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1.
Mult Scler ; 30(6): 664-673, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38481083

RESUMO

BACKGROUND: Serum neurofilament light (sNfL) reflects neuroaxonal damage and is now used as an outcome in treatment trials of relapsing-remitting multiple sclerosis (RRMS). However, the diagnostic properties of sNfL for monitoring disease activity in individual patients warrant further investigations. METHOD: Patients with suspected relapse and/or contrast-enhancing lesions (CELs) were consecutively included and performed magnetic resonance imaging (MRI) of the brain at baseline and weeks 28 and 48. Serum was obtained at baseline and 2, 4, 8, 16, 24, and 48 weeks. Neurofilament light concentration was measured using Single molecule array technology. RESULTS: We included 44 patients, 40 with RRMS and 4 with clinically isolated syndrome. The median sNfL level peaked at 2 weeks post-baseline (14.6 ng/L, interquartile range (IQR); 9.3-31.6) and reached nadir at 48 weeks (9.1 ng/L, IQR; 5.5-15.0), equivalent to the median sNfL of controls (9.1 ng/L, IQR; 7.4-12). A baseline Z-score of more than 1.1 (area under the curve; 0.78, p < 0.0001) had a sensitivity of 81% and specificity of 70% to detect disease activity. CONCLUSION: One out of five patients with relapse and/or CELs did not change significantly in post-baseline sNfL levels. The utility of repeated sNfL measurements to monitor disease activity is complementary rather than a substitute for clinical and MRI measures.


Assuntos
Biomarcadores , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente , Proteínas de Neurofilamentos , Humanos , Feminino , Proteínas de Neurofilamentos/sangue , Masculino , Adulto , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Estudos Prospectivos , Pessoa de Meia-Idade , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico por imagem
2.
J Asthma ; 61(2): 148-159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37610189

RESUMO

OBJECTIVE: Individuals with severe asthma often report poor Health-related quality of life (HRQoL) and more research is essential to increase understanding of how they may be helped to improve HRQoL. The main aim of the current paper is to evaluate HRQoL, and possible factors influencing HRQoL, in individuals with severe asthma. The aim is also to explore associations among anxiety, depression, beliefs of medication, self-efficacy, and HRQoL among individuals with severe and other asthma as well as those with no asthma. METHODS: Participants with severe asthma (n = 59), other asthma (n = 526), and no asthma (n = 902) were recruited from West Sweden Asthma Study, a population-based study, which includes both questionnaire surveys and clinical examinations. RESULTS: Individuals with severe asthma had worse physical HRQoL (measured with SF-8) than those with other and no asthma (median 48.4, 51.9, and 54.3, respectively). They also had worse mental HRQoL (median 46.7) and reported higher anxiety and depression scores (measured using HADS, median 5.0 and 3.5, respectively) compared to no asthma (median 4.0 and 2.0, respectively). HRQoL was particularly affected among women with severe asthma. Individuals with severe asthma believed that their asthma medication was more necessary than those with other asthma, but they reported more concern for the medication. Asthma control and packyears predicted physical HRQoL and anxiety predicted mental HRQoL among individuals with severe asthma. CONCLUSIONS: Efforts to improve asthma control and to reduce anxiety may improve HRQoL in individuals with severe asthma. Especially, women with severe asthma seem to need support to improve their HRQoL. Reducing concerns with asthma medication is most likely essential as high concerns may lead to poor adherence, which in turn may negatively affect asthma control and HRQoL.


