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1.
J Mater Chem B ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32495805

RESUMO

Nanopore technology holds remarkable promise for sequencing proteins and peptides. To achieve this, it is necessary to establish a characteristic profile for each individual amino acid through the statistical description of its translocation process. However, the subtle molecular differences among all twenty amino acids along with their unpredictable conformational changes at the nanopore sensing region result in very low distinguishability. Here we report the electrical sensing of individual amino acids using an α-hemolysin nanopore based on a derivatization strategy. Using derivatized amino acids as detection surrogates not only prolongs their interactions with the sensing region, but also improves their conformational variation. Furthermore, we show that distinct characteristics including current blockades and dwell times can be observed among all three classes of amino acids after 2,3-naphthalenedicarboxaldehyde (NDA)- and 2-naphthylisothiocyanate (NITC)-derivatization, respectively. These observable characteristics were applied towards the identification and differentiation of 9 of the 20 natural amino acids using their NITC derivatives. The method demonstrated herein will pave the way for the identification of all amino acids and further protein and peptide sequencing.

2.
Phytomedicine ; 76: 153231, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32535481

RESUMO

RATIONALE AND OBJECTIVE: IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients. STUDY DESIGN: Randomized, non-inferiority, double-blind, double-dummy multicenter trial. SETTING AND PARTICIPANTS: This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m2) across China. INTERVENTIONS: The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks. OUTCOMES: The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment). RESULTS: Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m2; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m2 and 0.76 ml/min/1.73 m2 in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m2 (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851). LIMITATIONS: The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m2. The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation. CONCLUSION: AM can be recommended as a promising treatment for IgAN patients.

3.
Bioorg Med Chem ; 28(12): 115553, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32503690

RESUMO

Conflicts with the notion that specific substrate interactions were required in the control of reaction path in active transport systems, P-glycoprotein showed extraordinarily low specificity. Therefore, overexpression P-glycoprotein excluded a large number of anticancer agents from cancer cells, and multidrug resistance happened. Several kinds of bisbenzylisoqunoline alkaloids were reported to modulate P-glycoprotein function and reverse drug resistance. In order to provide more information for their structure activity relationship on P-glycoprotein function, the effects of tetrandrine, isotetrandrine, fangchinoline, berbamine, dauricine, cepharanthine and armepavine on the P-glycoprotein function were compared by using daunorubicin-resistant leukemia MOLT-4 cells in the present study. Among them, tetrandrine exhibited the strongest P-glycoprotein inhibitory effect, followed with fangchinoline and cepharanthine, and subsequently with berbamine or isotetrandrine. However, dauricine and armepavine showed little influence on the P-glycoprotein function. These data revealed that the 18-membered ring of the bisbenzylisoquinoline alkaloids maintained the P-glycoprotein inhibitory activity, suggesting that double isoquinoline units connected by two oxygen bridges were indispensable. Moreover, stereo-configuration of bisbenzylisoquinoline 3D structures determined their inhibitory activities, which provided a new viewpoint to recognize the specificity of binding pocket in P-glycoprotein. Our data also indicated that 3D chemical structure was more sensitive than 2D to predict the P-glycoprotein inhibitory-potencies of bisbenzylisoqunoline alkaloids.

4.
Eur J Pharmacol ; 881: 173232, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32525004

RESUMO

Glucocorticoids are used as anticancer and immunosuppressive agents, whereas glucocorticoid resistance has been observed in a significant fraction of patients due to overexpression of P-glycoprotein encoded by multi-drug resistance-1 gene. Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from traditional herb Fangji. According to our previous report, tetrandrine potentiated glucocorticoid pharmacodynamics partially via inhibiting P-glycoprotein function. In the present study, we investigated whether glucocorticoid receptor translocation was influenced indirectly by tetrandrine via P-glycoprotein inhibition, using human T lymphoblastoid leukemia MOLT-4 cell line with little P-glycoprotein expression and its multidrug resistant sub-line MOLT-4/DNR exhibiting a large amount of P-glycoprotein. Molecular mechanism investigation suggested that overexpressed P-glycoprotein weakened the glucocorticoid receptor translocation in MOLT-4/DNR cells comparing with the parent MOLT-4 cells. Our data also suggested that tetrandrine enhanced nuclear glucocorticoid receptor translocation in MOLT-4/DNR cells indirectly by dual influences on P-glycoprotein, inhibiting the efflux function and downregulating the protein expression. Therefore, tetrandrine potentiated the cytotoxic effect of methylprednisolone against MOLT-4/DNR cells with less effects on MOLT-4 cells. These effects of tetrandrine were suggested to be beneficial for the treatment of glucocorticoid resistant diseases induced by the overexpression of P-glycoprotein.

