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Urban green waste and food waste are often used as bulking agents to prepare home compost in combination with animal manure in urban horticulture and community gardening. Although it is known that antimicrobial resistance genes (ARGs) persist in home compost, their origins have not been determined. In addition, the factors contributing to ARGs persistence remain unclear. In this study, we aim to (i) characterize the changes in the microbiome and antimicrobial resistome during the composting process of home compost using metagenomics shotgun sequencing, (ii) identify the source of the ARGs persisted in home compost using SourceTracker, and (iii) elucidate the collective effect of compost microbiome and environmental factors, including the physicochemical properties and antibiotics concentration of home compost, in contributing to ARG persistence using Procrustes analysis, co-occurrence network analysis, variation partitioning analysis, and structural equation modeling. SourceTracker analysis indicated that urban green waste bulking agent was the major source of the persisting ARGs in home compost instead of animal manure. Procrustes analysis and co-occurrence network analysis revealed a strong association between microbiome and antimicrobial resistome. Variation partitioning analysis and structural equation modeling suggested that physicochemical properties shaped the antimicrobial resistome directly and indirectly by influencing the microbiome. Our results indicated that the persistence of ARGs in home compost might be due to the succession of microbial species from the urban green waste bulking agent, and the physicochemical properties might have defined the compost environment to shape the microbiome in the compost, thus, in turn, the persisting antimicrobial resistome.
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Compostagem , Oxazolidinonas , Eliminação de Resíduos , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Esterco/análise , Alimentos , Genes BacterianosRESUMO
BACKGROUND AND PURPOSE: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. METHODS: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. RESULTS: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63-79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2-4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6-9] versus 6 [4-9]), similar favorable thrombus permeability (residual flow grades I-II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11-13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26-60.13]) were associated with successful recanalization among mild patients. CONCLUSIONS: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.
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Encéfalo/diagnóstico por imagem , Fibrinolíticos/uso terapêutico , AVC Isquêmico/diagnóstico por imagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
In an ever-changing environment, survival depends on learning which stimuli represent threat, and also on updating such associations when circumstances shift. It has been claimed that humans can acquire physiological responses to threat-associated stimuli even when they are unaware of them, but the role of awareness in updating threat contingencies remains unknown. This complex process-generating novel responses while suppressing learned ones-relies on distinct neural mechanisms from initial learning, and has only been shown with awareness. Can it occur unconsciously? Here, we present evidence that threat reversal may not require awareness. Participants underwent classical threat conditioning to visual stimuli that were suppressed from awareness. One of two images was paired with an electric shock; halfway through the experiment, contingencies were reversed and the shock was paired with the other image. Despite variations in suppression across participants, we found that physiological responses reflected changes in stimulus-threat pairings independently of stimulus awareness. These findings suggest that unconscious affective processing may be sufficiently flexible to adapt to changing circumstances.
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Conscientização/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Reversão de Aprendizagem/fisiologia , Inconsciente Psicológico , Adolescente , Adulto , Idoso , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologia , Adulto JovemRESUMO
BACKGROUND: Endovascular therapy (EVT) for patients with mild ischemic stroke (NIHSS ≤5) and visible intracranial occlusion remains controversial, including within 6 hours of symptom onset. We conducted a survey to evaluate global practice patterns of EVT in this population. METHODS: Vascular stroke clinicians and neurointerventionalists were invited to participate through professional stroke listservs. The survey consisted of six clinical vignettes of mild stroke patients with intracranial occlusion. Cases varied by NIHSS, neurological symptoms and occlusion site. All had the same risk factors, time from symptom onset (5h) and unremarkable head CT. Advanced imaging data was available upon request. We explored independent case and responder specific factors associated with advanced imaging request and EVT decision. RESULTS: A total of 482/492 responders had analyzable data ([median age 44 (IQR 11.25)], 22.7% women, 77% attending, 22% interventionalist). Participants were from USA (45%), Europe (32%), Australia (12%), Canada (6%), and Latin America (5%). EVT was offered in 48% (84% M1, 29% M2 and 19% A2) and decision was made without advanced imaging in 66% of cases. In multivariable analysis, proximal occlusion (M1 vs. M2 or A2, p<0.001), higher NIHSS (p<0.001) and fellow level training (vs. attending; p=0.001) were positive predictors of EVT. Distal occlusions (M2 and A2) and higher age of responders were independently associated with increased advanced imaging requests. Compared to US and Australian responders, Canadians were less likely to offer EVT, while those in Europe and Latin America were more likely (p<0.05). CONCLUSIONS: Treatment patterns of EVT in mild stroke vary globally. Our data suggest wide equipoise exists in current treatment of this important subset of mild stroke.