Assuntos
Asma , Qualidade de Vida , Humanos , Feminino , Depressão/epidemiologia , Autoeficácia , Asma/tratamento farmacológico , Asma/epidemiologia , Ansiedade/epidemiologia , Inquéritos e Questionários
3.
Philos Trans R Soc Lond B Biol Sci ; 376(1830): 20200218, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34121461

RESUMO

Farmed aquatic animals represent an increasingly important source of food for a growing human population. However, the aquaculture industry faces several challenges with regard to producing a profitable, ethical and environmentally sustainable product, which are exacerbated by the ongoing intensification of operations and increasingly extreme and unpredictable climate conditions. Fortunately, bio-sensors capable of measuring a range of environmental, behavioural and physiological variables (e.g. temperature, dissolved gases, depth, acceleration, ventilation, heart rate, blood flow, glucose and l-lactic acid) represent exciting and innovative tools for assessing the health and welfare of farmed animals in aquaculture. Here, we illustrate how these state-of-the-art technologies can provide unique insights into variables pertaining to the inner workings of the animal to elucidate animal-environment interactions throughout the production cycle, as well as to provide insights on how farmed animals perceive and respond to environmental and anthropogenic perturbations. Using examples based on current challenges (i.e. sub-optimal feeding strategies, sub-optimal animal welfare and environmental changes), we discuss how bio-sensors can contribute towards optimizing the growth, health and welfare of farmed animals under dynamically changing on-farm conditions. While bio-sensors currently represent tools that are primarily used for research, the continuing development and refinement of these technologies may eventually allow farmers to use real-time environmental and physiological data from their stock as 'early warning systems' and/or for refining day-to-day operations to ethically and sustainably optimize production. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.


Assuntos
Bem-Estar do Animal , Aquicultura/instrumentação , Técnicas Biossensoriais/veterinária , Peixes/fisiologia , Tecnologia de Sensoriamento Remoto/veterinária , Animais , Animais Domésticos/fisiologia , Técnicas Biossensoriais/instrumentação , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia/instrumentação
4.
Mult Scler Relat Disord ; 46: 102463, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32862040

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) levels of neurofilament light (NFL), a biomarker of axonal damage, and CXCL13, a chemokine involved in B-cell regulation, are both associated with disease activity in multiple sclerosis (MS). OBJECTIVE: To explore the potential of NFL and CXCL13 to detect residual disease activity in patients with no signs of clinical or ongoing radiological activity and to study the clinical relevance of such activity. METHODS: NFL and CXCL13 concentrations were determined with ELISA in CSF obtained from 90 relapsing-remitting (RR) MS and 47 Progressive (Pr) MS (including primary and secondary PrMS) at baseline and after 12 months of follow-up. The patients were assessed at baseline, before initiating or switching disease modifying therapy (DMT) and again after 12 and 27 months of follow-up. RESULTS: All patients with ongoing disease activity (relapse or contrast-enhancing lesions on MRI) had increased NFL or CXCL13. The proportion of RRMS and PrMS patients without ongoing disease activity with elevation of either NFL or CXCL13 (residual disease activity) was 39% and 50%, respectively, and both were increased in 11% and 16%, respectively. The treatment with DMTs decreased the proportion with residual disease activity in both RRMS and PrMS significantly. We could not show any significant association between residual disease activity and clinical or MRI measures at 12 or 27 months of follow-up. CONCLUSIONS: Although most of this real-world study population had been treated with second-line DMTs and achieved clinical and radiological stability, a significant proportion of patients still displayed increased CSF levels of both NFL and CXCL13, indicating residual disease activity. Thus, these markers seemed considerably more sensitive to disease activity than clinical and MRI measures. However, the long-term clinical significance of such activity remains to be determined.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Biomarcadores , Quimiocina CXCL13 , Humanos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Proteínas de Neurofilamentos
5.
Nature ; 575(7783): 459-463, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31748725

RESUMO

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

6.
Eur J Neurol ; 26(8): 1060-1067, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30762259

RESUMO

BACKGROUND AND PURPOSE: Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. METHODS: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. RESULTS: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. CONCLUSIONS: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Rituximab/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Suécia , Resultado do Tratamento
7.
Acta Neurol Scand ; 138(2): 143-150, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29624650

