RESUMEN

BACKGROUND: Habitat transitions have considerable consequences in organism homeostasis, as they require the adjustment of several concurrent physiological compartments to maintain stability and adapt to a changing environment. Within the range of molecules with a crucial role in the regulation of different physiological processes, neuropeptides are key agents. Here, we examined the coding status of several neuropeptides and their receptors with pleiotropic activity in Cetacea. RESULTS: Analysis of 202 mammalian genomes, including 41 species of Cetacea, exposed an intricate mutational landscape compatible with gene sequence modification and loss. Specifically for Cetacea, in the 12 genes analysed we have determined patterns of loss ranging from species-specific disruptive mutations (e.g. neuropeptide FF-amide peptide precursor; NPFF) to complete erosion of the gene across the cetacean stem lineage (e.g. somatostatin receptor 4; SSTR4). CONCLUSIONS: Impairment of some of these neuromodulators may have contributed to the unique energetic metabolism, circadian rhythmicity and diving response displayed by this group of iconic mammals.

Asunto(s)

Cetáceos , Receptores de Neuropéptido , Animales , Receptores de Neuropéptido/genética , Receptores de Neuropéptido/metabolismo , Cetáceos/genética , Cetáceos/fisiología , Neuropéptidos/genética , Neuropéptidos/metabolismo , Pleiotropía Genética , Mutación , Filogenia

RESUMEN

Uveitis is a heterogeneous collection of infrequent diseases, which poses significant challenges to cost-effective research in the field. Medical registries are being increasingly recognized as crucial tools to provide high-quality data, thus enabling prospective clinical research. This paper describes the design and technical structure development of an innovative countrywide electronic medical record for uveitis, Uveite.pt, and gives an overview of the cohort registered since its foundation, March 2020.Uveite.pt is an electronic medical record platform developed by the Portuguese Ocular Inflammation Group (POIG), a scientific committee of the Portuguese Ophthalmology Society. This is a nationwide customized web-based platform for uveitis patients useful for both clinical practice and real-world-based research, working as a central repository and reporting tool for uveitis. This paper describes the technical principles, the design and the development of a web-based interoperable registry for uveitis in Portugal and provides an overview of more than 400 patients registered in the first 18 months since inception.In infrequent diseases, the existence of registries enables to gather evidence and increase research possibilities to clinicians. The adoption of this platform enables standardization and improvement of clinical practice in uveitis. It is useful to apprehend the repercussion of medical and surgical treatments in uveitis and scleritis, supporting clinicians in the strict monitoring of drug adverse reactions and surgical outcomes.

Asunto(s)

Uveítis , Humanos , Portugal/epidemiología , Estudios Prospectivos , Uveítis/diagnóstico , Uveítis/epidemiología , Sistema de Registros , Trastornos de la Visión , Inflamación , Internet

RESUMEN

AIM: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). METHODS: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. RESULTS: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). CONCLUSION: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available. KEY-WORDS: juvenile idiopathic arthritis, uveitis, biological treatment, conventional immunosuppressive treatment, multidisciplinary management, guidelines, consensus, review, Delphi Technique.

Asunto(s)

Artritis Juvenil , Oftalmología , Reumatología , Uveítis , Artritis Juvenil/complicaciones , Niño , Humanos , Portugal , Uveítis/diagnóstico

RESUMEN

Although choroid has been shown to have a vital role in the pathophysiology of many ocular diseases, its role in the pathogenesis of several other conditions remains uncertain. The authors propose a novel methodology to establish a more accurate Peripapillary Choroidal Thickness (PPCT), using an image-processing software. This study sought to evaluate the reproducibility and repeatability of PPCT evaluation with ImageJ software in healthy volunteers. Forty-eight eyes of 24 volunteers were subjected to PPCT area determination, after imaging acquisition and recording with Spectral-domain Optical Coherence Tomography (SD-OCT) Heidelberg Spectralis®, during two different sessions, by two blinded assessors. The age of the subjects was 29.2 ± 4.5 years (mean ± SD). The Coefficient of Repeatability (CR) average measurements of PPCT area was 17.06 mm2 and 9.48 mm2 correspondingly, for the first and second examiners. Intra-class Correlation Coefficient (ICC) was 0.994 (95% CI 0.989 to 0.997) and 0.998 (95% CI 0.997 to 0.999). Inter-observer Concordance Correlation Coefficient (CCC) was 0.998 (95% CI 0.996 to 0.999) for both examiners. Intra-observer CCC ranged from 0.997 (95% CI 0.996 to 0.999) to 0.998 (95% CI 0.997 to 0.999), correspondingly, for the first and second examiners. The PPCT quantification by means of the proposed methodology showed good inter- and intra-observer agreement for both operators, indicating feasibility and good reproducibility of the proposed methodology. This approach might be used in different clinical settings and potentially contributes to elucidation of the choroid role in ocular pathology.