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Isquemia Encefálica/terapia , Procedimentos Endovasculares/tendências , Disparidades em Assistência à Saúde/tendências , Padrões de Prática Médica/tendências , Acidente Vascular Cerebral/terapia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Tomada de Decisão Clínica , Avaliação da Deficiência , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/tendências , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X/tendências , Adulto JovemRESUMO
The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. For insight into how GD management varies among countries, we analyzed treatment patterns in GOS. As of October 30, 2015, data on GD-specific treatment (enzyme replacement therapy, substrate reduction therapy, or chemical chaperone therapy) received at any time were available for 647 patients. At analysis, velaglucerase alfa (316/573, 55.1%) and imiglucerase (184/573, 32.1%) were the treatments most widely used. Of the 647 treated patients, 446 (68.9%) had been treated for >5years and 368 (56.9%) had received only one GD-specific drug therapy. There were 377 patients who received velaglucerase alfa. Velaglucerase alfa was most widely used at 60U/kg every other week (134/492 dose entries, 27.2%), but there were differences in dosing between the three highest-enrolling countries (defined as >100 GOS patients enrolled in each), with most patients in Israel receiving <20U/kg, most patients in the United Kingdom receiving 20 to <40U/kg, and most in the United States receiving 60U/kg. This analysis provides a foundation upon which to examine real-life outcomes data from different treatment regimens globally.
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Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Esquema de Medicação , Feminino , Doença de Gaucher/epidemiologia , Glucosilceramidase/administração & dosagem , Humanos , Masculino , Resultado do TratamentoRESUMO
This study examined the exercise barriers and preferences of head and neck cancer (HNC) survivors in relation to exercise experience. Participants (n = 22; 46.8% response rate) completed retrospective self-report questionnaires on demographic and medical information, exercise barriers and preferences. A subset of participants then completed semi-structured interviews (n = 18). Participants had previously engaged in the ENHANCE trial during, or immediately following, radiation treatment, an average of 22.1 ± 5.8 months before. Retrospective questionnaires revealed that before ENHANCE participation, lack of interest and time were the primary exercise barriers. After participation, there was a significant decrease in typical barriers including lack of interest (p = .008), exercise not a priority (p = .039) and exercise not in routine (p = .004). Number of barriers experienced after ENHANCE participation was negatively correlated with age, quality of life and minutes of resistance exercise training per week. After ENHANCE participation, significant increases were found in preference for exercising at a cancer centre (p = .031) and with other cancer survivors (p = .016). Four higher order themes emerged inductively from interview data analysis pertaining to preferences (i.e., class format) and three higher order themes regarding barriers (physical, psychological and external). By investigating participants' perspectives after ENHANCE participation, key factors for effective HNC exercise programme design were identified.
