RESUMEN
When a qubit or spin interacts with others under a many-body Hamiltonian, the information it contains progressively scrambles. Here, nuclear spins of an adamantane crystal are used as a quantum simulator to monitor such dynamics through out-of-time-order correlators, while a Loschmidt echo (LE) asses how weak perturbations degrade the information encoded in these increasingly complex states. Both observables involve the implementation of a time-reversal procedure which, in practice, involves inverting the sign of the effective Hamiltonian. Our protocols use periodic radio frequency pulses to modulate the natural dipolar interaction implementing a Hamiltonian that can be scaled down at will. Meanwhile, experimental errors and strength of perturbative terms remain constant and can be quantified through the LE. For each scaling factor, information spreading occurs with a timescale, T_{2}, inversely proportional to the local second moment of the Hamiltonian. We find that, when the reversible interactions dominate over the perturbations, the information scrambled among up to 10^{2} spins can still be recovered. However, we find that the LE decay rate cannot become smaller than a critical value 1/T_{3}≈(0.15±0.02)/T_{2}, which only depends on the interactions themselves, and not on the perturbations. This result shows the emergence of a regime of intrinsic irreversibility in accordance to a central hypothesis of irreversibility, hinted from previous experiments.
RESUMEN
In this work, we overview time-reversal nuclear magnetic resonance (NMR) experiments in many-spin systems evolving under the dipolar Hamiltonian. The Loschmidt echo (LE) in NMR is the signal of excitations which, after evolving with a forward Hamiltonian, is recovered by means of a backward evolution. The presence of non-diagonal terms in the non-equilibrium density matrix of the many-body state is directly monitored experimentally by encoding the multiple quantum coherences. This enables a spin counting procedure, giving information on the spreading of an excitation through the Hilbert space and the formation of clusters of correlated spins. Two samples representing different spin systems with coupled networks were used in the experiments. Protons in polycrystalline ferrocene correspond to an 'infinite' network. By contrast, the liquid crystal N-(4-methoxybenzylidene)-4-butylaniline in the nematic mesophase represents a finite proton system with a hierarchical set of couplings. A close connection was established between the LE decay and the spin counting measurements, confirming the hypothesis that the complexity of the system is driven by the coherent dynamics.
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OBJECTIVE: The present systematic review and meta-analysis intended to: 1) determine the extent of abnormalities in emotional processing linked to emotional event-related potentials (ERPs) in Fibromyalgia Syndrome (FMS) and 2) integrate data from similar emotional tasks into a meta-analysis to clearly demonstrate the scientific and clinical value of measuring emotional ERPs by electroencephalography (EEG) in FMS. METHODS: A systematic review and meta-analysis of studies comparing emotional processing indicated by ERPs in FMS patients and healthy controls was conducted. Fifteen articles were included in the systematic review after applying the eligibility criteria. RESULTS: Nine articles demonstrated disturbances in emotional processing in FMS. These emotional disturbances were distributed over the whole range of ERP latencies, mainly over central, parietal, temporal and occipital areas. Despite of this, quantitative analysis revealed only significant differences in N250 and LPP/LPC between FMS patients and healthy controls, with smaller LPP/LPC and greater N250 seen in FMS. DISCUSSION: N250 and LPP/LPC seem to be the ERPs with the greatest potential to determine emotional alterations in FMS. These ERPs are related to complex cognitive processes such as decoding features relevant to affect recognition (N250) as well differentiation between emotions, persistent engagement, conflict resolution or evaluation of emotional intensity (LPC/LPP). However, differences in task setup had an important impact on the variation of ERP outcomes. Systematization of protocols and tasks is indispensable for future studies.
Asunto(s)
Fibromialgia , Humanos , Electroencefalografía/métodos , Emociones/fisiología , Potenciales Evocados/fisiología , Reconocimiento en PsicologíaRESUMEN
BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder of unknown aetiopathogenesis, in which the role of activity of the hypothalamic-pituitary-adrenal (HPA) axis is not clearly established. METHODS: This study analysed the modulatory effects of disease chronicity and severity on cortisol levels. Hair cortisol concentrations (HCC) and clinical evaluation data (pain severity, impact of FM on daily activities, depression, anxiety, fatigue and insomnia) were collected from 47 female patients with FM and 36 healthy women (HW). RESULTS: The results showed that disease chronicity, with a negative effect, and symptom severity, with a positive effect, were independent predictors of HCC. Patients with a shorter disease duration had higher HCC than patients with a longer disease duration and healthy participants. Furthermore, patients with greater symptom severity had higher HCC than those patients with lower clinical severity and healthy participants. While disease chronicity in FM was associated with a decrease in HCC, clinical severity increased HCC. CONCLUSIONS: These results support the existence of a dysfunction in the regulation of the HPA axis in FM and its possible contribution to chronic pain development. SIGNIFICANCE: This is the first study to assess hair cortisol concentrations in a specific sample of patients with fibromyalgia (FM). This method is especially useful for the assessment of long-term regular cortisol excretion. Results showed a two-component model for explaining cortisol levels: disease chronicity, with a negative effect, and symptom severity, with a positive effect. This suggests that severe pain/stress evokes higher cortisol levels at earlier stages of FM, while in the longer term a decrease in cortisol levels was observed.