RESUMO

OBJECTIVES: Although the recovery from Guillain-Barré syndrome (GBS) is good in most patients, some develop permanent severe disability or even die. Early predictors would increase the likelihood to identify patients at risk for poor outcome at the acute stage, allowing them intensified therapeutic intervention. MATERIALS AND METHOD: Eighteen patients with a history of GBS 9-17 years ago were reassessed with scoring of neurological disability and quality of life assessment (QoL). Their previous diagnostic work-up included clinical examination with scoring of disability, neurophysiological investigation, a battery of serology tests for infections, and cerebrospinal fluid (CSF) examination. Aliquots of CSF were frozen, stored for 20-28 years, and analyzed by ELISA for determination of neurofilament light protein (NFL) and glial fibrillary acidic protein (GFAP). RESULTS: Patients with poor outcome (n = 3) had significantly higher NFL and GFAP levels at GBS nadir than those with good outcome (n = 15, P < .01 and P < .05, respectively). High NFL correlated with more prominent disability and worse QoL at long-term follow-up (r = .694, P < .001, and SF 36 dimension physical component summary (PCS) (r =-.65, P < .05), respectively, whereas GFAP did not correlate with clinical outcome or QoL. CONCLUSION: High NFL in CSF at the acute stage of GBS seems to predict long-term outcome and might, together with neurophysiological and clinical measures, be useful in treatment decisions and clinical care of GBS.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Síndrome de Guillain-Barré/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Adulto Jovem
8.
HIV Med ; 18(4): 305-307, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27535540

RESUMO

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. METHODS: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. RESULTS: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. CONCLUSIONS: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.


Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/uso terapêutico , Testes Diagnósticos de Rotina , Uso de Medicamentos , Resposta Viral Sustentada , Estudos de Coortes , Humanos , Suécia , Nações Unidas , Organização Mundial da Saúde
9.
Acta Neurol Scand ; 135(1): 17-24, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27558404

RESUMO

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.


Assuntos
Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Humanos , Imageamento por Ressonância Magnética/normas , Neurologia/organização & administração , Sociedades Médicas , Suécia
10.
Eur J Neurol ; 23(4): 796-806, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26822123

RESUMO

BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.


Assuntos
Doenças Autoimunes do Sistema Nervoso/líquido cefalorraquidiano , Progressão da Doença , Encefalite/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
11.
Animal ; 10(2): 294-301, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25959256

RESUMO

Studies that address fish welfare before slaughter have concluded that many of the traditional systems used to stun fish including CO2 narcosis are unacceptable as they cause avoidable stress before death. One system recommended as a better alternative is electrical stunning, however, the welfare aspects of this method are not yet fully understood. To assess welfare in aquaculture both behavioural and physiological measurements have been used, but few studies have examined the relationship between these variables. In an on-site study aversive behaviours and several physiological stress indicators, including plasma levels of cortisol and ions as well as blood physiological variables, were compared in Arctic char (Salvelinus alpinus) stunned with CO2 or electricity. Exposure to water saturated with CO2 triggered aversive struggling and escape responses for several minutes before immobilization, whereas in fish exposed to an electric current immobilization was close to instant. On average, it took 5 min for the fish to recover from electrical stunning, whereas fish stunned with CO2 did not recover. Despite this, the electrically stunned fish had more than double the plasma levels of cortisol compared with fish stunned with CO2. This result is surprising considering that the behavioural reactions were much more pronounced following CO2 exposure. These contradictory results are discussed with regard to animal welfare and stress physiological responses. The present results emphasise the importance of using an integrative and interdisciplinary approach and to include both behavioural and physiological stress indicators in order to make accurate welfare assessments of fish in aquaculture.


