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As demand for renewable energy is rising, wind power development is rapidly growing worldwide. In its wake, conflicts arise over land use changes converting pristine nature into industrial power plants and its associated adverse biodiversity effects, crowned by one of the most obvious and deadly consequences: bird collisions. Most post-construction studies report low levels of avian mortality, but the majority of these studies are conducted primarily on larger birds. However, the diversity and abundance of small passerine birds are rarely reflected in the carcass surveys, although they in numeric proportion to their abundances should be the most numerous. The assumption that surveys find all carcasses seems thus rarely fulfilled and passerine mortality is likely to be grossly underestimated. We therefore designed an experiment with dummy birds to estimate mortality of small-bodied passerines and other small-bodied birds during post-construction surveys, tested in a medium-sized wind farm in western Norway. The wind farm was surveyed weekly during the migration periods by carcass survey teams using trained dogs to find killed birds. The dogs in the carcass surveys were more successful in locating the large than the small dummy birds (60-200 g), where they found 74% of the large dummy birds. Detecting the smaller category (5-24 g) was more demanding and the dogs only found 17% of the small dummy birds. Correcting the post-construction carcass survey outcome with the results from the experiment leads to an almost fourfold increase in estimated mortality rates, largely due to the low detection rate of the smallest category. The detection rates will naturally vary between wind farms, depending on the specific habitat characteristics, the efficiency of the carcass surveys and the search intervals. Thus, implementing a simple experiment with dummy birds to future post-construction surveys will produce more accurate estimates of the wind turbine mortality rates, and thus improve our understanding of the biodiversity effects of conforming to a more sustainable future.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Passeriformes , Animais , Cães , Fontes Geradoras de Energia , Vento , Energia Renovável , Centrais ElétricasRESUMO
This Special Topic focuses on magnetohydrodynamic (MHD) processes in the deep interiors of planets, in which their fluid dynamos are in operation. The dynamo-generated, global, magnetic fields provide a background for our solar-terrestrial environment. Probing the processes within the dynamos is a significant theoretical and computational challenge and any window into interior dynamics greatly increases our understanding. Such a window is provided by exploring rapid dynamics, particularly MHD waves about the dynamo-defined basic state. This field is the subject of current attention as geophysical observations and numerical modellings advance. We here pay particular attention to torsional Alfvén waves/oscillations and magnetic Rossby waves, which may be regarded as typical axisymmetric and nonaxisymmetric modes, respectively, amongst a wide variety of wave classes of rapidly rotating MHD fluids. The excitation of those waves has been evidenced for the Earth - whilst their presence has also been suggested for Jupiter. We shall overview their dynamics, summarise our current understanding, and give open questions for future perspectives.
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Changes in dilution of wastewater to a treatment plant due to infiltration or surface runoff can have a great impact on treatment process performance. This paper presents a model-based approach in which realistic influent scenarios are generated and used as inputs to a dynamic plant-wide process model of the wastewater treatment plant. The simulated operation is subsequently evaluated using life-cycle assessment (LCA) to quantify the environmental impacts of the future influent scenarios. The results show that increased infiltration led to higher environmental impact per kg nitrogen removed. The increase in surface runoff had a minor impact.
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Eliminação de Resíduos Líquidos , Águas Residuárias , Meio Ambiente , NitrogênioRESUMO
BACKGROUND: Elevation of CXCL13, a key regulator of B-cell recruitment in cerebrospinal fluid (CSF) is implicated in multiple sclerosis (MS). OBJECTIVE: to evaluate if measurement of CXCL13 using a highly sensitive assay is of value in acute optic neuritis (ON) patients for the prediction of later MS. METHOD: CXCL13 was measured by Simoa in two independent treatment-naïve ON cohorts, a training cohort (TC, n = 33) originating from a population-based cohort, a validation cohort (VC, n = 30) consecutively collected following principles for population studies. Prospectively, 14/33 TC and 12/30 VC patients progressed to MS (MS-ON) while 19/33 TC and 18/30 VC patients, remained as isolated ON (ION). RESULTS: CXCL13 was detectable in all samples and were higher in ON compared with healthy controls (HC) (p = 0.012). In the TC, CSF levels in MS-ON were higher compared with ION patients and HC (p = 0.0001 and p<0.0001). In the VC, we confirmed the increase of CXCL13 in MS-ON compared to ION (p = 0.0091). Logistic regression analysis revealed an area under receiver operating characteristic curve of 0.83 [95% C.I: 0.73-0.93]. CONCLUSIONS: The highly sensitive CXCL13 Simoa assay demonstrated ability to identify ON patients and separate MS-ON from ION, and predictive diagnostic values indicates a promising potential of this assay.
