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1.
Proc Natl Acad Sci U S A ; 121(28): e2403699121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38954544

RESUMO

Despite the ubiquity of thermal convection in nature and artificial systems, we still lack a unified formulation that integrates the system's geometry, fluid properties, and thermal forcing to characterize the transition from free to confined convective regimes. The latter is broadly relevant to understanding how convection transports energy and drives mixing across a wide range of environments, such as planetary atmospheres/oceans and hydrothermal flows through fractures, as well as engineering heatsinks and microfluidics for the control of mass and heat fluxes. Performing laboratory experiments in Hele-Shaw geometries, we find multiple transitions that are identified as remarkable shifts in flow structures and heat transport scaling, underpinning previous numerical studies. To unveil the mechanisms of the geometrically controlled transition, we focus on the smallest structure of convection, posing the following question: How free is a thermal plume in a closed system? We address this problem by proposing the degree of confinement [Formula: see text]-the ratio of the thermal plume's thickness in an unbounded domain to the lateral extent of the system-as a universal metric encapsulating all the physical parameters. Here, we characterize four convective regimes different in flow dimensionality and time dependency and demonstrate that the transitions across the regimes are well tied with [Formula: see text]. The introduced metric [Formula: see text] offers a unified characterization of convection in closed systems from the plume's standpoint.

2.
Proc Natl Acad Sci U S A ; 121(25): e2322572121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38875148

RESUMO

Shear forces affect self-assembly processes ranging from crystallization to fiber formation. Here, the effect of mild agitation on amyloid fibril formation was explored for four peptides and investigated in detail for A[Formula: see text]42, which is associated with Alzheimer's disease. To gain mechanistic insights into the effect of mild agitation, nonseeded and seeded aggregation reactions were set up at various peptide concentrations with and without an inhibitor. First, an effect on fibril fragmentation was excluded by comparing the monomer-concentration dependence of aggregation kinetics under idle and agitated conditions. Second, using a secondary nucleation inhibitor, Brichos, the agitation effect on primary nucleation was decoupled from secondary nucleation. Third, an effect on secondary nucleation was established in the absence of inhibitor. Fourth, an effect on elongation was excluded by comparing the seeding potency of fibrils formed under idle or agitated conditions. We find that both primary and secondary nucleation steps are accelerated by gentle agitation. The increased shear forces facilitate both the detachment of newly formed aggregates from catalytic surfaces and the rate at which molecules are transported in the bulk solution to encounter nucleation sites on the fibril and other surfaces. Ultrastructural evidence obtained with cryogenic transmission electron microscopy and free-flow electrophoresis in microfluidics devices imply that agitation speeds up the detachment of nucleated species from the fibril surface. Our findings shed light on the aggregation mechanism and the role of detachment for efficient secondary nucleation. The results inform on how to modulate the relative importance of different microscopic steps in drug discovery and investigations.


Assuntos
Amiloide , Amiloide/metabolismo , Amiloide/química , Cinética , Humanos , Resistência ao Cisalhamento , Agregados Proteicos , Peptídeos/química , Peptídeos/metabolismo , Doença de Alzheimer/metabolismo
3.
Proc Natl Acad Sci U S A ; 121(44): e2321429121, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39436661

RESUMO

Transforming atmospheric water vapor into liquid form can be a way to supply water to arid regions for uses such as drinking water, thermal management, and hydrogen generation. Many current methods rely on solid sorbents that cycle between capture and release at slow rates. We envision a radically different approach where water is transformed and directly captured into a liquid salt solution that is suitable for subsequent distillation or other processing using existing methods. In contrast to other methods utilizing hydrogels as sorbents, we do not store water within hydrogels-we use them as a transport medium. Inspired by nature, we capture atmospheric water through a hydrogel membrane "skin" at an extraordinarily high rate of 5.50 kgm[Formula: see text]d[Formula: see text] at a low humidity of 35%. and up to 16.9 kgm[Formula: see text]d[Formula: see text] at higher humidities. For a drinking-water application, calculated performance of a hypothetical one-square-meter device shows that water could be supplied to two to three people in arid environments. This work is a significant step toward providing new resources and possibilities to water-scarce regions.

