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1.
Eur Rev Med Pharmacol Sci ; 28(5): 2068-2083, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497888

RESUMO

OBJECTIVE: Methyl-2-(4-chloro- phenyl)-5-benzoxazoleacetate (MCBA), a synthetic benzoxazole derivative with established antipsoriatic efficacy, was investigated for potential antinociceptive effects. This study employs various nociceptive assays in mice to elucidate MCBA's antinociceptive mechanisms. MATERIALS AND METHODS: MCBA's antinociceptive potential was tested against various nociception models induced by formalin, glutamate, capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator. It was then assessed using the hot plate test and examined within the acetic acid-induced writhing test. During the acetic acid-induced writhing test, MCBA was pre-challenged against selective receptor antagonists such as naloxone, caffeine, atropine, yohimbine, ondansetron, and haloperidol. It was also pre-challenged with ATP-sensitive potassium channel inhibitor (glibenclamide) to further elucidate its antinociceptive mechanism. RESULTS: The results showed that oral administration of MCBA led to a dose-dependent and significant inhibition (p < 0.05) of nociceptive effects across all evaluated models at doses of 60, 120, and 240 mg/kg. Moreover, the efficacy of MCBA's antinociceptive potential was significantly counteracted (p < 0.0001) by specific antagonists: (i) directed at adenosinergic, alpha-2 adrenergic, and cholinergic receptors using caffeine, yohimbine, and atropine, respectively; and (ii) targeting ATP-sensitive potassium channels, employing glibenclamide. Antagonists aimed at opioidergic and serotoninergic receptors (naloxone and ondansetron, respectively) had poor utility in inhibiting antinociceptive activity. Conversely, the dopaminergic receptor antagonist haloperidol potentiated locomotor abnormalities associated with MCBA treatment. CONCLUSIONS: MCBA-induced antinociception involves modulation of glutamatergic-, TRVP1 receptors- and PKC-signaling pathways. It impacts adenosinergic, alpha-2 adrenergic, and cholinergic receptors and opens ATP-sensitive potassium channels.


Assuntos
Cafeína , Glibureto , Animais , Camundongos , Haloperidol , Nociceptividade , Ondansetron , Adrenérgicos , Atropina , Canais KATP , Naloxona/farmacologia , Receptores Colinérgicos , Ioimbina , Analgésicos/farmacologia , Acetatos
2.
ACS Synth Biol ; 13(1): 15-24, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38163256

RESUMO

With the decline of cultivated land and increase of the population in recent years, an agricultural revolution is urgently needed to produce more food to improve the living standards of humans. As one of the foundations of synthetic biology, artificial chromosomes hold great potential for advancing crop improvement. They offer opportunities to increase crop yield and quality, while enhancing crop resistance to disease. The progress made in plant artificial chromosome technology enables selective modification of existing chromosomes or the synthesis of new ones to improve crops and study gene function. However, current artificial chromosome technologies still face limitations, particularly in the synthesis of repeat sequences and the transformation of large DNA fragments. In this review, we will introduce the structure of plant centromeres, the construction of plant artificial chromosomes, and possible methods for transforming large fragments into plant cells.


Assuntos
Cromossomos Artificiais , Telômero , Humanos , Cromossomos Artificiais/genética , Centrômero/genética , Cromossomos de Plantas , Produtos Agrícolas/genética
4.
Front Vet Sci ; 9: 871038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774982