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Esclerose Múltipla , Neurite Óptica , Biomarcadores , Quimiocina CXCL13 , Estudos de Coortes , Humanos , Esclerose Múltipla/diagnóstico , Neurite Óptica/diagnóstico , Curva ROCRESUMO
BACKGROUND: Given that unwanted hair growth (hirsutism, hypertrichosis) can cause major psychological distress, new pharmacological treatment strategies with safe and effective hair growth inhibitors that do not destroy the hair follicle (HF) and its stem cells need to be developed. OBJECTIVES: To establish if osteopontin-derived fragments may modulate human hair growth given that human HFs express the multifunctional, immunomodulatory glycoprotein, osteopontin. METHODS: Our hypothesis was tested ex vivo and in vivo by using a newly generated, toxicologically well-characterized, modified osteopontin-derived peptide (FOL-005), which binds to the HF. RESULTS: In organ-cultured human HFs and scalp skin, and in human scalp skin xenotransplants onto SCID mice, FOL-005 treatment (60 nmol L-1 to 3 µmol L-1 ) significantly promoted premature catagen development without reducing the number of keratin 15-positive HF stem cells or showing signs of drug toxicity. Genome-wide DNA microarray, quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry revealed decreased expression of the hair growth promoter, fibroblast growth factor-7 (FGF7) by FOL-005, while cotreatment of HFs with recombinant FGF7 partially abrogated FOL-005-induced catagen promotion. CONCLUSIONS: With caveats in mind, our study identifies this osteopontin-derived peptide as an effective, novel inhibitory principle for human hair growth ex vivo and in vivo, which deserves systematic clinical testing in hirsutism and hypertrichosis. What's already known about this topic? The treatment of unwanted hair growth (hypertrichosis, hirsutism) lacks pharmacological intervention, with only few and often unsatisfactory treatments available. Osteopontin is prominently expressed in human HFs and has been reported to be elevated during catagen in the murine hair cycle. What does this study add? We tested the effects on hair growth of a novel, osteopontin-derived fragment (FOL-005) ex vivo and in vivo. In human hair follicles, high-dose FOL-005 significantly reduces hair growth both ex vivo and in vivo. What is the translational message? High-dose FOL-005 may provide a new therapeutic opportunity as a treatment for unwanted hair growth.
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Folículo Piloso , Osteopontina , Animais , Cabelo , Humanos , Queratinócitos , Camundongos , Camundongos SCIDRESUMO
Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA.
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Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/classificação , Sistema de Registros , Fator Reumatoide/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Dinamarca , Ensaio de Imunoadsorção Enzimática , Humanos , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
The objectives were to study the expression of very late antigen (VLA)-4, melanoma cell adhesion molecule-1 (MCAM-1) and activated leukocyte cell adhesion molecule (ALCAM) on CD4+ T cells during natalizumab treatment and to investigate the association with disease activity. We find that subgroups of autoreactive T cells are retained in peripheral blood, in particular MOG-reactive CD4+ T cells expressing MCAM-1. The expression of MCAM-1 or ALCAM on CD4+ T cells was, however, not clearly associated with disease activity (clinical or MRI) during natalizumab treatment. We confirm upregulation of MCAM-1 on CD4+ T cells during natalizumab treatment while VLA-4 is downregulated.
