Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Ren Fail ; 46(2): 2357746, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38832498

RESUMO

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.


Assuntos
Nefropatias Diabéticas , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Nefropatias Diabéticas/microbiologia , Microbioma Gastrointestinal/genética
2.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37173227

RESUMO

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , Captopril
3.
J Clin Immunol ; 42(8): 1730-1741, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35947322

RESUMO

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.


Assuntos
Criptococose , Proteinose Alveolar Pulmonar , Humanos , Autoanticorpos , Criptococose/diagnóstico , Criptococose/epidemiologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia
4.
Nephrol Dial Transplant ; 37(11): 2093-2101, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-35512604

RESUMO

BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92-0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76-0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65-0.67) and estimated glomerular filtration rate (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.


Assuntos
Rim , Aprendizado de Máquina , Humanos , Creatinina , Fibrose , Reprodutibilidade dos Testes , Rim/patologia , Biópsia
5.
Entropy (Basel) ; 24(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37420467

RESUMO

In this paper, we address the problem of m-gram entropy variable-to-variable coding, extending the classical Huffman algorithm to the case of coding m-element (i.e., m-grams) sequences of symbols taken from the stream of input data for m>1. We propose a procedure to enable the determination of the frequencies of the occurrence of m-grams in the input data; we formulate the optimal coding algorithm and estimate its computational complexity as O(mn2), where n is the size of the input data. Since such complexity is high in terms of practical applications, we also propose an approximate approach with linear complexity, which is based on a greedy heuristic used in solving backpack problems. In order to verify the practical effectiveness of the proposed approximate approach, experiments involving different sets of input data were conducted. The experimental study shows that the results obtained with the approximate approach were, first, close to the optimal results and, second, better than the results obtained using the popular DEFLATE and PPM algorithms in the case of data that can be characterized by highly invariable and easy to estimate statistics.

6.
Small ; 17(30): e2101434, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34187085

RESUMO

Neuromorphic computing has emerged as the high-energy-efficiency and intelligent solution for processing sensory data. As a potential alternative to neuromorphic computing, photo-excited synaptic systems can integrate the functions of optoelectronic sensing and synaptic computing to realize the low-power and high-performance visual perception. However, one major challenge in high-efficient photo-excited synaptic system is to realize the complementarily enhanced and inhibited synaptic behaviors with small hardware cost as possible. Another challenge is to fabricate the photo-synapse devices with complementary metal oxide semiconductor (CMOS)-compatible process to achieve high enough integration density for practical application. Here, a CMOS-compatible Light-stimulated Porphyrin-coated Silicon Nanowire Field Effect Transistor (LPSNFET) technology is proposed and developed to form the complementary photo-synapses with only two CMOS-like transistors. LPSNFET exhibits fivefold improvement in photo-sensitivity compared to the bare silicon nanowire (SiNW) devices, and can still show obvious responses when incident illumination power is as low as 0.1 mW cm-2 . Moreover, it enables tunable dynamic synaptic plasticity and versatile synaptic functions. Especially, the complementarily enhanced and inhibited behaviors can be realized by modulating SiNW/porphyrin interface via simply changing the MOS type of LPSNFET, which acts like the photonic counterpart of CMOS technology to provide the basic brick for building complex neuromorphic circuits efficiently and economically. Finally, the CMOS process compatibility of LPSNFET provides potential application in future large scale in-sensor computing.


Assuntos
Nanofios , Porfirinas , Silício , Sinapses , Transistores Eletrônicos
7.
J Formos Med Assoc ; 120(1 Pt 1): 121-129, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32855034

RESUMO

BACKGROUND: To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. RESULTS: When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. CONCLUSION: With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.


