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1.
Pain Rep ; 7(6): e1055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570738

RESUMO

The Declaration of Lima on Pain in Childhood is a call into action to improve the care provided to children and adolescents with pain.

2.
Biosystems ; 221: 104777, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36070849

RESUMO

We study a three-species cyclic game system where organisms face a contagious disease whose virulence may change by a pathogen mutation. As a responsive defence strategy, organisms' mobility is restricted to reduce disease dissemination in the system. The impact of the collective self-preservation strategy on the disease infection risk is investigated by performing stochastic simulations of the spatial version of the rock-paper-scissors game. Our outcomes show that the mobility control strategy induces plasticity in the spatial patterns with groups of organisms of the same species inhabiting spatial domains whose characteristic length scales depend on the level of dispersal restrictions. The spatial organisation plasticity allows the ecosystems to adapt to minimise the individuals' disease contamination risk if an eventual pathogen alters the disease virulence. We discover that if a pathogen mutation makes the disease more transmissible or less lethal, the organisms benefit more if the mobility is not strongly restricted, thus forming large spatial domains. Conversely, the benefits of protecting against a pathogen causing a less contagious or deadlier disease are maximised if the average size of groups of individuals of the same species is significantly limited, reducing the dimensions of groups of organisms significantly. Our findings may help biologists understand the effects of dispersal control as a conservation strategy in ecosystems affected by epidemic outbreaks.


Assuntos
Ecossistema , Modelos Biológicos , Humanos
4.
Chaos ; 32(12): 123142, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36587336

RESUMO

Antipredator behavior is a self-preservation strategy present in many biological systems, where individuals join the effort in a collective reaction to avoid being caught by an approaching predator. We study a nonhierarchical tritrophic system, whose predator-prey interactions are described by the rock-paper-scissors game rules. We perform a set of spatial stochastic simulations where organisms of one out of the species can resist predation in a collective strategy. The drop in predation capacity is local, which means that each predator faces a particular opposition depending on the prey group size surrounding it. Considering that the interference in a predator action depends on the prey's physical and cognitive ability, we explore the role of a conditioning factor that indicates the fraction of the species apt to perform the antipredator strategy. Because of the local unbalancing of the cyclic predator-prey interactions, departed spatial domains mainly occupied by a single species emerge. Unlike the rock-paper-scissors model with a weak species because of a nonlocal reason, our findings show that if the predation probability of one species is reduced because individuals face local antipredator response, the species does not predominate. Instead, the local unbalancing of the rock-paper-scissors model results in the prevalence of the weak species' prey. Finally, the outcomes show that local unevenness may jeopardize biodiversity, with the coexistence being more threatened for high mobility.


Assuntos
Biodiversidade , Modelos Biológicos , Humanos , Animais , Comportamento Predatório/fisiologia
7.
Neurol Sci ; 42(5): 1995-2003, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32997282

RESUMO

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. METHODS: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. RESULTS: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. CONCLUSIONS: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Cloridrato de Fingolimode/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Portugal/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Rev Neurol ; 71(10): 388-390, 2020 Nov 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33145751

RESUMO

TITLE: La oftalmoscopia en la era del teléfono inteligente. Dispositivos actuales y comentarios sobre nuestra breve experiencia.


Assuntos
Oftalmoscopia , Smartphone , Humanos
9.
Talanta ; 212: 120735, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113527