Assuntos
Bem-Estar do Animal , Comportamento Animal/fisiologia , Dióxido de Carbono , Eletricidade , Peixes/fisiologia , Estresse Fisiológico/fisiologia , Animais , Aquicultura , Comportamento Animal/efeitos dos fármacos , Eletrólitos/sangue , Índices de Eritrócitos/veterinária , Peixes/sangue , Hematócrito/veterinária , Hemoglobinas/análise , Hidrocortisona/sangue , Concentração Osmolar , Estresse Fisiológico/efeitos dos fármacos , Fatores de Tempo , Truta/sangue , Truta/fisiologia , Água
12.
J Fish Biol ; 85(4): 1177-91, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25200031

RESUMO

The effects of hatchery rearing density (conventional or one third of conventional density) and feeding regime (high or reduced dietary fat levels) on burst-swim performance and oxygen transport capacity were studied in hatchery-reared Atlantic salmon Salmo salar, using wild fish as a reference group. There was no effect of rearing density or food regime on swimming performance in parr and smolts. The maximum swimming speed of wild parr was significantly higher than that of hatchery-reared conspecifics, while no such difference remained at the smolt stage. In smolts, relative ventricle mass was higher in wild S. salar compared with hatchery-reared fish. Moreover, wild S. salar had lower maximum oxygen consumption following a burst-swim challenge than hatchery fish. There were no effects of hatchery treatment on maximum oxygen consumption or relative ventricle mass. Haemoglobin and haematocrit levels, however, were lower in low-density fish than in fish reared at conventional density. Furthermore, dorsal-fin damage, an indicator of aggression, was similar in low-density reared and wild fish and lower than in S. salar reared at conventional density. Together, these results suggest that reduced rearing density is more important than reduced dietary fat levels in producing an S. salar smolt suitable for supplementary release.


Assuntos
Gorduras na Dieta/administração & dosagem , Consumo de Oxigênio , Salmo salar/fisiologia , Natação , Ração Animal , Animais , Oxigênio/metabolismo , Densidade Demográfica , Estações do Ano
13.
J Fish Biol ; 84(5): 1599-606, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24661216

RESUMO

The parasitic copepod Lernaeocera branchialis had a negative effect on cardiorespiratory function in Atlantic cod Gadus morhua such that it caused pronounced cardiac dysfunction with irregular rhythm and reduced stroke amplitude compared with uninfected fish. In addition, parasite infection depressed the postprandial cardiac output and oxygen consumption.


Assuntos
Copépodes/patogenicidade , Doenças dos Peixes/fisiopatologia , Gadus morhua/parasitologia , Coração/fisiopatologia , Consumo de Oxigênio , Animais , Doenças dos Peixes/parasitologia , Interações Hospedeiro-Parasita
14.
Science ; 343(6166): 51-4, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24263132

RESUMO

Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.

15.
Science ; 343(6166): 42-7, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24263133

RESUMO

The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest γ-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.

16.
Acta Neurol Scand ; 128(6): e33-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23763388

RESUMO

BACKGROUND: Neurofilaments are promising biomarkers in multiple sclerosis (MS) and increased levels in cerebrospinal fluid (CSF) indicate axonal damage or degeneration. In a previous study, neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment. AIMS OF THE STUDY: We compared the coherence between NfL and neurofilament heavy chain (NfH(SMI) (35) ) levels in longitudinal CSF samples in a subset of these patients. METHODS: In 30 patients with RRMS, CSF was obtained prior to and following 12 months of natalizumab treatment. NfH(SMI) (35) was measured by an electrochemiluminescence-based immunoassay. NfL levels were determined previously by the UmanDiagnostics NF-light(®) assay. RESULTS: NfH(SMI) (35) decreased in 73.3% and NfL in 90% of the patients following natalizumab treatment (32.4 vs 27.4 pg/ml, P = 0.002 and 820 vs 375 pg/ml, P < 0.0001). Patients experiencing a relapse showed higher NfH(SMI) (35) levels compared with patients in remission (47.7 vs 27.6 pg/ml, n = 8, P = 0.001). This difference was less obvious for NfL (1055 vs 725 pg/ml, P = 0.256). In patients in remission, NfL levels were lower following natalizumab treatment (830 vs 365 pg/ml, n = 20, P = 0.0002), whereas the same comparison failed significance for NfH(SMI) (35) (28.3 vs 26.9 pg/ml, P = 0.086). CONCLUSIONS: We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring NfH(SMI) (35) , using an assay with independent methodology. In comparison with NfH(SMI) (35) , NfL changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.