RESUMEN

BACKGROUND: Endothelial Progenitor Cells (EPCs) are a circulating stem cell population with in vivo capacity of promoting angiogenesis after ischemic events. Despite the promising preclinical data, their potential integration with reperfusion therapies and hemodynamic evolution of stroke patients is still unknown. Our aim was to determine the association of EPCs with acute, subacute and chronic hemodynamic features. METHODS: In this prospective study, we included consecutive patients with ages between 18 and 80years and non-lacunar ischemic stroke within the territory of a middle cerebral artery. All patients were subject to hemodynamic evaluation by ultrasound at baseline, seven days and three months. We quantified cerebral blood flow (CBF) and assessed early recanalization and collateral flow. Hemorrhagic transformation was graded in Magnetic Resonance imaging performed at seven days. EPCs were isolated from peripheral venous blood collected in the first 24h and seven days, counted and submitted to functional in vitro tests. RESULTS: We included 45 patients with a median age of 70±10years. The angiogenic and migratory capacities of EPCs were associated with increased collateral flow in the acute stage and day seven CBF, without statistically significant associations with recanalization nor haemorrhagic transformation. The number of EPCs was not associated with any hemodynamic variable. CONCLUSIONS: The functional properties of EPCs are associated with acute and subacute stroke hemodynamics, with no effect on haemorrhagic transformation.

Asunto(s)

Células Progenitoras Endoteliales/fisiología , Hemodinámica/fisiología , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Arteria Carótida Interna/fisiopatología , Circulación Cerebrovascular/fisiología , Femenino , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Hemorragia/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal , Adulto Joven

RESUMEN

OBJECTIVE: To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome. METHODS: We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at p < 0.05. RESULTS: We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; p = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway. CONCLUSIONS: The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.

Asunto(s)

Barrera Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Permeabilidad Capilar/fisiología , Células Progenitoras Endoteliales/metabolismo , Accidente Cerebrovascular/metabolismo , Anciano , Antígenos CD34/metabolismo , Barrera Hematoencefálica/diagnóstico por imagen , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/patología , Movimiento Celular/fisiología , Células Cultivadas , Células Progenitoras Endoteliales/patología , Femenino , Hemodinámica , Humanos , Estudios Longitudinales , Masculino , MicroARNs/metabolismo , Pronóstico , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/patología

RESUMEN

Spontaneous intracranial hypotension (SIH) is an important cause of new daily persistent headache. It is thought to be due to spontaneous spinal cerebrospinal fluid (CSF) leaks, which probably have a multifactorial etiology. The classic manifestation of SIH is an orthostatic headache, but other neurological symptoms may be present. An epidural blood patch is thought to be the most effective treatment, but a blind infusion may be ineffective. We describe the case of a young man who developed an acute severe headache, with pain worsening when assuming an upright posture and relief gained with recumbency. No history of previous headache, recent cranial or cervical trauma, or invasive procedures was reported. Magnetic resonance imaging showed pachymeningeal enhancement and other features consistent with SIH and pointed towards a cervical CSF leak site. After failure of conservative treatment, a targeted computer tomography-guided EBP was performed, with complete recovery.

RESUMEN

INTRODUCTION: White matter hypodensities of presumed vascular origin, are recognized as an important cause of morbidity with established clinical and cognitive consequences. Nonetheless, many doubts remain on its physiopathology. Our goal is to clarify the potential role of carotid atherosclerosis and other vascular risk factors in the development of white matter hypodensities of presumed vascular origin. MATERIAL AND METHODS: We included patients that underwent CT brain scan and neurosonologic evaluation within a one-month period. Full assessment of vascular risks factors was performed. We seek to find independent associations between white matter hypodensities of presumed vascular origin, carotid intima-media thickness and vascular risk factors. RESULTS: 472 patients were included, mean age was 67.32 (SD: 14.75), 274 (58.1%) were male. The independent predictors of white matter hypodensities of presumed vascular origin were age (OR: 1.067, 95% IC: 1.049 - 1.086, p < 0.001) and hypertension (OR: 1.726, 95% IC: 1.097 - 2.715, p = 0.018). No association was found between IMT (OR: 2.613, 95% IC: 0.886 - 7.708, p = 0.082) or carotid artery stenosis (OR: 1.021, 95% IC: 0.785 - 1.328, p = 0.877) and white matter hypodensities of presumed vascular origin. DISCUSSION: Only age and hypertension proved to have an independent association with white matter hypodensities of presumed vascular origin. Carotid atherosclerosis, evaluated by IMT and the degree of carotid artery stenosis, showed no association with white matter hypodensities of presumed vascular origin. Since atherosclerosis is a systemic pathology, these results suggest that alternative mechanisms are responsible for the development of white matter hypodensities of presumed vascular origin. CONCLUSION: Age and hypertension seem to be the main factors in the development of white matter hypodensities of presumed vascular origin. No association was found between carotid atherosclerosis and white matter hypodensities of presumed vascular origin.