Assuntos
Hiperaldosteronismo , Glândulas Suprarrenais , Aldosterona , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão , Renina , Taiwan
8.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208103

RESUMO

TAFRO syndrome is an extremely rare form of idiopathic MCD, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy, and organomegaly. Like idiopathic MCD, renal involvement is also a common presentation in patients with TAFRO syndrome. Furthermore, membranoproliferative glomerulonephritis (MPGN)-like injury and thrombotic microangiopathy (TMA) are the most reported histopathologic findings of renal biopsy. Several molecular mechanisms have been previously postulated in order to explain the TAFRO syndrome symptoms, including abnormal production of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. The role of these cytokines in renal injury, however, is not well understood. The aim of this review article is to summarize the latest knowledge of molecular mechanisms behind the TAFRO syndrome and their potential role in renal damage.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/terapia , Rim/patologia , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/terapia , Animais , Hiperplasia do Linfonodo Gigante/fisiopatologia , Humanos , Microangiopatias Trombóticas/fisiopatologia
9.
Small ; 16(50): e2004905, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33206460

RESUMO

Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re-education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co-loaded with doxorubicin (DOX) and resiquimod (R848) (D/R@LCFS) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. After local administration, D/R@LCFS turns tumor into in situ vaccine via DOX-triggered immunogenic cell death effect accompanied with immunostimulatory effect of R848. Meanwhile, combination treatment of D/R@LCFS facilitates the recruitment of effector CD8+ T cells and the polarization of myeloid-derived suppressor cells and immunosuppressive type 2-polarized macrophages to tumoricidal antigen-presenting cells, favoring antigen-specific T cell immune response and inducing more immunogenic phenotypes in tumors. The generated in situ vaccine as well as reshaped TME by D/R@LCFS elicited systematic immune response and long term immune-memory effect in combination with immune checkpoint blockade to significantly prevent postoperative B16F10 or 4T1 tumor recurrence and metastasis. Therefore, this combination strategy of spatiotemporal TME modulation is expected to provide a clinical available option for effective postoperative chemoimmunotherapy.


Assuntos
Cristais Líquidos , Neoplasias , Linfócitos T CD8-Positivos , Humanos , Imunoterapia , Microambiente Tumoral
10.
BMC Anesthesiol ; 19(1): 73, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092199

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is often used in critical patients with severe myocardial failure. However, the mortality rate of patients on ECMO is often high. Recent studies have suggested that endothelial activation with subsequent vascular barrier breakdown is a critical pathogenic mechanism of organ damage and is related to the outcome of critical illness. This study aimed to determine whether endothelial biomarkers can be served as prognostic factors for the outcome of patients on ECMO. METHODS: This prospective study enrolled 23 critically ill patients on veno-arterial ECMO in the intensive care units of a tertiary care hospital between March 2014 and February 2015. Serum samples were tested for thrombomodulin, angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF). Demographic, clinical, and laboratory data were also collected. RESULTS: The overall mortality rate was 56.5%. The combination of Ang-2 at the time of ECMO support (day 0) and VEGF at day 2 had the ability to discriminate mortality (area under receiver operating characteristic curve [AUROC], 0.854; 95% confidence interval: 0.645-0.965). CONCLUSIONS: In this study, we found that the combination of Ang-2 at day 0 and VEGF at day 2 was a modest model for mortality discrimination in this group of patients.


Assuntos
Endotélio Vascular/metabolismo , Oxigenação por Membrana Extracorpórea/métodos , Choque Cardiogênico/sangue , Choque Cardiogênico/diagnóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Proteínas de Transporte Vesicular/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Choque Cardiogênico/mortalidade
11.
J Formos Med Assoc ; 118(10): 1408-1415, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31133523

RESUMO

BACKGROUND/PURPOSE: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients. METHODS: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome. RESULTS: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m2, P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFR≧15 mL/min). CONCLUSION: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Anticorpos Anticitoplasma de Neutrófilos/sangue , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/enzimologia , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
Nanotechnology ; 29(46): 465301, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30168802

