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1.
Biomed Pharmacother ; 171: 116124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198957

RESUMO

Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR, MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Receptores ErbB/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-yes
2.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37602283

RESUMO

In Drosophila , multiple transgenic RNAi libraries have been generated to facilitate large-scale genetic screens in vivo . Although those libraries have helped generate many new discoveries, certain libraries are associated with technical drawbacks requiring caution in interpreting the results. Here, we report an unexpected effect of VDRC GD lines on proteostasis. When expressed in the larval skeletal muscle, 17 out of 20 GD lines induced protein aggregates enriched around the myonuclei while VDRC KK or TRiP counterparts had no effect. By contrast, the same GD lines failed to induce protein aggregates when expressed in the epidermal cells. Because the GD lines tested in this study target diverse classes of molecules and since the KK or TRiP counterparts exhibited no effect, we conclude that VDRC GD lines, for unknown reasons, tend to interfere with proteostasis in a tissue-specific and target-independent manner.

3.
Heliyon ; 9(4): e14818, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025778

RESUMO

Proinflammatory cytokines and NO play crucial roles in islet ß-cells dysfunction. Though anti-inflammatory effects of kaempferol were revealed in several studies, the detailed mechanisms remain unclear. This study explored protective actions of kaempferol in interleukin-1ß-treated RINm5F ß-cells. Kaempferol significantly inhibited NO generation, iNOS protein, and iNOS mRNA level. Promoter study, EMSA, and κB-dependent reporter assay showed that kaempferol inhibited NF-κB-mediated iNOS gene transcription. Also, we found that kaempferol accelerated iNOS mRNA instability in iNOS 3'-UTR construct and actinomycin D chase studies. Additionally, kaempferol reduced iNOS protein stability in cycloheximide chase study and it inhibited NOS enzyme activity. Kaempferol inhibited ROS generation and preserved cell viability, and it improved insulin release. These findings suggest that kaempferol appears to be helpful in protecting islet ß-cells, thereby supports kaempferol as a supplementary therapeutic candidate in inhibiting the incidence and progression of diabetes mellitus.

4.
Int J Artif Organs ; 45(10): 833-840, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35918871

RESUMO

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) has increased, although its survival benefit in trauma patients with severe adult respiratory distress syndrome (ARDS) remains controversial. We investigated the effect of veno-venous (VV)-ECMO on the clinical outcomes of trauma patients with severe ARDS. METHODS: This was a retrospective study at a single center comprising trauma patients admitted between January 2013 and December 2017, diagnosed with severe ARDS using the Berlin definition (PaO2/FiO2 ratio ⩽100), in the 7 days following trauma. Patients were managed with VV-ECMO or conventional mechanical ventilation (CMV). The primary outcome was in-hospital mortality (mortality at 60 days); secondary outcomes comprised 28-day mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, ICU-free days, duration of mechanical ventilation (MV), and MV-free days. Propensity score matching was performed to adjust for the baseline differences. RESULTS: Sixteen patients (22.5%) were managed with VV-ECMO and 55 were managed with CMV. After matching, the in-hospital mortality rate (43.8% vs 53.1%; p = 0.760), 28-day mortality rate (37.5% vs 31.3%; p = 0.750), median hospital LOS (39.5 vs 36.5 days; p = 0.533), ICU-free days (0 vs 0 days; p = 0.241), and MV-free days (0 vs 0 days; p = 0.272) did not significantly differ between the VV-ECMO and CMV groups. CONCLUSION: In-hospital mortality (mortality at 60 days) did not differ significantly between the VV-ECMO and CMV groups. Although the safety of ECMO in trauma patients requires further investigation, VV-ECMO may be considered as a rescue therapy.


Assuntos
Infecções por Citomegalovirus , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Adulto , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos
5.
Chem Asian J ; 17(14): e202200289, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35546083

RESUMO

Aqueous zinc-ion batteries (ZIBs) are promising candidates for the next-generation high-energy storage devices, owing to their resource availability, low cost, eco-friendliness, and high safety. The zinc (Zn) metal anode in a suitable battery system, including an electrolyte and a high-performance cathode electrode, can deliver an excellent electrochemical performance. However, several obstacles must be overcome to utilize aqueous ZIBs. Among these, Zn dendrite growth, corrosion, and side reactions severely impair the performance of rechargeable ZIBs. To deal with these issues, a profound understanding of the mechanism of the matter occurring in electrochemical cycles is essential to thoroughly solve the challenges. Instead of focusing solely on techniques for improving the performance of Zn metal anodes, this review delves into and summarizes the causes of side reactions and dendrite formation, thereby establishing a logical system of methodologies for improving the electrochemical performance of mild aqueous ZIBs. The correlation between the Zn metal anode, aqueous electrolyte, separators and the performance of ZIBs is also discussed in detail. There is also a brief perspective on the future development of Zn metal anodes in aqueous solutions. This study sheds a light on the challenges associated with the construction of high-performance ZIBs, which will significantly aid in their practical implementation.