RESUMO

Fowl adenovirus serotype 4 (FAdV-4) is a highly pathogenic virus with a broad host range that causes huge economic losses for the poultry industry worldwide. RNA sequencing has provided valuable and important mechanistic clues regarding FAdV-4-host interactions. However, the pathogenic mechanism and host's responses after FAdV-4 infection remains limited. In this study, we used transcriptome analysis to identify dynamic changes in differentially expressed genes (DEGs) at five characteristic stages (12, 24, 36, 48, and 60 h) post infection (hpi) with FAdV-4. A total of 8,242 DEGs were identified based on comparison of five infection stages: 0 and 12, 12 and 24, 24 and 36, 36 and 48, and 48 and 60 hpi. In addition, at these five important time points, we found 37 common upregulated or downregulated DEGs, suggesting a common role for these genes in host response to viral infection. The predicted function of these DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these DEGs were associated with viral invasion, host metabolic pathways and host immunosuppression. Interestingly, genes involved in viral invasion, probably EGR1, SOCS3, and THBS1, were related to FAdV-4 infection. Validation of nine randomly selected DEGs using quantitative reverse-transcription PCR produced results that were highly consistent with those of RNA sequencing. This transcriptomic profiling provides valuable information for investigating the molecular mechanisms underlying host-FAdV-4 interactions. These data support the current molecular knowledge regarding FAdV-4 infection and chicken defense mechanisms.

5.
Sensors (Basel) ; 23(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36617031

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for accurate early diagnosis and monitoring. A label-free rapid electrochemical point-of-care (POC) biosensor for SARS-CoV-2 detection in human saliva is reported here to help address the shortcomings of traditional nucleic acid amplification methods and give a quantitative assessment of the viral load to track infection status anywhere, using disposable electrochemical sensor chips. A new chemical construct of gold nanoparticles (GNp) and thionine (Th) are immobilized on carboxylic acid functionalized carbon nanotubes (SWCNT-COOH) for high-performance biosensing. The sensor uses saliva with a one-step pretreatment and simple testing procedure as an analytical medium due to the user-friendly and non-invasive nature of its procurement from patients. The sensor has a response time of 5 min with a limit of detection (LOD) reaching 200 and 500 pM for the freely suspended spike (S) protein in phosphate buffer saline (PBS) and human saliva, respectively. The sensor's performance was also proven for detecting a COVID-19 pseudovirus in an electrolyte solution with a LOD of 106 copies/mL. The results demonstrate that the optimized POC sensor developed in this work is a promising device for the label-free electrochemical biosensing detection of SARS-CoV-2 and different species of viruses.


Assuntos
Técnicas Biossensoriais , COVID-19 , Nanopartículas Metálicas , Nanotubos de Carbono , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Ouro , Sistemas Automatizados de Assistência Junto ao Leito
6.
J Vis Exp ; (176)2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34661582

RESUMO

In cardiac muscle, intracellular Ca2+ transients activate contractile myofilaments, causing contraction, macroscopic shortening, and geometric deformation. Our understanding of the internal relationships between these events has been limited because we can neither 'see' inside the muscle nor precisely track the spatio-temporal nature of excitation-contraction dynamics. To resolve these problems, we have constructed a device that combines a suite of imaging modalities. Specifically, it integrates a brightfield microscope to measure local changes of sarcomere length and tissue strain, a fluorescence microscope to visualize the Ca2+ transient, and an optical coherence tomograph to capture the tissue's geometric changes throughout the time-course of a cardiac cycle. We present here the imaging infrastructure and associated data collection framework. Data are collected from isolated rod-like tissue structures known as trabeculae carneae. In our instrument, a pair of position-controlled platinum hooks hold each end of an ex vivo muscle sample while it is continuously superfused with nutrient-rich saline solution. The hooks are under independent control, permitting real-time control of muscle length and force. Lengthwise translation enables the piecewise scanning of the sample, overcoming limitations associated with the relative size of the microscope imaging window (540 µm by 540 µm) and the length of a typical trabecula (>2000 µm). Platinum electrodes at either end of the muscle chamber stimulate the trabecula at a user-defined rate. We exploit the stimulation signal as a trigger for synchronizing the data from each imaging window to reconstruct the entire sample twitching under steady-state conditions. Applying image-processing techniques to these brightfield imaging data provides tissue displacement and sarcomere length maps. Such a collection of data, when incorporated into an experiment-modeling pipeline, will provide a deeper understanding of muscle contractile homogeneity and heterogeneity in physiology and pathophysiology.