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Linfócitos T CD4-Positivos/metabolismo , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Adulto , Idoso , Antígeno CD146/biossíntese , Antígeno CD146/sangue , Linfócitos T CD4-Positivos/efeitos dos fármacos , Estudos de Coortes , Feminino , Expressão Gênica , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Recent climate change has led to advanced spring phenology in many temperate regions. The phenological response to variation in the local environment, such as the habitat characteristics of the territories birds occupy, is less clear. The aim of this study is to understand how ecological conditions affect breeding time, and its consequences for reproduction, in a white-throated dipper Cinclus cinclus population in a river system in Norway during 34 years (1978-2011). Hatching date advanced almost nine days, indicating a response to higher temperatures and the advanced phenology in the area. Earlier breeding was found in warm springs and at lower altitudes. High population density facilitated earlier breeding close to the coast. Furthermore, when population density was low, breeding was early at territories that were rarely occupied, while in years with high density, breeding was early at territories that were frequently occupied. Also, when population density was low, earlier breeding occurred at territories that on average produced more offspring than other territories, while there was no difference in breeding time in high population years. Selection for early breeding was dependent on spring temperatures and high spring temperatures contributed to higher breeding success during the study period. We found that breeding phenology may have strong effects on fitness in the white-throated dipper, and thus that breeding time is an important ecological factor in a species that feeds mainly on aquatic rather than terrestrial prey.
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Distribuição Animal , Mudança Climática , Passeriformes/fisiologia , Reprodução , Animais , Biomassa , TempoRESUMO
BACKGROUND: Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. METHODS: Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19-41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2-38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons ("q"). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. RESULTS: CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r > 0.69 and p < 0.002) and IgG index (r > 0.55, p < 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p < 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one ("candidate") and IgG index, OCB, and leukocytes in another ("routine"). Area under the curve was 0.89 [95% CI 0.77-1] and 0.86 [0.74-0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. CONCLUSIONS: CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS.
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Citocinas/líquido cefalorraquidiano , Progressão da Doença , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/etiologia , Neurite Óptica/complicações , Adolescente , Adulto , Idoso , Quimiocinas CXC/líquido cefalorraquidiano , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Humanos , Interleucina-10/líquido cefalorraquidiano , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Bandas Oligoclonais/líquido cefalorraquidiano , Valor Preditivo dos Testes , Curva ROC , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto JovemRESUMO
In a population-based study of older Swedish women, we investigated the proportion of women treated with osteoporosis medication in relation to the proportion of women eligible for treatment according to national guidelines. We found that only a minority (22%) of those eligible for treatment were prescribed osteoporosis medication. INTRODUCTION: Fracture rates increase markedly in old age and the incidence of hip fracture in Swedish women is among the highest in the world. Although effective pharmacological treatment is available, treatment rates remain low. Limited data are available regarding treatment rates in relation to fracture risk in a population-based setting in older women. Therefore, we aimed to investigate the proportion of older women eligible for treatment according to Swedish Osteoporosis Society (SvOS) guidelines. METHODS: A population-based study was performed in Gothenburg in 3028 older women (77.8 ± 1.6 years [mean ± SD]). Bone mineral density of the spine and hip was measured with dual-energy X-ray absorptiometry. Clinical risk factors for fracture and data regarding osteoporosis medication was collected with self-administered questionnaires. Logistic regression was used to evaluate whether the 10-year probability of sustaining a major osteoporotic fracture (FRAX-score) or its components predicted treatment with osteoporosis medication. RESULTS: For the 2983 women with complete data, 1107 (37%) women were eligible for treatment using SvOS criteria. The proportion of these women receiving treatment was 21.8%. For women eligible for treatment according to SvOS guidelines, strong predictors for receiving osteoporosis medication were glucocorticoid treatment (odds ratio (95% CI) 2.88 (1.80-4.59)) and prior fracture (2.58 (1.84-3.61)). CONCLUSION: This study demonstrates that a substantial proportion of older Swedish women should be considered for osteoporosis medication given their high fracture risk, but that only a minority receives treatment.