4.
Proc Natl Acad Sci U S A ; 121(11): e2319777121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437554

RESUMO

Enzymatic reactions in solution drive the convection of confined fluids throughout the enclosing chambers and thereby couple the processes of reaction and convection. In these systems, the energy released from the chemical reactions generates a force, which propels the fluids' spontaneous motion. Here, we use theoretical and computational modeling to determine how reaction-convection can be harnessed to tailor and control the dynamic behavior of soft matter immersed in solution. Our model system encompasses an array of surface-anchored, flexible posts in a millimeter-sized, fluid-filled chamber. Selected posts are coated with enzymes, which react with dissolved chemicals to produce buoyancy-driven fluid flows. We show that these chemically generated flows exert a force on both the coated (active) and passive posts and thus produce regular, self-organized patterns. Due to the specificity of enzymatic reactions, the posts display controllable kaleidoscopic behavior where one regular pattern is smoothly morphed into another with the addition of certain reactants. These spatiotemporal patterns also form "fingerprints" that distinctly characterize the system, reflecting the type of enzymes used, placement of the enzyme-coated posts, height of the chamber, and bending modulus of the elastic posts. The results reveal how reaction-convection provides concepts for designing soft matter that readily switches among multiple morphologies. This behavior enables microfluidic devices to be spontaneously reconfigured for specific applications without construction of new chambers and the fabrication of standalone sensors that operate without extraneous power sources.

5.
Proc Natl Acad Sci U S A ; 121(12): e2314265121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38470930

RESUMO

The debate on the sign of the soil moisture-precipitation feedback remains open. On the one hand, studies using global coarse-resolution climate models have found strong positive feedback. However, such models cannot represent convection explicitly. On the other hand, studies using km-scale regional climate models and explicit convection have reported negative feedback. Yet, the large-scale circulation is prescribed in such models. This study revisits the soil moisture-precipitation feedback using global, coupled simulations conducted for 1 y with explicit convection and compares the results to coarse-resolution simulations with parameterized convection. We find significant differences in a majority of points with feedback that is weaker and dominantly negative with explicit convection. The model with explicit convection is more often in a wet regime and prefers the triggering of convection over dry soil in the presence of soil moisture heterogeneity, in contrast to the coarse-resolution model. Further analysis indicates that the feedback not only between soil moisture and evapotranspiration but also between evapotranspiration and precipitation is weaker, in better agreement with observations. Our findings suggest that coarse-resolution models may not be well suited to study aspects of climate change over land such as changes in droughts and heatwaves.

6.
Proc Natl Acad Sci U S A ; 120(21): e2217705120, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37186830

RESUMO

Inspired by the superrotation of the Earth's solid core, we investigate the dynamics of a free-rotating body as it interacts with the large-scale circulation (LSC) of the Rayleigh-Bénard thermal convection in a cylindrical container. A surprising and persistent corotation of both the free body and the LSC emerges, breaking the axial symmetry of the system. The corotational speed increases monotonically with the intensity of thermal convection, measured by the Rayleigh number Ra, which is proportional to the temperature difference between the heated bottom and cooled top. The rotational direction occasionally and spontaneously reverses, occurring more frequently at higher Ra. The reversal events follow a Poisson process; it is feasible that flow fluctuations randomly interrupt and reestablish the rotation-sustaining mechanism. This corotation is powered by thermal convection alone and promoted by the addition of a free body, enriching the classical dynamical system.