Assuntos
Cálcio , Contração Miocárdica , Coração , Miofibrilas , Sarcômeros
7.
Chem Sci ; 12(19): 6737-6746, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-34040750

RESUMO

Hybrid materials comprised of inorganic quantum dots functionalized with small-molecule organic chromophores have emerged as promising materials for reshaping light's energy content. Quantum dots in these structures can serve as light harvesting antennas that absorb photons and pass their energy to molecules bound to their surface in the form of spin-triplet excitons. Energy passed in this manner can fuel upconversion schemes that use triplet fusion to convert infrared light into visible emission. Likewise, triplet excitons passed in the opposite direction, from molecules to quantum dots, can enable solar cells that use singlet fission to circumvent the Shockley-Queisser limit. Silicon QDs represent a key target for these hybrid materials due to silicon's biocompatibility and preeminence within the solar energy market. However, while triplet transfer from silicon QDs to molecules has been observed, no reports to date have shown evidence of energy moving in the reverse direction. Here, we address this gap by creating silicon QDs functionalized with perylene chromophores that exhibit bidirectional triplet exciton transfer. Using transient absorption, we find triplet transfer from silicon to perylene takes place over 4.2 µs while energy transfer in the reverse direction occurs two orders of magnitude faster, on a 22 ns timescale. To demonstrate this system's utility, we use it to create a photon upconversion system that generates blue emission at 475 nm using photons with wavelengths as long as 730 nm. Our work shows formation of covalent linkages between silicon and organic molecules can provide sufficient electronic coupling to allow efficient bidirectional triplet exchange, enabling new technologies for photon conversion.

8.
Bratisl Lek Listy ; 122(1): 78-84, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33393325

RESUMO

AIMS: The aim was to investigate the improvement properties of apocynin and its potential mechanism on diabetes-associated cognitive decline. METHODS: In this study, the model of diabetic rat was established by STZ (50 mg/kg) and treated with apocynin (16 mg/kg/d for 12 weeks). The cognitive ability was evaluated by Morris water maze test. The indicators of oxidative stress (SOD and MDA) were analyzed by spectrophotometer. The inflammatory cytokines were measured by real time-PCR and ELISA. The protein expressions of Nrf-2, HO-1, Bcl-2 and Bax were determined by Western blot. RESULTS: Treatment with apocynin ameliorated diabetes-related learning and memory injury, as represented by decreasing escape latency and enhancement of the number of times of crossing platform, in the Morris water maze test. In hippocampus, apocynin markedly augmented SOD activity and inhibited MDA level to alleviate oxidative stress. Moreover, apocynin obviously relieved inflammatory reaction by suppressing TNF-α, IL-1ß and IL-6 concentrations. Concomitantly, apocynin also statistically enhanced Nrf-2 and HO-1 protein expression to improve DACD. Lastly, apocynin notably ameliorated Bax/Bcl-2 ratio by regulating Bax and Bcl-2 protein expression to mitigate apoptosis. CONCLUSION: Our results have shown that apocynin may be a valid therapeutic agent against DACD via modulation of antioxidant, anti-inflammatory, and anti-apoptosis (Tab. 1, Fig. 18, Ref. 35).


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Acetofenonas , Animais , Cognição , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Diabetes Mellitus Experimental/complicações , Hipocampo , Aprendizagem em Labirinto , Estresse Oxidativo , Ratos , Estreptozocina
9.
RSC Adv ; 11(49): 31042-31046, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35498919

RESUMO

Here, films using CdSe nanocrystal (NC) triplet photosensitizers in conjunction with diphenylanthracene (DPA) emitters were assembled to address several challenges to practical applications for solution-based photon upconversion. By using poly(9-vinylcarbazole) as a phosphorescent host in this film, volatile organic solvents are eliminated, the spontaneous crystallization of the emitter is significantly retarded, and ∼1.5% photon upconversion quantum yield (out of a maximum of 50%) is obtained. Transient absorption spectroscopy on nanosecond-to-microsecond time scales reveals this efficiency is enabled by an exceptionally long triplet lifetime of 3.4 ± 0.3 ms. Ultimately, we find the upconversion efficiency is limited by incomplete triplet-triplet annihilation, which occurs with a rate 3-4 orders of magnitude slower than in solution-phase upconversion systems.