5.
ACS Sens ; 5(6): 1707-1716, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32403927

RESUMO

Nanopore technology has been employed as a powerful tool for DNA sequencing and analysis. To extend this method to peptide sequencing, a necessary step is to profile individual amino acids (AAs) through their nanopore stochastic signals, which remains a great challenge because of the low signal-to-noise ratio and unpredictable conformational changes of AAs during their translocation through nanopores. We showed that the combination of an N-terminal derivatization strategy of AAs with nanopore technology could lead to effective in situ differentiation of AAs. Four different derivatization reactions have been tested with five selected AAs: Ala, Phe, Tyr, His, and Asp. Using an α-hemolysin nanopore, we demonstrated the feasibility of derivatization-assisted identification of AAs regardless of their charge composition and polarity. The method was further applied to discriminate each individual AA in testing data sets using their established nanopore profiles from training data sets. We envision that this proof-of-concept study will not only pave a way for identification of individual AAs but also lead to future applications in protein/peptide sequencing using the nanopore technology.

6.
Neuroscience ; 437: 54-63, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32353459

RESUMO

A hallmark of the aging process is increased connectivity between networks and decreased connectivity within networks, which to some extent reflects the reorganization of the brain networks during normal aging. Considering the brain as a complex dynamic system, emerging evidence suggests the time-varying connectivity patterns to be more informative of brain functions. However, the age effect on the dynamic reconfiguration of intrinsic resting state networks is still elusive. By tracking the ongoing formation and dissipation of putative functional modules across time and space, we explored the age-related changes of segregation and integration and further elucidated the underlying brain network dynamics mechanism during normal aging. Results showed that aging strongly weakened dynamic global segregation while enhanced dynamic global integration across the whole brain. Aging was associated with decreasing dynamic segregation of most networks (except the cerebellum) while increasing dynamic integration of only a few networks at the large-scale network level. Notably, the fronto-parietal network, the default mode network, the visual network, and a small group of nodes from these networks, whose dynamic segregation and integration, were both modulated by age. These findings provide direct evidence that there are remarkable changes of dynamic network architecture across the human adult lifespan and suggest the age-related modulations of dynamic segregation and integration intuitively reflect the adaptive changes of the functional dedifferentiation and compensation in older adults.

7.
Int J Cardiol ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32349937

RESUMO

PURPOSE: Atherosclerosis is the leading cause of cardiovascular diseases (CVD) with high incidence rate and mortality rate. Long non-coding RNAs (lncRNAs) are important functional molecules in atherosclerosis. Present study aimed to explore the functional role and underlying mechanism of ZFAS1 in atherosclerosis. METHODS: The in-vitro cell model of atherosclerosis was established by using oxidized low-density lipoprotein (ox-LDL) to induce THP-1 macrophage-derived foam cells. qRT-PCR measured the mRNA levels of ZFAS1, miR-654-3p, ADAM10 and RAB22A. Western blot detected the protein levels of ADAM10 and RAB22A. The levels of IL-1ß, IL-6 and TNF-ɑ (inflammatory biomarkers) were tested with ELISA assay. Detection of cholesterol efflux rate was experimented. The interaction between RNAs was affirmed with luciferase reporter and RNA pull-down experiments. RESULTS: The expression of ZFAS1 was significantly up-regulated in in-vitro cell model of atherosclerosis at a dose- and time-dependent manner. Knockdown of ZFAS1 impaired inflammatory responses and promoted cholesterol efflux rate. Overexpression of ZFAS1 accelerated inflammatory responses and hampered cholesterol efflux rate. Then, the cytoplasmic role of ZFAS1 was revealed. By bio-informatics analysis and mechanism assays, miR-654-3p was identified to bind with ZFAS1. Moreover, ADAM10 and RAB22A were targeted and suppressed by miR-654-3p. ZFAS1 served as a ceRNA to positively regulate ADAM10 and RAB22A expression through endogenously sponging miR-654-3p. CONCLUSION: In conclusion, ZFAS1 elevated ADAM10/RAB22A expression to reduce cholesterol efflux rate and facilitate inflammatory responses in atherosclerosis at a miR-654-3p-dependent way, suggesting a prospective treatment method for amelioration of atherosclerosis.