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Introdução: As hipodensidades da substância branca de provável etiologia vascular, são uma causa importante de morbilidade, condicionando deterioração cognitiva. No entanto, numerosas dúvidas persistem quanto à sua fisiopatologia. O objectivo deste estudo é clarificar o papel da aterosclerose carotídea e outros factores de risco vascular no desenvolvimento das hipodensidades da substância branca de provável etiologia vascular.Material e Métodos: Realizou-se uma avaliação imagiológica, por tomografia computadorizada crânio-encefálica e ecografia carotídea, com menos de um mês de intervalo. Procedeu-se à recolha de informação sobre os factores de risco vascular. Determinámos associações independentes entre hipodensidades da substância branca de provável etiologia vascular, espessura da íntima média carotídea, estenose carotídea ateromatosa e factores de risco vascular.Resultados: Foram incluídos 472 doentes, idade média de 67,32 (DP: 14.75), 274 (58,1%) sexo masculino. Os preditores independentes da hipodensidades da substância branca de provável etiologia vascular foram: idade (OR: 1,067, 95% IC: 1,049 – 1,086, p < 0,001) e a hipertensão (OR: 1,726, 95% IC: 1,097 – 2,715, p = 0,018). Não foi encontrada uma associação entre a espessura da intima média carotídea (OR: 2,613, 95% IC: 0,886 – 7,708, p = 0,082) ou grau de estenose carotídea (OR: 1,021, 95% IC: 0,785 – 1,328, p = 0,877) e hipodensidades da substância branca de provável etiologia vascular.Discussão: Dos diversos factores de risco analisados, apenas a idade e hipertensão se associaram de forma independente às hipodensidades da substância branca de provável etiologia vascular. Não foi encontrada uma relação entre a aterosclerose extracraniana, expressa pela espessura do complexo intima-média ou grau de estenose, com o desenvolvimento de hipodensidades da substância branca de provável etiologia vascular. Sendo a aterosclerose um fenómeno sistémico, estes achados sugerem que as hipodensidades da substância branca de provável etiologia vascular, tenham um mecanismo alternativo ou concorrente à aterosclerose no seu desenvolvimento.Conclusão: Os dados deste estudo, sugerem que a idade e hipertensão sejam os principais factores de risco no desenvolvimento de hipodensidades da substância branca de provável etiologia vascular. Não foi encontrada uma associação independente entre a aterosclerose carotídea e as hipodensidades da substância branca de provável etiologia vascular.

Asunto(s)

Enfermedades de las Arterias Carótidas/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/etiología , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

INTRODUCTION: MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a mitochondrial hereditary dysfunction in which the physiopathological mechanism of cerebral lesions is not totally understood as yet. Typically, these lesions are described as having normal to increased apparent diffusion coefficient (ADC), and this has been used to distinguish stroke-like lesions from ischemic lesions. Notwithstanding this, within the last few years, there have been reports of diffusion restriction in stroke-like episodes. OBJECTIVES: Analysis of the diffusion characteristics on serial magnetic resonance imaging (MRI) over a 16 month period, on a patient with MELAS and stroke-like lesions, to investigate the controversial changes of the ADC, reported in the last years. Evaluation of the proton spectroscopy changes in stroke-like lesions and apparently spared brain. METHODS: We performed four serial magnetic resonance imaging (MRI), including two stroke-like episodes, in a 28-year-old man with MELAS (mitochondrial DNA mutation A3243G). Qualitative analysis of the magnetic resonance images, including the single voxel spectroscopy and ADC maps, with analysis of evolution patterns of the last ones. RESULTS: Both MRI that were performed during those episodes of stroke-like lesion revealed areas of diffusion restriction, coexisting areas of high ADC. During the chronic phase, there was a regression of those changes. Proton spectroscopy showed the presence of lactate and reduction of N-acetyl aspartate peak in stroke-like lesion and the presence of lactate in apparently spared brain. CONCLUSIONS: All alterations that were recorded strengthen the view that cytotoxic oedema can occur in stroke-like lesions. Thus, their presence should not weaken the possibility of MELAS, especially if those lesions affect the temporal, parietal and/or occipital lobes, or if they predominantly involve the cortical gray matter, spanning vascular borders and if proton spectroscopy reveals lactate peak in the apparently spared brain.