10.
J Dermatolog Treat ; 32(3): 350-354, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31403355

RESUMO

BACKGROUND: To systematically explore the risk factors of cutaneous warts and influence factor for the effectiveness of 5-fluorouracil (5-FU). METHODS: This is a case-control study of 408 cutaneous warts patients and 408 controls of Chinese Han population in southern China. In addition, 244 patients who presented with an initial episode of warts without treatment were treated with intralesional 5-FU. The influence factors of 5-FU therapeutic effects were analyzed. RESULTS: After adjustment, we found age (≤14 years old), lower education attainment, alcohol intake, smoking, less daily sleeping hours, severe psychological stress, hyperhidrosis, living in house or apartment, having cutaneous warts roommates, and sharing personal items with other persons to be risk factors for warts. Importantly, physical fitness played a protective role against warts. Two hundred and twenty-seven patients in 244 (93.03%) were successfully treated with 5-FU. Multivariate analysis indicated that smoking, alcohol intake, severe psychological stress, more than six months' duration of cutaneous warts, lesions on foot and warts diameter ≥5 mm adversely affected the effectiveness of 5-FU. CONCLUSIONS: The newly identified risk factors for cutaneous warts and influence factors for efficacy of 5-FU provided clues for warts prevention and treatment of Chinese Han population.


Assuntos
Fluoruracila/uso terapêutico , Verrugas/tratamento farmacológico , Adolescente , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Injeções Intralesionais , Estilo de Vida , Modelos Logísticos , Masculino , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
11.
J Immunother ; 44(3): 95-105, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33284140

RESUMO

In 2013, an innovative MAGE-A3-directed cancer therapeutic of great potential value was terminated in the clinic because of neurotoxicity. The safety problems were hypothesized to originate from off-target T-cell receptor activity against a closely related MAGE-A12 peptide. A combination of published and new data led us to test this hypothesis with current technology. Our results call into question MAGE-A12 as the source of the neurotoxicity. Rather, the data imply that an alternative related peptide from EPS8L2 may be responsible. Given the qualities of MAGE-A3 as an onco-testis antigen widely expressed in tumors and largely absent from normal adult tissues, these findings suggest that MAGE-A3 may deserve further consideration as a cancer target. As a step in this direction, the authors isolated 2 MAGE-A3 peptide-major histocompatibility complex-directed chimeric antigen receptors, 1 targeting the same peptide as the clinical T-cell receptor. Both chimeric antigen receptors have improved selectivity over the EPS8L2 peptide that represents a significant risk for MAGE-A3-targeted therapeutics, showing that there may be other options for MAGE-A3 cell therapy.


Assuntos
Antígenos de Neoplasias/imunologia , Proteínas de Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linhagem Celular , Linhagem Celular Tumoral , Células HCT116 , Células HEK293 , Humanos , Células Jurkat , Leucócitos Mononucleares/imunologia , Células MCF-7 , Complexo Principal de Histocompatibilidade/imunologia , Neoplasias/imunologia , Células PC-3 , Receptores de Antígenos Quiméricos/imunologia
12.
Future Oncol ; 17(3): 301-313, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32996773

RESUMO

Screening and therapeutic programs for colorectal cancer (CRC) are invasive or not effective and unable to meet patient needs. Major advances in immunogenomics may change this status but need more exploration. Differentially expressed genes and immune-related genes (IRGs) were identified by computational methods. A prognostic model was established and validated based on survival-related IRGs via stepwise multivariate Cox regression analysis. Nine IRGs were selected and identified as survival-related genes. A 7-gene prognostic model could offer a preliminary and valid determination of risk in CRC patients. The area under the curve of the receiver operating characteristic was 0.672. The 7-gene prognostic model might be used as a novel prognostic tool in CRC patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Imunidade/genética , Prognóstico , Curva ROC , Medição de Risco , Análise de Sobrevida
13.
Acc Chem Res ; 54(1): 70-80, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33141563

