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1.
Bioscience ; 72(10): 978-987, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36196222

RESUMEN

The early twenty-first century has witnessed massive expansions in availability and accessibility of digital data in virtually all domains of the biodiversity sciences. Led by an array of asynchronous digitization activities spanning ecological, environmental, climatological, and biological collections data, these initiatives have resulted in a plethora of mostly disconnected and siloed data, leaving to researchers the tedious and time-consuming manual task of finding and connecting them in usable ways, integrating them into coherent data sets, and making them interoperable. The focus to date has been on elevating analog and physical records to digital replicas in local databases prior to elevating them to ever-growing aggregations of essentially disconnected discipline-specific information. In the present article, we propose a new interconnected network of digital objects on the Internet-the Digital Extended Specimen (DES) network-that transcends existing aggregator technology, augments the DES with third-party data through machine algorithms, and provides a platform for more efficient research and robust interdisciplinary discovery.

2.
Mod Pathol ; 33(11): 2139-2146, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32620916

RESUMEN

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.


Asunto(s)
Infecciones por Coronavirus/patología , Histiocitos/patología , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/virología , Neumonía Viral/patología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/virología , Anciano , Anciano de 80 o más Años , Betacoronavirus , Médula Ósea/patología , COVID-19 , Femenino , Humanos , Hiperplasia/patología , Hiperplasia/virología , Pulmón/patología , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2
3.
Am J Hum Genet ; 92(4): 621-6, 2013 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-23541344

RESUMEN

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2α (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.


Asunto(s)
Anomalías Múltiples/etiología , Síndrome Branquio Oto Renal/etiología , Displasia Ectodérmica/etiología , Exoma/genética , Hipospadias/etiología , Hipotonía Muscular/etiología , Mutación Missense/genética , Proteínas Represoras/genética , Anomalías Múltiples/patología , Secuencia de Aminoácidos , Síndrome Branquio Oto Renal/patología , Proteínas Co-Represoras , Oído Externo/anomalías , Oído Externo/patología , Displasia Ectodérmica/patología , Femenino , Humanos , Hipospadias/patología , Masculino , Datos de Secuencia Molecular , Hipotonía Muscular/patología , Pezones/anomalías , Pezones/patología , Linaje , Fenotipo , Estructura Terciaria de Proteína , Cuero Cabelludo/anomalías , Cuero Cabelludo/patología , Homología de Secuencia de Aminoácido
4.
Am J Dermatopathol ; 37(9): e107-11, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25943241

RESUMEN

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor characterized by a relatively high risk for local recurrence and low risk for metastasis. Many histopathologic variants of DFSP have been described, including the fibrosarcomatous and myoid variants, which may obscure the diagnosis in some cases, especially when arising in unusual locations. Of all the variants described so far, the only one with prognostic relevance is the FS-DFSP variant, which implies tumor progression and a higher possibility for metastasis. The authors report a case of a giant DFSP, located on the vulvar area, which histopathologically showed areas of fibrosarcomatous and myoid differentiation, and discuss the importance of the myoid variant in regards of the debated histogenesis of DFSP.


Asunto(s)
Dermatofibrosarcoma/patología , Neoplasias de la Vulva/patología , Adulto , Diferenciación Celular , Femenino , Humanos
5.
Acta Neurochir (Wien) ; 157(8): 1339-43; discussion 1343, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26085111

RESUMEN

Sparganosis is a severe parasitic infection caused by the larvae of Spirometra mansoni, also called "sparganum." In human hosts, the Spirometra mansoni larva commonly targets the subcutaneous tissue or muscle. Sometimes it can also migrate into the brain, resulting in cerebral sparganosis, mainly characterized by focal neurological symptoms such as seizures and radiological "wandering lesions" on magnetic resonance images (MRIs). Clinical cases of cerebral sparganosis have been reported worldwide, mainly in Asian countries, but also in North America, South America and Australia. Only two cases have been previously reported in Europe. A 29-year-old male from Bolivia, who lived in Spain, presented to our service for seizures and a multicystic brain lesion, initially suspected to be a dysembryoplastic neuroepithelial tumor (DNET). He underwent gross total resection of the mixed solid/cystic lesion. Pathology revealed gliosis, multiple interconnected cystic cavities with fibrous walls, inflammatory cell infiltration and no necrotizing granulomatous reaction. Inside the cavities, a parasitic form was identified as the larva of the cestode Spirometra mansoni. At 1-year follow-up, the patient had no deficits and was seizure free. Clinicians should be alerted to the possible existence of this rare entity in Europe, especially in patients from endemic areas with a possible infection history as well as "wandering lesions" on the MRI.


