Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 139
Filtrar
1.
Nat Commun ; 14(1): 3293, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280197

RESUMEN

Lissencephaly-1 (LIS1) is associated with neurodevelopmental diseases and is known to regulate the molecular motor cytoplasmic dynein activity. Here we show that LIS1 is essential for the viability of mouse embryonic stem cells (mESCs), and it governs the physical properties of these cells. LIS1 dosage substantially affects gene expression, and we uncovered an unexpected interaction of LIS1 with RNA and RNA-binding proteins, most prominently the Argonaute complex. We demonstrate that LIS1 overexpression partially rescued the extracellular matrix (ECM) expression and mechanosensitive genes conferring stiffness to Argonaute null mESCs. Collectively, our data transforms the current perspective on the roles of LIS1 in post-transcriptional regulation underlying development and mechanosensitive processes.


Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa , Proteínas Argonautas , Células Madre Embrionarias , Proteínas Asociadas a Microtúbulos , Animales , Ratones , 1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Blastocisto/citología , Blastocisto/metabolismo , Supervivencia Celular , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Células Madre Pluripotentes , Mapas de Interacción de Proteínas , Proteínas Argonautas/metabolismo
2.
Circ Cardiovasc Qual Outcomes ; 16(1): e008997, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36484251

RESUMEN

BACKGROUND: Discrete choice experiment is a survey method used to understand how individuals make decisions and to quantify the relative importance of features. Using discrete choice experiment methods, we quantified patient benefit-risk preferences for hypertension treatments, including pharmaceutical and interventional treatments, like renal denervation. METHODS: Respondents from the United States with physician-confirmed uncontrolled hypertension selected between treatments involving a procedure or pills, using a structured survey. Treatment features included interventional, noninterventional, or no hypertension treatment; number of daily blood pressure (BP) pills; expected reduction in office systolic BP; duration of effect; and risks of drug side effects, access site pain, or vascular injury. The results of a random-parameters logit model were used to estimate the importance of each treatment attribute. RESULTS: Among 400 patients completing the survey between 2020 and 2021, demographics included: 52% women, mean age 59.2±13.0 years, systolic BP 155.1±12.3 mm Hg, and 1.8±0.9 prescribed antihypertensive medications. Reduction in office systolic BP was the most important treatment attribute. The remaining attributes, in decreasing order, were duration of effect, whether treatment was interventional, number of daily pills, risk of vascular injury, and risk of drug side effects. Risk of access site pain did not influence choice. In general, respondents preferred noninterventional over interventional treatments, yet only a 2.3 mm Hg reduction in office systolic BP was required to offset this preference. Small reductions in office systolic BP would offset risks of vascular injury or drug side effects. At least a 20% risk of vascular injury or drug side effects would be tolerated in exchange for improved BP. CONCLUSIONS: Reduction in systolic BP was identified as the most important driver of patient treatment preference, while treatment-related risks had less influence. The results indicate that respondents would accept interventional treatments in exchange for modest reductions in systolic BP compared with those observed in renal denervation trials.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipertensión , Lesiones del Sistema Vascular , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Prioridad del Paciente , Lesiones del Sistema Vascular/tratamiento farmacológico , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Riñón , Presión Sanguínea , Antihipertensivos/efectos adversos , Dolor/tratamiento farmacológico , Preparaciones Farmacéuticas , Resultado del Tratamiento
3.
J Clin Med ; 11(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36431141

RESUMEN

Oropharyngeal and esophageal dysmotility can cause serious clinical complications such as aspiration pneumonia, cachexia, and sarcopenia, with a resulting increase in mortality and disability. The current standard of care for the treatment of SSc-associated swallowing dysfunction is mainly supportive, although severe cases are usually refractory to conventional management. Recent studies have shown that the abnormal production of functional autoantibodies such as anti-cholinergic muscarinic receptor III antibodies may participate in the pathogenesis of SSc-associated gastrointestinal dysmotility and may provide a novel target for therapeutic intervention. We describe two patients with severe and rapid onset of SSc-associated severe swallowing dysfunction and esophageal dysmotility who had failed standard of care therapy, requiring complete enteral and parenteral nutrition. Both patients were positive for the presence of circulating antimuscarinic III receptor antibodies. They were treated with IVIG at a dose of 2 g/Kg/month divided in two consecutive days, for six months. Following IVIG therapy, both patients markedly improved their symptoms as shown by a reduction in their UCLA2.0 score, and achieved an improvement of esophageal motility documented radiologically. Both patients resumed oral feeding and had their feeding tubes removed within the treatment period. None of the patients developed severe adverse events attributable to IVIG, except for low-grade fever during IVIG infusion in one of the cases. These results provide support for the role of functional autoantibodies in the development of SSc-associated gastrointestinal dysfunction.