RESUMO

Changes in expression of Klotho gene are associated with chronic kidney disease and its potential as early biomarker is being studied. We report, for the first time, the detection of Klotho gene by a biosensor platform. Self-assembled mixed monolayers (SAMs) as DNA immobilization method in screen-printed gold electrodes and a sandwich format detection were used in the development of an electrochemical genosensor for the detection of a 100-mer DNA fragment, copy of the partial region of the mRNA Klotho gene. The use of different binary and ternary SAMs based on aliphatic (mercaptohexanol, MCH, and hexanedithiol, HDT) and aromatic (mercaptophenylacetic acid, MPAA) thiol diluents and capture probe (CP) as sensing phases was evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. Multiple configurations were studied, changing the order of component addition and comparing co-immobilization and two-step immobilization processes. The procedure for binary SAM preparation consisting of sequential addition of a thiol diluent followed by CP was found to have the least detrimental impact on electrochemical performance. The signal-to-blank ratios increased considerably in the case of thioaromatic binary DNA monolayers, MPPA/CP, compared to the values obtained for aliphatic SAMs. Ternary monolayers formed by MCH and HDT rendered good fractional coverage levels and generated more reversible redox reactions at the surface, mostly when CP was firstly immobilized, CP/HDT/MCH. A significant reduction of the blank and non-specific (non-complementary sequence) signals was obtained with this ternary SAM, compared to binary SAMs and an increase of 2.42-fold of the S/B ratio (10 nM of target) compared with MPAA/CP SAMs. A linear response in the range of 5·10-10 to 5·10-8 M was obtained with CP/HDT/MCH monolayer, with a detection limit of 0.5 nM and RSD of 8.10%.


Assuntos
Técnicas Biossensoriais/métodos , DNA/análise , Técnicas Eletroquímicas/métodos , Glucuronidase/genética , Compostos de Sulfidrila/química , Fosfatase Alcalina/química , DNA/química , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/genética , Proteínas Klotho , Limite de Detecção , Naftalenos/química , Hibridização de Ácido Nucleico , Compostos Organofosforados/química
10.
Pain Rep ; 4(1): e692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30801041

RESUMO

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

11.
Fish Shellfish Immunol ; 83: 348-358, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30227256

RESUMO

This study aimed to evaluate the protective effects of four autochthonous bacteria isolated from juvenile sole (Solea senegalensis) intestine as dietary probiotic supplement against bacterial pathogen infection and handling/transport stressors. Growth performance and immune responses were evaluated after 85 days of feeding trial. Sole (IBW = 16.07 ±â€¯0.11 g) were fed six experimental diets, a control diet (CTRL, without the dietary probiotic supplementation), and five diets supplemented with probiotic bacteria: PB1 (Shewanella hafniensis), PB2 (Enterococcus raffinosus), PB3 (Shewanella hafniensis + Arthrobacter soli), PB4 (Pseudomonas protegens + Arthrobacter soli) and PB5 (Shewanella hafniensis + Arthrobacter soli + Enterococcus raffinosus). All bacteria were selected based on their in vitro antimicrobial activity. After the growth trial, fish were submitted to a stress factor (transport) and then each dietary group was divided in two additional groups: non-infected (placebo) and infected with Photobacterium damselae subsp. piscicida. Immune and antioxidant responses were evaluated at day 10 post-infection. In infection trial A, fish were infected on the same day of transport, whereas in trial B fish were infected after a 7-day recovery from the transport stress. At the end of the feeding trial, fish fed with PB2 and PB4 showed lower final body weight when compared with the other dietary groups. Respiratory burst activity and nitric oxide production were not affected by probiotic supplementation. Fish fed with PB5 presented lower peroxidase activity compared to CTRL. Lysozyme and alternative complement pathway activity (ACH50) showed no significant differences between treatments. The innate immune responses were significantly affected after handling stress and bacterial infection. In trial A, the ACH50 levels of infected fish were significantly lower than the placebo groups. On the other hand, in trial B fish infected with Pdp demonstrated higher ACH50 levels when compared to placebos. Peroxidase levels were strongly modulated by bacterial infection and handling stress. In trials A and B, infection had a clear downgrade effect in peroxidase levels. Lipid peroxidation, catalase, glutathione S-transferase and glutathione reductase were altered by both bacterial infection and transport. Overall, dietary probiotic supplementation did not influence growth performance of sole. The immune and oxidative defenses of sole responded differently to infection depending on the probiotic and the synergy between pathogen infection and transport.