Asunto(s)
Dolor Crónico , Fibromialgia , Humanos , Femenino , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , CabelloRESUMEN
INTRODUCTION: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. OBJECTIVES: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. PATIENTS AND METHODS: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. RESULTS: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031). CONCLUSIONS: ICH-OAC has a high mortality rate, related to the use of acenocoumarol and regardless of the initial clinical situation. A lower rate of early mortality was found among patients who received ART.
TITLE: Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO).Introducción. La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos. El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos. Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados. Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p lower than 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031). Conclusiones. La HIC-ACO presenta una elevada mortalidad, relacionada con la toma de acenocumarol y de forma independiente con la situación clínica inicial. Se comprobó una menor tasa de mortalidad precoz entre pacientes que recibieron TRA.
Asunto(s)
Anticoagulantes/efectos adversos , Reversión de la Anticoagulación , Antídotos/uso terapéutico , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/mortalidad , Protocolos Clínicos , Inhibidores del Factor Xa/efectos adversos , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neuroimagen , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria/estadística & datos numéricos , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vitamina K/antagonistas & inhibidoresRESUMEN
INTRODUCTION: The excess of visceral abdominal adipose tissue is one of the major concerns in obesity and its clinical treatment. OBJECTIVE: To apply the two-dimensional predictive equation proposed by Garaulet et al. to determine the abdominal fat distribution and to compare the results with the body composition obtained by multi-frequency bioelectrical impedance analysis (M-BIA). SUBJECTS/METHODS: We studied 230 women, who underwent anthropometry and M-BIA. The predictive equation was applied. Multivariate lineal and partial correlation analyses were performed with control for BMI and % body fat, using SPSS 15.0 with statistical significance P < 0.05. RESULTS: Overall, women were considered as having subcutaneous distribution of abdominal fat. Truncal fat, regional fat and muscular mass were negatively associated with VA/SA(predicted), while the visceral index obtained by M-BIA was positively correlated with VA/SA(predicted). DISCUSSION/CONCLUSION: The predictive equation may be useful in the clinical practice to obtain an accurate, costless and safe classification of abdominal obesity.
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Grasa Abdominal , Composición Corporal , Adulto , Impedancia Eléctrica , Femenino , Predicción , Humanos , Grasa Intraabdominal , MatemáticaRESUMEN
Ventilator-induced diaphragm dysfunction (VIDD) is the loss of diaphragmatic muscle strength'related to of mechanical ventilation, noticed during the first day or 48hours after initiating controlled mechanical ventilation. This alteration has been related to disruption on the insulin growth factor/phosphoinositol 3-kinase/kinase B protein pathway (IGF/PI3K/AKT), in addition to an overexpression of FOXO, expression of NF-kB signaling, increase function of muscular ubiquitin ligase and activation of caspasa-3. VIDD has a negative impact on quality of life, duration of mechanical ventilation, and hospitalization stance and cost. More studies are necessary to understated the process and impact of VIDD. This is a narrative review of non-systematic literature, aiming to explain the molecular pathways involved in VIDD.