Assuntos
Eletrólitos , Zinco , Dendritos
6.
Langmuir ; 37(15): 4419-4431, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33834786

RESUMO

In this feature article, we provide an account of the Langmuir Lecture delivered by Kristen Fichthorn at the Fall 2020 Virtual Meeting of the American Chemical Society. We discuss how multiscale theory and simulations based on first-principles DFT were useful in uncovering the intertwined influences of kinetics and thermodynamics on the shapes of Ag and Cu cubes and nanowires grown in solution. We discuss how Ag nanocubes can form through PVP-modified deposition kinetics and how the addition of chloride to the synthesis can promote thermodynamic cubic shapes for both Ag and Cu. We discuss kinetic factors contributing to nanowire growth: in the case of Ag, we show that high-aspect-ratio nanowires can form as a consequence of Ag atom surface diffusion on the strained surfaces of Marks-like decahedral seeds. On the other hand, solution-phase chloride enhances Cu nanowire growth due to a synergistic interaction between adsorbed chloride and hexadecylamine (HDA), which leaves the {111} nanowire ends virtually bare while the {100} sides are fully covered with HDA. For each of these topics, a synergy between theory and experiment led to significant progress.

7.
ACS Appl Mater Interfaces ; 13(10): 11940-11947, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33650852

RESUMO

The activity of electrocatalysts can be improved by modifying their electronic structures and surface morphologies. In electrochemical reactions with gas evolution, the performance of an electrocatalyst is also affected by how easily gas bubbles depart from an electrocatalyst surface. However, it is difficult to quantitatively estimate the improvement in the performance that can be achieved by promoting the departure of gas bubbles from the electrocatalyst surface. This study investigated the effect of surface hydrophilicity on the hydrogen evolution reaction (HER). The water contact angles of the nickel phosphorous (NiP) films were controlled from 40.3 to 77.2° with imperceptible differences in their intrinsic electronic structures and surface areas. Electrochemical analyses and in situ visualization of the gas evolution on the NiP films indicated that an increase in the hydrophilicity of the electrocatalysts reduced the size of gas bubbles formed on the NiP films and shortened the duration of the bubbles' stay on the NiP surface. A faster gas departure enabled continuous participation of the electrocatalyst surface in hydrogen evolution, leading to a stable electrochemical behavior of the electrocatalyst and a decrease in the overpotential at a given current density. A full-cell test revealed that the enhancement of hydrogen bubble departure on a hydrophilic NiP surface with a contact angle of 40.3° reduced the overpotential by 134 mV at a current density of 100 mA/cm2 compared to a more hydrophobic film with a contact angle of 77.2°.

8.
Eye Contact Lens ; 47(1): 15-19, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32443016

RESUMO

PURPOSE: To analyze the pathophysiological differences between patients with dry eye disease (DED) having different tear film break-up patterns (TBUPs). METHODS: This investigative analysis involved 91 eyes of 91 patients with DED who were divided into two groups: those with "dot" break-up pattern (group I) and those with "random" break-up pattern (group II). Clinical severity was evaluated using the Ocular Surface Disease Index (OSDI), Oxford stain score system (OSS) score, and tear film break-up time (TF-BUT). Eighteen patients in group I and 17 patients in group II were selected for sampling of tears and the conjunctiva, and the concentrations of inflammatory cytokines and mucin in the tears and conjunctival tissue were measured. RESULTS: Thirty-seven patients were classified as group I and 54 patients as group II. Patients in group I had a statistically lower TF-BUT and a higher OSS score than those in group II, whereas the OSDI was not statistically different between the groups. The concentrations of interleukin (IL)-6 and IL-8 were statistically higher in group I than those in group II. Impression cytology showed that the expression of IL-1ß and IL-8 was higher in group I, whereas that of other genes was not statistically different. CONCLUSIONS: We were able to clearly classify patients with DED with different TBUPs into two groups, and each group had different clinical and pathophysiological characteristics. In patients with the dot break-up pattern, the disease was strongly associated with ocular surface inflammation, as opposed to that in patients without this pattern.