Asunto(s)
Encefalopatías/diagnóstico , Encefalopatías/parasitología , Imagen por Resonancia Magnética , Esparganosis/diagnóstico , Esparganosis/patología , Adulto , Animales , Encéfalo/parasitología , Encéfalo/patología , Encéfalo/cirugía , Encefalopatías/cirugía , Craneotomía , Europa (Continente) , Humanos , Masculino , Procedimientos Neuroquirúrgicos , Convulsiones/etiología , Convulsiones/parasitología , España , Esparganosis/cirugía , Spirometra/aislamiento & purificación , Resultado del Tratamiento
6.
Sci Data ; 10(1): 419, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37369663

RESUMEN

Commonly used data citation practices rely on unverifiable retrieval methods which are susceptible to content drift, which occurs when the data associated with an identifier have been allowed to change. Based on our earlier work on reliable dataset identifiers, we propose signed citations, i.e., customary data citations extended to also include a standards-based, verifiable, unique, and fixed-length digital content signature. We show that content signatures enable independent verification of the cited content and can improve the persistence of the citation. Because content signatures are location- and storage-medium-agnostic, cited data can be copied to new locations to ensure their persistence across current and future storage media and data networks. As a result, content signatures can be leveraged to help scalably store, locate, access, and independently verify content across new and existing data infrastructures. Content signatures can also be embedded inside content to create robust, distributed knowledge graphs that can be cited using a single signed citation. We describe applications of signed citations to solve real-world data collection, identification, and citation challenges.

7.
Inj Prev ; 18(6): 399-404, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22328634

RESUMEN

OBJECTIVES: Child fatality review (CFR) is the systematic, interdisciplinary, multi-agency examination of paediatric deaths. While CFR findings may influence policies and reduce preventable fatalities, limited resources challenge accurate CFR data collection and prevention recommendations. Therefore, using technology to improve efficiency of reviews and access to remote participants could enhance the CFR experience. This project aimed to adapt a previously developed collaborative web-based appliance for remote, secure, collaborative review of crash investigations for use with CFR. METHODS: The user-centred design and evaluation process included: (1) key informant interviews and visits to CFR sessions to determine current practices, (2) an anonymous, qualitative, internet-based survey of 64 Pennsylvania CFR team leaders, (3) redesign and adaptation of the Telecenter appliance based on survey results and team feedback and (4) pilot-testing of the adapted Telecenter application at an actual local CFR. RESULTS: The qualitative informant interviews identified facilitators and barriers for adoption of the Telecenter. Facilitators included: team member training, improved communication and collaboration, more efficient reviews, and enhanced preventive efforts. Barriers identified included: concern for confidentiality and security, concern about accepting a novel CFR method, low interest in using technology, cost and maintenance. The survey of CFR team leaders identified themes for improving CFR team functioning including the need for evidence-based prevention resources, increased team training and efficient information gathering. The Telecenter was redesigned and adapted based on the information gathered and was successfully piloted for use with CFR. CONCLUSIONS: Telecenter met the design goal to improve information dissemination and identification of fatality prevention strategies for CFR.


Asunto(s)
Mortalidad del Niño , Recolección de Datos/normas , Servicios Preventivos de Salud/normas , Telemedicina/normas , Niño , Conducta Cooperativa , Recolección de Datos/métodos , Humanos , Proyectos Piloto , Servicios Preventivos de Salud/métodos , Investigación Cualitativa , Telemedicina/métodos , Estados Unidos
8.
Sci Rep ; 10(1): 15466, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32963342