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Terapia por Exercício/psicologia , Neoplasias de Cabeça e Pescoço/psicologia , Neoplasias de Cabeça e Pescoço/terapia , Preferência do Paciente , Depressão/etiologia , Exercício Físico/psicologia , Feminino , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Qualidade de Vida , Estudos Retrospectivos , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: No standardized measures specifically assess cancer survivors' and healthcare providers' experience of Survivor Care Plans (scps). We sought to develop two care plan evaluation (cpe) measures, one for survivors (cpe-s) and one for healthcare providers (cpe-p), examine initial psychometric qualities in Alberta, and assess generalizability in Manitoba, Canada. METHODS: We developed the initial measures using convenience samples of breast (n = 35) and head and neck (n = 18) survivors who received scps at the end of active cancer-centre treatment. After assessing Alberta's scp concordance with Institute of Medicine (iom) recommendations using a published coding scheme, we examined psychometric qualities for the cpe-s and cpe-p. We examined generalizability in Manitoba, Canada, with colorectal survivors discharged to primary care providers for follow-up (n = 75). RESULTS: We demonstrated acceptable internal consistency for the cpe-s and cpe-p subscales and total score after eliminating one item per subscale for cpe-s, two for cpe-p, resulting in revised scales with four 7-item and 6-item subscales, respectively. Subscale scores correlated highly indicating that for each measure the total score may be the most reliable and valid. We provide initial cpe-s discriminant, convergent, and predictive validity using the total score. Using the Manitoba sample, initial psychometrics similarly indicated good generalizability across differences in tumour groups, scp, and location. CONCLUSIONS: We recommend the revised cpe-s and cpe-p for further use and development. Studies documenting the creation and standardization of scp evaluations are few, and we recommend further development of patient experience measures to improve both clinical practice and the specificity of research questions.
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BACKGROUND: There is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for example, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM criteria, and is largely based on the widely used Composite International Diagnostic Interview (CIDI). Here, we tested the feasibility and determined the sensitivity and specificity for measuring lifetime MDD with this new questionnaire, with a regular CIDI as reference. METHOD: Sensitivity and specificity analyses of the online lifetime MDD questionnaire were performed in adults with (n = 177) and without (n = 87) lifetime MDD according to regular index CIDIs, selected from the Netherlands Study of Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility was tested in an additional non-selective, population-based sample of NTR participants (n = 245). RESULTS: Of the 753 invited persons, 509 (68%) completed the LIDAS, of which 419 (82%) did this online. User-friendliness of the instrument was rated high. Median completion time was 6.2 min. Sensitivity and specificity for lifetime MDD were 85% [95% confidence interval (CI) 80-91%] and 80% (95% CI 72-89%), respectively. This LIDAS instrument gave a lifetime MDD prevalence of 20.8% in the population-based sample. CONCLUSIONS: Measuring lifetime MDD with an online instrument was feasible. Sensitivity and specificity were adequate. The instrument gave a prevalence of lifetime MDD in line with reported population prevalences. LIDAS is a promising tool for rapid determination of lifetime MDD status in large samples, such as needed for genomics studies.
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Transtorno Depressivo Maior/diagnóstico , Internet , Escalas de Graduação Psiquiátrica/normas , Sistema de Registros/estatística & dados numéricos , Autorrelato/normas , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/epidemiologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: Adenoid cystic carcinoma (acc) is often treated with surgery, with or without adjuvant radiation therapy (rt). We evaluated disease characteristics, treatments, and potentially prognostic variables in patients with acc. METHODS: Our retrospective analysis considered consecutive cases of acc presenting at a tertiary care hospital between 2000 and 2014. Factors predictive of overall survival (os) and disease-free survival (dfs) were identified by univariate analysis. RESULTS: The 60 patients analyzed had a mean age of 58 years (range: 22-88 years), with a 2:1 female:male ratio. Tumour locations included the major salivary glands (40% parotid, 17% submandibular and sublingual), the oro-nasopharyngeal cavity (27%), and other locations (16%). Of the 60 patients, 35 (58%) received surgery with adjuvant rt; 12 (20%), rt only; 13 (22%), surgery only. Of 18 patients (30%) who experienced a recurrence within 5 years, 3 (5%) developed local recurrence only, and the remaining 15 (25%), distant metastasis. The 5-year os and dfs were 64.5% [95% confidence interval (ci): 45.9% to 78.1%] and 46.2% (95% ci: 29.7% to 61.2%) respectively. In patients without recurrence, 5-year os was 77% (95% ci: 52.8% to 89.9%), and in patients with recurrence, it was 42.7% (95% ci: 15.8% to 67.6%). Patients treated with rt only had a 5-year os of 9.2%. Predictors of 5-year dfs were TNM stage, T stage, nodal status, treatment received, and margin status; age, nodal status, treatment received, and margin status predicted 5-year os. CONCLUSIONS: Despite surgery and rt, one third of patients with acc experience distant recurrence. Patients whose tumours are not amenable to surgery have a poor prognosis, indicating a need for alternative approaches to improve outcomes.