4.
Sensors (Basel) ; 22(18)2022 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-36146391

RESUMEN

A protocol for successfully depositing [001] textured, 2−3 µm thick films of Al0.75Sc0.25N, is proposed. The procedure relies on the fact that sputtered Ti is [001]-textured α-phase (hcp). Diffusion of nitrogen ions into the α-Ti film during reactive sputtering of Al0.75,Sc0.25N likely forms a [111]-oriented TiN intermediate layer. The lattice mismatch of this very thin film with Al0.75Sc0.25N is ~3.7%, providing excellent conditions for epitaxial growth. In contrast to earlier reports, the Al0.75Sc0.25N films prepared in the current study are Al-terminated. Low growth stress (<100 MPa) allows films up to 3 µm thick to be deposited without loss of orientation or decrease in piezoelectric coefficient. An advantage of the proposed technique is that it is compatible with a variety of substrates commonly used for actuators or MEMS, as demonstrated here for both Si wafers and D263 borosilicate glass. Additionally, thicker films can potentially lead to increased piezoelectric stress/strain by supporting application of higher voltage, but without increase in the magnitude of the electric field.

5.
EMBO Rep ; 23(7): e54755, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35642585

RESUMEN

Malaria is the most serious mosquito-borne parasitic disease, caused mainly by the intracellular parasite Plasmodium falciparum. The parasite invades human red blood cells and releases extracellular vesicles (EVs) to alter its host responses. It becomes clear that EVs are generally composed of sub-populations. Seeking to identify EV subpopulations, we subject malaria-derived EVs to size-separation analysis, using asymmetric flow field-flow fractionation. Multi-technique analysis reveals surprising characteristics: we identify two distinct EV subpopulations differing in size and protein content. Small EVs are enriched in complement-system proteins and large EVs in proteasome subunits. We then measure the membrane fusion abilities of each subpopulation with three types of host cellular membranes: plasma, late and early endosome. Remarkably, small EVs fuse to early endosome liposomes at significantly greater levels than large EVs. Atomic force microscope imaging combined with machine-learning methods further emphasizes the difference in biophysical properties between the two subpopulations. These results shed light on the sophisticated mechanism by which malaria parasites utilize EV subpopulations as a communication tool to target different cellular destinations or host systems.


Asunto(s)
Vesículas Extracelulares , Malaria , Parásitos , Animales , Eritrocitos/parasitología , Vesículas Extracelulares/metabolismo , Humanos , Plasmodium falciparum
6.
ACS Omega ; 7(51): 47747-47754, 2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36591209

RESUMEN

The spontaneous gelation of poly(4-vinyl pyridine)/pyridine solution produces materials with conductive properties that are suitable for various energy conversion technologies. The gel is a thermoelectric material with a conductivity of 2.2-5.0 × 10-6 S m-1 and dielectric constant ε = 11.3. On the molecular scale, the gel contains various types of hydrogen bonding, which are formed via self-protonation of the pyridine side chains. Our measurements and calculations revealed that the gelation process produces bias-dependent polymer complexes: quasi-symmetric, strongly hydrogen-bonded species, and weakly bound protonated structures. Under an applied DC bias, the gelled complexes differ in their capacitance/conductive characteristics. In this work, we exploited the bias-responsive characteristics of poly(4-vinyl pyridine) gelled complexes to develop a prototype of a thermal energy harvesting device. The measured device efficiency is S = ΔV/ΔT = 0.18 mV/K within the temperature range of 296-360 K. Investigation of the mechanism underlying the conversion of thermal energy into electric charge showed that the heat-controlled proton diffusion (the Soret effect) produces thermogalvanic redox reactions of hydrogen ions on the anode. The charge can be stored in an external capacitor for heat energy harvesting. These results advance our understanding of the molecular mechanisms underlying thermal energy conversion in the poly(4-vinyl pyridine)/pyridine gel. A device prototype, enabling thermal energy harvesting, successfully demonstrates a simple path toward the development of inexpensive, low-energy thermoelectric generators.