7.
Proc Natl Acad Sci U S A ; 120(32): e2301947120, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523527

RESUMO

We show that unconstrained asymmetric dissolving solids floating in a fluid can move rectilinearly as a result of attached density currents which occur along their inclined surfaces. Solids in the form of boats composed of centimeter-scale sugar and salt slabs attached to a buoy are observed to move rapidly in water with speeds up to 5 mm/s determined by the inclination angle and orientation of the dissolving surfaces. While symmetric boats drift slowly, asymmetric boats are observed to accelerate rapidly along a line before reaching a terminal velocity when their drag matches the thrust generated by dissolution. By visualizing the flow around the body, we show that the boat velocity is always directed opposite to the horizontal component of the density current. We derive the thrust acting on the body from its measured kinematics and show that the propulsion mechanism is consistent with the unbalanced momentum generated by the attached density current. We obtain an analytical formula for the body speed depending on geometry and material properties and show that it captures the observed trends reasonably. Our analysis shows that the gravity current sets the scale of the body speed consistent with our observations, and we estimate that speeds can grow slowly as the cube root of the length of the inclined dissolving surface. The dynamics of dissolving solids demonstrated here applies equally well to solids undergoing phase change and may enhance the drift of melting icebergs, besides unraveling a primal strategy by which to achieve locomotion in active matter.

8.
Proc Natl Acad Sci U S A ; 120(47): e2217064120, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38033310

RESUMO

The intertropical convergence zone (ITCZ) plays a key role in regulating tropical hydroclimate and global water cycle through changes in its convection strength, latitudinal position, and width. The long-term variability of the ITCZ, along with the corresponding driving mechanisms, however, remains obscure, mainly because it is difficult to separate different ITCZ variables in paleoclimate proxy records. Here, we report a speleothem oxygen isotope (δ18O) record from southwestern Sulawesi, Indonesia, and compile it with other speleothem records from the Maritime Continent. Using the spatial gradient of speleothem δ18O along a transect across the ITCZ, we constrain ITCZ variabilities over the Maritime Continent during the past 30,000 y. We find that ITCZ convection strength overall intensified from the last glacial period to the Holocene, following changes in climate boundary conditions. The mean position of the regional ITCZ has moved latitudinally no more than 3° in the past 30,000 y, consistent with the deduction from the atmospheric energy framework. However, different from modern observations and model simulations for future warming, the ITCZ appeared narrower during both the late Holocene and most part of the last glacial period, and its expansion occurred during Heinrich stadials and the early-to-mid Holocene. We also find that during the last glacial and deglacial period, prominent millennial-scale ITCZ changes were closely tied to the variability of the Atlantic meridional overturning circulation (AMOC), whereas during the Holocene, they were predominantly modulated by the long-term variability of the Walker circulation.

9.
Proc Natl Acad Sci U S A ; 120(20): e2216158120, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155849

RESUMO

Accurate prediction of precipitation intensity is crucial for both human and natural systems, especially in a warming climate more prone to extreme precipitation. Yet, climate models fail to accurately predict precipitation intensity, particularly extremes. One missing piece of information in traditional climate model parameterizations is subgrid-scale cloud structure and organization, which affects precipitation intensity and stochasticity at coarse resolution. Here, using global storm-resolving simulations and machine learning, we show that, by implicitly learning subgrid organization, we can accurately predict precipitation variability and stochasticity with a low-dimensional set of latent variables. Using a neural network to parameterize coarse-grained precipitation, we find that the overall behavior of precipitation is reasonably predictable using large-scale quantities only; however, the neural network cannot predict the variability of precipitation (R2 ∼ 0.45) and underestimates precipitation extremes. The performance is significantly improved when the network is informed by our organization metric, correctly predicting precipitation extremes and spatial variability (R2 ∼ 0.9). The organization metric is implicitly learned by training the algorithm on a high-resolution precipitable water field, encoding the degree of subgrid organization. The organization metric shows large hysteresis, emphasizing the role of memory created by subgrid-scale structures. We demonstrate that this organization metric can be predicted as a simple memory process from information available at the previous time steps. These findings stress the role of organization and memory in accurate prediction of precipitation intensity and extremes and the necessity of parameterizing subgrid-scale convective organization in climate models to better project future changes of water cycle and extremes.