Assuntos
Síndromes do Olho Seco , Lágrimas , Túnica Conjuntiva , Citocinas , Humanos , Inflamação
9.
Development ; 148(1)2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33234715

RESUMO

The Myostatin/Activin branch of the TGF-ß superfamily acts as a negative regulator of vertebrate skeletal muscle size, in part, through downregulation of insulin/insulin-like growth factor 1 (IGF-1) signaling. Surprisingly, recent studies in Drosophila indicate that motoneuron-derived Activin signaling acts as a positive regulator of muscle size. Here we demonstrate that Drosophila Activin signaling promotes the growth of muscle cells along all three axes: width, thickness and length. Activin signaling positively regulates the insulin receptor (InR)/TORC1 pathway and the level of Myosin heavy chain (Mhc), an essential sarcomeric protein, via increased Pdk1 and Akt1 expression. Enhancing InR/TORC1 signaling in the muscle of Activin pathway mutants restores Mhc levels close to those of the wild type, but only increases muscle width. In contrast, hyperactivation of the Activin pathway in muscles increases overall larval body and muscle fiber length, even when Mhc levels are lowered by suppression of TORC1. Together, these results indicate that the Drosophila Activin pathway regulates larval muscle geometry and body size via promoting InR/TORC1-dependent Mhc production and the differential assembly of sarcomeric components into either pre-existing or new sarcomeric units depending on the balance of InR/TORC1 and Activin signals.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Desenvolvimento Muscular , Receptor de Insulina/metabolismo , Transdução de Sinais , Animais , Retroalimentação Fisiológica , Regulação da Expressão Gênica , Larva/metabolismo , Modelos Biológicos , Músculos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Fosforilação , Proteínas Quinases S6 Ribossômicas/metabolismo , Sarcômeros/metabolismo , Transcrição Gênica , Fator de Crescimento Transformador beta/metabolismo
10.
Ann Surg Treat Res ; 99(6): 352-361, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304863

RESUMO

PURPOSE: Recently, several studies have demonstrated symptom-based, non-zonal algorithms for approaching penetrating neck injuries. The purpose of this study was to confirm the effectiveness of the "no zone" approach in traumatic neck injuries. METHODS: Medical charts of patients with traumatic neck injuries who presented at the Regional Trauma Center in South Korea between January 2014 and December 2018 were retrospectively reviewed. Negative final neck findings (FNFs) were compared with positive FNFs (which include major vascular, aerodigestive, nerve, endocrine gland, cartilage, or hyoid bone injuries) using multivariate logistic regression analysis including values of the "zone" and/or no zone approach. RESULTS: Out of 168 trauma patients, 70 patients with a minor injury and 7 patients under the age of 18 years were excluded. Of the remaining 91 patients, 74 (81.3%) had penetrating neck injuries and 17 (18.7%) had blunt neck injuries. Initial diagnosis most frequently revealed external wounds in zone II (84.6%). Twenty (22.0%) and 36 (39.5%) patients had hard and soft signs, respectively, using the no zone approach. Further, there was a significant difference between the negative and positive FNFs in patients with hard signs (11.6% vs. 54.5%; P < 0.01, respectively). According to the multivariate logistic regression analysis, the hard signs were associated with an odds ratio (OR) for FNFs (OR, 18.92; 95% confidence interval, 3.55-157.60). CONCLUSION: Traumatic neck injuries classified as having hard signs based on the no zone approach may be correlated with internal organ injuries of the neck.

11.
Elife ; 92020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633716

RESUMO

Organ growth and size are finely tuned by intrinsic and extrinsic signaling molecules. In Drosophila, the BMP family member Dpp is produced in a limited set of imaginal disc cells and functions as a classic morphogen to regulate pattern and growth by diffusing throughout imaginal discs. However, the role of TGFß/Activin-like ligands in disc growth control remains ill-defined. Here, we demonstrate that Myoglianin (Myo), an Activin family member, and a close homolog of mammalian Myostatin (Mstn), is a muscle-derived extrinsic factor that uses canonical dSmad2-mediated signaling to regulate wing size. We propose that Myo is a myokine that helps mediate an allometric relationship between muscles and their associated appendages.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/genética , Discos Imaginais/crescimento & desenvolvimento , Proteínas Smad Reguladas por Receptor/fisiologia , Fator de Crescimento Transformador beta/genética , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Discos Imaginais/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Músculos/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
12.
Nanoscale ; 11(45): 21709-21723, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31714552