7.
Polymers (Basel) ; 13(21)2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34771407

RESUMEN

Poly(L-lactic acid) (PLLA) is a biocompatible, biodegradable, and semi-crystalline polymer with numerous applications including food packaging, medical implants, stents, tissue engineering scaffolds, etc. Hydroxyapatite (HA) is the major component of natural bone. Conceptually, combining PLLA and HA could produce a bioceramic suitable for implants and bone repair. However, this nanocomposite suffers from poor mechanical behavior under tensile strain. In this study, films of PLLA and HA were prepared with small amounts of nontoxic WS2 nanotubes (INT-WS2). The structural aspects of the films were investigated via electron microscopy, X-ray diffraction, Raman microscopy, and infrared absorption spectroscopy. The mechanical properties were evaluated via tensile measurements, micro-hardness tests, and nanoindentation. The thermal properties were investigated via differential scanning calorimetry. The composite films exhibited improved mechanical and thermal properties compared to the films prepared from the PLLA and HA alone, which is advantageous for medical applications.

8.
Beilstein J Nanotechnol ; 12: 878-901, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34476169

RESUMEN

Progress in computing capabilities has enhanced science in many ways. In recent years, various branches of machine learning have been the key facilitators in forging new paths, ranging from categorizing big data to instrumental control, from materials design through image analysis. Deep learning has the ability to identify abstract characteristics embedded within a data set, subsequently using that association to categorize, identify, and isolate subsets of the data. Scanning probe microscopy measures multimodal surface properties, combining morphology with electronic, mechanical, and other characteristics. In this review, we focus on a subset of deep learning algorithms, that is, convolutional neural networks, and how it is transforming the acquisition and analysis of scanning probe data.

9.
ACS Nano ; 15(9): 14643-14652, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34516094

RESUMEN

We demonstrate the solvent-free amorphous-to-cocrystalline transformations of nanoscale molecular films. Exposing amorphous films to vapors of a haloarene results in the formation of a cocrystalline coating. This transformation proceeds by gradual strengthening of halogen-bonding interactions as a result of the crystallization process. The gas-solid diffusion mechanism involves formation of an amorphous metastable phase prior to crystallization of the films. In situ optical microscopy shows mass transport during this process, which is confirmed by cross-section analysis of the final structures using focused ion beam milling combined with scanning electron microscopy. Nanomechanical measurements show that the rigidity of the amorphous films influences the crystallization process. This surface transformation results in molecular arrangements that are not readily obtained through other means. Cocrystals grown in solution crystallize in a monoclinic centrosymmetric space group, whereas the on-surface halogen-bonded assembly crystallizes into a noncentrosymmetric material with a bulk second-order nonlinear optical response.

10.
Adv Sci (Weinh) ; 8(18): e2101773, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34292678

RESUMEN

It is established that electron transmission through chiral molecules depends on the electron's spin. This phenomenon, termed the chiral-induced spin selectivity (CISS), effect has been observed in chiral molecules, supramolecular structures, polymers, and metal-organic films. Which spin is preferred in the transmission depends on the handedness of the system and the tunneling direction of the electrons. Molecular motors based on overcrowded alkenes show multiple inversions of helical chirality under light irradiation and thermal relaxation. The authors found here multistate switching of spin selectivity in electron transfer through first generation molecular motors based on the four accessible distinct helical configurations, measured by magnetic-conductive atomic force microscopy. It is shown that the helical state dictates the molecular organization on the surface. The efficient spin polarization observed in the photostationary state of the right-handed motor coupled with the modulation of spin selectivity through the controlled sequence of helical states, opens opportunities to tune spin selectivity on-demand with high spatio-temporal precision. An energetic analysis correlates the spin injection barrier with the extent of spin polarization.

11.
Angew Chem Int Ed Engl ; 60(33): 18256-18264, 2021 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-34115416

RESUMEN

We demonstrate here a unique metallo-organic material where the appearance and the internal crystal structure are in contradiction. The egg-shaped (ovoid) crystals have a brain-like texture. Although these micro-sized crystals are monodispersed; like fingerprints their grainy surfaces are never exactly alike. Remarkably, our X-ray and electron diffraction studies unexpectedly revealed that these structures are single-crystals comprising a continuous coordination network of two differently shaped homochiral channels. By using the same building blocks under different reaction conditions, a rare series of crystals have been obtained that are uniquely rounded in their shape. In stark contrast to the brain-like crystals, these isostructural and monodispersed crystals have a comparatively smooth appearance. The sizes of these crystals vary by several orders of magnitude.

