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1.
Artigo em Inglês | MEDLINE | ID: mdl-32561922

RESUMO

OBJECTIVE: Plasma clusterin, a promising biomarker of Alzheimer's disease (AD), has been associated with diabetes mellitus (DM). However, clusterin has not been investigated considering a relationship with both DM and AD. In this study, we aimed to investigate the individual and interactive relationships of plasma clusterin levels with both diseases. DESIGN: Cross-sectional observation study. METHODS: We classified participants by the severity of cognitive (normal cognition, mild cognitive impairment (MCI), and AD) and metabolic (healthy control, prediabetes, and DM) impairments. We evaluated the cognitive and metabolic functions ofA the participants with neuropsychological assessments, brain MRI, and various blood tests, to explore potential relationships with clusterin. RESULTS: Plasma clusterin levels were higher in participants with AD and metabolic impairment (prediabetes, and DM). A two-way ANCOVA revealed no synergistic, but an additive effect of AD and DM on clusterin. Clusterin was negatively correlated with cognitive scores. It was also associated with metabolic status indicated by HbA1c, the Homeostatic Model Assessment for Insulin Resistance index, and fasting C-peptide. It showed correlations between medial temporal atrophy and periventricular white matter lesions, indicating neurodegeneration and microvascular insufficiency, respectively. Further mediation analysis to understand the triadic relationship between clusterin, AD, and DM revealed that the association between DM and AD was significant when clusterin is considered as a mediator of their relationship. CONCLUSIONS: Clusterin is a promising biomarker of DM as well as of AD. Additionally, our data suggest that clusterin may have a role in linking DM with AD as a potential mediator.

2.
Inorg Chem ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32379436

RESUMO

Thin films often exhibit fascinating properties, but the understanding of the underlying mechanism behind such properties is not simple. This is partially because of the limited structural information available. The hurdle in obtaining such information is especially high for textured thin films such as Mg-rich MgxTi1-x, a promising switchable smart coating material. Although these metastable thin films are seen as solid solution alloys by conventional crystallographic methods, their hydrogen-induced optical transition is hardly understood by a solid solution model. In this study, we collect atomic pair distribution function (PDF) data for a Mg0.7Ti0.3Hy thin film in situ on hydrogenation and successfully resolve TiH2 clusters of an average size of 30 Å embedded in the Mg matrix. This supports the chemically segregated model previously proposed for this system. We also observe the emergence of a previously unknown intermediate face-centered tetragonal phase during hydrogenation of the Mg matrix. This phase appears between Mg and MgH2 to reduce lattice mismatch, thereby preventing pulverization and facilitating rapid hydrogen uptake. This work may shed new light on the hydrogen-induced properties of Mg-rich MgxTi1-x thin films.

3.
Inorg Chem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058704

RESUMO

Magnesium-based transition-metal hydrides are attractive hydrogen energy materials because of their relatively high gravimetric and volumetric hydrogen storage capacities combined with low material costs. However, most of them are too stable to release the hydrogen under moderate conditions. Here we synthesize the hydride of Mg2FexSi1-x, which consists of Mg2FeH6 and Mg2Si with the same cubic structure. For silicon-rich hydrides (x < 0.5), mostly the Mg2Si phase is observed by X-ray diffraction, and Mössbauer spectroscopy indicates the formation of an octahedral FeH6 unit. Transmission electron microscopy measurements indicate that Mg2FeH6 domains are nanometer-sized and embedded in a Mg2Si matrix. This synthesized metallographic structure leads to distortion of the Mg2FeH6 lattice, resulting in thermal destabilization. Our results indicate that nanometer-sized magnesium-based transition-metal hydrides can be formed into a matrix-forced organization induced by the hydrogenation of nonequilibrium Mg-Fe-Si composites. In this way, the thermodynamics of hydrogen absorption and desorption can be tuned, which allows for the development of lightweight and inexpensive hydrogen storage materials.