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Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Densidade Óssea/fisiologia , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Colo do Fêmur/fisiopatologia , Articulação do Quadril/fisiopatologia , Humanos , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Medição de Risco/métodos , Fatores de Risco , Suécia/epidemiologiaRESUMO
AIM: This literature review explores the need for greater prominence of gerodontology in the undergraduate dental curriculum, focusing on the significance of gerodontology for dental students on clinical placements. BACKGROUND: As Australia's population ages the number of dentate older people is increasing. An assessment of the dental profession's preparedness, including that of future providers, is needed to ensure that this public health issue is addressed. METHODS: A database search was performed in MEDLINE (Ovid), CINAHL and JCU OneSearch. Of the 41 articles identified, 31 were selected for review using a narrative approach. DISCUSSION: Of the 31 articles reviewed, 12 were Australian, 9 North American and 5 European. Five overarching themes were identified, including preparedness for residential aged care facilities; barriers to oral health services provision; attitudes to aged care; gerodontology as part of a dental school curriculum and service-based learning. CONCLUSION: There are differences in the gerodontology curricula of dental schools, with a wide variation of clinical exposure to older patients. There is evidence that exposure to gerodontology curriculum prior to treating older people may help dental students feel more prepared for managing patients in aged care. The current marginal status of gerodontology in dental school curricula is in need of review.
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Currículo , Assistência Odontológica para Idosos , Educação em Odontologia , Idoso , Idoso de 80 Anos ou mais , Austrália , Humanos , Faculdades de Odontologia , Estudantes de OdontologiaRESUMO
OBJECTIVE: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS. METHOD: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed. RESULTS: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1ß, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS. CONCLUSION: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.
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Fator Ativador de Células B/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Síndrome de Sjogren/metabolismo , Escarro/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos , Masculino , Pessoa de Meia-Idade , Escarro/citologiaRESUMO
A sixth-order differential equation governing the flexural vibration of sandwich plates is derived. The sandwich plates considered consist of laminates bonded to honeycomb or foam cores. The structures are assumed to be symmetric. Shear and rotation in core are included in the model. The effect on the bending stiffness of rotation and shear in the core is discussed. Shear effects are of great importance, whereas rotation of the core has only a marginal effect on the bending stiffness of lightweight sandwich plates. The bending stiffness of a sandwich plate is found to strongly depend on frequency. The bending stiffness of a structure determines its acoustical coupling to any surrounding fluid and thus its sound transmission loss and sound radiation ratio. Loss factors of sandwich plates are discussed. Boundary conditions are formulated for rectangular plates having simply supported, clamped, or free edges. There are five boundary conditions to be satisfied at each edge of the plate. The bending stiffness of simply supported and infinite plates is presented as a function of frequency. Expressions for the point mobility for infinite or simply supported finite panels are given.
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BACKGROUND: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. METHODS: In this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 1010 colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD). RESULTS: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. CONCLUSIONS: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.
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Densidade Óssea , Limosilactobacillus reuteri , Osteoporose/terapia , Probióticos/administração & dosagem , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Osteoporose/diagnóstico , Estudos Prospectivos , SuéciaRESUMO
Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.
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Neoplasias/metabolismo , Neoplasias/patologia , Técnicas de Cultura de Células , Humanos , Células Tumorais CultivadasRESUMO
BACKGROUND: Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune dependency remains poorly characterized. OBJECTIVE: To investigate autoimmune and immunogenetic aspects of ON. METHOD: In a prospective population-based cohort 51 patients with ON were included. At follow up 20 patients had progressed to multiple sclerosis (MS-ON). All patients were screened for neuronal and systemic autoantibodies. HLA genotypes and allele and genotype frequencies of the PTPN22 C1858T and the PD-1.3 single-nucleotide polymorphisms (SNPs) were determined and compared to a cohort of Danish blood donors, acting as healthy controls. RESULTS: Median follow-up was 366 days (301-430) for MS-ON patients and 375 (range 50-436) for isolated ON (ION). Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), were positive in two patients, no patients had anti-aquaporin-4 antibodies. Coexisting neural autoantibodies were detected in two patients and in 12 patients other systemic autoantibodies were found. Four (8%) had other autoimmune disorders. A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease in six patients (12%). In MS-ON patients the frequencies of HLA-DQB1*06:02 and HLA-DRB1*15:01 tended to be higher compared to controls (pâ¯=â¯0.08). Stratification of patients with presence of oligoclonal bands (OCB) showed an association to the HLA-DQB1*06:02-HLA-DRB1*15:01 haplotype in ION (HLA-DQB1*06:02 and HLA-DRB1*15:01 (pâ¯=â¯0.03)), and in MS-ON patients (HLA-DQB1*06:02 and HLA-DRB1*15:01 (pâ¯=â¯0.03)). No significant associations to PTPN22 1858C/T or PD-1.3â¯G/A were found in any group comparison. CONCLUSIONS: ON patients had a general susceptibility to autoimmunity and two were MOG-IgG positive. HLA-DQB1*06:02 and HLA-DRB1*15:01 were associated with the presence of OCB in ON patients.