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Diafragma , Enfermedades Musculares/etiología , Respiración Artificial/efectos adversos , Factores de Edad , Caspasa 3/metabolismo , Diafragma/lesiones , Factores de Transcripción Forkhead/metabolismo , Glucocorticoides/efectos adversos , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Enfermedades Musculares/metabolismo , FN-kappa B/metabolismo , Estado Nutricional , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Calidad de Vida , Sarcopenia/etiología , Sarcopenia/metabolismo , Factores de Tiempo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Cavernous angiomas are cerebral vascular malformations that are usually congenital. These lesions are characterized as dynamic. The most common phenomenon in the course of these lesions is bleeding, which can result in significant fluctuations in their size and even lead to their disappearance. This article aims to describe the behavior of a cavernous angioma in its natural history, documenting: a) its de novo appearance, a very uncommon observation, and b) its changes on imaging studies, where it grew progressively like an expanding lesion but had no clinical repercussions. On magnetic resonance imaging, atypical signs can orient the etiological diagnosis of cavernous angioma versus other alternatives: de novo appearance, fluid-fluid or air-fluid level, incomplete hypointense ring due to hemosiderin deposition, pseudotumor-like growth, pseudocyst-like or multiloculated shape, vasogenic edema, mass effect, and size greater than 3cm.
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Neoplasias Encefálicas/diagnóstico por imagen , Hemangioma Cavernoso/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Neoplasias Encefálicas/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Epilepsia/etiología , Epilepsia/terapia , Hemangioma Cavernoso/complicaciones , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/terapia , Masculino , Tomografía Computarizada por Rayos X/métodosRESUMEN
SARS-CoV-2 infection can produce neurological features. The most common are headache, anosmia and dysgeusia but patients may also develop other central nervous system (CNS) injuries. We present a patient affected by Covid-19 who initially consulted for decreased visual acuity. The MRI showed inflammation in the right optic nerve and demyelinating lesions in the CNS. We speculate that an immune mechanism induced by SARS-CoV-2, which can activate lymphocytes and an inflammatory response, plays a role in the clinical onset of the disease. This pathogen may be associated with either the triggering or the exacerbation of inflammatory/demyelinating disease.
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Infecciones por Coronavirus/complicaciones , Esclerosis Múltiple/epidemiología , Neumonía Viral/complicaciones , Adulto , Betacoronavirus , COVID-19 , Femenino , Humanos , Esclerosis Múltiple/patología , Pandemias , SARS-CoV-2RESUMEN
UNLABELLED: The health organisations have moved from being centred on the professionals and are now centred on users and their expectations. The new health institutions want to know patients' perception of the quality of the care received, with particular respect to the information received, consent and decision making. It is necessary to have available measuring instruments that explore the different components of the process of information, consent and decision making. BACKGROUND: To identify the dimensions related to the process of information, consent and decision making of most importance to patients and susceptible to evaluation by questionnaire. SUBJECTS AND METHODS: Adult persons who have been hospitalised for at least two days. Qualitative study using semi-structured interviews. RESULTS: The participants wish to be informed and to participate in decision making; they do not know the meaning of the charter of patients' rights; they wish to share the whole care process with their family; written information is incomprehensible to them; and they feel that their pain and discomfort do not receive appropriate attention. CONCLUSION: It would be convenient to include the following dimensions in the questionnaires on satisfaction: a) the possibility of clarifying doubts; b) real knowledge of the rights and duties of patients; c) participation by the family in the care process; d) continuity of the same informer throughout hospitalisation; d) degree of understanding of the written information; e) involvement in decision making; and f) attention to pain and discomfort.
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Hospitalización , Satisfacción del Paciente , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Sistemas de Registros Médicos Computarizados , Persona de Mediana Edad , Participación del Paciente , Encuestas y CuestionariosRESUMEN
The nursing profession has always placed great importance on the ethical requirements linked to its activities. However, the understanding and content to these activities has evolved over the course of history. Two approaches have been developed as the principal issues of nursing ethics: the ethics of virtue and the ethics of principles. The first approach enquires into the attitudes that must be held by a person in order to act as a good nurse. The second follows an inverse course and considers the actions and principles that must be respected in order to be a good professional. An approach that harmonises both perspectives must pose the following questions: What do we understand by nursing care? On what ethical principles is this form of understanding care based? What moral attitudes are related to caring correctly? In a modern professional model, the definition and exercise of care necessarily include consideration of team work. Similarly, carrying out a good caring function, that is to say quality nursing, requires apprenticeship on the one hand, and, on the other, the assimilation of the attitudes that are required in a person involved in caring. Both elements improve the capacity of the professionals to prevent and resolve ethical conflicts in the practice of care.