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OBJECTIVE: To identify specific angiographic factors associated with haemorrhagic presentation of brain arteriovenous malformation in Chinese paediatric patients. DESIGN: Retrospective cross-sectional observational study. SETTING: Four locoregional tertiary neurosurgical centres in Hong Kong: Queen Elizabeth Hospital, Tuen Mun Hospital, Kwong Wah Hospital, and Pamela Youde Nethersole Eastern Hospital. PATIENTS: Patients aged 18 years or younger who underwent pretreatment digital subtraction angiography for brain arteriovenous malformation between 1 January 2005 and 31 July 2013 were included. Patients were divided into haemorrhagic and non-haemorrhagic groups based on the initial presentation. Pretreatment digital subtraction angiographies were independently reviewed by two experienced neuroradiologists. MAIN OUTCOME MEASURES: The following parameters were evaluated for their association with haemorrhagic presentation by univariate and multivariate analyses: nidus location, nidus size, nidus morphology (diffuse or compact); origin and number of arterial feeders; venous drainage; number of draining veins; presence of aneurysms, venous varices, and venous stenosis. RESULTS: A total of 67 children and adolescents (28 male, 39 female) with a mean age of 12 years were included. Of them, 52 (78%) presented with haemorrhage. Arteriovenous malformation size (P=0.004) and morphology (P=0.05) were found to be associated with haemorrhagic presentation by univariate analysis. Small arteriovenous malformation nidus size and diffuse nidal morphology were identified as independent risk factors for haemorrhage by multivariate analysis. CONCLUSION: Smaller arteriovenous malformation size and diffuse nidal morphology are angiographic factors independently associated with haemorrhagic presentation. Bleeding risk is important in determining the therapeutic approach (aggressive vs conservative) and timeframe, particularly in paediatric patients.
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Angiografia Cerebral , Hemorragia Cerebral/etiologia , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Adolescente , Angiografia Digital , Hemorragia Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Hong Kong , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Vesicoureteric reflux is an important association of paediatric urinary tract infection. Fluoroscopic micturating cystourethrography and radionuclide cystography have been employed for detecting and grading vesicoureteric reflux. However, both modalities involve ionising radiation, which can pose significant radiation risk to growing children. They also have a lower detection rate due to intermittent fluoroscopic technique in micturating cystourethrography, and lower spatial resolution in radionuclide cystography. Therefore, newer radiation-free ultrasound-based contrast-enhanced voiding urosonography has been developed in Europe for 15 years. This article aimed to summarise the current literature and discuss the first local pilot study in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding urosonography. Contrast-enhanced voiding urosonography is a valid alternative to micturating cystourethrography in assessing vesicoureteric reflux, based on its superior diagnostic performance, reliability, safety, feasibility, and radiation safety for children. Therefore, it should be incorporated in the guideline for investigating paediatric urinary tract infection.