4.
Sci Total Environ ; 718: 137267, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088476

RESUMO

Particulate matter (PM) exposure is related to an increased risk of sporadic Alzheimer's disease (AD), the pathogenesis of which is explained by chronic neurometabolic disturbance. Therefore, PM-induced alterations in neurometabolism might herald AD. We aimed to identify brain region-specific changes in metabolic pathways associated with ultrafine particle (UFP) exposure and to determine whether such metabolic alterations are linked to susceptibility to AD. We constructed UFP exposure chambers and generated UFP by the pyrolysis method, which produces no toxic oxidized by-products of combustion, such as NOx and CO. Twenty male C57BL6 mice (11-12 months old) were exposed either to UFP or room air in the chambers for 3 weeks. One week following completion of UFP exposure, regional brain tissues, including the olfactory bulb, cortex, hippocampus, and cerebellum, were obtained and analyzed by metabolomics based on GC-MS and LC-MS, western blot analysis, and immunohistochemistry. Our results demonstrated that the metabolomic phenotype was distinct within the 4 different anatomical regions following UFP exposure. The highest level of metabolic change was identified in the hippocampus, a vulnerable region involved in AD pathogenesis. In this region, one of the key changes was perturbed redox homeostasis via alterations in the methionine-glutathione pathway. UFP exposure also induced oxidative stress and neuroinflammation, and importantly, increased Alzheimer's beta-amyloid levels in the hippocampus. These results suggest that inhaled UFP-induced perturbation in hippocampal redox homeostasis has a role in the pathogenesis of AD. Therefore, chronic exposure to UFP should be regarded as a cumulative environmental risk factor for sporadic AD.


Assuntos
Poluentes Atmosféricos , Doença de Alzheimer , Animais , Glutationa , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Tamanho da Partícula , Material Particulado
5.
Transbound Emerg Dis ; 67(2): 473-475, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955520

RESUMO

African swine fever, a fatal haemorrhagic disease of swine, was confirmed in domestic pigs for the first time in South Korea in September 2019. The causative virus belonged to the p72 genotype II and had an additional tandem repeat sequence in the intergenic region (IGR) between the I73R and I329L.


Assuntos
Vírus da Febre Suína Africana/genética , Febre Suína Africana/epidemiologia , Surtos de Doenças/veterinária , Febre Suína Africana/virologia , Animais , Feminino , Genótipo , Masculino , Filogenia , República da Coreia/epidemiologia , Sus scrofa , Suínos , Sequências de Repetição em Tandem/genética
6.
J Cerebrovasc Endovasc Neurosurg ; 21(1): 33-39, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31832385

RESUMO

Background: Achondroplasia is one of the most common types of dwarfism and is inherited as an autosomal dominant disease. The patients with achondroplasia suffer from various complications such as craniofacial, central nervous system, spinal, respiratory and cardiac anomalies. Case Description: We report a case of a 35-year-old man with achondroplasia who visited the emergency room with right hemiplegia and aphasia within 6 hours after onset. An Initial CT angiography showed the total occlusion of a left internal cerebral artery due to the thrombus. We treated the patient with endovascular thrombectomy using "Solumbra technique" with balloon guiding catheter. The procedure was successful and result was completely recanalized with Thrombolysis in Cerebral Infarction (TICI) scale 3 and the weakness also improved from grade II to grade IV. Conclusion: Acute ischemic stroke patients with achondroplasia could be treated with mechanical thrombectomy.