Assuntos
Doenças dos Peixes/imunologia , Linguados/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Photobacterium , Probióticos/farmacologia , Estresse Fisiológico/imunologia , Animais , Dieta/veterinária , Linguados/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/veterinária
12.
Rev Neurol ; 67(2): 41-49, 2018 Jul 15.
Artigo em Espanhol | MEDLINE | ID: mdl-29971757

RESUMO

AIM: To know the differences in the patterns of functional connectivity, the topological characteristics of the network and the relationship between these latter and the interictal epileptiform anomalies in children with primary and secondary autism spectrum disorder (ASD). PATIENTS AND METHODS: A retrospective study was conducted with 27 children aged between 3 and 13 years diagnosed with ASD. Subjects were submitted to an electroencephalogram in a functional state of spontaneous sleep. Functional connectivity and the properties of the network were analysed using data obtained from the electroencephalogram during the N2 stage of non-REM sleep. The frequency of discharge of the interictal epileptiform activity (FDIEA) was determined and was correlated with the topological properties of the network. RESULTS: Synchronisation was diminished in patients with secondary ASD for the alpha frequency and increased for the theta and delta frequency compared with patients with primary ASD. Local alpha efficiency was higher in patients who presented interictal epileptiform activity. Additionally, in patients with secondary ASD there was a statistically significant positive and negative correlation between FDIEA and the topological properties of the network. CONCLUSIONS: Patients with secondary ASD display patterns of functional connectivity that are weaker for the alpha frequency and stronger for theta and delta than patients with primary ASD. In patients with secondary ASD, the interictal epileptiform activity is related to local and global connectivity of the network for the alpha and beta bands during non-REM sleep.


TITLE: Conectividad funcional derivada del electroencefalograma durante el sueño no REM en los trastornos del espectro autista.Objetivo. Conocer las diferencias en los patrones de conectividad funcional, las caracteristicas topologicas de la red y la relacion de estas con las anomalias epileptiformes interictales en niños con trastorno del espectro autista (TEA) primario y secundario. Pacientes y metodos. Se realizo un estudio retrospectivo con 27 niños de 3-13 años diagnosticados con TEA, a los que se les realizo un electroencefalograma en estado funcional de sueño espontaneo. Se analizo la conectividad funcional y las propiedades de la red a partir de los datos obtenidos del electroencefalograma durante la etapa N2 del sueño no REM. Se determino la frecuencia de descarga de la actividad epileptiforme interictal (FDAEI) y se correlaciono con las propiedades topologicas de la red. Resultados. Los pacientes con TEA secundario tenian una disminucion de la sincronizacion para la frecuencia alfa y un incremento para la frecuencia theta y delta en comparacion con los pacientes con TEA primario. La eficiencia local alfa fue mayor en los pacientes que presentaban actividad epileptiforme interictal. Ademas, en los pacientes con TEA secundario, existia una correlacion positiva y negativa estadisticamente significativa entre la FDAEI y las propiedades topologicas de red. Conclusiones. Los pacientes con TEA secundario muestran patrones de conectividad funcional mas debiles para la frecuencia alfa y mas fuerte para la theta y delta que los pacientes con TEA primario. En pacientes con TEA secundario, la actividad epileptiforme interictal se relaciona con la conectividad local y global de la red para las bandas de frecuencia alfa y beta durante el sueño no REM.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Sincronização de Fases em Eletroencefalografia/fisiologia , Eletroencefalografia , Fases do Sono/fisiologia , Adolescente , Ondas Encefálicas/fisiologia , Criança , Pré-Escolar , Conectoma , Feminino , Humanos , Masculino , Estudos Retrospectivos
13.
J Clin Neurosci ; 45: 257-260, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28844615