RESUMEN

Loss of cerebral autoregulation in normal perfusion pressure breakthrough (NPPB) phenomenon has been reported in other Central Nervous System diseases such as neonatal intraventricular haemorrhage. Several studies have demonstrated that low-dose indomethacin prevents this latter condition. A previous rat model was used to resemble NPPB phenomenon. Study animals were distributed in 4 groups that received 3 doses of indomethacin at different concentrations prior to fistula occlusion 60 days after its creation. Control animals received saline solution. Intracranial pressure (ICP) increased in all groups following fistula creation, whereas mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) decreased as a manifestation of cerebral hypoperfusion and intracranial hypertension. The administration of indomethacin was associated with raised MAP and CPP, as well as decreased ICP. Sodium fluorescein extravasation was slight in study animals when comparing with control ones. Histological analysis evidenced diffuse ischaemic changes with signs of neuronal apoptosis in all brain layers in control animals. These findings were only focal and slight in study animals. The results suggest the usefulness of indomethacin to revert, at least partially, the haemodynamic effects of NPPB phenomenon in this experimental model, as well as to reduce BBB disruption and histological ischemia observed in absence of indomethacin.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Circulación Cerebrovascular/efectos de los fármacos , Indometacina/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Barrera Hematoencefálica/patología , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Masculino , Perfusión , Ratas , Ratas Wistar
9.
Neurocirugia (Astur : Engl Ed) ; 31(5): 209-215, 2020.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31948841

RESUMEN

BACKGROUND: Normal perfusion pressure breakthrough (NPPB) phenomenon is a major life-threatening complication that restricts the treatment of complex intracranial arteriovenous malformations. The aim of the study it to develop a rat model mimicking NPPB phenomenon that enables the evaluation of any therapy to prevent such complication. METHODS: Twenty Wistar male rats were randomly assigned to either a study or a control group. Study animals underwent an end-to-side left external jugular vein-common carotid artery anastomosis and ligation of bilateral external carotid arteries. Control animals only underwent ligation of bilateral external carotid arteries. All animals were sacrificed sixty days after the procedure. Hemodynamic parameters [mean arterial pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP)], blood-brain barrier (BBB) permeability (measured by fluorescein staining) and histological features were then compared between both groups. RESULTS: A significant decrease in MAP and CPP was confirmed in the study group. An increase in ICP was also observed. A significant decrease in MAP and CPP was also present in the study group when comparing preoperative values with those recorded on days 0 (postoperative), 7 and 60. Fluorescein staining findings were consistent with signs of BBB disruption in study animals. Histological analysis demonstrated an increased number of pyknotic neurons in the ipsilateral hemisphere of rat brains included in the study group. CONCLUSION: These results confirm that this model mimics a vascular steal state with chronic cerebral hypoperfusion comparable to patients with AVMs behavior and disruption of the BBB after fistula closure comparable to NPPB phenomenon disorders.


Asunto(s)
Isquemia Encefálica , Animales , Isquemia Encefálica/etiología , Circulación Cerebrovascular , Humanos , Presión Intracraneal , Masculino , Perfusión , Ratas , Ratas Wistar , Reperfusión
10.
Panminerva Med ; 59(1): 67-75, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27701367

RESUMEN

Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of diabetes mellitus type 2, affecting about one­third of the patients. DKD results in increased hospitalizations and mortality rates, especially due to cardiovascular complications. This high burden of kidney disease is mainly due to the increasing complexity of in- outpatient care for patients with DM. There is a strikingly complex interaction of kidney dysfunction with many aspects of diabetes care, such as redefinition of targets of treatment, interactions of traditional and non­traditional risk factors, and pharmacological issues related to pharmacokinetic and side effects of drugs. Particularly when not carefully managed, DKD increases the demand for renal replacement therapies, such as dialysis and kidney transplants. The combined economic and social costs of this disease are high and of concern to the world's health systems. The main objective of this review is to provide insight into the recommendations for the evaluation and stratification of DKD and how the presence of kidney disease changes the optimal management of diabetic patients from an integrated renal­cardio­endocrine perspective.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Nefropatías Diabéticas/terapia , Automonitorización de la Glucosa Sanguínea , Presión Sanguínea , Sistema Endocrino , Fibrinolíticos/uso terapéutico , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Corazón/fisiopatología , Homeostasis , Humanos , Hiperglucemia/tratamiento farmacológico , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Riñón/fisiopatología , Metformina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , alfa-Glucosidasas
11.
J Nephrol ; 19(5): 588-98, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17136686

RESUMEN

BACKGROUND: Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. METHODS: Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. RESULTS: Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. CONCLUSIONS: Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.