RESUMO

Control over the nanoscopic structure of a material allows one to tune its properties for a wide variety of applications. Colloidal synthesis has become a convenient way to produce anisotropic metal nanostructures with a desired set of properties, but in most syntheses, the facet-selective surface chemistry causing anisotropic growth is not well-understood. This review highlights the recent use of electrochemical methods and single-crystal electrodes to investigate the roles of organic and inorganic additives in modulating the rate of atomic addition to different crystal facets. Differential capacitance and chronocoulometric techniques can be used to extract thermodynamic data on how additives selectively adsorb, while mixed potential theory can be used to observe the effect of additives on the rate of atomic addition to a specific facet. Results to date indicate that these experimental methods can provide new insights into the role capping agents and halides play in controlling anisotropic growth.

13.
Genetics ; 213(4): 1447-1464, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585954

RESUMO

Correct scaling of body and organ size is crucial for proper development, and the survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. The identity of additional factors that might contribute to scaling of organs and appendages with body size is unknown. Here, we report that loss-of-function mutations in DrosophilaActivinß (Actß), a member of the TGF-ß superfamily, lead to the production of small larvae/pupae and undersized rare adult escapers. Morphometric measurements of escaper adult appendage size (wings and legs), as well as heads, thoraxes, and abdomens, reveal a disproportional reduction in abdominal size compared to other tissues. Similar size measurements of selected Actß mutant larval tissues demonstrate that somatic muscle size is disproportionately smaller when compared to the fat body, salivary glands, prothoracic glands, imaginal discs, and brain. We also show that Actß control of body size is dependent on canonical signaling through the transcription-factor dSmad2 and that it modulates the growth rate, but not feeding behavior, during the third-instar period. Tissue- and cell-specific knockdown, and overexpression studies, reveal that motoneuron-derived Actß is essential for regulating proper body size and tissue scaling. These studies suggest that, unlike in vertebrates, where Myostatin and certain other Activin-like factors act as systemic negative regulators of muscle mass, in Drosophila, Actß is a positive regulator of muscle mass that is directly delivered to muscles by motoneurons. We discuss the importance of these findings in coordinating proportional scaling of insect muscle mass to appendage size.


Assuntos
Tamanho Corporal , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/metabolismo , Neurônios Motores/metabolismo , Envelhecimento , Animais , Núcleo Celular/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Masculino , Músculos/anatomia & histologia , Mutação/genética , Tamanho do Órgão , Pupa/anatomia & histologia , Transdução de Sinais
14.
ACS Nano ; 13(6): 6998-7009, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31084021

RESUMO

Flow-through electrodes such as carbon paper are used in redox flow batteries, water purification, and electroorganic syntheses. This work examines the extent to which reducing the size of the fibers to the nanoscale in a flow-through electrode can increase the productivity of electrochemical processes. A Cu nanowire felt, made from nanowires 45 times smaller than the 10 µm wide fibers in carbon paper, can achieve a productivity 278 times higher than carbon paper for mass-transport-limited reduction of Cu ions. Higher increases in productivity were predicted for the Cu nanowire felt based on the mass-transport-limited current, but Cu ion reduction became charge transfer-limited on Cu nanowire felt at high concentrations and flow rates when the mass-transport-limited current became comparable to the charge transfer-limited current. In comparison, the reaction rate on carbon paper was mass-transport-limited under all concentrations and flow rates because its mass-transport-limited current was much lower than its charge transfer-limited current. Higher volumetric productivities were obtained for the Cu nanowire felt by switching from Cu ion reduction to Alizarin Red S (ARS) reduction, which has a higher reaction rate constant. An electroorganic intramolecular cyclization reaction with Cu nanowire felt achieved a productivity 4.2 times higher than that of carbon paper, although this reaction was also affected by charge transfer kinetics. This work demonstrates that large gains in productivity can be achieved with nanostructured flow-through electrodes, but the potential gains can be limited by the charge transfer kinetics of a reaction.

15.
Chem Rev ; 119(15): 8972-9073, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30854849

RESUMO

This Review offers a comprehensive review of the colloidal synthesis, mechanistic understanding, physicochemical properties, and applications of one-dimensional (1D) metal nanostructures. After a brief introduction to the different types of 1D nanostructures, we discuss major concepts and methods typically involved in a colloidal synthesis of 1D metal nanostructures, as well as the current mechanistic understanding of how the nanostructures are formed. We then highlight how experimental studies and computational simulations have expanded our knowledge of how and why 1D metal nanostructures grow. Following specific examples of syntheses for monometallic, multimetallic, and heterostructured systems, we showcase how the unique structure-property relationships of 1D metal nanostructures have enabled a broad spectrum of applications, including sensing, imaging, plasmonics, photonics, display, thermal management, and catalysis. Throughout our discussion, we also offer perspectives with regard to the future directions of development for this class of nanomaterials.