RESUMO

Multiple Sclerosis (MS) treatment with natalizumab is associated with Progressive Multifocal Leukoencephalopathy (PML). The risk of PML being related to the anti-JCV antibody index is well established, but there is less known about seroconversion rates in natalizumab-treated patients and longitudinal variation in the anti-JCV antibody index. Our objective was to assess anti-JCV antibody prevalence in an MS population and to evaluate the evolution of the anti-JCV antibody index in natalizumab-treated patients. To assess anti-JCV antibody prevalence, we included all patients who had the anti-JCV antibody test in our consultation, regardless of the treatment. To evaluate the evolution of the anti-JCV antibody index and seroconversion, only natalizumab-treated patients with at least two samples were selected. Demographic characteristics were evaluated. From a total of 371 patients included, 68.19% (n=253) were seropositive for anti-JCV antibodies (JCV+). There was a significant difference in anti-JCV antibody seropositivity concerning gender (male 76.27% vs. female 64.43%, p=0.023), but not age. To evaluate seroconversion, 85 patients who were initially seronegative (JCV-) were selected. The annual rate of seroconversion in the first two years was stable, but after that there was a significant increase with treatment duration (ρ=0.90, p=0.037): in the first year it was 5.88% (n=5/85); in the second, 5.71% (n=4/70); in the third, 6.82% (n=3/44); in the fourth, 10.34% (n=3/29); and in the fifth, 15.0% (n=3/20). The mean index variability was higher in patients who experienced seroconversion (1.16±0.97), followed by JCV+ patients (0.44±0.48), compared to JCV- patients (0.08±0.05). In conclusion, anti-JCV antibody prevalence in our population is comparable to other reported cohorts. The seroconversion rate increased with treatment duration. We found a high fluctuation in the antibody index in JCV+ patients.


Assuntos
Anticorpos Antivirais/sangue , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Soroconversão , Adulto , Feminino , Humanos , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Prevalência , Estudos Retrospectivos , Caracteres Sexuais
14.
Int Immunopharmacol ; 46: 105-111, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28282574

RESUMO

OBJECTIVES: Natalizumab long-term effectiveness data in real-world relapsing-remitting multiple sclerosis (RRMS) is needed. Our objective is to report the long-term effectiveness and safety of natalizumab in a cohort of RRMS patients. METHODS: This is a retrospective study of natalizumab treatment for two years or longer in RRMS. Annualized relapse rate, Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging T2 lesion volume, JC virus antibody status, previous treatments and adverse events were analysed. RESULTS: Seventy-one patients were included with a mean treatment duration of 44.86±17.39months. Over the treatment duration there was a significant decrease in annualized relapse rate (88.37%) and EDSS (28.57%); no evidence of clinical disease activity in 73.24% and 61.97% after one and two-years respectively; and brain magnetic resonance imaging T2 lesion volume remained stable. Forty patients suspended natalizumab, in 85% due to high risk of developing progressive multifocal leukoencephalopathy (PML). The major complication was PML (n=3). CONCLUSIONS: Natalizumab showed effectiveness in the long-term follow up period of our cohort, with reduction of ARR, EDSS, and MRI lesion load stabilization. PML was the major complication.


Assuntos
Encéfalo/efeitos dos fármacos , Leucoencefalopatia Multifocal Progressiva/prevenção & controle , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Portugal , Estudos Retrospectivos , Risco , Suspensão de Tratamento , Adulto Jovem
15.
Animal ; 11(8): 1259-1269, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28077192