Asunto(s)
Antihipertensivos/farmacología , Doxazosina/farmacología , Hipertensión/tratamiento farmacológico , Tetrahidroisoquinolinas/farmacología , Animales , Antihipertensivos/efectos adversos , Apoptosis/efectos de los fármacos , Enfermedad Crónica , Modelos Animales de Enfermedad , Doxazosina/efectos adversos , Fibrosis/inducido químicamente , Fibrosis/prevención & control , Humanos , Hipertensión/complicaciones , Hipertensión/patología , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/prevención & control , Masculino , Miocitos Cardíacos/patología , Quinapril , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Tetrahidroisoquinolinas/efectos adversos
12.
Crit Rev Oncol Hematol ; 98: 170-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26597015

RESUMEN

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Therapeutic approach is often unclear, and considerable controversy exists regarding MCC pathogenesis and optimal management. Due to its rising incidence and poor prognosis, it is imperative to establish the optimal therapy for both the tumor and the lymph node basin, and for treatment to include sentinel node biopsy. Sentinel node biopsy is currently the most consistent predictor of survival for MCC patients, although there are conflicting views and a lack of awareness regarding node management. Tumor and node management involve different specialists, and their respective decisions and interventions are interrelated. No effective systemic treatment has been made available to date, and therefore patients continue to experience distant failure, often without local failure. This review aims to improve multidisciplinary decision-making by presenting scientific evidence of the contributions of each team member implicated in MCC management. Following this review of previously published research, the authors conclude that multidisciplinary team management is beneficial for care, and propose a multidisciplinary decision algorithm for managing this tumor.


Asunto(s)
Algoritmos , Carcinoma de Células de Merkel/terapia , Terapia Combinada/métodos , Toma de Decisiones , Comunicación Interdisciplinaria , Neoplasias Cutáneas/terapia , Humanos , Ganglios Linfáticos/patología , Tumores Neuroendocrinos/terapia , Grupo de Atención al Paciente , Biopsia del Ganglio Linfático Centinela , Piel/patología , Resultado del Tratamiento
13.
Case Rep Hematol ; 2016: 7297920, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27807488

RESUMEN

NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

14.
Clin Cancer Res ; 9(2): 686-92, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12576436

RESUMEN

PURPOSE: This is one of the first reports of weekly docetaxel (Taxotere) in the neoadjuvant treatment of stage II and III breast cancer. We evaluated docetaxel's efficacy and safety and analyzed correlations between response and the expression of c-erbB2, ER status, and Ki-67 labeling index. EXPERIMENTAL DESIGN: Patients with previously untreated, stage II and III breast cancer were entered into the study. Docetaxel (40 mg/m(2)) was given i.v. once weekly for the first 6 weeks of an 8-week cycle for 2 cycles. RESULTS: A total of 56 patients were evaluated by intention-to-treat analysis for efficacy and safety. The overall clinical response rate was 68% (complete and partial response, 29 and 39%, respectively). Nine patients (16%) achieved a pathological complete response. There was no correlation between response to docetaxel and the expression of molecular markers, however, the majority of the pathological complete responses were observed in patients with c-erbB2-negative tumors. Nonhematological toxicity was more common than hematological toxicity, with alopecia and asthenia the most frequently reported adverse events (89 and 77% of patients, respectively). Severe hematological toxicity was rare. CONCLUSIONS: Weekly docetaxel appears to be very effective in the neoadjuvant setting. A high pathological response rate was achieved with tolerable toxicity.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapéutico , Taxoides , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Docetaxel , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Menopausia , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , España , Resultado del Tratamiento
15.
J Hypertens ; 20(3): 463-70, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11875314