10.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35101987

RESUMO

Trends in surface air temperature (SAT) are a common metric for global warming. Using observations and observationally driven models, we show that a more comprehensive metric for global warming and weather extremes is the trend in surface equivalent potential temperature (Thetae_sfc) since it also accounts for the increase in atmospheric humidity and latent energy. From 1980 to 2019, while SAT increased by 0.79[Formula: see text], Thetae_sfc increased by 1.48[Formula: see text] globally and as much as 4[Formula: see text] in the tropics. The increase in water vapor is responsible for the factor of 2 difference between SAT and Thetae_sfc trends. Thetae_sfc increased more uniformly (than SAT) between the midlatitudes of the southern hemisphere and the northern hemisphere, revealing the global nature of the heating added by greenhouse gases (GHGs). Trends in heat extremes and extreme precipitation are correlated strongly with the global/tropical trends in Thetae_sfc. The tropical amplification of Thetae_sfc is as large as the arctic amplification of SAT, accounting for the observed global positive trends in deep convection and a 20% increase in heat extremes. With unchecked GHG emissions, while SAT warming can reach 4.8[Formula: see text] by 2100, the global mean Thetae_sfc can increase by as much as 12[Formula: see text], with corresponding increases of 12[Formula: see text] (median) to 24[Formula: see text] (5% of grid points) in land surface temperature extremes, a 14- to 30-fold increase in frequency of heat extremes, a 40% increase in the energy available for tropical deep convection, and an up to 60% increase in extreme precipitation.

11.
Proc Natl Acad Sci U S A ; 119(40): e2206990119, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161913

RESUMO

Rapid detection of pathogenic bacteria within a few minutes is the key to control infectious disease. However, rapid detection of pathogenic bacteria in clinical samples is quite a challenging task due to the complex matrix, as well as the low abundance of bacteria in real samples. Herein, we employ a label-free single-particle imaging approach to address this challenge. By tracking the scattering intensity variation of single particles in free solution, the morphological heterogeneity can be well identified with particle size smaller than the diffraction limit, facilitating the morphological identification of single bacteria from a complex matrix in a label-free manner. Furthermore, the manipulation of convection in free solution enables the rapid screening of low-abundance bacteria in a small field of view, which significantly improves the sensitivity of single-particle detection. As a proof of concept demonstration, we are able to differentiate the group B streptococci (GBS)-positive samples within 10 min from vaginal swabs without using any biological reagents. This is the most rapid and low-cost method to the best of our knowledge. We believe that such a single-particle imaging approach will find wider applications in clinical diagnosis and disease control due to its high sensitivity, rapidity, simplicity, and low cost.


Assuntos
Bactérias , Doenças Transmissíveis , Análise de Célula Única , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Doenças Transmissíveis/diagnóstico por imagem , Feminino , Humanos , Tamanho da Partícula , Análise de Célula Única/métodos , Esfregaço Vaginal
12.
Small ; 20(42): e2403141, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38874056

RESUMO

Unique suspension solar evaporator is one of the effective measures to address the major bottleneck of the emerging interfacial evaporators, i.e., the accumulation of salts on the surface. Yet, it remains a considerable challenge to avoid substantial heat loss underwater. Herein, a suspension wood-based evaporator is proposed with a thermal convection structure that effectively balances the contradiction between salt-resistance ability and heat loss. Benefitting from the heat centralization due to thermal convection, such suspension evaporator exhibits an excellent steam generation rate, which increases from 1.23 to 1.63 kg m-2 h-1 compared to the conventional suspension evaporator. Simultaneously, the steam generation rate retention improves from 64.9% over 20 test cycles to nearly 100% compared to the interfacial evaporator. This work provides an effective pathway for exploring efficient and stable suspension evaporators, offering essential directions for the future development and application of solar-driven evaporation technologies.