RESUMO

Arrays of 14 nm thick L10-FePt nanodots with diameter of 27 nm and center-to-center spacing of 39 nm were produced by block copolymer patterning of an FePt film and their magnetic reversal and thermal stability were characterized. A self-assembled polystyrene-b-polydimethylsiloxane diblock copolymer film was used as a lithographic mask and a pattern transfer process based on ion beam etching and rapid thermal annealing of the sputtered FePt film was developed. The dot arrays exhibited perpendicular magnetic anisotropy with K = 4.8 × 107 erg cm-3 and a saturation magnetization of 960 emu cm-3. First order reversal curves indicate a softer magnetic component attributed to the ion-milled material at the edges of the dots. The switching volume and the thermal stability were obtained from relaxation measurements and DC demagnetization curves. Micromagnetic simulations reproduce the magnetic domain structure obtained for the continuous and patterned FePt thin film.

13.
Nanotechnology ; 29(27): 275302, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29633719

RESUMO

Dense arrays of pillars, with diameters of 64 and 25 nm, were made from a perpendicular CoFeB magnetic tunnel junction thin film stack using block copolymer lithography. While the soft layer and hard layer in the 64 nm pillars reverse at different fields, the reversal of the two layers in the 25 nm pillars could not be distinguished, attributed to the strong interlayer magnetostatic coupling. First-order reversal curves were used to identify the steps that occur during switching, and the thermal stability and effective switching volume were determined from scan rate dependent hysteresis measurements.

14.
Transfus Apher Sci ; 57(4): 537-543, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29880246

RESUMO

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n = 45) and ALF (n = 10) who received standard-volume PE (1-1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P = 0.008), post-PE hemoglobin (P = 0.039), and post-PE CLIF-C ACLF scores (P = 0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve = 0.719, P = 0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.


Assuntos
Insuficiência Hepática Crônica Agudizada/terapia , Falência Hepática Aguda/terapia , Troca Plasmática/métodos , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Estudos de Coortes , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
15.
Chem Biodivers ; 15(12): e1800395, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30294975

RESUMO

Eight secondary metabolites, including a new polyketide, named asperetide (1) and a new prenylxanthone derivative, called asperanthone (4), and six known compounds, (S)-3-butyl-7-methoxyphthalide (2), ruguloxanthone C (3), tajixanthone hydrate (5), tajixanthone methanoate (6), salimyxin B (7), and ergosterol (8), were isolated and identified from the medicinal plant-derived fungus, Aspergillus sp. TJ23. The new structures and their absolute configurations were elucidated via multiple methods, including 1D- and 2D-NMR, HR-ESI-MS, UV, IR, and the electronic circular dichroism (ECD) calculations. All of the isolates were characterized from the strain for the first time. The in vitro bioassay showed that compounds 3-5 and 8 exerted inhibitory activities against five cancer cell lines (B16, MDA-MB-231, 4T1, HepG2, and LLC) with IC50 values ranging from 5.13 to 36.8 µm.


Assuntos
Aspergillus/química , Policetídeos/química , Xantonas/química , Aspergillus/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Xantonas/isolamento & purificação , Xantonas/farmacologia
16.
J Clin Immunol ; 37(2): 143-152, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28013480

RESUMO

INTRODUCTION: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. METHODS: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. RESULTS: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. CONCLUSIONS: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.


Assuntos
Autoanticorpos/imunologia , Criptococose/etiologia , Criptococose/microbiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Antifúngicos/uso terapêutico , Autoanticorpos/sangue , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Quimiocina CCL3/biossíntese , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunofenotipagem , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/etiologia , Infecções Oportunistas/microbiologia , Fosforilação , Proteinose Alveolar Pulmonar/etiologia , Radiografia Torácica , Fator de Transcrição STAT5/metabolismo , Tomografia Computadorizada por Raios X
17.
Am J Kidney Dis ; 70(5): 619-626, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28663061