16.
Nutrients ; 10(11)2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30380680

RESUMO

Modified NUTRIC (mNUTRIC) score is a useful assessment tool to determine the risk of malnutrition in patients on mechanical ventilation (MV). We identified associations between postoperative calorie adequacy, 30-day mortality, and surgical outcomes in patients with high mNUTRIC scores. Medical records of 272 patients in the intensive care unit who required MV support for >24 h after emergency gastro-intestinal (GI) surgery between January 2007 and December 2017 were reviewed. Calorie adequacy in percentage (Calorie intake in 5 days ÷ Calorie requirement for 5 days × 100) was assessed in patients with high (5⁻9) and low (0⁻4) mNUTRIC scores. In the high mNUTRIC score group, patients with inadequate calorie supplementation (calorie adequacy <70%) had higher 30-day mortality than those with adequate supplementation (31.5% vs. 11.1%; p = 0.010); this was not observed in patients with low mNUTRIC scores. This result was also confirmed through Kaplan⁻Meier survival curve (p = 0.022). Inadequate calorie supplementation in the high mNUTRIC score group was not associated with Intra-abdominal infection (p = 1.000), pulmonary complication (p = 0.695), wound complication (p = 0.407), postoperative leakage (p = 1.000), or infections (p = 0.847). Inadequate calorie supplementation after GI surgery was associated with higher 30-day mortality in patients with high mNUTRIC scores. Therefore, adequate calorie supplementation could contribute to improved survival of critically ill postoperative patients with high risk of malnutrition.


Assuntos
Estado Terminal/mortalidade , Desnutrição/mortalidade , Avaliação Nutricional , Terapia Nutricional/mortalidade , Complicações Pós-Operatórias/mortalidade , Idoso , Ingestão de Energia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Respiração Artificial/mortalidade , Estudos Retrospectivos , Medição de Risco/métodos
17.
J Am Chem Soc ; 140(44): 14740-14746, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30351013

RESUMO

Shape-control is used to tune the properties of metal nanostructures in applications ranging from catalysts to touch screens, but the origins of anisotropic growth of metal nanocrystals in solution are unknown. We show single-crystal electrochemistry can test hypotheses for why nanostructures form and predict conditions for anisotropic growth by quantifying the degree to which different species cause facet-selective metal deposition. Electrochemical measurements show disruption of alkylamine monolayers by chloride ions causes facet-selective Cu deposition. An intermediate range of chloride concentrations maximizes facet-selective Cu deposition on single crystals and produces the highest aspect ratio nanowires in a solution-phase synthesis. DFT calculations similarly show an intermediate monolayer coverage of chloride displaces the alkylamine capping agent from the ends but not the sides of a nanowire, facilitating anisotropic growth.

18.
Medicine (Baltimore) ; 97(40): e12741, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30290686

RESUMO

Mechanical ventilation (MV) is the most common therapeutic modality used for critically ill patients. However, prolonged MV is associated with high morbidity and mortality. Therefore, it is important to avoid both premature extubation and unnecessary prolongation of MV. Although some studies have determined the predictors of early weaning success and failure, only a few have investigated these factors in critically ill surgical patients who require postoperative MV. The aim of this study was to evaluate predictors of early weaning failure from MV in critically ill patients who had undergone emergency gastrointestinal (GI) surgery.The medical records of 3327 adult patients who underwent emergency GI surgery between January 2007 and December 2016 were reviewed retrospectively. Clinical and laboratory parameters before surgery and within 2 days postsurgery were investigated.This study included 387 adult patients who required postoperative MV. A low platelet count (adjusted odds ratio [OR]: 0.995; 95% confidence interval [CI]: 0.991-1.000; P = .03), an elevated delta neutrophil index (DNI; adjusted OR: 1.025; 95% CI: 1.005-1.046; P = .016), a delayed spontaneous breathing trial (SBT; adjusted OR: 14.152; 95% CI: 6.571-30.483; P < .001), and the presence of postoperative shock (adjusted OR: 2.436; 95% CI: 1.138-5.216; P = .022) were shown to predict early weaning failure from MV in the study population.Delayed SBT, a low platelet count, an elevated DNI, and the presence of postoperative shock are independent predictors of early weaning failure from MV in critically ill patients after emergency GI surgery.