RESUMEN

OBJECTIVE: The aim of the present study was to analyse the nitric oxide (NO)/cyclic GMP (cGMP) relaxing system in spontaneously hypertensive rats of the stroke-prone substrain (SHRSP). DESIGN: The study was performed in 20-week-old SHRSP rats. A group of normotensive Wistar-Kyoto (WKY) rats was used as control. RESULTS: The endothelium-dependent relaxation to acetylcholine was reduced in SHRSP rats (n = 15). No modifications in the expression of the endothelial nitric oxide synthase were found in the vascular wall of WKY rats (n = 15) and SHRSP rats. SHRSP rats demonstrated an impaired relaxing response to the NO-donor sodium nitroprusside that was accompanied by a reduction in the level of the main second messenger of NO, cyclic GMP. The expression of the soluble guanylate cyclase (sGC) beta1-subunit was markedly reduced in the vascular wall of SHRSP rats. In the experimental model of SHRSP, an increased concentration of catecholamines has been reported. Therefore, we evaluated the effect of an alpha1-receptor blocker, doxazosin, on the NO/cGMP system. Doxazosin [10 mg/kg body weight (bw) per day for 15 days, n = 15] reduced mean arterial pressure (MAP) in SHRSP rats. Treatment with doxazosin preserved the endothelium-independent relaxation response to sodium nitroprusside in aortic segments from SHRSP rats which was associated with an increased expression of the sGC beta1-subunit. A dose of doxazosin (1 mg/kg bw per day, n = 15) that did not modify MAP partially prevented sGC protein expression in the vascular wall. CONCLUSIONS: Independently of the endothelial NO-generating system, impaired vasorelaxation could also result from vascular smooth muscle cell layer dysfunction. Doxazosin treatment improved the endothelial-independent relaxation and preserved the cGMP generating system in the vascular wall of SHRSP rats.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Aorta/fisiopatología , GMP Cíclico/metabolismo , Doxazosina/farmacología , Hipertensión/fisiopatología , Ratas Endogámicas SHR/fisiología , Vasodilatación , Acetilcolina/farmacología , Animales , Aorta/efectos de los fármacos , Endotelio Vascular/fisiopatología , Predisposición Genética a la Enfermedad , Guanilato Ciclasa/metabolismo , Técnicas In Vitro , Isoenzimas/metabolismo , Masculino , Músculo Liso Vascular/fisiopatología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo III , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas WKY , Solubilidad , Accidente Cerebrovascular/genética , Vasodilatadores/farmacología
16.
J Comput Surg ; 3(12): 1-23, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26702394

RESUMEN

Development of more sophisticated implantable brain-machine interface (BMI) will require both interpretation of the neurophysiological data being measured and subsequent determination of signals to be delivered back to the brain. Computational models are the heart of the machine of BMI and therefore an essential tool in both of these processes. One approach is to utilize brain biomimetic models (BMMs) to develop and instantiate these algorithms. These then must be connected as hybrid systems in order to interface the BMM with in vivo data acquisition devices and prosthetic devices. The combined system then provides a test bed for neuroprosthetic rehabilitative solutions and medical devices for the repair and enhancement of damaged brain. We propose here a computer network-based design for this purpose, detailing its internal modules and data flows. We describe a prototype implementation of the design, enabling interaction between the Plexon Multichannel Acquisition Processor (MAP) server, a commercial tool to collect signals from microelectrodes implanted in a live subject and a BMM, a NEURON-based model of sensorimotor cortex capable of controlling a virtual arm. The prototype implementation supports an online mode for real-time simulations, as well as an offline mode for data analysis and simulations without real-time constraints, and provides binning operations to discretize continuous input to the BMM and filtering operations for dealing with noise. Evaluation demonstrated that the implementation successfully delivered monkey spiking activity to the BMM through LAN environments, respecting real-time constraints.

18.
IEEE Pulse ; 3(1): 57-9, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22344954

RESUMEN

The debilitating effects of injury to the nervous system can have a profound effect on daily life activities of the injured person. In this article, we present a project overview in which we are utilizing computational and biological principles, along with simulation and experimentation, to create a realistic computational model of natural and injured sensorimotor control systems. Through the development of hybrid in silico/biological coadaptive symbiotic systems, the goal is to create new technologies that yield transformative neuroprosthetic rehabilitative solutions and a new test bed for the development of integrative medical devices for the repair and enhancement of biological systems.


Asunto(s)
Modelos Biológicos , Redes Neurales de la Computación , Programas Informáticos , Animales , Humanos
19.
Rev. psicol. organ. trab ; 16(3): 259-273, set. 2016. ilus, tab
Artículo en Portugués | LILACS-Express | LILACS | ID: lil-791850

RESUMEN

A área de security, e especificamente de security no canal de inspeção de segurança da aviação civil brasileira, apresenta carência de estudos quanto à identificação, à quantificação, à causa e ao impacto de fatores e erros humanos. Este estudo teve o objetivo de identificar os fatores e erros humanos envolvidos no processo de inspeção de segurança da aviação civil brasileira. Empregando-se a teoria do sistema geral de modelagem do erro - GEMS "Generic Error-Modelling System"- e os quatro eixos temáticos sobre fatores humanos preconizados pela Organização de Aviação Civil Internacional (OACI), elaborou-se o instrumento da pesquisa constituído por 60 questões. A amostra foi composta por 602 (seiscentos e dois) profissionais AVSEC (segurança da aviação civil contra atos de interferência ilícita) que laboram no canal de inspeção, distribuídos em 18 (dezoito) aeroportos brasileiros. Os resultados foram retratados por meio de estatística descritiva e Análise de Componentes Principais (ACP). Os principais pontos da etapa descritiva fazem referência ao tempo de serviço majoritário no canal de inspeção, ao grau de escolaridade e ao de rendimento mensal bruto. Após as etapas da ACP, 46 itens do questionário foram categorizados em 7 (sete) componentes principais, os quais representaram 42, 04% da proporção total da variância explicada dos dados, isto é, dos erros e fatores humanos pesquisados. Concluiu-se, a partir da ACP, que há incidência de fatores e erros humanos no processo de inspeção de segurança, cujos percentuais são retratados neste artigo.