8.
Clin Sci (Lond) ; 134(11): 1279-1293, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32463458

RESUMO

Long non-coding RNAs (lncRNAs) play important roles in hematological malignancies. We have previously identified several differentially expressed lncRNAs in myelodysplastic syndromes (MDS) by microarray analysis. In the present study, we explored the regulatory circuitry, potential functions, clinical and prognostic relevance of these lncRNAs in MDS by developing a lncRNA regulation network. We identified a novel lncRNA, LOC101928834, which was significantly up-regulated in the bone marrow of patients with MDS and acute myeloid leukemia (AML). We further evaluated the clinical relevance of LOC101928834 in 89 MDS and 110 AML patients and found that higher level of LOC101928834 expression was associated with higher white blood cell count, higher blast percentage, the subtype of refractory cytopenia with excess blasts (RAEB) and shorter overall survival in MDS patients. Receiver operating characteristic (ROC) curve analysis showed that LOC101928834 expression could discriminate MDS-RAEB patients from control with an area under the receiver-operating curve (AUC) of 0.9048. Moreover, functional analysis showed that LOC101928834 promoted cell proliferation and cell cycle progression, and activated Wnt/ß-catenin signaling pathway in vitro. In conclusion, LOC101928834 expression is correlated with clinical and biological features of MDS and may serve as a novel diagnostic and prognostic biomarker.

9.
J Food Sci ; 85(5): 1450-1461, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32249418

RESUMO

Bound phenolic compounds have rarely been reported in vegetable oils and this may be due to little research about the extraction. Deep eutectic solvents (DESs), recently applied in the extraction of phenolic compounds as alternatives to organic solvents, were adopted in the extraction of free and bound phenolic compounds from tea seed oil in this work. First, the phenolic compounds were analyzed by ultra-high-performance liquid chromatography with quadrupole-time-of-flight and triple-quadrupole tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) for characterization and UHPLC-QqQ-MS/MS for quantification and 25 phenolic compounds were found to exist in both free and bound forms. Then, DESs were screened for extraction of free and bound phenolic compounds from tea seed oil as the pretreatment for analysis and the results showed that hydrogen bond donors (HBDs) and temperature significantly affected the extraction efficiency of DESs. Finally, free phenolic compounds (83.91 µg/g) and bound phenolic compounds (25.71 µg/g), extracted by the DES with glycerol as HBD at 50 °C, were 51.0% and 93.2% higher than those extracted by methanol/water (60%, v/v), respectively. This work not only advanced the basic data of phenolic compounds in tea seed oil but also explored an efficient extraction method for scientific analysis of free and bound phenolic compounds.

10.
Chem Biol Drug Des ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32305047

RESUMO

The present study was undertaken to evaluate cytotoxic effects of vitamin K1 (phylloquinone), vitamin K2 (menaquinones) and vitamin K3 (menadione) against human T lymphoblastoid leukemia cells, Jurkat T cells, MOLT-4 cells, and P-glycoprotein-expressing multidrug-resistant MOLT-4/DNR cells. Vitamin K2 and K3, but not vitamin K1, reduced viabilities of Jurkat, MOLT-4 and MOLT-4/DNR cells. The influence potency of vitamin K3 was larger than that of vitamin K2 in all of the three cell lines. MOLT-4/DNR cells seemed to be more sensitive towards the effects of vitamin K2 and K3. The cytotoxicity of vitamin K2 and K3 on these leukemia cells seems to be related to apoptosis induction and cell cycle arrest. Vitamin K2 and K3 treatment induced cleavage of PARP obviously. Moreover, vitamin K2 and K3 specifically down-regulated the expressions of cyclin A2 in all of the three cell lines. However, the effects of vitamin K2 and K3 on the cell cycle profiling in Jurkat, MOLT-4 and MOLT-4/DNR cells varied with the cell-type. Vitamin K2 and K3 also decreased the viability of mitogen-activated human peripheral blood mononuclear cells. Our observations suggest that vitamin K2 and K3 have bilateral cytotoxic effects on activated human peripheral lymphocytes and the human leukemic T cells.