RESUMO

The semiconductor-nanocrystal-sensitized, three-component upconversion system has made great strides over the past 5 years. The three components (i.e., triplet photosensitizer, mediator, and emitter) each play critical roles in determining the input and output photon energy and overall quantum efficiency (QE). The nanocrystal photosensitizer converts the absorbed photon into singlet excitons and then triplet excitons via intersystem crossing. The mediator accepts the triplet exciton via either direct Dexter-type triplet energy transfer (TET) or sequential charge transfer (CT) while extending the exciton lifetime. Through a second triplet energy-transfer step from the mediator to the emitter, the latter is populated in its lowest excited triplet state. Triplet-triplet annihilation (TTA) between two triplet emitters generates the emitter in its bright singlet state, which then emits the upconverted photon. Quantum dots (QD) have a tunable band gap, large extinction coefficient, and small singlet-triplet energy losses compared to metal-ligand charge-transfer complexes. This high triplet exciton yield makes QDs good candidates for photosensitizers. In terms of driving triplet energy transfer, the triplet energy of the mediator should be slightly lower than the triplet exciton energy of the QD sensitizer for a downhill energy landscape with minimal energy loss. The same energy cascade is also required for the transfer from the mediator to the emitter. Finally, the triplet energy of the emitter must be slightly larger than one-half of its singlet energy to ensure that TTA is exothermic. Optimization of the sensitizer, mediator, and emitter will lead to an increase in the anti-Stokes shift and the total quantum efficiency. Evaluating each individual step's efficiency and kinetics is necessary for the understanding of the limiting factors in existing systems.This review summarizes chalcogenide QD-based photon upconversion systems with a focus on the mechanistic aspects of triplet energy transfer conducted by the Tang and Lian groups. Via time-resolved spectroscopy, the rates and major loss pathways associated with the two triplet energy-transfer steps were identified. The studies are focused on the near-infrared (NIR) to visible (VIS) PbS-tetracene-based systems as they allow systematic control of the QD, mediator, and emitter. Our results show that the mediator triplet state is mostly formed by direct TET from the QD and the transfer rate is influenced by the density of bound mediator molecules. Charge transfer, a loss pathway, does not produce triplet excitons and can be minimized by adding an inert shell to the QD. This transfer rate decreases exponentially with the distance between the QD and mediator molecule. The second TET rate was found to be much slower than the diffusion-limited collision rate, which results in the triplet lifetime of the mediator being the main factor limiting its efficiency. Finally, the total quantum efficiency can be calculated using these measured quantities including the TET1 and TET2 efficiencies. The agreement between calculated and measured quantum efficiencies suggests a firm understanding of QD-sensitized photon upconversion. We believe the above conclusions are general and should be widely applicable to similar systems, including singlet fission in hybrid organic-nanocrystal materials.

14.
Biomark Res ; 8: 29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817791

RESUMO

BACKGROUND: The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. METHODS: In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, N = 185) who received intensive chemotherapy. Models were validated in an independent set of similarly treated patients (validation cohort, N = 166). RESULTS: Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age < 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for ASXL1, CEBPA, RUNX1 and TP53, demonstrated that these mutations provide a limited overall contribution to risk stratification across the entire population, given the low frequency of mutations and confounding risk factors. CONCLUSIONS: While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification.