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Bioética , Ética en Enfermería , Atención de Enfermería/ética , Humanos , Relaciones InterprofesionalesRESUMEN
Introducción: La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos: El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos: Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados: Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p < 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031)...(AU)
Introduction: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. Objectives: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. Patients and methods: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. Results: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031)...(AU)
Asunto(s)
Humanos , Masculino , Femenino , Hemorragia Cerebral/mortalidad , Inhibidores del Factor Xa , Anticoagulantes/efectos adversos , Protocolos Clínicos , Resultado del Tratamiento , Estudios Prospectivos , Neurología , Enfermedades del Sistema Nervioso , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/tratamiento farmacológicoRESUMEN
Rats' performance on a progressive-ratio schedule maintained by sucrose (0.6M, 50 µl) and corn oil (100%, 25 µl) reinforcers was assessed using a model derived from Killeen's (1994) theory of schedule-controlled behaviour, 'Mathematical Principles of Reinforcement'. When the rats were maintained at 80% of their free-feeding body weights, the parameter expressing incentive value, a, was greater for the corn oil than for the sucrose reinforcer; the response-time parameter, δ, did not differ between the reinforcer types, but a parameter derived from the linear waiting principle (T0), indicated that the minimum post-reinforcement pause was longer for corn oil than for sucrose. When the rats were maintained under free-feeding conditions, a was reduced, indicating a reduction of incentive value, but δ was unaltered. Under the food-deprived condition, the CB1 cannabinoid receptor agonist Δ(9)-tetrahydrocannabinol (THC: 0.3, 1 and 3 mg kg(-1)) increased the value of a for sucrose but not for corn oil, suggesting a selective enhancement of the incentive value of sucrose; none of the other parameters was affected by THC. The results provide new information about the sensitivity of the model's parameters to deprivation and reinforcer quality, and suggest that THC selectively enhances the incentive value of sucrose.
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Estimulantes del Apetito/farmacología , Condicionamiento Operante/efectos de los fármacos , Dronabinol/farmacología , Privación de Alimentos/fisiología , Alimentos , Desempeño Psicomotor/efectos de los fármacos , Animales , Aceite de Maíz/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Ratas , Ratas Wistar , Esquema de Refuerzo , Sacarosa/farmacología , Edulcorantes/farmacologíaRESUMEN
Transmissible gastroenteritis coronavirus (TGEV) infects both, the enteric and the respiratory tract of swine. S protein, that is recognized by the cellular receptor, has been proposed that plays an essential role in controlling the dominant tropism. The genetic relationship of S gene from different enteric strains and non-enteropathogenic porcine respiratory coronaviruses (PRCVs) was determined. A correlation between tropism and the genetic structure of the S gene was established. PRCVs, derived from enteric isolates have a large deletion at the N-terminus of the S protein. Interestingly, two respiratory isolates, attenuated Purdue type virus (PTV-ATT) and Toyama (TOY56) have a full-length S gene. PTV-ATT has two specific amino acid differences with the S protein of the enteric viruses. One is located around position 219, within the deleted area, suggesting that alterations around this amino acid may result in the loss of enteric tropism. To study the role of different genes in tropism, a cluster of viruses closely related to PUR46 strain was analyzed. All of them have been originated by accumulating point mutations from a common, virulent isolate which infected the enteric tract. During their evolution these viruses have lost, virulence first, and then, enteric tropism. Sequencing analysis proved that enteric tropism could be lost without changes in ORFs 3a, 3b, 4, 6, and 7, and in 3'-end untranslated regions (3'-UTR). To study the role of the S protein in tropism recombinants were obtained between an enteric and a respiratory virus of this cluster. Analysis of the recombinants supported the hypothesis on the role in tropism of S protein domain around position 219.
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Genes Virales , Familia de Multigenes , ARN Viral/biosíntesis , Recombinación Genética , Virus de la Gastroenteritis Transmisible/genética , Virus de la Gastroenteritis Transmisible/fisiología , Animales , Células Cultivadas , Masculino , Sistemas de Lectura Abierta , ARN Viral/química , Especificidad de la Especie , Porcinos , Testículo , Virus de la Gastroenteritis Transmisible/patogenicidad , Proteínas Virales/biosíntesis , Proteínas Virales/genética , VirulenciaRESUMEN
The minimum sequence required for the replication and packaging of transmissible gastroenteritis virus (TGEV)-derived minigenomes has been determined. To this end, cDNAs encoding defective RNAs have been cloned and used to express heterologous spike proteins, to determine the influence of the peplomer protein in the control of TGEV tropism. A TGEV defective interfering RNA of 9.7 kb (DI-C) was isolated, and a cDNA complementary to DI-C RNA was cloned under the control of T7 promoter. In vitro transcribed DI-C RNA was replicated in trans upon transfection of helper virus-infected cells. A collection of DI-C deletion mutants (TGEV minigenomes) was generated and tested for their ability to be replicated and packaged. The size of the smallest minigenome replicated in trans was 3.3 kb. The rescue system was used to express the spike protein of an enteric TGEV isolate (C11) using as helper virus a TGEV strain (C8) that replicates very little in the gut. A mixture of two pseudorecombinant viruses containing either the helper virus genome or the minigenome was obtained. These pseudorecombinants display in the surface the S proteins from the enteric and the attenuated virus, and showed 10(4)-fold increase in their gut replication levels as compared to the helper isolate (C8). In addition, the pseudorecombinant virus increased its enteric pathogenicity as compared to the C8 isolate.