12.
J Am Coll Cardiol ; 77(23): 2909-2919, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33957242

RESUMEN

BACKGROUND: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. OBJECTIVES: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. METHODS: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. RESULTS: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. CONCLUSIONS: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).


Asunto(s)
Presión Sanguínea/fisiología , Hipertensión/sangre , Arteria Renal/inervación , Renina/sangre , Simpatectomía/métodos , Biomarcadores/sangre , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Hipertensión/fisiopatología , Hipertensión/cirugía , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina/fisiología , Método Simple Ciego , Sístole , Resultado del Tratamiento
13.
ACS Appl Mater Interfaces ; 13(17): 20269-20276, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33886271

RESUMEN

The technologically important frequency range for the application of electrostrictors and piezoelectrics is tens of Hz to tens of kHz. Sm3+- and Gd3+-doped ceria ceramics, excellent intermediate-temperature ion conductors, have been shown to exhibit very large electrostriction below 1 Hz. Why this is so is still not understood. While optimal design of ceria-based devices requires an in-depth understanding of their mechanical and electromechanical properties, systematic investigation of the influence of dopant size on frequency response is lacking. In this report, the mechanical and electromechanical properties of dense ceria ceramics doped with trivalent lanthanides (RE0.1Ce0.9O1.95, RE = Lu, Yb, Er, Gd, Sm, and Nd) were investigated. Young's, shear, and bulk moduli were obtained from ultrasound pulse echo measurements. Nanoindentation measurements revealed room-temperature creep in all samples as well as the dependence of Young's modulus on the unloading rate. Both are evidence for viscoelastic behavior, in this case anelasticity. For all samples, within the frequency range f = 0.15-150 Hz and electric field E ≤ 0.7 MV/m, the longitudinal electrostriction strain coefficient (|M33|) was 102 to 104-fold larger than expected for classical (Newnham) electrostrictors. However, electrostrictive strain in Er-, Gd-, Sm-, and Nd-doped ceramics exhibited marked frequency relaxation, with the Debye-type characteristic relaxation time τ ≤ 1 s, while for the smallest dopants-Lu and Yb-little change in electrostrictive strain was detected over the complete frequency range studied. We find that only the small, less-studied dopants continue to produce useable electrostrictive strain at the higher frequencies. We suggest that this striking difference in frequency response may be explained by postulating that introduction of a dopant induces two types of polarizable elastic dipoles and that the dopant size determines which of the two will be dominant.

14.
Clin Res Cardiol ; 110(5): 609-619, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33646357

RESUMEN

Renal denervation has emerged as a safe and effective therapy to lower blood pressure in hypertensive patients. In addition to the main renal arteries, branch vessels are also denervated in more contemporary studies. Accurate and reliable imaging in renal denervation patients is critical for long-term safety surveillance due to the small risk of renal artery stenosis that may occur after the procedure. This review summarizes three common non-invasive imaging modalities: Doppler ultrasound (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). DUS is the most widely used owing to cost considerations, ease of use, and the fact that it is less invasive, avoids ionizing radiation exposure, and requires no contrast media use. Renal angiography is used to determine if renal artery stenosis is present when non-invasive imaging suggests renal artery stenosis. We compiled data from prior renal denervation studies as well as the more recent SPYRAL-HTN OFF MED Study and show that DUS demonstrates both high sensitivity and specificity for detecting renal stenosis de novo and in longitudinal assessment of renal artery patency after interventions. In the context of clinical trials DUS has been shown, together with the use of the baseline angiogram, to be effective in identifying stenosis in branch and accessory arteries and merits consideration as the main screening imaging modality to detect clinically significant renal artery stenosis after renal denervation and this is consistent with guidelines from the recent European Consensus Statement on Renal Denervation.