11.
Zhongguo Zhong Yao Za Zhi ; 45(3): 689-696, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237530

RESUMO

Indigenous knowledge and traditional culture for sustainable use of native plants in Juenang cultural region of Rangtang county, Aba Zang and Qiang Prefecture of Sichuan province, have been characterized in this paper followed the principles and methods of ethnobotany. The results indicate that 38 species from 27 families(including 6 species of fungi) are ethnobotanically used commonly in this area. Of 38 species of the native plants, 13 species from 12 families are collected for eatables and vegetables, 12 families and 16 species of indigenous plants for medicinal and edible use, 4 species from 4 families for decoration, 4 species from 4 families used for building materials or firewood, and 1 species from 1 families used for religious folklore. Under the influence of Juenang culture and Tibetan culture, indigenous knowledge such as instinctive reverence and gratitude for nature, protection ecological environment and habitats, and moderate use of natural resources(especially wild bioresource), have been gotten passed on from generation to generation in Juenang culture region of Rangtang county, which is of great significance to the protection of local bioresources and environment, including ethnic medicinal plants, and also to provide practical guidance for biodiversity conservation and ecological restoration in those alpine ecological vulnerable areas.


Assuntos
Etnobotânica , Fungos/classificação , Plantas Medicinais/classificação , Biodiversidade , China , Conservação dos Recursos Naturais , Humanos , Conhecimento , Fitoterapia
12.
Environ Sci Pollut Res Int ; 27(15): 17730-17737, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157538

RESUMO

Natural halloysite nanotubes (HNTs) with a hollow lumen have been widely applied in many fields, such as water purification, drug carriers, cosmetics, antibacterial, and scaffolds for tissue engineering. However, their in vivo toxicity is still largely unclear. The aim of this study is to evaluate sub-chronic oral toxicity of HNTs in the small intestine of mice. The results demonstrated that oral HNTs at low dose (5 mg/kg) for 30 days promoted mouse growth with no obvious adverse effect on the small intestine. The promotive effect on mouse growth disappeared after cessation of oral administration of HNTs. Oral HNTs at high dose (50 mg/kg) for 30 days induced aluminum (Al) and silicon (Si) accumulation and oxidative stress in the small intestine, which caused significant increases in the levels of cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) and inflammatory response and iNOS-mediated damages in the organ. Oral HNTs-induced changes in the small intestine at high dose were not observed after a 30-day recovery period. These findings provided the first evidence that oral HNTs-induced sub-chronic toxicity in the small intestine was reversible. The results suggest that HNTs at low concentration in environments have no adverse effect on mice, while there are health risks to mice under severe contamination by HNTs.

13.
J Affect Disord ; 265: 468-474, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090774

RESUMO

BACKGROUND: Higher neuroticism personality trait individuals have more negative mood states, more sensitive to negative information, and higher risk of mental illness. Good emotion regulation ability play an important role in healthy psychological, social and physical outcomes. Previous studies have suggested that higher neuroticism individuals have a diminished ability to regulate emotion regulation. Up to now, few studies investigate the neural basis between neuroticism and emotion regulation. METHOD: In present study, we want to explore the neuroticism and the activity of some brain regions and functional amygdala connectivity (psycho-physiological interaction [PPI]) in a cognitive reappraisal task. Thus, 160 healthy young participants were scanned during a cognitive reappraisal task. RESULTS: The results revealed that neuroticism scores showed a significant negative association with the activity of the dorsomedial prefrontal cortex (dmPFC), inferior frontal cortex and middle frontal cortex in regulation of negative emotion. PPI analyses revealed that neuroticism scores were negatively associated with amygdala-dmPFC connectivity in regulation of negative emotion. LIMITATION: Only cognitive reappraisal were investigated in this study. Other emotion regulation strategies such as expressive suppression need to be explored in the future study. CONCLUSION: These results may suggest that highly neurotic participants display diminished cognitive reappraisal and diminished control function of the dmPFC over the amygdala in regulation of negative emotion.