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ARN Viral/biosíntesis , Virus de la Gastroenteritis Transmisible/fisiología , Proteínas Virales/fisiología , Animales , Secuencia de Bases , Línea Celular , Virus Defectuosos/fisiología , Expresión Génica , Genoma Viral , Datos de Secuencia Molecular , Porcinos , Virus de la Gastroenteritis Transmisible/genética , Virión/fisiología , Ensamble de Virus , Replicación ViralRESUMEN
Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response. Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication. The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry. Then, it is of high interest to develop strategies to prevent infections of these areas. Virus growth can be interfered intracellularly, extracellularly or both. The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known. In addition, antibodies efficiently neutralize viruses in the mucosal areas. The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium. These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection. A similar role could be played by antimicrobial peptides in the case of bacteria. Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins. All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes. We have developed two strategies to target into mucosal areas either antibodies to provide immediate protection, or antigens to elicit immune responses in the enteric or respiratory surfaces in order to prevent virus infection. One strategy is based on the development of expression vectors using coronavirus derived defective RNA minigenomes, and the other relies on the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation. Two types of expression vectors are being engineered based on transmissible gastroenteritis coronavirus (TGEV) defective minigenomes. The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase. The minigenomes expressing the heterologous gene have been improved by using a two-step amplification system based on cytomegalovirus (CMV) and viral promoters. Expression levels around 5 micrograms per 10(6) cells were obtained. The engineered minigenomes will be useful to understand the mechanism of coronavirus replication and for the tissue specific expression of antigen, antibody or virus interfering molecules. To protect from viral infections of the enteric tract, transgenic animals secreting virus neutralizing recombinant antibodies in the milk during lactation have been developed. Neutralizing antibodies with isotypes IgG1 or IgA were produced in the milk with titers of 10(6) in RIA that reduced virus infectivity by one million-fold. The recombinant antibodies recognized a conserved epitope apparently essential for virus replication. Antibody expression levels were transgene transgene copy number independent and were related to the transgene integration site. This strategy may be of general use since it could be applied to protect newborn animals against infections of the enteric tract by viruses or bacteria for which a protective MAb has been identified. Alternatively, the same strategy could be used to target the expression of antibio
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Anticuerpos Antivirales/inmunología , Bacterias/inmunología , Replicación Viral/inmunología , Animales , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antivirales/biosíntesis , Bacterias/crecimiento & desarrollo , Humanos , Inmunidad Mucosa , Mucosa Intestinal/inmunologíaRESUMEN
The present work describes the process by which the pilot project of clinical management of the Hospital Complex Juan Canalejo, designated as "Heart Area", was implemented. In the first section, the needs and reasons that led to the undertaking of this project are explained. The project's objectives and operative strategies are listed. In the Material and Methods section, three basic aspects of the "Heart Area" are described: selection criteria of the "Area", its structure and function, and its foundation and development. In the Results section, we compare the activity undertaken in the "Area" to the situation present prior to its implementation, in relation to quality and costs. Finally, in the Conclusions, we comment on the important implications that our project can have within the Hospital Complex Juan Canalejo as well as in the health care field in general.
Asunto(s)
Servicio de Cardiología en Hospital , Procedimientos Quirúrgicos Cardíacos , Servicio de Cardiología en Hospital/economía , Servicio de Cardiología en Hospital/organización & administración , Urgencias Médicas , Estudios de Evaluación como Asunto , Cardiopatías/complicaciones , Cardiopatías/cirugía , Cardiopatías/terapia , Humanos , Proyectos Piloto , España , Procedimientos Quirúrgicos OperativosRESUMEN
Pulmonary or pleural involvement from prostate cancer is an uncommon clinical finding. We report on a patient with prostate cancer and a diagnosis of malignant pleural effusion made by determination of pleural fluid prostate specific antigen.