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Autoanticorpos/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Neurite Óptica/genética , Neurite Óptica/imunologia , Adolescente , Adulto , Idoso , Aquaporina 4/imunologia , Autoimunidade/genética , Progressão da Doença , Feminino , Seguimentos , Estudos de Associação Genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Fenômenos Imunogenéticos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Estudos Prospectivos , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto JovemRESUMO
The continuing threat of antimicrobial resistance presents a considerable challenge to researchers to develop novel strategies ensuring that bacterial infections remain treatable. Many plant extracts have been shown to have antibacterial properties and could potentially be combined with other antibacterial agents to create more effective formulations. In this study, the antibacterial activity of three plant extracts and virulent bacteriophages have been assessed as individual components and in combination. When assessed with a modified suspension test, these plant extracts also exhibit antiviral activity at bacterial inhibitory concentrations. Hence, to investigate any potential additive effects between the extracts and virulent phages, the extracts were tested at subantiviral concentrations. Phages alone and in combination with plant extracts significantly reduced (P < 0·05) the bacterial concentration compared to untreated and extract treated controls up to 6 h (2-3log10 ), but this reduction did not extend to 24 h. In most cases, the phage and extract combinations did not significantly reduce bacterial content compared to phages alone. Additionally, there was little impact on the ability of the phages to reproduce within their bacterial hosts. To our knowledge, this study represents the first of its kind, in which antimicrobial plant extracts have been combined with virulent phages and has highlighted the necessity for plant extracts to be functionally characterized prior to the design of combinatorial therapies. Significance and Impact of Study This preliminary study provides insights into the potential combination of bacteriophages and antimicrobial plant bulk extracts to target bacterial pathogens. It is to our knowledge the first time in which virulent bacteriophages have been combined with antimicrobial plant extracts.
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Antibacterianos/farmacologia , Agentes de Controle Biológico/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Myoviridae/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Siphoviridae/crescimento & desenvolvimento , Bignoniaceae/química , Farmacorresistência Bacteriana Múltipla , Escherichia coli/virologia , Medicina Tradicional do Leste Asiático , Testes de Sensibilidade Microbiana , Estudo de Prova de Conceito , Stephania/química , Zingiberaceae/químicaRESUMO
Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated with the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. Mast cell-deficient C57BL/6-KitW-sh (Wsh) mice engrafted with either wild-type (Wsh + MC-WT) or ST2-deficient bone marrow-derived mast cells (Wsh + MC-ST2KO) were exposed to HDM delivered intranasally. An exacerbated development of AHR in response to HDM was seen in Wsh + MC-ST2KO compared with Wsh + MC-WT mice. The contribution of this IL-33/ST2-dependent mast cell response to AHR seems to reside within the smaller airways in the peripheral parts of the lung, as suggested by the isolated yet marked effect on tissue resistance. Considering the absence of a parallel increase in cellular inflammation in bronchoalveolar lavage fluid (BALF) and lung, the aggravated AHR in Wsh + MC-ST2KO mice seems to be independent of cellular inflammation. We observed an association between the elevated AHR and reduced PGE2 levels in BALF. Due to the protective properties of PGE2 in airway responses, it is conceivable that IL-33/ST2-dependent mast cell induction of PGE2 could be responsible for the dampening effect on AHR. In conclusion, we reveal that IL-33/ST2-dependent mast cell responses can have a protective, rather than causative role, in the development of AHR.