Asunto(s)
Desnervación/métodos , Hipertensión/cirugía , Arteria Renal/cirugía , Angiografía por Tomografía Computarizada/métodos , Desnervación/efectos adversos , Humanos , Angiografía por Resonancia Magnética/métodos , Arteria Renal/diagnóstico por imagen , Arteria Renal/inervación , Obstrucción de la Arteria Renal/diagnóstico por imagen , Sensibilidad y Especificidad , Ultrasonografía Doppler/métodos
15.
Nat Commun ; 12(1): 1172, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608523

RESUMEN

Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. Pf, while growing inside its natural host, the human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential host cell remains unknown. Here we demonstrate that Pf parasites, cultured in fresh human donor blood, secrete within such EVs assembled and functional 20S proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve human RBCs by remodeling their cytoskeletal network. Furthermore, we identify four degradation targets of the secreted 20S proteasome, the phosphorylated cytoskeletal proteins ß-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome secretion mechanism employed by the human malaria parasite, which primes RBCs for parasite invasion by altering membrane stiffness, to facilitate malaria parasite growth.


Asunto(s)
Transporte Biológico/fisiología , Eritrocitos/metabolismo , Interacciones Huésped-Parásitos/fisiología , Malaria Falciparum/metabolismo , Plasmodium falciparum/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Citoesqueleto/metabolismo , Eritrocitos/citología , Eritrocitos/parasitología , Humanos , Malaria Falciparum/parasitología , Proteínas de la Membrana/metabolismo , Fosforilación , Plasmodium falciparum/crecimiento & desarrollo , Proteómica
16.
Beilstein J Org Chem ; 17: 42-51, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33488830

RESUMEN

The facile fabrication of free-floating organic nanocrystals (ONCs) was achieved via the kinetically controlled self-assembly of simple perylene diimide building blocks in aqueous medium. The ONCs have a thin rectangular shape, with an aspect ratio that is controlled by the content of the organic cosolvent (THF). The nanocrystals were characterized in solution by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering. The ONCs retain their structure upon drying, as was evidenced by TEM and atom force microscopy. Photophysical studies, including femtosecond transient absorption spectroscopy, revealed a distinct influence of the ONC morphology on their photonic properties (excitation energy transfer was observed only in the high-aspect ONCs). Convenient control over the structure and function of organic nanocrystals can enhance their utility in new and developed technologies.

17.
Commun Chem ; 4(1): 62, 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-36697777

RESUMEN

The process of amyloid nanofibril formation has broad implications including the generation of the strongest natural materials, namely silk fibers, and their major contribution to the progression of many degenerative diseases. The key question that remains unanswered is whether the amyloidogenic nature, which includes the characteristic H-bonded ß-sheet structure and physical characteristics of protein assemblies, can be modified via controlled intervention of the molecular interactions. Here we show that tailored changes in molecular interactions, specifically in the H-bonded network, do not affect the nature of amyloidogenic fibrillation, and even have minimal effect on the initial nucleation events of self-assembly. However, they do trigger changes in networks at a higher hierarchical level, namely enhanced 2D packaging which is rationalized by the 3D hierarchy of ß-sheet assembly, leading to variations in fibril morphology, structural composition and, remarkably, nanomechanical properties. These results pave the way to a better understanding of the role of molecular interactions in sculpting the structural and physical properties of protein supramolecular constructs.

18.
EuroIntervention ; 16(18): e1496-e1502, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33226002

RESUMEN

AIMS: Multiple endpoints with varying clinical relevance are available to establish the efficacy of device-based treatments. Given the variance among blood pressure measures and medication changes in hypertension trials, we performed a win ratio analysis of outcomes in a sham-controlled, randomised trial of renal denervation (RDN) in patients with uncontrolled hypertension despite commonly prescribed antihypertensive medications. We propose a novel prioritised endpoint framework for determining the treatment benefit of RDN compared with sham control. METHODS AND RESULTS: We analysed the SPYRAL HTN-ON MED pilot study data using a prioritised hierarchical endpoint comprised of 24-hour mean ambulatory systolic blood pressure (SBP), office SBP, and medication burden. A generalised pairwise comparisons methodology (win ratio) was extended to examine this endpoint. Clinically relevant thresholds of 5 and 10 mmHg were used for comparisons of ambulatory and office SBP, respectively, and therefore to define treatment "winners" and "losers". For a total number of 1,596 unmatched pairs, the RDN subject was the winner in 1,050 pairs, the RDN subject was the loser in 378 pairs, and 168 pairs were tied. The win ratio in favour of RDN was 2.78 (95% confidence interval [CI]: 1.58 to 5.48; p<0.001) and corresponding net benefit statistic was 0.42 (95% CI: 0.20 to 0.63). Sensitivity analyses performed with differing blood pressure thresholds and according to drug adherence testing demonstrated consistent results. CONCLUSIONS: The win ratio method addresses prior limitations by enabling inclusion of more patient-oriented results while prioritising those endpoints considered most clinically important. Applying these methods to the SPYRAL HTN-ON MED pilot study (ClinicalTrials.gov Identifier: NCT02439775), RDN was determined to be superior regarding a hierarchical endpoint and a "winner" compared with sham control patients.