7.
Inorg Chem ; 58(21): 14600-14607, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31647662

RESUMO

Hydrogen storage is a key technology for the advancement of hydrogen and fuel cell power technologies in stationary and portable applications. MgH2, an example of a high-capacity hydrogen storage material, has two major material challenges for practical applications: slow hydrogen desorption kinetics and high hydrogen desorption temperature. Numerous studies have reported enhancements in kinetics but only a few in thermodynamics. Here, we present a simple but effective way to improve upon both the kinetic and thermodynamic aspects of desorption by utilizing the immiscibility of Mn, a non-hydrogen absorbing metal, with Mg. Mg0.25Mn0.75, prepared through ball milling MgH2 and Mn powders, is a nanocomposite where the nanometer-sized MgH2 domains are randomly embedded in a Mn matrix. This sample readily and reversibly absorbs and desorbs deuterium even at a temperature of 200 °C without the addition of any catalysts. This is nearly 180 °C lower than the typical operating temperature of conventional bulk Mg. Furthermore, at a given temperature, its deuterium desorption pressure is clearly elevated compared to that of pure Mg, indicating the destabilization of MgD2. The average crystallite size of MgD2 in deuterated Mg0.25Mn0.75 determined from X-ray diffraction data is around 9 nm. Nuclear magnetic resonance spectroscopy studies show that MgD2 domains are heavily strained and some of the D atoms are coordinated by a few Mn atoms, suggesting that a large number of lattice defects, including the partial substitution of Mg with Mn, are introduced during ball milling. Furthermore, the Mn matrix firmly locks nanosized MgD2, preventing the agglomeration of MgD2 below 250 °C. Our study suggests that a synergistic effect created by nanosizing, large lattice distortions, and robust interfaces between MgD2 and the Mn matrix can effectively and concurrently improve the kinetics and thermodynamics of MgD2 in Mg0.25Mn0.75. Our work demonstrates the possibility of utilizing the immiscibility of metals with Mg to synthesize a robust nanostructure that can alter the kinetics and stability of MgH2.

8.
Sci Rep ; 9(1): 13854, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554894

RESUMO

Osteoarthritis (OA) is a degenerative condition of the temporomandibular joint (TMJ) characterised by chronic inflammation and damage to joint structures. Because of the complexity of TMJ-OA, only symptomatic treatments are currently available. Recent reports have shown that many of stem cells can exert anti-inflammatory and tissue-regenerating effects. In this study, we investigated the potential cartilage-regenerating and anti-inflammatory effects of human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs) for the treatment of TMJ-OA. hUCM-MSC lines, isolated from different donors, which showed different activities in vitro. Using a selected cell line, we used different concentrations of hUCM-MSCs to assess therapeutic effects in a rabbit model of monosodium iodoacetate-induced TMJ-OA. Compared with the untreated control group, the potential regenerative result and anti-inflammatory effects of hUCM-MSCs were evident at all the tested concentrations in rabbits with induced TMJ-OA. The median dose of hUCM-MSCs showed the prominent cartilage protective effect and further cartilage regeneration potential. This effect occurred via upregulated expression of growth factors, extracellular matrix markers, and anti-inflammatory cytokines, and reduced expression of pro-inflammatory cytokines. The anti-inflammatory effect of hUCM-MSCs was comparable to that of dexamethasone (DEX). However, only hUCM-MSCs showed potential chondrogenesis effects in this study. In conclusion, our results indicate that hUCM-MSCs may be an effective treatment option for the treatment of TMJ-OA.

9.
Pediatr Cardiol ; 40(8): 1584-1590, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473799

RESUMO

Because Fontan circulation does not have a subpulmonary ventricle, the preload is limited. In Fontan circulation with extracardiac conduit, the size of conduit could be an important factor in determining the preload. We compared exercise capacity with each conduit size and tried to search for optimal conduit size in Fontan circulation. We reviewed the medical record of 677 patients with Fontan circulation. Patients who had other type Fontan circulation (Kawashima, atriopulmonary, lateral tunnel), SpO2 < 85%, protein losing enteropathy, results of inappropriate exercise test were excluded. As a result, 150 patients were enrolled and classified according to conduit size. We compared with their exercise capacity and analyzed correlation between exercise capacity and conduit size per body surface area (BSA). 97 Males were included and mean age was 17.5 ± 5.1 years old. In cardiac catheterization, central venous pressure (CVP) was 12.4 ± 2.5 mmHg and pulmonary vascular resistance was 1.2 ± 0.5 wu m2. In cardiopulmonary exercise test, predictive peak VO2 was 59.1 ± 9.7% and VE/VCO2 was 36.2 ± 6.9. In analysis using quadratic model, impacts of gender, age at Fontan operation, ventricular morphology, isomerism, and fenestration on exercise capacity were excluded and conduit size per BSA had a significant curved correlation with predictive peak VO2 and VE/VCO2. Our results showed that patients with about 12.5 mm/m2 conduit per BSA have the best exercise capacity. Patients with larger than smaller-sized conduit were found to be more attenuated in their ability to exercise.


Assuntos
Tolerância ao Exercício , Exercício Físico/fisiologia , Técnica de Fontan/efeitos adversos , Adolescente , Adulto , Cateterismo Cardíaco , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
10.
Medicine (Baltimore) ; 98(15): e15159, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985694

RESUMO

BACKGROUND: Despite recent advances in gastric cancer surgery, open gastrectomy is often needed to treat gastric cancer. Due to the large incision in the abdomen, the amount of opioid required during surgery increases and postoperative pain becomes worse. It is well known that postoperative pain has a negative impact on the patient's immune system. Herein, we performed an ultrasound-guided bilateral rectus sheath block (RSB) in patients undergoing open gastrectomy under general anesthesia and analyzed the analgesic effectiveness of RSB in open gastrectomy. METHODS: A total of 46 patients scheduled for open gastrectomy were randomly divided into 2 groups: Group A (n = 21) consisted of patients who received an RSB using 40 mL of 0.375% ropivacaine under ultrasound guidance and Group B (n = 20) consisted of patients who received an RSB using 40 mL of normal saline. An electronic injection pump was connected to each patient for patient-controlled analgesia (PCA) immediately after the skin closure. The amount of remifentanil required during the surgery was analyzed. After using PCA, data on the use of PCA bolus dose were extracted and analyzed using Excel. RESULTS: Group A used significantly less remifentanil (1021.4 ±â€Š172.0 µg) than group B (1415.0 ±â€Š330.6 µg; P = .03). The number of PCA bolus dose provided to the patients after surgery was significantly lower in group A (1 h: 1.14 ±â€Š0.9, 2 h: 0.85 ±â€Š0.7) than in group B (1 h: 1.85 ±â€Š0.7, 2 h: 1.45 ±â€Š1.0) until 2 hours after the surgery (1 h, P = .008; 2 h, P = .03), but after 3 hours, there were no significant differences between the 2 groups. CONCLUSIONS: If ultrasound-guided bilateral RSB with 40 mL of 0.35% ropivacaine is performed precisely in patients undergoing open gastrectomy, the requirement for remifentanil during surgery can be reduced. In addition, it significantly reduces the use of PCA bolus dose for acute postoperative pain within 2 hours after surgery.


Assuntos
Anestésicos Locais/administração & dosagem , Gastrectomia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Dor Processual/tratamento farmacológico , Ropivacaina/administração & dosagem , Analgesia Controlada pelo Paciente , Anestesia Geral , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Ultrassonografia de Intervenção
11.
J Neurol Sci ; 401: 81-86, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31035190

RESUMO

BACKGROUND: Clonazepam is considered to be a first-line treatment for rapid eye movement sleep-related behavior disorder (RBD) in Parkinson's disease (PD). The purpose of this study was to determine the short-term efficacy and safety of clonazepam for the treatment of probable RBD (pRBD) in patients with PD. METHODS: We conducted a four-week, randomized, double-blind, placebo-controlled trial of clonazepam (0.5 mg/day at bedtime) compared to a placebo for RBD symptoms in patients with PD. Patients aged 30 years or older who had a caregiver that could observe RBD symptoms were recruited between April 2015 and February 2016. The primary outcome was the Clinical Global Impressions-Improvement (CGII) score at week four, and we compared scores between the clonazepam and placebo groups. RESULTS: A total of 40 patients were enrolled, with 20 assigned to receive clonazepam and 20 to receive the placebo. The CGI-I score at four weeks indicated an improvement in RBD symptoms in both the clonazepam (median score [minimum, maximum] = 2 [1,5]) and placebo (3 [1,6]) groups, with no significant difference between the groups (p = .253). The secondary outcomes were not significantly different between the clonazepam and placebo groups. CONCLUSIONS: Both clonazepam and placebo tended toward improvement on pRBD symptoms in patients with PD. No firm conclusion on efficacy of clonazepam was drawn due to limitations in the study design. This study emphasized the importance of conducting future large-scale, randomized trials with better assessment tools and polysomnography to provide evidence for the benefit of clonazepam.

12.
Chemphyschem ; 20(5): 745-751, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30614177

RESUMO

Metal-organic frameworks (MOFs) are very promising host materials for nanoscale guest materials. However, some MOFs such as MIL-53 are known to undergo phase transitions which can complicate the guest particle size control. In this study, Pd nanoparticles embedded in Al-MIL-53 were synthesised via (a) electrodeposition and (b) gas-phase reduction. A thorough structural investigation revealed that each synthesis method most likely favoured a different phase of Al-MIL-53, presenting the possibility of MOF phase selection as a technique for size control of embedded nanoparticles. For the first time, we hereby report the use of pair distribution function analysis to successfully investigate the structure and morphology of guest particles embedded in a MOF host.

13.
Micromachines (Basel) ; 10(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577464

RESUMO

(1) Background: Quantification of platelet division is challenging because automated Coulter cell counters produce equivocal platelet counts. (2) Methods: We applied the flow cytometric cell tracking dye dilution assay as a popular immunological method to evaluate lymphocyte proliferation to prove and quantitate platelet division. We also devised a method relying on platelet culture in a semisolid medium which enabled dividing platelets to be identified by limiting the diffusive movement of platelets. Mixing platelets of different labeling colors in semisolid medium and counting the platelet doublets of each color combination enabled us to prove and quantitate platelet division. (3) Results: The tracking dye dilution assay revealed that 75.5 to 85.6% of platelets were dividing after 20 hours in culture. Platelets labeled with two different tracking dyes were mixed and cultured in semisolid medium for differential doublet counting. We counted platelet singlets and doublets of each color and color combination using confocal microscopy after six hours of culture and compared the relative number of two-colored doublets with binomial prediction to prove platelet division (P < 0.01). Division was suppressed by taxol, nocodazole, or cytochalasin D treatment. We derived a formula for determining the fraction of dividing platelets using the numbers of singlets and doublets of each color and color combination. The platelet division fraction ranged from 8.8 to 17.5%. (4) Conclusion: We successfully measured platelet division using a simple biometric image analysis method with possible future application to microfluidic devices.

14.
Psychiatry Investig ; 15(10): 935-944, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30301309

RESUMO

OBJECTIVE: A radial arm maze (RAM) is an essential tool for assessing spatial learning and memory. Although this tool is widely used to study deficits in spatial memory in animal models, it has several restrictions that prevent its adaptation to human research and training. Therefore, we developed a head-mounted-display RAM (HMD-RAM) program for humans and verified its validity by comparing it to the results obtained by previous RAM studies. We also compared the HMD and a flat monitor as experimental devices. METHODS: Forty participants were recruited for the current study (Study 1: 20 participants with the HMD device; Study 2: 20 participants with the flat monitor). They navigated a virtual room as a first-person viewer and used environmental landmarks to remember their spatial position and orientation. The main dependent measures were working memory error, reference memory error, detection time, travel distance, and participant's head movements. To validate the program, participants also conducted neuropsychological assessments and self-reported measures. RESULTS: The results for HMD-RAM tasks were consistent with the results of previous research conducted on animals, and the HMD elicited a higher sense of presence, immersion, and simulator sickness than the flat monitor. According to post-experiment questions on navigation strategy, creating landmarks was important when people were discovering locations in their environment, and an HMD was beneficial for better navigation strategy. CONCLUSION: These results suggest that the HMD-RAM is valuable for estimating spatial learning and memory in humans and may be a useful tool for early diagnosis of deficits in spatial learning and memory, including amnestic mild cognitive impairment and Alzheimer's disease.

15.
Iran J Public Health ; 47(Suppl 1): 9-18, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30186807

RESUMO

Background: This study aimed to investigate the trend of physical activity and daily sports participation in the Korean aged population through the review of 'Research on Public Daily Sports Participation' published by the Ministry of Culture, Sports and Tourism. The main purpose was to suggest the best health and sports policy for the future. Methods: The result of the research conducted by the government was published 13 times in total from 1989 to 2015. The aged were defined as people in their 60s and 70s since 2006. Based on the research published 7 times from 2006 to 2015, this study analyzed the changes and the trend recognition of health status, physical activities, sports activity effects and environment in the aged population in South Korea. Results: Majority of the aged population was found to hardly recognize their health status, but positively aware of physical and sports activity effect, particularly that the sports facility environment has been improving. Therefore, it is encouraged to set up elderly-friendly routine sports environment to motivate their participation and consequently establish healthy exercise culture. Conclusion: This study has great significance as it suggests the direction of future health and sports policy by analyzing the trend of previous physical activities and daily sports participation among the aged population based on the government-published research.

16.
Inorg Chem ; 57(18): 11831-11838, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30178993

RESUMO

Hydrogenation of nonequilibrium alloys may form nanometer-sized metal hydride clusters, depending on the alloy compositions and hydrogenation conditions. Here in the Ti-rich compositions of the immiscible Mg-Ti system MgH2 clusters are embedded in a Ti-H matrix. Our previous works have indicated that the interface energy between the two metal hydrides reduces the stability of MgH2. The aim of our study is to obtain the structural information on the nanometer-sized clusters. Indeed, MgD2 clusters embedded in a face-centered-cubic (FCC) Ti-D matrix is found in Mg0.25Ti0.75D1.65 by means of 2H magic angle spinning nuclear magnetic resonance (MAS NMR). The atomic pair distribution function (PDF) analysis of neutron total scattering data suggests that the MgD2 clusters have an orthorhombic structure, which is different from a rutile-type body-centered-tetragonal (BCT) structure of α-MgD2 observed in the Mg-rich compositions. Our results suggest that we can tune the thermodynamics of hydrogen absorption and desorption in Mg-H using the interface energy effect and accompanying stress-induced structural change, which contributes to the substantial development of lightweight and inexpensive hydrogen storage materials.

17.
Nanoscale ; 10(37): 17557-17566, 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30226520

RESUMO

Field-effect transistors (FETs) with non-covalently functionalised molybdenum disulfide (MoS2) channels grown by chemical vapour deposition (CVD) on SiO2 are reported. The dangling-bond-free surface of MoS2 was functionalised with a perylene bisimide derivative to allow for the deposition of Al2O3 dielectric. This allowed the fabrication of top-gated, fully encapsulated MoS2 FETs. Furthermore, by the definition of vertical contacts on MoS2, devices, in which the channel area was never exposed to polymers, were fabricated. The MoS2 FETs showed some of the highest mobilities for transistors fabricated on SiO2 with Al2O3 as the top-gate dielectric reported so far. Thus, gate-stack engineering using innovative chemistry is a promising approach for the fabrication of reliable electronic devices based on 2D materials.

18.
Ann Hematol ; 97(12): 2309-2317, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30073392

RESUMO

Predictive factors for initiating hypomethylating agents' (HMAs) treatment and the survival benefit of HMAs for lower-risk myelodysplastic syndrome (LR-MDS) are still unknown. This study evaluated the factors affecting the use of HMAs and compared long-term outcomes between best supportive care (BSC) and HMA groups after matching baseline clinical factors. Data of 353 patients diagnosed with LR-MDS by International Prognostic Scoring System between October 1992 and July 2013 were retrospectively analyzed. HMAs were administered continuously until a clinical response or progression. HMAs were administered to 243 patients with median 45 days (range 0-7078 days) after diagnosis, while 110 patients were treated with BSC. HMAs were administered over a median of 5 cycles and overall response was achieved in 104 patients (42.8%). The cumulative incidence of HMA treatment increased in higher-risk groups by other risk scoring systems. Three-year overall survival (OS) rate was higher in BSC group (69.1%) than HMA responders (47.4%, p = 0.065) or HMA non-responders (46.3%, p = 0.005). Among 162 case-matched cohorts, 3-year OS rates were comparable between the BSC group (67.1%) and HMA responders (58.1%, p = 0.914), while that of HMA non-responder was low (32.2%, p < 0.001). In the case-matched cohorts, HMA non-responder were associated with inferior OS rate in the multivariate analysis (hazard ratio 3.01, p = 0.001). Higher-risk groups by other clinical risk scoring systems among IPSS lower-risk patients showed an increased incidence of using HMAs. The OS rate of HMA responders among case-matched cohorts showed an improved OS rate similar to the BSC group.