RESUMO

Probiotic administration can be a nutritional strategy to improve the immune response and growth performance of fish. The current study aimed to evaluate the effects of a probiotic blend (Bacillus sp., Pediococcus sp., Enterococcus sp., Lactobacillus sp.) as a dietary supplement on growth performance, feed utilization, innate immune and oxidative stress responses and intestinal morphology in juvenile Nile tilapia (Oreochromis niloticus). The probiotic was incorporated into a basal diet at three concentrations: 0 g/kg (A0: control), 3 g/kg (A1: 1.0×106 colony forming unit (CFU)/g) and 6 g/kg (A2: 2.3×106 CFU/g diet). After 8 weeks of probiotic feeding, weight and specific growth rate where significantly higher in fish-fed A1 diet than in fish-fed A0. Alternative complement in plasma was significantly enhanced in fish-fed A2 when compared with A0. The hepatic antioxidant indicators were not affected by probiotic supplementation. Villi height and goblet cell counts increased significantly in the intestine of fish-fed A1 and A2 diets compared with A0. The dietary probiotic supplementation was maintained until 20 weeks of feeding. Then the selected immune parameters, digestive enzymes and apparent digestibility of diets were studied. No effect of probiotic feeding was observed after that longer period supplementation. The dietary supplementation of mixed species probiotic may constitute a valuable nutritional approach towards a sustainable tilapia aquaculture. The improvement of the immune responses and intestinal morphology play an important role in increasing growth performance, nutrient absorption and disease resistance in fish, important outcomes in such a competitive and developing aquaculture sector.


Assuntos
Ração Animal , Ciclídeos/crescimento & desenvolvimento , Suplementos Nutricionais , Probióticos/administração & dosagem , Animais , Aquicultura , Ciclídeos/anatomia & histologia , Ciclídeos/imunologia , Dieta/veterinária , Imunidade , Intestinos/anatomia & histologia , Masculino
16.
Acta Neurol Scand ; 136(2): 109-115, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27778334

RESUMO

OBJECTIVES: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. MATERIALS AND METHODS: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. RESULTS: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=-.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. CONCLUSION: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/psicologia , Adulto , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/epidemiologia , Testes Neuropsicológicos , Tálamo/diagnóstico por imagem
17.
Genes Brain Behav ; 15(7): 669-77, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27415614

RESUMO

Pseudohypoparathyroidism type 1b (PHP1b) is characterized by hypocalcemia, hyperphosphatemia, increased levels of circulating parathyroid hormone (PTH), and no skeletal or developmental abnormalities. The goal of this study was to perform a full characterization of a familial case of PHP1b with neurological involvement and to identify the genetic cause of disease. The initial laboratory profile of the proband showed severe hypocalcemia, hyperphosphatemia and normal levels of PTH, which was considered to be compatible with primary hypoparathyroidism. With disease progression the patient developed cognitive disturbance, PTH levels were found to be slightly elevated and a picture of PTH resistance syndrome seemed more probable. The diagnosis of PHP1b was established after the study of family members and blunted urinary cAMP results were obtained in a PTH stimulation test. Integration of whole genome genotyping and exome sequencing data supported this diagnosis by revealing a novel homozygous missense mutation in PTH1R (p.Arg186His) completely segregating with the disease. Here, we demonstrate segregation of a novel mutation in PTH1R with a phenotype of PHP1b presenting with neurological symptoms, but no bone defects. This case represents the extreme end of the spectrum of cognitive impairment in PTH dysfunction and defines a possible novel form of PHP1b resulting from the impaired interaction between PTH and PTH1R.


Assuntos
Mutação , Pseudo-Hipoparatireoidismo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genoma , Homozigoto , Humanos , Hiperfosfatemia/genética , Hipocalcemia/genética , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/genética , Hormônio Paratireóideo/metabolismo , Linhagem , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Pseudo-Hipoparatireoidismo
18.
Appl Microbiol Biotechnol ; 100(16): 7223-38, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27183997