Asunto(s)
Hipertensión , Simpatectomía , Antihipertensivos/uso terapéutico , Presión Sanguínea , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/cirugía , Riñón , Proyectos Piloto , Resultado del Tratamiento
19.
Clin Res Cardiol ; 110(5): 725-731, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32740754

RESUMEN

BACKGROUND: Catheter-based renal denervation (RDN) reduces blood pressure (BP) throughout the 24-h period, as reported in several randomized sham-controlled trials. Reduction of BP in the early morning hours is especially important due to increased cardiovascular risks during that time. OBJECTIVE: In this report, we examine the impact of RDN on systolic BP (SBP) and diastolic BP (DBP) during the critical morning surge period in a post-hoc analysis of patients in the SPYRAL HTN-ON MED trial. METHODS AND RESULTS: Ambulatory BP measurements were collected at baseline and 6 months for treatment and control patient groups over 24-h periods. Average morning BP surge is the difference between average morning BP and average nighttime BP, and the morning surge slope reflects the rate of change of BP from nighttime to morning. Mean morning DBP surge slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6 mmHg/h; p = 0.029). In the RDN group, morning DBP surge slopes were significantly lower at 6 months compared to baseline (1.1 vs. 4.1 mmHg/h; p = 0.006). Similar patterns were observed for mean morning SBP surge slope but did not reach statistical significance. CONCLUSIONS: This decrease in the morning DBP surge slope, an index of the sympathetically-mediated morning BP surge, thus indicates a drop in late morning BP relative to early morning/nocturnal BP in the RDN group. Thus, RDN appears effective in attenuating the slope of morning surge in DBP that might indicate possible benefits in a high-risk hypertensive population. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov (NCT02439775), registered May 12, 2015.


Asunto(s)
Presión Sanguínea/fisiología , Hipertensión/cirugía , Arteria Renal/cirugía , Simpatectomía/métodos , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Arteria Renal/inervación , Factores de Tiempo , Resultado del Tratamiento
20.
Environ Sci Technol ; 54(19): 11827-11837, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32870663

RESUMEN

Transformations of biomass burning brown carbon aerosols (BB-BrC) over their diurnal lifecycle are currently not well studied. In this study, the aging of BB tar proxy aerosols processed by NO3• under dark conditions followed by the photochemical OH• reaction and photolysis were investigated in tandem flow reactors. The results show that O3 oxidation in the dark diminishes light absorption of wood tar aerosols, resulting in higher particle single-scattering albedo (SSA). NO3• reactions augment the mass absorption coefficient (MAC) of the aerosols by a factor of 2-3 by forming secondary chromophores, such as nitroaromatic compounds (NACs) and organonitrates. Subsequent OH• oxidation and direct photolysis both decompose the organic nitrates (ONs, representing bulk functionalities of NACs and organonitrates) in the NO3•-aged wood tar aerosols, thus decreasing particle absorption. Moreover, NACs degrade faster than organonitrates by photochemical aging. The NO3•-aged wood tar aerosols are more susceptible to photolysis than to OH• reactions. The photolysis lifetimes for the ONs and for the absorbance of the NO3•-aged aerosols are on the order of hours under typical solar irradiation, while the absorption and ON lifetimes toward OH• oxidation are substantially longer. Overall, nighttime aging via NO3• reactions increases the light absorption of wood tar aerosols and shortens their absorption lifetime under daytime conditions.


Asunto(s)
Contaminantes Atmosféricos , Carbono , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Biomasa , Carbono/análisis , Laboratorios , Fotólisis
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...