13.
Small ; 20(21): e2309956, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38145329

RESUMO

Lateral-flow assay (LFA) is one of the most commonly used detection technologies, in which the chromatographic membranes are currently used as the lateral-flow membrane (e.g., nitrocellulose membrane, NC Mem). However, several disadvantages of existing chromatographic membranes limit the performance of LFA, including relatively low flow velocity of sample solution and relatively more residuals of sample on membrane, which increase detection time and detection noise. Herein, a surface structure membrane (SS Mem) is proposed, which enables fast self-transport of water with a convection manner and realizes low residuals of sample on membrane surface after the flow. On SS Mem, the flow velocity of water is 7.1-fold higher, and the residuals of sample are decreased by 60-67%, comparing those in NC Mem. SS Mem is used as lateral-flow membrane to prepare lateral-flow strips of nanogold LFA and fluorescence LFA for rapid detection of SARS CoV-2 nucleocapsid protein. These LFAs require 210 s per detection, with limits of detection of 3.98 pg mL-1 and 53.3 fg mL-1, sensitivity of 96.5%, and specificity of 90%. The results suggest that SS Mem enables ultrafast, highly sensitive lateral-flow immunoassays and shows great potential as a new type of lateral-flow membrane to broaden the application of LFA.


Assuntos
SARS-CoV-2 , Água , Água/química , SARS-CoV-2/isolamento & purificação , Membranas Artificiais , COVID-19 , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Humanos
14.
Small ; : e2405946, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246162

RESUMO

Under large current densities, the excessive hydroxide ion (OH) consumption hampers alkaline water splitting involving the oxygen evolution reaction (OER). High OH concentration (≈30 wt.%) is often used to enhance the catalytic activity of OER, but it also leads to higher corrosion in practical systems. To achieve higher catalytic activity in low OH concentration, catalysts on magnetic frame (CMF) are built to utilize the local magnetic convection induced from the host frame's magnetic field distributions. This way, a higher reaction rate can be achieved in relatively lower OH concentrations. A CMF model system with catalytically active CoFeOx nanograins grown on the magnetic Ni foam is demonstrated. The OER current of CoFeOx@NF receives ≈90% enhancement under 400 mT (900 mA cm-2 at 1.65 V) compared to that in zero field, and exhibits remarkable durability over 120 h. As a demonstration, the water-splitting performance sees a maximum 45% magnetic enhancement under 400 mT in 1 m KOH (700 mA cm-2 at 2.4 V), equivalent to the concentration enhancement of the same electrode in a more corrosive 2 m KOH electrolyte. Therefore, the catalyst-on-magnetic-frame strategy can make efficient use of the catalysts and achieve higher catalytic activity in low OH concentration by harvesting local magnetic convection.

15.
Electrophoresis ; 45(13-14): 1155-1170, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38115169

RESUMO

Drug delivery systems, where the nanofluid flow with electroosmosis and mixed convection can help in efficient and targeted drug delivery to specific cells or organs, could benefit from understanding the behavior of nanofluids in biological systems. In current work, authors have studied the theoretical model of two-dimensional ciliary flow of blood-based (Eyring-Powell) nanofluid model with the insertion of ternary hybrid nanoparticles along with the effects of electroosmosis, magnetohydrodynamics, thermal radiations, and mixed convection. Moreover, the features of entropy generation are also taken into consideration. The system is modeled in a wave frame with the approximations of large wave number and neglecting turbulence effects. The problem is solved numerically by using the shooting method with the assistance of computational software "Mathematica" for solving the governing equation. According to the temperature curves, the temperature will increase as the Hartman number, fluid factor, ohmic heating, and cilia length increase. It is also disclosed that ternary hybrid nanoparticles result in a change in flow rate when other problem parameters are varied, and the same is true for temperature graphs. Engineers and scientists can make better use of nanofluid-based cooling systems in electronics, automobiles, and industrial processes with the aid of the study's findings.


