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Gástricas/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Procedimientos Quirúrgicos del Sistema Digestivo/tendencias , Esófago/patología , Esófago/cirugía , Humanos , Tiempo de Internación , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Procedimientos Quirúrgicos Mínimamente Invasivos/tendencias , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/normas , Procedimientos Quirúrgicos Robotizados/tendencias , Nivel de Atención , Estómago/patología , Estómago/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Transient bone marrow suppression, characterized by acute inability of the bone marrow to produce circulating blood cells, may strongly relate to the pathogenesis of some viral infections. OBJECTIVE: To study the prevalence of some DNA and RNA viruses in patients with transient bone marrow suppression. METHODS: EDTA-treated blood samples were collected from 27 patients with clinically- and laboratory-confirmed transient bone marrow suppression. The genomic DNA of hepatitis B virus, adenovirus, polyomavirus BK, and parvovirus B19, and genomic RNA of hepatitis C and G viruses were extracted and amplified by sensitive and specific in-house simple and nested PCR and RT-PCR protocols, respectively. The risk factors that might be related to the studied viral infections were analyzed. RESULTS: Hepatitis B virus infection was diagnosed in 9 (33%) of 27 patients; adenovirus infection in 2 (7%); and parvovirus B19 infection in 7 (26%) of 27 patients. The genomic DNA of polyomovirus BK was not detected in any patients. Both hepatitis C and G viruses were found in 3 (11%) of 27 patients. CONCLUSION: Diagnosis of the high prevalence of hepatitis B virus, and parvovirus B19 in patients with transient bone marrow suppression, reflects the importance of these viral infections in introducing bone marrow suppression. This hypothesis should be confirmed in further studies.
RESUMEN
The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.