This study aimed at identifying human factors and errors that may exist in the Brazilian civil aviation security inspection process. Employing the theory of the Generic Error Modeling System (GEMS) and the four themes about human factors recommended by the International Civil Aviation Organization - ICAO, the research instrument was formulated, being composed of 60 questions. The sample was composed of six hundred and two (602) AVSEC professionals (civil aviation security against acts of unlawful interference) who work in security check points, covering eighteen (18) Brazilian airports. The results were presented using descriptive statistics and Principal Components Analysis - PCA. The main points of the descriptive stage related to the preponderant length of service, level of education, and monthly income. After the PCA steps, 46 questionnaire items were categorized into seven (7) principal components, which represented 42.04% of the total variance being explained by the data. It was concluded from the PCA that there is incidence of human factors and errors in the security inspection process, whose percentages are described in this article.


El área de la seguridad, y, específicamente, en el canal de inspección de seguridad de la aviación civil brasileña, muestra carencia de estudios sobre la identificación, cuantificación, causas e impacto al respecto de errores y factores humanos. Este estudio tuvo como objetivo identificar los factores y los errores humanos que intervienen en el proceso de inspección de seguridad de la aviación civil brasileña. Al emplearse la teoría del sistema de modelación del error -GEMS "Generic Error - Modelling System- y de las cuatro áreas temáticas de los factores humanos recomendados por la Organización de Aviación Civil Internacional (OACI), se elaboró un instrumento de investigación constituido de 60 preguntas. La muestra consistió en 602 (seiscientos dos) profesionales AVSEC (seguridad de la aviación civil contra actos de interferencia ilícita), que trabajan en el canal de inspección de seguridad, repartidos en dieciocho (18) aeropuertos. Los resultados fueron retratados a través de estadística descriptiva y Análisis de Componentes Principales (ACP). Los puntos principales de la etapa descriptiva se refieren al tiempo de servicio en el canal de la inspección, el nivel de escolaridad y el ingreso bruto mensual. Tras los pasos de la ACP, 46 ítems del cuestionario fueron clasificados en 7 (siete) componentes principales, que representaron el 42.04% de la proporción total de varianza explicada de los datos. Se concluyó, a partir de la ACP, que hay incidencia de factores y errores humanos en el proceso de inspección de seguridad, cuyos porcentajes son retratados en este artículo.

20.
Front Neuroeng ; 2: 17, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20126436

RESUMEN

A Cyber-Workstation (CW) to study in vivo, real-time interactions between computational models and large-scale brain subsystems during behavioral experiments has been designed and implemented. The design philosophy seeks to directly link the in vivo neurophysiology laboratory with scalable computing resources to enable more sophisticated computational neuroscience investigation. The architecture designed here allows scientists to develop new models and integrate them with existing models (e.g. recursive least-squares regressor) by specifying appropriate connections in a block-diagram. Then, adaptive middleware transparently implements these user specifications using the full power of remote grid-computing hardware. In effect, the middleware deploys an on-demand and flexible neuroscience research test-bed to provide the neurophysiology laboratory extensive computational power from an outside source. The CW consolidates distributed software and hardware resources to support time-critical and/or resource-demanding computing during data collection from behaving animals. This power and flexibility is important as experimental and theoretical neuroscience evolves based on insights gained from data-intensive experiments, new technologies and engineering methodologies. This paper describes briefly the computational infrastructure and its most relevant components. Each component is discussed within a systematic process of setting up an in vivo, neuroscience experiment. Furthermore, a co-adaptive brain machine interface is implemented on the CW to illustrate how this integrated computational and experimental platform can be used to study systems neurophysiology and learning in a behavior task. We believe this implementation is also the first remote execution and adaptation of a brain-machine interface.

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