RESUMO

BACKGROUND: Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. STUDY DESIGN: Population-based cross-sectional cohort study. SETTING & PARTICIPANTS: All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013. Among these, 47.45%, 57.45%, 47.29%, and 1.51% had a known parent, child, sibling, or twin, respectively. We identified 87,849 patients who had a diagnosis of ESRD. PREDICTOR: Family history of ESRD. OUTCOMES & MEASUREMENTS: ESRD and heritability defined as the proportion of phenotypic variance attributable to genetic factors. RESULTS: Having an affected first-degree relative with ESRD was associated with an adjusted relative risk of 2.46 (95% CI, 2.32-2.62). Relative risks were 96.38 (95% CI, 48.3-192.34) for twins of patients with ESRD, 2.15 (95% CI, 2.02-2.29) for parents, 2.78 (95% CI, 2.53-3.05) for offspring, 4.96 (95% CI, 4.19-5.88) for siblings, and 1.66 (95% CI, 1.54-1.78) for spouses without genetic similarities. Heritability in this study was 31.1% to 11.4% for shared environmental factors and 57.5% for nonshared environmental factors. LIMITATIONS: This was a registry database study and we did not have detailed information about clinical findings or the definite causes of ESRD. CONCLUSIONS: This whole population-based family study in Asia confirmed, in a Taiwanese population, that a family history of ESRD is a strong risk factor for this disease. Moderate heritability was noted and environmental factors were related to disease. Family history of ESRD is an important piece of clinical information.


Assuntos
Povo Asiático/genética , Família , Falência Renal Crônica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Taiwan/epidemiologia , Adulto Jovem
18.
Nanotechnology ; 28(14): 145301, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-28221161

RESUMO

The self-assembly of block copolymers with large feature sizes is inherently challenging as the large kinetic barrier arising from chain entanglement of high molecular weight (MW) polymers limits the extent over which long-range ordered microdomains can be achieved. Here, we illustrate the evolution of thin film morphology from a diblock copolymer of polystyrene-block-poly(dimethylsiloxane) exhibiting total number average MW of 123 kg mol-1, and demonstrate the formation of layers of well-ordered cylindrical microdomains under appropriate conditions of binary solvent mix ratio, commensurate film thickness, and solvent vapor annealing time. Directed self-assembly of the block copolymer within lithographically patterned trenches occurs with alignment of cylinders parallel to the sidewalls. Fabrication of ordered cobalt nanowire arrays by pattern transfer was also implemented, and their magnetic properties and domain wall behavior were characterized.

19.
Nanotechnology ; 27(46): 465301, 2016 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-27736809

RESUMO

The response of polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS) thin films to UV exposure during solvent vapor annealing is described, in order to improve their applicability in nanolithography and nanofabrication. Two BCPs were examined, one with the PS block as majority (f PS = 68%, M n = 53 kg mol-1), the other with PDMS block as majority (f PDMS = 67%, M n = 44 kg mol-1). A 5 min UV irradiation was applied during solvent vapor annealing which led to both partial crosslinking of the polymer and a small increase in the temperature of the annealing chamber. This approach was effective for improving the correlation length of the self-assembled microdomain arrays and in limiting subsequent flow of the PDMS in the PDMS-majority BCP to preserve the post-anneal morphology. Ordering and orientation of microdomains were controlled by directed self-assembly of the BCPs in trench substrates. Highly-ordered perpendicular nanochannel arrays were obtained in the PDMS-majority BCP.

20.
Nanotechnology ; 27(18): 185302, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-27005330

RESUMO

Perpendicular magnetic tunnel junctions (p-MTJs) were patterned into nanopillars using electron-beam lithography to study their scaling and switching behaviour. Magnetoresistance measurements of annealed and unannealed p-MTJ films using scanning probe microscopy showed good agreement with Monte Carlo modeling. p-MTJ pillars demonstrated clear parallel magnetic states, both 'up' or both 'down' following AC-demagnetization. Significant variability in the resistance of p-MTJ pillars was observed and attributed to edge features generated during patterning or local inhomogeneity in the MgO layer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA