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1.
ESMO Open ; 8(4): 101586, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37356359

RESUMO

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Carcinoma Pulmonar de Células não Pequenas , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Neoplasias Ovarianas , Neoplasias da Próstata , Masculino , Feminino , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Ovarianas/genética , Neoplasias da Mama/genética , Oncologia , Sequenciamento de Nucleotídeos em Larga Escala
2.
J Healthc Qual Res ; 38(4): 197-205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36581557

RESUMO

BACKGROUND: Total hip arthroplasty (THA) and hemiarthroplasty are common treatments for severe hip joint disease. To predict the probability of re-admission after discharge when patients are hospitalized will support providing appropriate health education and guidance. METHODS: The research aims to use logistic regression (LR), decision trees (DT), random forests (RF), and artificial neural networks (ANN) to establish predictive models and compare their performances on re-admissions within 30 days after THA or hemiarthroplasty. The data of this study includes patient demographics, physiological measurements, disease history, and clinical laboratory test results. RESULTS: There were 508 and 309 patients in the THA and hemiarthroplasty studies respectively from September 2016 to December 2018. The accuracies of the four models LR, DT, RF, and ANN in the THA experiment are 94.3%, 93.2%, 97.3%, and 93.9%, respectively. In the hemiarthroplasty experiment, the accuracies of the four models are 92.4%, 86.1%, 94.2%, and 94.8%, respectively. Among these, we found that the RF model has the best sensitivity and ANN model has the best area under the receiver operating characteristic (AUROC) score in both experiments. CONCLUSIONS: The THA experiment confirmed that the performance of the RF model is better than the other models. The key factors affecting the prognosis after THA surgery are creatinine, sodium, anesthesia duration, and dialysis. In the hemiarthroplasty experiment, the ANN model showed more accurate results. Poor kidney function increases the risk of hospital re-admission. This research highlights that RF and ANN model perform well on the hip replacement surgery outcome prediction.


Assuntos
Artroplastia de Quadril , Hemiartroplastia , Humanos , Artroplastia de Quadril/métodos , Hemiartroplastia/métodos , Readmissão do Paciente , Hospitais , Aprendizado de Máquina
3.
Geophys Res Lett ; 49(20): e2022GL098274, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36582354

RESUMO

There is a lack of satellite-based aerosol retrievals in the vicinity of low-topped clouds, mainly because reflectance from aerosols is overwhelmed by three-dimensional cloud radiative effects. To account for cloud radiative effects on reflectance observations, we develop a Convolutional Neural Network and retrieve aerosol optical depth (AOD) with 100-500 m horizontal resolution for all cloud-free regions regardless of their distances to clouds. The retrieval uncertainty is 0.01 + 5%AOD, and the mean bias is approximately -2%. In an application to satellite observations, aerosol hygroscopic growth due to humidification near clouds enhances AOD by 100% in regions within 1 km of cloud edges. The humidification effect leads to an overall 55% increase in the clear-sky aerosol direct radiative effect. Although this increase is based on a case study, it highlights the importance of aerosol retrievals in near-cloud regions, and the need to incorporate the humidification effect in radiative forcing estimates.

4.
Hong Kong Med J ; 28(1): 4-5, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35249889
5.
Gait Posture ; 92: 191-198, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864484

RESUMO

RESEARCH QUESTION: What is the intra- and inter-assessor error of the Oxford Foot Model (OFM) during healthy adult walking when applied by three assessors with different professional backgrounds and lower limb marker placement experience, not native to the originators of the model and with no prior clinical experience of the model? BACKGROUND: No previous OFM studies have examined the repeatability of more than two assessors with different backgrounds, and many of the studies have been conducted by the model originators METHODS: The OFM was applied to ten healthy adults on three separate occasions by three different assessors with varied professional experience and no prior involvement with the OFM (other than local training). Participants walked at self-selected speeds and intra/inter assessor error was calculated using the SEM + 95% upper confidence limit. RESULTS: Inter-assessor errors ranged from 2.2° to 5.5° whereas intra-assessor errors fell between 1.8° and 5.5°. The error difference between assessors over the same joint angle varied from 0.4° (hindfoot/tibia dorsiflexion) to 1.5° (hindfoot/tibia inversion). The percentage of error to total range of motion varied from 11% (hindfoot/tibia dorsiflexion) to 126% (forefoot/hindfoot adduction). SIGNIFICANCE: Based on commonly used recommendations, the OFM is a largely repeatable tool for measuring foot kinematics during healthy adult walking when applied by assessors with no prior OFM experience, varied experience and not native to the model originators. Intra-assessor error was lower for assessors with prior anatomical knowledge and significant lower limb marker placement experience. The proportion of inter-assessor error to movement exceeded 50% of the total range of motion for four movements, notably forefoot/hindfoot adduction (126%). As such, this movement cannot be recommended as an outcome measure. Inter- and intra-assessor error, specific to each laboratory, should be considered, along with the proportion of error to range of motion when interpreting patient data.


Assuntos
, Marcha , Adulto , Fenômenos Biomecânicos , Humanos , Amplitude de Movimento Articular , Caminhada
6.
Geophys Res Lett ; 48(2): e2020GL091236, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33678926

RESUMO

We introduce new parameterizations for autoconversion and accretion rates that greatly improve representation of the growth processes of warm rain. The new parameterizations capitalize on machine-learning and optimization techniques and are constrained by in situ cloud probe measurements from the recent Atmospheric Radiation Measurement Program field campaign at Azores. The uncertainty in the new estimates of autoconversion and accretion rates is about 15% and 5%, respectively, outperforming existing parameterizations. Our results confirm that cloud and drizzle water content are the most important factors for determining accretion rates. However, for autoconversion, in addition to cloud water content and droplet number concentration, we discovered a key role of drizzle number concentration that is missing in current parameterizations. The robust relation between autoconversion rate and drizzle number concentration is surprising but real, and furthermore supported by theory. Thus, drizzle number concentration should be considered in parameterizations for improved representation of the autoconversion process.

7.
J Pediatr Hematol Oncol ; 42(7): e696-e697, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31415279

RESUMO

Glucose phosphate isomerase (GPI) deficiency is the second most common red blood cell enzymopathy involving the glycolysis pathway. It is an autosomal recessive disorder. Chronic hemolytic anemia is a common manifestation. The most severe one can present as hydrops fetalis. It can also be associated with neurologic dysfunction. We report a girl with severe hemolytic anemia at birth because of GPI deficiency. Enzyme activity assays were inconclusive because of previous blood transfusions. She was found to be compound heterozygous for 2 novel missense mutations, c.490C>A p.(Pro164Thr) and c.817C>T p.(Arg273Cys), in the GPI gene. Other than the chronic hemolytic anemia, she also has mild fine motor, gross motor delay, and developed cerebella ataxia since 5 years old.


Assuntos
Anemia Hemolítica Congênita/etiologia , Anemia Hemolítica Congênita/patologia , Glucose-6-Fosfato Isomerase/genética , Mutação de Sentido Incorreto , Citocinas/genética , Feminino , Humanos , Recém-Nascido , Prognóstico
8.
Ultrasound Obstet Gynecol ; 53(4): 512-519, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30043402

RESUMO

OBJECTIVES: Global and regional myocardial deformation have not been well described in fetuses with pulmonary atresia and intact ventricular septum (PA/IVS). Speckle-tracking echocardiography (STE), an angle-independent technique for assessing global and regional strain, may be a more sensitive way of determining ventricular systolic dysfunction compared with traditional 2D echocardiography. The aim of this study was to assess myocardial deformation in fetuses with PA/IVS compared with control fetuses and to determine if, in fetuses with PA/IVS, strain differs between those with and those without right ventricle-dependent coronary circulation (RVDCC). METHODS: This was a retrospective analysis of fetuses with PA/IVS examined at two medical centers between June 2005 and October 2017. Left ventricular (LV) and right ventricular (RV) regional and global longitudinal strain (GLS) and strain rate were obtained using STE, and comparisons were made between fetuses with PA/IVS and gestational age (GA)-matched controls. Postnatal outcome was assessed, including the presence of RVDCC. RESULTS: Fifty-seven fetuses with PA/IVS and 57 controls were analyzed at a mean GA of 26.5 ± 5 weeks. LV-GLS was significantly decreased in fetuses with PA/IVS compared with controls (-17.4 ± 1.7% vs -23.7 ± 2.0%, P < 0.001). LV strain rate was also significantly decreased (-1.01 ± 0.21/s vs -1.42 ± 0.20/s, P < 0.001). Fetuses with PA/IVS had decreased strain in all segments. Similarly, RV strain was significantly decreased in fetuses with PA/IVS (-11.6 ± 3.8% vs -24.6 ± 2.5%, P < 0.0001). Thirty-six patients had postnatal cardiac catheterization performed to define coronary anatomy; 10 fetuses had RVDCC. Fetuses with RVDCC had decreased LV strain compared with those without (-15.8 ± 1.2% vs -17.9 ± 1.7%, P = 0.009). RV strain was also decreased in fetuses with RVDCC vs those without (-7.0 ± 2.9% vs -12.1 ± 3.2%, P = 0.0004). CONCLUSIONS: Fetuses with PA/IVS have decreased global and regional LV and RV strain compared with controls. The finding of decreased LV strain may be due to altered ventricular mechanics in the context of a hypertensive right ventricle and/or abnormal coronary perfusion. Moreover, fetuses that were found to have RVDCC postnatally had decreased LV and RV strain compared with those that did not. These results encourage further investigation to assess whether fetal ventricular strain could be a prenatal predictor of RVDCC. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Anomalias dos Vasos Coronários/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Atresia Pulmonar/diagnóstico por imagem , Estudos de Casos e Controles , Anomalias dos Vasos Coronários/complicações , Ecocardiografia , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Humanos , Atresia Pulmonar/mortalidade , Atresia Pulmonar/fisiopatologia , Estudos Retrospectivos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem
9.
J Thromb Haemost ; 16(11): 2322-2335, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30207066

RESUMO

Essentials Nitric oxide synthesis controls protein disulfide isomerase (PDI) function. Nitric oxide (NO) modulation of PDI controls endothelial thrombogenicity. S-nitrosylated PDI inhibits platelet function and thrombosis. Nitric oxide maintains vascular quiescence in part through inhibition of PDI. SUMMARY: Background Protein disulfide isomerase (PDI) plays an essential role in thrombus formation, and PDI inhibition is being evaluated clinically as a novel anticoagulant strategy. However, little is known about the regulation of PDI in the vasculature. Thiols within the catalytic motif of PDI are essential for its role in thrombosis. These same thiols bind nitric oxide (NO), which is a potent regulator of vessel function. To determine whether regulation of PDI represents a mechanism by which NO controls vascular quiescence, we evaluated the effect of NO on PDI function in endothelial cells and platelets, and thrombus formation in vivo. Aim To assess the effect of S-nitrosylation on the regulation of PDI and other thiol isomerases in the vasculature. Methods and results The role of endogenous NO in PDI activity was evaluated by incubating endothelium with an NO scavenger, which resulted in exposure of free thiols, increased thiol isomerase activity, and enhanced thrombin generation on the cell membrane. Conversely, exposure of endothelium to NO+ carriers or elevation of endogenous NO levels by induction of NO synthesis resulted in S-nitrosylation of PDI and decreased surface thiol reductase activity. S-nitrosylation of platelet PDI inhibited its reductase activity, and S-nitrosylated PDI interfered with platelet aggregation, α-granule release, and thrombin generation on platelets. S-nitrosylated PDI also blocked laser-induced thrombus formation when infused into mice. S-nitrosylated ERp5 and ERp57 were found to have similar inhibitory activity. Conclusions These studies identify NO as a critical regulator of vascular PDI, and show that regulation of PDI function is an important mechanism by which NO maintains vascular quiescence.


Assuntos
Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Trombose/metabolismo , Músculos Abdominais/metabolismo , Animais , Plaquetas/citologia , Plaquetas/metabolismo , Membrana Celular/metabolismo , Fator Xa/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Selectina-P/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Proteínas Recombinantes/metabolismo , Compostos de Sulfidrila/metabolismo , Trombina/metabolismo
10.
Rev Geophys ; 56(2): 409-453, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30148283

RESUMO

The cloud droplet number concentration (N d) is of central interest to improve the understanding of cloud physics and for quantifying the effective radiative forcing by aerosol-cloud interactions. Current standard satellite retrievals do not operationally provide N d, but it can be inferred from retrievals of cloud optical depth (τ c) cloud droplet effective radius (r e) and cloud top temperature. This review summarizes issues with this approach and quantifies uncertainties. A total relative uncertainty of 78% is inferred for pixel-level retrievals for relatively homogeneous, optically thick and unobscured stratiform clouds with favorable viewing geometry. The uncertainty is even greater if these conditions are not met. For averages over 1° ×1° regions the uncertainty is reduced to 54% assuming random errors for instrument uncertainties. In contrast, the few evaluation studies against reference in situ observations suggest much better accuracy with little variability in the bias. More such studies are required for a better error characterization. N d uncertainty is dominated by errors in r e, and therefore, improvements in r e retrievals would greatly improve the quality of the N d retrievals. Recommendations are made for how this might be achieved. Some existing N d data sets are compared and discussed, and best practices for the use of N d data from current passive instruments (e.g., filtering criteria) are recommended. Emerging alternative N d estimates are also considered. First, new ideas to use additional information from existing and upcoming spaceborne instruments are discussed, and second, approaches using high-quality ground-based observations are examined.

11.
Neurobiol Dis ; 113: 11-22, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29367010

RESUMO

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood. Previously we have shown that FXS results in learning impairments that involve deficits in N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity in the hippocampal dentate gyrus (DG). Here we tested whether chronic treatment with minocycline can improve these deficits by enhancing NMDA receptor-dependent functional and structural plasticity in the DG. Minocycline treatment resulted in a significant enhancement in NMDA receptor function in the dentate granule cells. This was accompanied by an increase in PSD-95 and GluN2A and GluN2B subunits in hippocampal synaptoneurosome fractions. Minocycline treatment also enhanced dentate granule cell dendritic length and branching. In addition, our results show that chronic minocycline treatment can rescue performance in novel object recognition in FXS mice. These findings indicate that minocycline treatment has both structural and functional benefits for hippocampal cells, which may partly contribute to the pro-cognitive effects minocycline appears to have for treating FXS.


Assuntos
Proteína do X Frágil da Deficiência Intelectual/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Minociclina/administração & dosagem , Neurônios/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Esquema de Medicação , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/patologia , Técnicas de Cultura de Órgãos , Resultado do Tratamento
12.
Neurobiol Dis ; 96: 261-270, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27659109

RESUMO

Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmr1 knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmr1 gene (Fmr1+/-) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1+/- mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1+/- mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments.


Assuntos
Giro Denteado/patologia , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/patologia , Plasticidade Neuronal/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/genética , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Síndrome do Cromossomo X Frágil/genética , Genótipo , Glicina/uso terapêutico , Elevação dos Membros Posteriores , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Natação/psicologia , Valina/análogos & derivados , Valina/farmacologia , Valina/uso terapêutico
13.
Postgrad Med J ; 92(1085): 123-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26917775
14.
Parasit Vectors ; 9: 109, 2016 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-26920563

RESUMO

BACKGROUND: There is growing evidence that the widespread use of Long-Lasting Insecticidal Nets (LLINs) is prompting malaria vectors to shift their biting towards times and places where people are not protected, such as earlier in the evening and/or outdoors. It is uncertain whether these behavioural shifts are due to phenotypic plasticity and/or ecological changes within vector communities that favour more exophilic species, or involve genetic factors within vector species to limit their contact with LLINs. Possibly variation in the time and location of mosquito biting has a genetic basis, but as yet this phenomenon has received little investigation. Here we used a candidate gene approach to investigate whether polymorphisms in selected circadian clock genes could explain variation in the time and location of feeding (indoors versus outside) within a natural population of the major African malaria vector Anopheles arabiensis. METHODS: Host-seeking An. arabiensis were collected from two villages (Lupiro and Sagamaganga) in Tanzania by Human Landing Catch (HLC) technique. Mosquitoes were classified into phenotypes of "early" (7 pm-10 pm) or "late" biting (4 am -7 am), and host-seeking indoors or outdoors. In these samples we genotyped 34 coding SNPs in 8 clock genes (PER, TIM, CLK, CYC, PDP1, VRI, CRY1, and CRY2), and tested for associations between these SNPs and biting phenotypes. SNPs in 8 mitochondrial genes (ATP6, ATP8, COX1, COX2, COX3, ND3, ND5 and CYTB) were also genotyped to test population subdivision within An. arabiensis. RESULTS: The candidate clock genes exhibited polymorphism within An. arabiensis, but it was unrelated to variation in the timing and location of their biting activity. However, there was evidence of strong genetic structure within An. arabiensis populations in association with the TIM, which was unrelated to geographic distance. Substructure within An. arabiensis was also detected using mitochondrial markers. CONCLUSIONS: The variable timing and location of biting in An. arabiensis could not be linked to candidate clock genes that are known to influence behaviour in other Diptera. This finding does not rule out the possibility of a genetic basis to biting behaviour in this malaria vector, but suggests these are complex phenotypes that require more intensive ecological, neuronal and genomic analyses to understand.


Assuntos
Anopheles/genética , Anopheles/fisiologia , Relógios Circadianos/genética , Comportamento Alimentar , Insetos Vetores , Polimorfismo de Nucleotídeo Único , Animais , Genótipo , Técnicas de Genotipagem , Humanos , Tanzânia , Fatores de Tempo
15.
Cell Death Dis ; 6: e1827, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26181207

RESUMO

Disturbed cell autophagy is found in various cardiovascular disease conditions. Biomechanical stimuli induced by laminar blood flow have important protective actions against the development of various vascular diseases. However, the impacts and underlying mechanisms of shear stress on the autophagic process in vascular endothelial cells (ECs) are not entirely understood. Here we investigated the impacts of shear stress on autophagy in human vascular ECs. We found that shear stress induced by laminar flow, but not that by oscillatory or low-magnitude flow, promoted autophagy. Time-course analysis and flow cessation experiments confirmed that this effect was not a transient adaptive stress response but appeared to be a sustained physiological action. Flow had no effect on the mammalian target of rapamycin-ULK pathway, whereas it significantly upregulated Sirt1 expression. Inhibition of Sirt1 blunted shear stress-induced autophagy. Overexpression of wild-type Sirt1, but not the deacetylase-dead mutant, was sufficient to induce autophagy in ECs. Using both of gain- and loss-of-function experiments, we showed that Sirt1-dependent activation of FoxO1 was critical in mediating shear stress-induced autophagy. Shear stress also induced deacetylation of Atg5 and Atg7. Moreover, shear stress-induced Sirt1 expression and autophagy were redox dependent, whereas Sirt1 might act as a redox-sensitive transducer mediating reactive oxygen species-elicited autophagy. Functionally, we demonstrated that flow-conditioned cells are more resistant to oxidant-induced cell injury, and this cytoprotective effect was abolished after inhibition of autophagy. In summary, these results suggest that Sirt1-mediated autophagy in ECs may be a novel mechanism by which laminar flow produces its vascular-protective actions.


Assuntos
Autofagia/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Mecanotransdução Celular/genética , Sirtuína 1/genética , Proteína 5 Relacionada à Autofagia , Proteína 7 Relacionada à Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Linhagem Celular Transformada , Cultura em Câmaras de Difusão , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Hemorreologia , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Luciferases/genética , Luciferases/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação , Oxirredução , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Estresse Mecânico , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo
16.
Bull Entomol Res ; 105(3): 364-72, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25804294

RESUMO

Drosophila suzukii (Spotted Wing Drosophila) has recently become a serious invasive pest of fruit crops in the USA, Canada, and Europe, leading to substantial economic losses. D. suzukii is a direct pest, ovipositing directly into ripe or ripening fruits; in contrast, other Drosophilids utilize decaying or blemished fruits and are nuisance pests at worst. Immature stages of D. suzukii are difficult to differentiate from other Drosophilids, posing problems for research and for meeting quarantine restrictions designed to prevent the spread of this pest in fruit exports. Here we used a combined phylogenetic and bioinformatic approach to discover genetic markers suitable for a species diagnostic protocol of this agricultural pest. We describe a molecular diagnostic for rapid identification of single D. suzukii larva using multiplex polymerase chain reaction. Our molecular diagnostic was validated using nine different species of Drosophila for specificity and 19 populations of D. suzukii from different geographical regions to ensure utility within species.


Assuntos
Drosophila/genética , Marcadores Genéticos/genética , Genômica/métodos , Controle de Insetos/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Filogenia , Animais , Biologia Computacional/métodos , Sequência Conservada/genética , Primers do DNA/genética , Geografia , Sensibilidade e Especificidade , Especificidade da Espécie
17.
Indian J Cancer ; 52(3): 398-401, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26905151

RESUMO

PURPOSE: This study aimed to evaluate the salivary gland function changes by sialoscintigraphy in locally advanced nasopharyngeal cancer (NPC) after intensity modulated radiotherapy (IMRT). MATERIALS AND METHODS: Salivary function was assessed by sialoscintigraphy. Quantitative sialoscintigraphy was performed in 24 NPC patients prior to and after IMRT. Results were categorized in four groups according to the duration of treatment. The sialoscintigraphy parameters were examined. RESULTS: Sialoscintigraphy showed a significant difference in the secretion of each interval groups. The parameters of scintigraphy, except maximum accumulation (MA) of submandibular glands, decreased first after radiotherapy, and then recovered. However, the MA of submandibular glands was continuously downhill after radiation. CONCLUSIONS: The sialoscintigraphy parameters of each gland changed with the different radiation dose and follow-up intervals. The salivary function was influenced after radiotherapy in locally advanced NPC, especially, in the submandibular gland. Strategies to improve the salivary function should be assessed.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Glândulas Salivares/diagnóstico por imagem , Adulto , Idoso , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
18.
Mar Pollut Bull ; 85(2): 418-24, 2014 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-24855975

RESUMO

Biofilms on submerged surfaces are important in determining larval settlement of most marine benthic invertebrates. We investigated if exposure of biofilms to hypoxia would alter the larval settlement pattern and result in a shift in benthic invertebrate community structure in the field. Biofilms were first exposed to hypoxia or normoxia in laboratory microcosms for 7 days, and then deployed in the field for another 7 days to allow for larval settlement and recruitment to occur. Using terminal-restriction fragment length polymorphism of the 16S rRNA gene, this study showed that hypoxia altered the biofilm bacterial community composition, and the difference between the hypoxic and normoxic treatments increased with the time of exposure period. This study also demonstrated significantly different benthic invertebrate community structures as a result of biofilm exposure to hypoxia and that the hypoxic and normoxic treatments were dominated by Hydroides sp. and Folliculina sp., respectively.


Assuntos
Biofilmes/crescimento & desenvolvimento , Invertebrados/fisiologia , Oxigênio/análise , Água do Mar/química , Anaerobiose , Animais , Invertebrados/metabolismo , Larva/metabolismo , Larva/fisiologia , Análise Multivariada , Oxigênio/metabolismo , Poliquetos/efeitos dos fármacos , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética
19.
Mar Pollut Bull ; 85(2): 439-45, 2014 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-24661460

RESUMO

Hypoxia likely compromises the reproductive success of those marine organisms carrying out external fertilization because their gametes and embryos are inevitably exposed to the external environment. Hydroides elegans, a dominant serpulid polychaete in Hong Kong waters, can spawn throughout the year but the number of recruits drops during summer when hypoxia commonly occurs. This study attempted to explain such observation by investigating the gamete quality, including sperm motility, egg size, complexity and viability, after 1-h hypoxic exposure (1 mg O2 l(-1)). In addition, how gamete quality affects fertilization success and embryonic development was examined. After 1-h hypoxic exposure, sperm motility was significantly reduced, compromising fertilization success. Although the eggs remained viable, more malformed embryos and retarded embryonic development were observed. We interpreted that the harmful effect of hypoxia on embryonic development was attributed to the teratogenicity and induced oxidative stress, ultimately causing the reduction in recruitment during summer.


Assuntos
Desenvolvimento Embrionário , Fertilização , Poliquetos/fisiologia , Água do Mar/química , Anaerobiose , Animais , Embrião não Mamífero , Feminino , Células Germinativas/fisiologia , Hong Kong , Masculino , Óvulo/fisiologia , Poliquetos/embriologia , Reprodução/fisiologia , Motilidade dos Espermatozoides
20.
Mar Pollut Bull ; 76(1-2): 291-7, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24050126

RESUMO

Hydroides elegans, a worldwide fouling polychaete, can spawn throughout the year, but its recruitment drops during summer when hypoxia prevails. Here, the influence of hypoxia on larval development and settlement of H. elegans was investigated. Results showed that larval development was compromised at 1mg O2 l(-1) with a lower proportion of competent larvae and a higher proportion of malformed larvae, probably due to reduction in clearance rate. Regarding larval settlement, although most of the larvae were reluctant to settle at 1mg O2 l(-1), regardless of the biofilm nature, they settled quickly within 24h in response to the resumption of dissolved oxygen. Furthermore, only about 5% of the larvae settled on the biofilms developed under hypoxia, regardless of dissolved oxygen levels of the seawater. The delayed larval development and potential alteration of biofilm nature owing to hypoxia explained why the recruitment of H. elegans declines during summer.


Assuntos
Biofilmes/crescimento & desenvolvimento , Eutrofização , Larva/fisiologia , Poliquetos/fisiologia , Água do Mar/química , Animais , Poluição da Água
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