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Micção , Refluxo Vesicoureteral/diagnóstico por imagem , Criança , Pré-Escolar , Técnicas de Diagnóstico Urológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , UltrassonografiaRESUMO
BACKGROUND: The treatment of head-and-neck cancer is complex and requires the involvement of various health care professionals with a wide range of expertise. We describe the process of developing a practice guideline with recommendations about the organization and delivery of health care services for head-and-neck cancer patients in Alberta. METHODS: Outcomes of interest included composition of the health care team, qualification requirements for team members, cancer centre and team member volumes, infrastructure needs, and wait times. A search for existing practice guidelines and a systematic review of the literature addressing the organization and delivery of health care services for head-and-neck cancer patients were conducted. The search included the Standards and Guidelines Evidence (sage) directory of cancer guidelines and PubMed. RESULTS: One practice guideline was identified for adaptation. Three additional practice guidelines provided supplementary evidence to inform guideline recommendations. Members of the Alberta Provincial Head and Neck Tumour Team (consisting of various health professionals from across the province) provided expert feedback on the adapted recommendations through an online and in-person review process. Selected experts in head-and-neck cancer from outside the province participated in an external online review. SUMMARY: The recommendations outlined in this practice guideline are based on existing guidelines that have been modified to fit the Alberta context. Although specific to Alberta, the recommendations lend credence to similar published guidelines and could be considered for use by groups lacking the resources of appointed guideline panels. The recommendations are meant to be a guide rather than a fixed protocol. The implementation of this practice guideline will depend on many factors, including but not limited to availability of trained personnel, adequate funding of infrastructure, and collaboration with other associations of health care professionals in the province.
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BACKGROUND: Survivorship care plans (scps) have been recommended as a way to ease the transition from active cancer treatment to follow-up care, to reduce uncertainty for survivors in the management of their ongoing health, and to improve continuity of care. The objective of the demonstration project reported here was to assess the value of scps for cancer survivors in western Canada. METHODS: The Alberta CancerBridges team developed, implemented, and evaluated scps for 36 breast and 21 head-and-neck cancer survivors. For the evaluation, we interviewed 12 of the survivors, 9 nurses who delivered the scps, and 3 family physicians who received the scps (n = 24 in total). We asked about satisfaction, usefulness, emotional impact, and communication value. We collected written feedback from the three groups about positive aspects of the scps and possible improvements (n = 85). We analyzed the combined data using qualitative thematic analysis. RESULTS: Survivors, nurses, and family physicians agreed that scps could ease the transition to survivorship partly by enhancing communication between survivors and care providers. Survivors appreciated the individualized attention and the comprehensiveness of the plans. They described positive emotional impacts, but wanted a way to ensure that their physicians received the scps. Nurses and physicians responded positively, but expressed concern about the time required to implement the plans. Suggestions for streamlining the process included providing survivors with scp templates in advance, auto-populating the templates for the nurses, and creating summary pages for physicians. CONCLUSIONS: The results suggest ways in which scps could help to improve the transition to cancer survivorship and provide starting points for larger feasibility studies.
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BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.