Assuntos
Convecção , Eletro-Osmose , Entropia , Eletro-Osmose/métodos , Nanopartículas/química , Modelos Teóricos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Hidrodinâmica , Sistemas de Liberação de Medicamentos/instrumentação
16.
Mov Disord ; 39(8): 1412-1417, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38718138

RESUMO

OBJECTIVE: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD). METHODS: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo 18F-Fluorodopa (18F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion. RESULTS: Parkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2-GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline 18F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF. CONCLUSION: After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial , Doença de Parkinson , Tomografia por Emissão de Pósitrons , Putamen , Humanos , Masculino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Putamen/metabolismo , Dependovirus/genética , Terapia Genética/métodos
17.
J Neurooncol ; 166(2): 243-255, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38261143

RESUMO

BACKGROUND: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies. METHODS: The authors performed a review of the literature for the terms "convection enhanced delivery", "glioblastoma", and "glioma". Selectclinical trials were summarized based on their various biological mechanisms and technological innovation, focusing on more recently publisheddata when possible. RESULTS: We describe the properties, features and landmark clinical trials associated with convection-enhanced delivery for malignant gliomas.We also discuss future trends that will be vital to CED innovation and improvement. CONCLUSION: Efficacy of CED for malignant glioma to date has been mixed, but improvements in technology and therapeutic agents arepromising.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias Encefálicas , Glioma , Humanos , Convecção , Sistemas de Liberação de Medicamentos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioma/tratamento farmacológico , Glioma/patologia , Produtos Biológicos/uso terapêutico , Antineoplásicos/uso terapêutico
18.
Curr Neurol Neurosci Rep ; 24(5): 123-139, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578405

RESUMO

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Barreira Hematoencefálica/patologia , Glioblastoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Microambiente Tumoral
19.
Artif Organs ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377155

RESUMO

INTRODUCTION: Hyperkalemia is frequently encountered and associated with cardio-vascular mortality in chronic hemodialysis (HD) patients. While online hemodiafiltration (OL-HDF) is thought to offer clinical benefit over high-flux HD, the impact of convective clearance on intra-dialytic potassium removal is unknown. METHODS: Chronic dialysis patients undergoing outpatient HD or OL-HDF at a single center attached to a university hospital were recruited in a prospective observational study. Spent dialysate along with clinical and biological variables were collected during a single mid-week session. RESULTS: We included 141 patients, with 21 treated with HD and 120 with OL-HDF. Mean age was 65.7 ± 15.6 years with 87 (61.7%) men. Mean intra-dialytic potassium removal was 69.9 ± 34.2 mmol. Patients on OL-HDF and HD have similar intra-dialytic potassium removal, with mean values of 69.1 ± 34.2 and 74.3 ± 35.0, respectively. In multivariate analysis, factors associated with intra-dialytic potassium removal were (decreasing order of effect size): dialysate potassium (ß -15.5, p < 0.001), pre-HD serum potassium (ß 9.1, p < 0.001), and session time (ß 7.8, p = 0.003). In OL-HDF patients, substitution flow was not associated with potassium removal. CONCLUSION: In chronic dialysis patients, convective therapy provided by OL-HDF does not affect potassium removal when compared with high-flux HD. Moreover, the importance of convective volume is not associated with potassium clearance in OL-HDF. Overall, session length and serum-to-dialysate potassium gradient are the main determinants of potassium clearance regardless of dialysis modality. Those results should inform clinicians on the optimal therapy in chronic dialysis patients in the era of OL-HDF.

20.
BMC Nephrol ; 25(1): 372, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438899

RESUMO

INTRODUCTION: Previous randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence. METHODS: We systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. RESULTS: Our study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72-0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61-0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64-1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47-1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69-0.96, P = 0.01; RR 0.93, 95% CI 0.77-1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65-0.88, P = 0.0002, RR 0.73, 95% CI 0.54-0.94, P = 0.01, respectively). CONCLUSION: In maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.


Assuntos
Hemodiafiltração , Falência Renal Crônica , Diálise Renal , Hemodiafiltração/métodos , Humanos , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Diálise Renal/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Causas de Morte , Doenças Cardiovasculares/mortalidade
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