Assuntos
Esclerose Múltipla/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Adulto , Fatores Etários , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/líquido cefalorraquidiano , Avaliação da Deficiência , Feminino , Humanos , Masculino , Esclerose Múltipla/tratamento farmacológico , Natalizumab , Estatísticas não Paramétricas
17.
Lupus ; 22(4): 372-80, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23553780

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with multiple organ involvement. B-lymphocyte activity plays a pivotal role in the development and course of the disease. A newly developed agent called belimumab has recently been approved to treat active, autoantibody positive SLE as an add-on to standard therapy. Specifically binding to soluble B-lymphocyte stimulator protein, it reduces the formation of immunoglobulins and autoantibodies. Its effects have been studied in one phase II and two phase III clinical trials, showing sustained improvement across various clinical indicators and no evidence of increased risk of serious adverse events. Further post-hoc analyses indicate that treatment with belimumab lowers levels of autoimmune antibodies, normalizes low complement and improves SLE activity predominantly in musculoskeletal and mucocutaneous organ domains. Further studies are needed to determine the efficacy of belimumab for patients with severe lupus nephritis and with active involvement of the central nervous system. The introduction of belimumab as the first biological drug approved for the management of SLE likely heralds a surge in the development and use of selectively addressed agents for this heterogeneous and complex disease.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Autoanticorpos/imunologia , Fator Ativador de Células B/antagonistas & inibidores , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Desenho de Fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/imunologia
18.
Med Microbiol Immunol ; 202(1): 77-86, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22706797

RESUMO

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.


Assuntos
Técnicas de Laboratório Clínico/métodos , Testes Diagnósticos de Rotina/métodos , Anticorpos Anti-HIV/sangue , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , HIV-1/imunologia , HIV-2/imunologia , Humanos , Imunoensaio/métodos , Sensibilidade e Especificidade
19.
J Fish Biol ; 81(3): 1111-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22880741

RESUMO

Behavioural fever, manifested as an increased preferred temperature, was shown in rainbow trout Oncorhynchus mykiss following an injection of bacterial lipopolysaccharide. Simulated behavioural fever, through a 2·5° C water temperature rise following bacterial lipopolysaccharide injection, enhanced the expression of the cytokine interleukin-1ß, in comparison with an untreated group held at the initial temperature. The present findings show that an important mediator in the immune response can be boosted through behavioural fever in fishes.


Assuntos
Comportamento Animal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Oncorhynchus mykiss/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Temperatura
20.
Lab Anim ; 45(4): 240-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21771807

RESUMO

The current study investigated how the gastric evacuation rate (GER) was affected after surgically introducing dummies of a blood flow biotelemetry system into the abdominal cavity of Atlantic cod, Gadus morhua. Gastric evacuation experiments were performed two and 10 days postsurgery on surgically implanted and control G. morhua force-fed sandeel, Ammodytes tobianus. The results were compared with previously obtained estimates from unstressed conspecifics voluntarily feeding on a similar diet. After two days, GER was significantly lower in the group of fish with the dummy implants compared with the control group, but following 10 days of recovery no significant difference was seen between the two groups. The difference between implanted and control fish observed two days postsurgery may have resulted either from surgery, postsurgical stress and/or the presence of the implant. The conclusion is that 10 days of postsurgical recovery will stabilize GER in G. morhua, thus indicating that at this point the implant per se did not affect GER. Both the fish with surgical implants and controls in this study evacuated their stomachs much slower and with much higher interindividual variation compared with G. morhua feeding voluntarily on similar prey items. The lower GER and higher interindividual variation for force-fed fish indicate that handling, anaesthetization and force-feeding impair GER and that individual fish respond differently to the suppressing effects.


Assuntos
Gadus morhua/fisiologia , Gadus morhua/cirurgia , Esvaziamento Gástrico/fisiologia , Recuperação de Função Fisiológica/fisiologia , Procedimentos Cirúrgicos Operatórios/veterinária , Animais , Telemetria/instrumentação , Fatores de Tempo
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