15.
ACS Appl Mater Interfaces ; 12(32): 36558-36567, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32677433

RESUMO

Lead sulfide (PbS) quantum dots (QDs) have shown promising performance as a sensitizer in infrared-to-visible photon upconversion systems. To investigate the key design rules, we compare three PbS-sensitized upconversion systems using three mediator molecules with the same tetracene triplet acceptor at different distances from the QD. Using transient absorption spectroscopy, we directly measure the triplet energy-transfer rates and efficiencies from the QD to the mediator and from the mediator to the emitter. With increasing distance between the mediator and PbS QD, the efficiency of the first triplet energy transfer from the QD to the mediator decreases because of a decrease in the rate of this triplet energy-transfer step, while the efficiency of the second triplet energy transfer from the mediator to the emitter increases because of a reduction in the QD-induced mediator triplet state decay. The latter effect is a result of the slow rate constant of the second triplet energy-transfer process, which is 3 orders of magnitude slower than the diffusion-limited value. The combined results lead to a net decrease of the steady-state upconversion quantum yield with distance, which could be predicted by our kinetic model. Our result shows that the QD/mediator interface affects both the first and second triplet energy transfer processes in the photon upconversion system, and the QD/mediator distance has an opposite effect on the efficiencies of the first and second triplet energy transfer. These findings provide important insight for the further rational improvement of the overall efficiency of QD-based upconversion systems.

16.
Faraday Discuss ; 222(0): 190-200, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32104858

RESUMO

The photophysics of silicon quantum dots (QDs) is not well understood despite their potential for many optoelectronic applications. One of the barriers to the study and widespread adoption of Si QDs is the difficulty in functionalizing their surface, to make, for example, a solution-processable electronically-active colloid. While thermal hydrosilylation of Si QDs is widely used, the high temperature typically needed may trigger undesirable side-effects, like uncontrolled polymerization of the terminal alkene. In this contribution, we show that this high-temperature method for installing aromatic and aliphatic ligands on non-thermal plasma-synthesized Si QDs can be replaced with a low-temperature, radical-initiated hydrosilylation method. Materials prepared via this low-temperature route perform similarly to those created via high-temperature thermal hydrosilylation when used in triplet fusion photon upconversion systems, suggesting the utility of low-temperature, radical-initiated methods for creating Si QDs with a range of functional behavior.

17.
Nephrology (Carlton) ; 25(8): 644-651, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31900988

RESUMO

AIM: Many patients, especially the elderly, who require renal replacement therapies (RRT) have delayed or rejected dialysis for various reasons. Current dialysis guidelines may not be relevant for the elderly or frail patients. We aim to determine survival advantage of initiating dialysis in patients deemed to require RRT. METHODS: This was an observational cohort on incident end-stage kidney disease (ESKD) patients from January 1, 2007 to December 31, 2008. The primary outcome was all-cause mortality. Patients contributed person-time from the date of ESKD diagnosis until death, transplant or end of study on December 31, 2014, whichever occurred first. An extended Cox regression model with time-varying exposure to dialysis was used to account for immortal time bias. RESULTS: Of 3990 incident ESKD patients included, 70.2% patients initiated dialysis; 78.8% with haemodialysis (HD) while the remaining 21.2% with peritoneal dialysis (PD). Dialysis reduced hazard of death in both elderly and non-elderly patients even after controlling for comorbidities (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.50, 0.68 and HR 0.76, 95% CI 0.69, 0.85, respectively). HD was protective in both the elderly and non-elderly (HR 0.53, 95% CI 0.45, 0.63 and HR 0.71, 95% CI 0.64, 0.80, respectively). PD significantly reduced risk of death compared to no dialysis in the elderly but not in the non-elderly. CONCLUSION: Dialysis improved survival in all incident ESKD patients. The findings suggested a larger protection offered by HD. Although improvement in survival from initiating dialysis was large, its true benefit should take overall quality of life into account. SUMMARY AT A GLANCE This observational study showed that initiation of dialysis improves the survival of end-stage kidney disease (ESKD) patients of all age groups, but the quality of life is an important aspect that has not been explored.