Asunto(s)

Imagen de Difusión por Resonancia Magnética , Síndrome MELAS/diagnóstico , Espectroscopía de Resonancia Magnética , Adulto , Humanos , Masculino , Protones

RESUMEN

Mitochondrial respiratory chain (MRC) disorders have variable clinical manifestations which are mainly neurologic. Diagnosis in children is more complex than in adults because the classic phenotype, ragged red fibers, and mtDNA mutations are rarely seen in children. Moreover, clinical manifestations of disease in developing brains are less explicit. Although not specific, neuroimaging may be contributory to the diagnosis of these disorders in pediatric patients. Brain magnetic resonance images were reviewed for 133 pediatric patients investigated for a MRC disorder at a single center over a period of 10 years (1997-2006), in an attempt to identify distinctive neuroimaging features of MRC defects. Patients fit into four groups, according to the Bernier criteria: definite (63 cases), probable (53 cases), possible (7 cases) and unlikely diagnosis (10 cases). Brain atrophy (41 cases), supratentorial white matter lesions (14 cases), basal ganglia involvement (9 cases), and delayed myelination (9 cases) were the most frequent anomalies in the definite group, and 8 patients presented Leigh syndrome. Neuroimaging findings of the 63 children in the definite group were compared with the remainder and with those in the possible and unlikely groups. There were no significant differences in brain images between the groups analyzed, and therefore no distinctive brain imaging features were identified specific for MRC disorders.

Asunto(s)

Encéfalo/patología , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/fisiopatología , Acidosis Láctica/epidemiología , Acidosis Láctica/patología , Adolescente , Atrofia/epidemiología , Atrofia/patología , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Niño , Preescolar , ADN Mitocondrial/genética , Femenino , Humanos , Enfermedad de Leigh/diagnóstico , Enfermedad de Leigh/epidemiología , Enfermedad de Leigh/genética , Síndrome MELAS/epidemiología , Síndrome MELAS/genética , Síndrome MELAS/patología , Masculino , Proteínas de la Membrana/genética , Enfermedades Mitocondriales/genética , Miopatías Mitocondriales/epidemiología , Miopatías Mitocondriales/patología , Proteínas Mitocondriales/genética , Fenotipo , Mutación Puntual/genética , Retinitis Pigmentosa/epidemiología , Retinitis Pigmentosa/patología , Índice de Severidad de la Enfermedad

RESUMEN

Although synaptic transmission was assumed to use the same mechanisms in the case of different synapses of the central and peripheral nervous system, recent research revealed a great variety of different processes. Time might be a crucial factor to be considered in this diversity. It is recalled that the speed of a chemical reaction is inversely related to affinity. "Time is gained at the expense of sensitivity" as noticed by Bernard Katz (1989). Therefore, synaptic transmission will occur at a high speed only if it is supported by low affinity reactions. In the present work, we compare two examples of ultra-rapid transmission (the Torpedo nerve electroplaque synapse and the rat hippocampus mossy fiber/CA3 synapses), with a cholinergic process operating with high affinity but at a low speed: the release of glutamate elicited by nicotine from mossy fibers of the rat hippocampus.

Asunto(s)

Sistema Nervioso Central/fisiología , Órgano Eléctrico/fisiología , Fibras Musgosas del Hipocampo/fisiología , Sistema Nervioso Periférico/fisiología , Tiempo de Reacción/fisiología , Transmisión Sináptica/fisiología , Animales , Sistema Nervioso Central/ultraestructura , Órgano Eléctrico/ultraestructura , Potenciales Postsinápticos Excitadores/fisiología , Ácido Glutámico/metabolismo , Fibras Musgosas del Hipocampo/ultraestructura , Agonistas Nicotínicos/farmacología , Sistema Nervioso Periférico/ultraestructura , Ratas , Tiempo de Reacción/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Factores de Tiempo

RESUMEN

Pulmonary embolism (PE) is an important health problem and often a major clinical challenge, not only because of the low specificity of its clinical manifestations but also because of the increasing number of medical circumstances that are risk factors for this illness and the importance of early identification, since prompt and appropriate treatment can decrease mortality from this disease by about 25%. In recent years research on PE has been extensive, directed mainly at trying to determine and characterize its risk factors, establish new clinical probability algorithms, develop new diagnostic methods and put existing ones into perspective, seek new therapeutic approaches (pharmacological and non-pharmacological), and above all establish protocols that can guide the clinician from the stage of clinical suspicion to measures to prevent recurrence. It was the authors' aim to review the most significant literature on this subject, in order to produce a text that reflects the state of the art concerning PE and that can be used as a guide in the clinical approach to this pathology.

Asunto(s)

Embolia Pulmonar , Diagnóstico Diferencial , Humanos , Pronóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/terapia , Factores de Riesgo