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Anafilaxia/tratamento farmacológico , Antimaláricos/farmacologia , Artemisininas/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Anafilaxia/imunologia , Animais , Antialérgicos/farmacologia , Artesunato , Asma/tratamento farmacológico , Asma/imunologia , Asma/fisiopatologia , Degranulação Celular/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Cobaias , Humanos , Imunidade Celular/fisiologia , Immunoblotting , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Técnicas In Vitro , Mastócitos/fisiologia , Camundongos , Distribuição AleatóriaRESUMO
BACKGROUND: The microelectrode array (MEA) was used to investigate the pharmacological relevance of chloride (Cl-) ions in antigen-dependent mast cell activation and the inhibitory effect of disodium cromoglycate (DSCG) on mast cell activation. METHODS: The movements of ions across the cellular membrane and the potential relationship between Cl- channels and DSCG during immunological activation were investigated using the MEA. The results were then subsequently compared with the amount of histamine released from anti-IgE activated peritoneal mast cells. RESULTS: The inclusion of charybdotoxin (ChTX) in Cl--free buffer showed that the measured field potentials during antigen-stimulated peritoneal mast cell were a combination of Cl- influx and K+ efflux. The delayed onset time of Cl- influx indicated the presence of a delayed outwardly-rectifying Cl- current in the antigen-stimulated peritoneal mast cells. The use of 5-nitro-2-(3-phenylpropylamino) benzoic acid demonstrated that the activated mast cell membrane potential can be stabilised, thereby reducing the amount of histamine released from the anti-IgE activated mast cells. The correlation between the results of the histamine release assay and the electrophysiological measurements demonstrated the importance of Cl- to anti-IgE dependent mast cell activation. The inhibitory effect of DSCG on anti-IgE activated cells, however, did not correlate with the presumed influx of Cl-. CONCLUSIONS: The MEA data suggest that Cl- influx is crucial to IgE-dependent mast cell degranulation. GENERAL SIGNIFICANCE: While the MEA cannot yield information about single channel properties, it is convenient to use and can provide information on the global changes in electrophysiological responses of non-excitable cells.
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Cloretos/farmacologia , Cromolina Sódica/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Receptores de IgE/fisiologia , Animais , Anticorpos Anti-Idiotípicos/farmacologia , Charibdotoxina/farmacologia , Canais de Cloreto/efeitos dos fármacos , Canais de Cloreto/metabolismo , Liberação de Histamina/genética , Masculino , Microeletrodos , Nitrobenzoatos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de IgE/efeitos dos fármacosRESUMO
Little data concerning hospital charges and long-term outcomes of LDLT in North American children according to transplant indications have been published. To compare outcomes of patient and graft survival and healthcare charges for LDLT for those with BA vs. other diagnoses (non-BA). A retrospective review of 52 children receiving 53 LDLT (38 BA and 14 non-BA) from 1992 to 2010 at our institution was performed. One-, five-, and 10-yr patient and graft survival data were comparable to national figures reported to UNOS. Average one-yr charges for recipients and donors were $242 849 for BA patients and $183 614 for non-BA (p = 0.074). BA patients were 1.23 ± 1.20 yr of age vs. 4.25 ± 5.02 for non-BA, p = 0.045. Examination of the total population of patients who were alive in 2010 in five chronological groupings showed that the crude five-yr survival rates were 1992-1995: 9/11 (82%); 1995-1997: 6/10 (60%); 1997-1999: 8/10 (80%); 1999-2001: 9/10 (90%); and 2001-2003: 7/7 (100%). Thus, examination of the clinical and financial data together over the entire period of the transplant program suggests that the dramatic improvement in patient survival was accomplished without a dramatic increase in indexed charges. All 53 donors survived, and only 10% had complications requiring hospitalization. LDLT in children results in excellent outcomes for patients and donors. Ways to lower costs and maximize graft outcome should be investigated.
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Atresia Biliar/complicações , Doença Hepática Terminal/cirurgia , Transplante de Fígado , Doadores Vivos , Adolescente , Atresia Biliar/economia , Atresia Biliar/mortalidade , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Doença Hepática Terminal/economia , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Preços Hospitalares/estatística & dados numéricos , Humanos , Lactente , Estimativa de Kaplan-Meier , Transplante de Fígado/economia , Transplante de Fígado/mortalidade , Masculino , Maryland , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
An 18-month-old female status post-orthotopic liver transplant for biliary atresia presented nine months after transplant with severe diarrhea and intolerance of feeds. She was found to have a PLE as evidenced by a low serum albumin and a persistent elevation of fecal A1AT. Investigation eventually revealed that the cause of the PLE was a stricture at the anastomosis site between the hepatic vein and inferior cava, supported by resolution of the PLE after venoplasty of the stricture. The patient has subsequently required several repeat venoplasties for recurrence of her symptoms correlating with recurrence of the stricture. This is a very rare presentation of hepatic venous outflow obstruction. Moreover, normal duplex ultrasound imaging of liver vasculature and her unusual presentation led to a delay in her diagnosis highlighting the need for an increased index of suspicion.