RESUMO

The effects of using plant ingredients in Senegalese sole (Solea senegalensis) diet on immune competence and intestine morphology and microbial ecology are still controversial. Probiotics or immunostimulants can potentially alter the intestinal microbiota in a way that protects fish against pathogens. The current study aimed to examine the intestine histology and microbiota and humoral innate immune response in juvenile sole fed diets with low (35 %) or high (72 %) content of plant protein (PP) ingredients supplemented with a multispecies probiotic bacteria or autolysed yeast. Fish fed the probiotic diet had lower growth performance. Lysozyme and complement activities were significantly higher in fish fed PP72 diets than in their counterparts fed PP35 diets after 17 and 38 days of feeding. At 2 days of feeding, fish fed unsupplemented PP72 showed larger intestine section area and longer villus than fish fed unsupplemented PP35. At 17 days of feeding, fish fed unsupplemented PP72 showed more goblet cells than the other dietary groups, except the group fed yeast supplemented PP35 diet. High dietary PP level, acutely stimulate fish innate immune defence of the fish after 2 and 17 days of feeding. However, this effect does not occur after 73 days of feeding, suggesting a habituation to dietary treatments and/or immunosuppression, with a reduction in the number of the goblet cells. Fish fed for 38 days with diets supplemented with autolysed yeast showed longer intestinal villus. The predominant bacteria found in sole intestine were Vibrio sp. and dietary probiotic supplementation caused a reduction in Vibrio content, regardless of the PP level.


Assuntos
Linguados/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/imunologia , Intestinos/microbiologia , Proteínas de Vegetais Comestíveis/farmacologia , Probióticos/farmacologia , Ração Animal , Animais , Aquicultura/métodos , Dieta , Suplementos Nutricionais , Linguados/crescimento & desenvolvimento , Linguados/imunologia , Leveduras
19.
Mult Scler Relat Disord ; 6: 41-48, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27063621

RESUMO

INTRODUCTION: Fingolimod is an oral treatment for Relapsing-Remitting Multiple Sclerosis (RRMS) with established efficacy in clinical trials. Post-marketing studies are important to assess its effectiveness in real-world populations. OBJECTIVES: To report the effectiveness and safety of fingolimod in a real-world population. METHODS: A retrospective study of patients with RRMS treated with fingolimod for at least six months. The demographic characteristics, Annualized Relapse Rate (ARR), Expanded Disability Status Score (EDSS), previous treatments and Adverse Events (AE) were analysed. RESULTS: 104 patients were included, with a mean treatment duration of 21.06 months. First-line disease modifying therapy failure patients (n=56) had an ARR decrease of 68.53% (1.43 vs. 0.45, p<0.001), 66.07% of them were relapse-free, EDSS significantly decreased (2.5 vs. 2.0, p<0.001) and 91.07% showed no disability progression. In patients previously treated with natalizumab as a second-line drug mainly switched due to safety concerns (n=41), although the differences were not statistically significant, both the ARR and EDSS increased in 41.46% and 19.51% of patients, respectively. In treatment-naive patients (n=7) the ARR decreased 94.90% (1.57 vs. 0.08, p=0.027) and there was no disability progression. 56.7% of all patients experienced AE not considered serious in any of the cases. CONCLUSION: In this population, fingolimod was an effective treatment after first-line treatment failure, decreasing both the ARR and EDSS, and may be an effective option after natalizumab.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Idoso , Avaliação da Deficiência , Progressão da Doença , Feminino , Cloridrato de Fingolimode/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Natalizumab/uso terapêutico , Portugal , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
PLoS One ; 10(11): e0141886, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26524084

RESUMO

The chronicity of osteoarthritis (OA), characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA). The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae) as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE) of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24): clean (C), negative control (CTL-), positive control (CTL+), HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA) (8 mg/kg) on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate) and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity). On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.


Assuntos
Chenopodium ambrosioides/química , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Monoterpenos Cicloexânicos , Modelos Animais de Doenças , Simulação de Acoplamento Molecular , Monoterpenos/administração & dosagem , Monoterpenos/química , Monoterpenos/farmacologia , Dor/etiologia , Peróxidos/administração & dosagem , Peróxidos/química , Peróxidos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Ratos Wistar , Líquido Sinovial/efeitos dos fármacos , Resultado do Tratamento
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