Assuntos
Cuidados Críticos/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/etiologia , Respiração Artificial/efeitos adversos , Desmame do Respirador/efeitos adversos , Idoso , Extubação/efeitos adversos , Extubação/métodos , Estado Terminal , Procedimentos Cirúrgicos do Sistema Digestório , Tratamento de Emergência , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Razão de Chances , Contagem de Plaquetas , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Desmame do Respirador/métodos
19.
Biol Open ; 7(4)2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29615416

RESUMO

The Drosophila Activin signaling pathway employs at least three separate ligands - Activin-ß (Actß), Dawdle (Daw), and Myoglianin (Myo) - to regulate several general aspects of fruit fly larval development, including cell proliferation, neuronal remodeling, and metabolism. Here we provide experimental evidence indicating that both Daw and Myo are anti-ageing factors in adult fruit flies. Knockdown of Myo or Daw in adult fruit flies reduced mean lifespan, while overexpression of either ligand in adult muscle tissues but not in adipose tissues enhanced mean lifespan. An examination of ubiquitinated protein aggregates in adult muscles revealed a strong inverse correlation between Myo- or Daw-initiated Activin signaling and the amount of ubiquitinated protein aggregates. We show that this correlation has important functional implications by demonstrating that the lifespan extension effect caused by overexpression of wild-type Daw or Myo in adult muscle tissues can be completely abrogated by knockdown of a 26S proteasome regulatory subunit Rpn1 in adult fly muscle, and that the prolonged lifespan caused by overexpression of Daw or Myo in adult muscle could be due to enhanced protein levels of the key subunits of 26S proteasome. Overall, our data suggest that Activin signaling initiated by Myo and Daw in adult Drosophila muscles influences lifespan, in part, by modulation of protein homeostasis through either direct or indirect regulation of the 26S proteasome levels. Since Myo is closely related to the vertebrate muscle mass regulator Myostatin (GDF8) and the Myostatin paralog GDF11, our observations may offer a new experimental model for probing the roles of GDF11/8 in ageing regulation in vertebrates.This article has an associated First Person interview with the first author of the paper.

20.
World J Emerg Surg ; 13: 14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29563963

RESUMO

Background: The quick sequential organ failure assessment (qSOFA) alone has a poor sensitivity for predicting mortality in patients with complicated intra-abdominal infections, and plasma lactate levels have been shown to have a strong association with mortality in critically ill patients. Therefore, this study aimed to compare the performance of qSOFA with a score derived from a combination of qSOFA and serum lactate levels for predicting mortality in surgical patients with complicated intra-abdominal infections. Methods: This retrospective study was performed at a university hospital. The medical records of 457 patients who presented to the emergency department (ED) between January 2008 and December 2016 and required emergency gastrointestinal surgery for a complicated intra-abdominal infection were reviewed retrospectively. qSOFA criteria, sequential organ failure assessment (SOFA) scores, and plasma lactate levels during their ED stay were collected. We performed area under receiver operating characteristic (AUROC) curve and sensitivity analysis to compare the performance of qSOFA alone with that of a score derived from the use of a combination of the qSOFA and lactate levels for predicting patient mortality. Results: Fifty patients (10.9%) died during hospitalization. The combined qSOFA and lactate level score was superior to qSOFA alone (AUROC = 0.754 vs. 0.717, p = 0.039, respectively) and comparable to the full SOFA score (AUROC = 0.754 vs. 0.795, p = 0.127, respectively) in predicting mortality. Sensitivity and specificity of qSOFA alone were 46 and 86%, respectively, and those of the combined score were 72 and 73%, respectively (p < 0.001). Conclusion: A score derived from the qSOFA and serum lactate levels had better predictive performance with higher sensitivity than the qSOFA alone in predicting mortality in patients with complicated intra-abdominal infections and had a comparable predictive performance to that of the full SOFA score.


Assuntos
Técnicas de Apoio para a Decisão , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Infecções Intra-Abdominais/mortalidade , Ácido Láctico/análise , Escores de Disfunção Orgânica , Peritonite/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Procedimentos Cirúrgicos do Sistema Digestório/normas , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Hospitais Universitários/organização & administração , Hospitais Universitários/estatística & dados numéricos , Humanos , Infecções Intra-Abdominais/cirurgia , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Estatísticas não Paramétricas
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