Assuntos
Ascite/complicações , Síndrome de Budd-Chiari/etiologia , Diarreia/complicações , Falência Hepática/complicações , Transplante de Fígado/efeitos adversos , Enteropatias Perdedoras de Proteínas/complicações , Anastomose Cirúrgica , Ascite/etiologia , Síndrome de Budd-Chiari/complicações , Constrição Patológica , Diarreia/etiologia , Feminino , Humanos , Lactente , Fígado/diagnóstico por imagem , Fígado/patologia , Falência Hepática/terapia , Complicações Pós-Operatórias , Enteropatias Perdedoras de Proteínas/etiologia , Recidiva , Albumina Sérica/metabolismo , Ultrassonografia/métodos , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Aluminium anodization under optimized conditions can naturally generate close-packed and aligned nanopore arrays, but the spatial extent of such regular pore arrangement is generally limited. Here we demonstrated the use of soft ultraviolet nanoimprint lithography to guide the formation of nanopores at specific locations, using an elastomer negative mold for the process. By anodizing at voltages which naturally led to the formation of pores with matching averaged interpore separation, pre-patterned triangular holes (diameter 100 nm, periodicity 350 nm) on aluminium thin films induced conformal growth of nanopores at pre-defined positions. In addition, pores in geometries other than close-packed patterns were prepared, with square pore arrangement being demonstrated in this work. The influence of the anodization voltage on the final pore formation was also studied. Our results illustrated the possibility to fabricate well-organized nanopore arrays with conditions far less stringent than those reported in literature, which has the potential to be adopted for applications where regular pore alignment are critical.
RESUMO
Reliable estimates of the morbidity burden caused by the 2009 pandemic influenza (pH1N1) are important for assessing the severity of the pandemic. Poisson regression models were fitted to weekly numbers of cause-specific hospitalisation in Hong Kong from 2005 to 2010. Excess hospitalisation associated with the 2009 pandemic and seasonal influenza was derived from the model by incorporating the proxy variables of weekly proportions of specimens positive for the pandemic influenza A(H1N1)pdm09, seasonal influenza A (subtypes H3N2 and H1N1) and B viruses. Compared with seasonal influenza, pH1N1 influenza was associated with higher hospitalisation rates for acute respiratory disease (ARD) among children younger than 18 years and adults aged between 18 and 64 years, but among the elderly aged 65 years and older the hospitalisation rates were lower for pH1N1 than for seasonal H3N2 and H1N1 influenza. Hospitalisation rates for chronic diseases associated with pH1N1 influenza were generally higher than those associated with seasonal influenza. The reported hospitalised cases with laboratory-confirmed pandemic infections accounted for only 16% of pH1N1 influenza-associated hospitalisations for ARD in the age group 75 years and older, and 5â66% of hospitalisations for chronic diseases in those older than 40 years. The 2009 H1N1 influenza pandemic was associated with a dramatically increased risk of hospitalisation among children and young adults. The morbidity burden of pandemic was underreported in old people and in those with chronic conditions.
Assuntos
Hospitalização/estatística & dados numéricos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Pandemias , Estações do Ano , Adolescente , Adulto , Idoso , Feminino , Hong Kong/epidemiologia , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The anti-IL-5 biologic reslizumab for the treatment of severe eosinophilic asthma is administered intravenously. In the current study home administration of intravenous reslizumab was evaluated in 24 patients included between 2019 (July) and 2020 (July). This is the first study to show that intravenous reslizumab can be administered safely and successfully in an outpatient setting. Notably, not all patients prefer home administration and severe asthma patients may have different needs when it comes to choosing treatment at home or in the hospital.