14.
Artigo em Chinês | MEDLINE | ID: mdl-32086925

RESUMO

Objective:The aim of this study is to evaluate the application of carbon nanoparticle lymphatic tracer in total thyroidectomy and bilateral Central District's thyroidectomy for papillary thyroid carcinoma. Method:Sixty-four patients with cN0 papillary thyroid carcinoma that primary treated were random divided into two groups: Trial group and control group. Carbon nanoparticles suspension was injected into the thyroid gland of trial group patients.After ten minutes, total thyroidectomy plus bilateral central neck dissection was performed in the all patients. The black stained tissue in the dissection specimen of trial group was separated. The control group underwent total thyroidectomy plus bilateral central neck dissection. Total lymph node and parathyroid gland in the black stained tissue,and non-black stained tissue in the central compartment dissection specimen of trial group and central compartment dissection specimen of control group were counted respectively.Total lymph node, the mis-cut parathyroid glands in the adipose tissue of central lymph node,post-operative blood calcium and parathyroid hormone(PTH)of two groups were contrasted and analyzed. Result:There are 235 lymph nodes in the black-stained tissue of central compartment dissection specimen of trial group.No parathyroid gland was found in the black-stained tissue.Five lymph nodes and 2 parathyroid glands were found in the non-black stained tissue of central compartment dissection specimen of trial group. There were 164 lymph nodes and 9 parathyroid glands in central compartment dissection specimen of control group. There is statistic difference between the number of lymph nodes in black stain tissue and that of control group(t=8.291, P=0.000).Rate of staining lymph node were 97.9 percent. No parathyroid glands were found in the black stained tissue. Nine mis-cut parathyroid glands(7.0%) were observed in the control group,while 2(1.6%) in the trial group(P<0.05).None permanent hypocalcemia and PTH decrease were observed in the two groups.There were 10 patients(31.3%) with temporary hypocalcemia and 9 patients(28.1%)with temporary PTH decrease respectively in the control group,and there was 1 patient(3.1%) and 1 patient(3.1%) respectively in the trial group(P<0.05). Conclusion:The effect of nano-carbon is ideal, and the parathyroid gland can not be stained black. It can distinguish the thyroid tissue from the surrounding lymphoid adipose tissue and clearly mark the Central District lymph nodes, reduce the risk of parathyroid gland injury during thyroid cancer. Neck dissection in the central region can improve the efficiency of lymph node dissection, protect the parathyroid gland and reduce the risk of postoperative complications.


Assuntos
Nanopartículas , Coloração e Rotulagem , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Carbono , Humanos , Excisão de Linfonodo , Linfonodos , Esvaziamento Cervical , Estudos Retrospectivos
16.
J Agric Food Chem ; 68(11): 3415-3424, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32078319

RESUMO

trans-Cinnamic acid (CA) is a precursor of many phenylpropanoid compounds, including catechins and aroma compounds, in tea (Camellia sinensis) leaves and is derived from l-phenylalanine (l-Phe) deamination. We have discovered an alternative CA formation pathway from l-Phe via phenylpyruvic acid (PPA) and phenyllactic acid (PAA) in tea leaves through stable isotope-labeled precursor tracing and enzyme reaction evidence. Both PPA reductase genes (CsPPARs) involved in the PPA-to-PAA pathway were isolated from tea leaves and functionally characterized in vitro and in vivo. CsPPAR1 and CsPPAR2 transformed PPA into PAA and were both localized in the leaf cell cytoplasm. Rosa hybrida flowers (economic crop flower), Lycopersicon esculentum Mill. fruits (economic crop fruit), and Arabidopsis thaliana leaves (leaf model plant) also contained this alternative CA formation pathway, suggesting that it occurred in most plants, regardless of different tissues and species. These results improve our understanding of CA biosynthesis in tea plants and other plants.

17.
Clin Chim Acta ; 505: 34-42, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32027887

RESUMO

Accurate estimation of glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Thus far, few studies in China have systematically assessed the differences among the various estimated GFR (eGFR) equations in large cohort. A total of 6287 CKD patients and 679 healthy individuals were enrolled. To estimate the GFR values in patients, MDRD, MDRD-China (MDRD-C), CKD-EPI, cystatin-C-China (CysC-C), cystatin-C-KDIGO (CysC-K), and creatinine-cystatin C-KDIGO (Cr-CysC) equations were used. The κ values between the MDRD, MDRD-C, Cr-CysC, CysC-K, and CysC-C equations and the CKD-EPI equation were 0.864, 0.914, 0.638, 0.487, and 0.388, respectively. For patients with lower-stage CKD, the GFR values from MDRD and MDRD-C equations were the highest compared with other equations, whereas the GFR values from CysC-C and CysC-K equations were the lowest. For patients with higher-stage CKD, the CKD-EPI, MDRD, MDRD-C, and Cr-CysC equations showed good consistencies among each other, whereas eGFR from CysC-C equation were higher and the CysC-C and CysC-K equations showed many obviously overestimated outliers. CKD-EPI and Cr-CysC equations were better correlated and consistent with each other in most of the CKD stages. The CKD-EPI and Cr-CysC equations may be more suitable for the comprehensive estimation of GFR in patients with CKD.


Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Estudos Transversais , Progressão da Doença , Humanos , Lactente , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Caracteres Sexuais , Adulto Jovem
18.
PLoS Comput Biol ; 16(2): e1007627, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32069272

RESUMO

In primary auditory cortex, slowly repeated acoustic events are represented temporally by the stimulus-locked activity of single neurons. Single-unit studies in awake marmosets (Callithrix jacchus) have shown that a sub-population of these neurons also monotonically increase or decrease their average discharge rate during stimulus presentation for higher repetition rates. Building on a computational single-neuron model that generates stimulus-locked responses with stimulus evoked excitation followed by strong inhibition, we find that stimulus-evoked short-term depression is sufficient to produce synchronized monotonic positive and negative responses to slowly repeated stimuli. By exploring model robustness and comparing it to other models for adaptation to such stimuli, we conclude that short-term depression best explains our observations in single-unit recordings in awake marmosets. Together, our results show how a simple biophysical mechanism in single neurons can generate complementary neural codes for acoustic stimuli.


Assuntos
Córtex Auditivo/fisiologia , Callithrix/fisiologia , Estimulação Acústica , Adaptação Fisiológica , Animais , Potenciais Evocados Auditivos/fisiologia
19.
J Am Coll Radiol ; 17(6): 796-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32068005

RESUMO

OBJECTIVES: Performance of recently developed deep learning models for image classification surpasses that of radiologists. However, there are questions about model performance consistency and generalization in unseen external data. The purpose of this study is to determine whether the high performance of deep learning on mammograms can be transferred to external data with a different data distribution. MATERIALS AND METHODS: Six deep learning models (three published models with high performance and three models designed by us) were evaluated on four different mammogram data sets, including three public (Digital Database for Screening Mammography, INbreast, and Mammographic Image Analysis Society) and one private data set (UKy). The models were trained and validated on either Digital Database for Screening Mammography alone or a combined data set that included Digital Database for Screening Mammography. The models were then tested on the three external data sets. The area under the receiver operating characteristic curve (auROC) was used to evaluate model performance. RESULTS: The three published models reported validation auROC scores between 0.88 and 0.95 on the validation data set. Our models achieved between 0.71 (95% confidence interval [CI]: 0.70-0.72) and 0.79 (95% CI: 0.78-0.80) auROC on the same validation data set. However, the same evaluation criteria of all six models on the three external test data sets were significantly decreased, only between 0.44 (95% CI: 0.43-0.45) and 0.65 (95% CI: 0.64-0.66). CONCLUSION: Our results demonstrate performance inconsistency across the data sets and models, indicating that the high performance of deep learning models on one data set cannot be readily transferred to unseen external data sets, and these models need further assessment and validation before being applied in clinical practice.

20.
J Clin Rheumatol ; 26(2): 54-59, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32073515

RESUMO

OBJECTIVE: The aim of this study was to assess the quality of global clinical practice guidelines (CPGs) on gout. METHODS: We systematically searched MEDLINE, CBM (Chinese Biomedical Literature database), GIN (Guidelines International Network), NICE (National Institute for Health and Clinical Excellence), NGC (National Guideline Clearinghouse), WHO (World Health Organization), SIGN (Scottish Intercollegiate Guidelines Network), DynaMed, UpToDate, and Best Practice databases from their inception until January 2017 to identify and select CPGs related to gout. Two reviewers independently assessed the eligible gout CPGs using the AGREE II instrument. RESULTS: We evaluated 15 CPGs published between 2007 and 2017, produced by 13 different developers. Quality of evidence and strength of recommendations were presented in 14 (93%) and 13 (87%) CPGs, respectively. The mean scores (±SD) for each AGREE II domain were as follows: (i) scope and purpose: 75% (±17%), (ii) stakeholder involvement: 39% (±19%), (iii) rigor of development: 43% (±17%), (iv) clarity and presentation: 82% (±14%), (v) applicability: 31% (±12%), and (vi) editorial independence: 23% (±29%). CONCLUSIONS: The quality of gout CPGs was suboptimal, and various incompatible grading systems of quality of evidence and strength of recommendations were used. The use of a standardized international grading system is essential to ensure high methodological quality of gout CPGs. Tools such as AGREE II could substantially improve the development and update of future gout CPGs.

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