Assuntos
Falência Renal Crônica , Qualidade de Vida , Terapia de Substituição Renal , Tempo para o Tratamento , Fatores Etários , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Terapia de Substituição Renal/métodos , Terapia de Substituição Renal/estatística & dados numéricos , Tempo para o Tratamento/normas , Tempo para o Tratamento/estatística & dados numéricos
18.
J Chem Phys ; 151(17): 174701, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703522

RESUMO

In this study, the role that primary amines play during triplet energy transfer from photoexcited CdSe nanocrystals (NCs) was examined. Colloidally synthesized CdSe NCs were placed in varying concentrations of 1-propyl- or 1-octylamine, with and without 2-anthracenecarboxylic acid transmitter ligands attached. This primary amine increases upconversion quantum yield approximately 5-fold. Further addition of amine does not improve photon upconversion, as CdSe NC photoluminescence (PL) increases at the expense of triplet energy transfer. Transient absorption measurements show that the amine plays three key roles. Primary amines enhance NC PL by decreasing the nonradiative decay rate, increase the rate of triplet energy transfer, and enable the broad trap state in these CdSe NCs to participate in triplet photosensitization.

19.
Cancer Genet ; 238: 62-68, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425927

RESUMO

Hyperdiploidy with greater than 50 chromosomes is usually associated with favorable prognosis in pediatric acute lymphoblastic leukemia (ALL), whereas hypodiploidy with ≤43 chromosomes is associated with extremely poor prognosis. Sometimes, hypodiploidy is "masked" and patients do not have a karyotypically visible clone with ≤43 chromosomes. Instead, their abnormal karyotypes contain 50-78 or more chromosomes from doubling of previously hypodiploid cells. When the hypodiploid and doubled hyperdiploid clones are both present, patients can be identified by traditional test methods [karyotype, DNA Index (DI), fluorescence in situ hybridization (FISH)], but the incidence of masked hypodiploid cases in which only the doubled clone is visible is unknown. We analyzed 7013 patients with B-ALL enrolled in COG AALL03B1 (2003-2011) for whom chromosome studies were available. Of 115 patients with hypodiploidy (25-39 chromosomes), karyotypes of 40 showed only the hypodiploid clone, 47 showed mosaicism with both hypodiploid and hyperdiploid (doubled) karyotypes, and 28 with masked hypodiploidy showed only a hyperdiploid (doubled) clone. Unique karyotypic signatures were identified, and widespread loss of heterozygosity (LOH) was seen in the microsatellite panel for all patients with masked hypodiploidy. An increased awareness of the unusual karyotypic profile associated with a doubled hypodiploid clone and coordinated use of DI, FISH, and LOH studies when indicated can identify patients with masked hypodiploidy and allow appropriate treatment selection.


Assuntos
Diploide , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Cromossomos Humanos , Humanos , Cariotipagem , Mosaicismo
20.
J Am Chem Soc ; 141(25): 9769-9772, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31180212

RESUMO

Photon upconversion employing semiconductor nanocrystals (NCs) makes use of their large and tunable absorption to harvest light in the near-infrared (NIR) wavelengths as well as their small gap between singlet and triplet excited states to reduce energy losses. Here, we report the highest QY (11.8%) thus far for the conversion of NIR to yellow photons by improving the quality of the PbS NC. This high QY was achieved by using highly purified lead and thiourea precursors. This QY is 2.6 times higher than from NCs prepared with commercially available lead and sulfide precursors. Transient absorption spectroscopy reveals two reasons for the enhanced QY: longer intrinsic exciton lifetimes of PbS NCs and the ability to support a longer triplet lifetime for the surface-bound transmitter molecule. Overall, this results in a higher efficiency of triplet exciton transfer from the PbS NC light absorber to the emitter and thus a higher photon upconversion QY.


Assuntos
Chumbo/química , Fármacos Fotossensibilizantes/química , Pontos Quânticos/química , Sulfetos/química , Raios Infravermelhos , Chumbo/efeitos da radiação , Fármacos Fotossensibilizantes/efeitos da radiação , Pontos Quânticos/efeitos da radiação , Sulfetos/efeitos da radiação
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