Assuntos
Azacitidina/análogos & derivados , Azacitidina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Decitabina , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
19.
Clin Nucl Med ; 43(7): e220-e225, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29762247

RESUMO

PURPOSE: Distant failure is a major concern in patients with nasopharyngeal carcinoma. We evaluated whether the metabolic features on F-FDG PET/CT can predict distant metastasis-free survival (DMFS) in patients with locally advanced nasopharyngeal carcinoma. METHODS: We retrospectively reviewed 51 patients stage III, IVA, and IVB nasopharyngeal carcinoma who underwent F-FDG PET/CT at staging. The SUVmax for the primary site and the lymph nodes with the highest uptake as well as at the farthest station were divided by the SUVmean of the background liver (TLR, NLR-H, and NLR-F, respectively). The prognostic value of clinicopathologic factors and SUV parameters for predicting DMFS were assessed using a Cox proportional hazards model. Differences in DMFS were examined by the Kaplan-Meier method. RESULTS: In the median follow-up period of 50.4 ± 39.3 months (median ± interquartile range; range, 3.8-130.9), distant metastasis developed in 11 patients (21.6%). In univariate analyses, N stage (N3b) (P = 0.003) and NLR-H >5.70 (P = 0.02) were significant prognostic factors for DMFS, and remained significant in multivariate analysis, whereas TLR (P = 0.18) and NLR-F (P = 0.76) did not. The Kaplan-Meier curves showed significantly poorer DMFS in patients with NLR-H >5.70 than in those with lower NLR-H (≤5.70) (1-year DMFS rate, 84.2% vs 93.5%; P = 0.01). CONCLUSIONS: In addition to anatomical N stage, higher NLR-H on pretreatment F-FDG PET/CT is an independent prognostic factor for worse DMFS in patients with locally advanced nasopharyngeal carcinoma.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Idoso , Carcinoma/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Compostos Radiofarmacêuticos , Análise de Sobrevida
20.
Biochem Biophys Res Commun ; 500(2): 333-338, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29654761

RESUMO

Exposure to air pollutants, such as particulate matter (PM), has been implicated in neurodegenerative disorders including Alzheimer's disease (AD). However, direct effects of PM on production of ß-amyloid (Aß), a key pathogenic molecule in AD, and its underlying mechanism are still elusive. Given PM's potential to induce oxidative stress in other tissues, we hypothesized that poly(ADP-ribose) polymerase (PARP-1) might be involved in PM-induced neurotoxicity. To address this, we used an ex vivo model of AD, the organotypic hippocampal slice tissue culture from old (12-14 months-of-age) triple transgenic 3xTg-AD mice. First, we observed that fine PM (aerodynamic diameter < 4 µm) can dose-dependently activate PARP-1 and decrease NAD+ levels in Neuro2A cells. PARP-1 activation did occur under concentrations of PM which did not affect cell viability. Next, we observed that direct treatment of PM increased Aß levels and activated glial cells in the ex vivo hippocampal tissues of 3xTg-AD mice. PM-induced glial activation was most prominent in CA1 region of the hippocampal tissue. Notably, we found that pharmacological inhibition of PARP-1 reversed both PM-induced Aß increase and glial activation, arguing the possible involvement of PARP-1 in PM-induced AD pathogenesis. Our findings suggest that PARP-1 might be a potential molecular target, responsible for mediating negative effects of PM on the brain. Modulating PARP-1 activity could be a promising approach to prevent or alleviate PM-related environmental neurotoxicity which could initiate AD pathogenesis.


Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Hipocampo/patologia , Neuroglia/metabolismo , Neuroglia/patologia , Material Particulado/efeitos adversos , Poli(ADP-Ribose) Polimerases/metabolismo , Animais , Linhagem Celular Tumoral , Forma Celular , Sobrevivência Celular , Camundongos Transgênicos , Modelos Biológicos , Neuroglia/efeitos dos fármacos
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