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1.
Nano Lett ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775731

RESUMO

New approaches such as selective area growth (SAG), where crystal growth is lithographically controlled, allow the integration of bottom-up grown semiconductor nanomaterials in large-scale classical and quantum nanoelectronics. This calls for assessment and optimization of the reproducibility between individual components. We quantify the structural and electronic statistical reproducibility within large arrays of nominally identical selective area growth InAs nanowires. The distribution of structural parameters is acquired through comprehensive atomic force microscopy studies and transmission electron microscopy. These are compared to the statistical distributions of the cryogenic electrical properties of 256 individual SAG nanowire field effect transistors addressed using cryogenic multiplexer circuits. Correlating measurements between successive thermal cycles allows distinguishing between the contributions of surface impurity scattering and fixed structural properties to device reproducibility. The results confirm the potential of SAG nanomaterials, and the methodologies for quantifying statistical metrics are essential for further optimization of reproducibility.

2.
Cir Esp (Engl Ed) ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38508388

RESUMO

INTRODUCTION: Because of the obesity epidemic, more obese patients are on liver transplant (LT) waiting lists. The diseases associated with obesity may increase complications and limit survival after LT. However, there is no established measure or cut-off point to determine this impact and aid decision making. The aim of the present study is to evaluate obesity in patients undergoing LT via BMI and CT-based measurement of adipose tissue (AAT). These parameters will be used to predict the risk of postoperative complications and 5-year survival. METHODS: A retrospective, single-center study was carried out at a tertiary Spanish hospital, including all patients who received LT between January 2012 and July 2019 (n = 164). The patients were adults who underwent LT using the 'piggyback' technique, preserving the recipient vena cava. Visceral adipose tissue (VAT) and BMI were calculated to examine correlations with postoperative complications and 5-year survival. RESULTS: No significant association was found between postoperative complications by Comprehensive Complication Index, BMI, AAT/height, subcutaneous fat/height and VAT/height. Kaplan-Meier curves for 5-year survival compared LT recipients with BMI < 30.45 vs ≥30.45, with an estimated survival of 58.97 months versus 43.11 months, respectively (P < .001) (Fig. 3) and for LT recipients with an AAT/height <27.35 mm versus ≥27.35 mm, with an estimated survival of 57.69 months versus 46.34 months (P = .001). CONCLUSIONS: This study does not show a higher rate of postoperative complications in obese patients. There is a significantly lower long-term survival in patients with AAT/height ≥27.35 mm and BMI ≥ 30.45. BMI is a valid estimate of obesity and is predictive of survival.

3.
Nanoscale Horiz ; 9(4): 555-565, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38353654

RESUMO

Germanium nanowires could be the building blocks of hole-spin qubit quantum computers. Selective area epitaxy enables the direct integration of Ge nanowires on a silicon chip while controlling the device design, density, and scalability. For this to become a reality, it is essential to understand and control the initial stages of the epitaxy process. In this work, we highlight the importance of surface treatment in the reactor prior to growth to achieve high crystal quality and connected Ge nanowire structures. In particular, we demonstrate that exposure to AsH3 during the high-temperature treatment enhances lateral growth of initial Ge islands and promotes faster formation of continuous Ge nanowires in trenches. The Kolmogorov-Johnson-Mehl-Avrami crystallization model supports our explanation of Ge coalescence. These results provide critical insight into the selective epitaxy of horizontal Ge nanowires on lattice-mismatched Si substrates, which can be translated to other material systems.

4.
Nat Nanotechnol ; 19(4): 514-523, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212522

RESUMO

One of the critical factors determining the performance of neural interfaces is the electrode material used to establish electrical communication with the neural tissue, which needs to meet strict electrical, electrochemical, mechanical, biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin-film technology and its engineering to form flexible neural interfaces. The developed technology allows the fabrication of small microelectrodes (25 µm diameter) while achieving low impedance (∼25 kΩ) and high charge injection (3-5 mC cm-2). In vivo brain recording performance assessed in rodents reveals high-fidelity recordings (signal-to-noise ratio >10 dB for local field potentials), while stimulation performance assessed with an intrafascicular implant demonstrates low current thresholds (<100 µA) and high selectivity (>0.8) for activating subsets of axons within the rat sciatic nerve innervating tibialis anterior and plantar interosseous muscles. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical (12 week) and intraneural (8 week) implantation. This work describes a graphene-based thin-film microelectrode technology and demonstrates its potential for high-precision and high-resolution neural interfacing.


Assuntos
Grafite , Nanoporos , Ratos , Animais , Microeletrodos , Próteses e Implantes , Estimulação Elétrica
5.
Environ Manage ; 73(4): 697-712, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38263340

RESUMO

In recent decades, there has been a discernible reduction in temperate and Mediterranean grasslands with consequences on the decline of biodiversity and landscape heterogeneity. When this decline is due to agricultural abandonment, a renewed joint management, combining bush clearing by conservationists and grazing by farmers, should favor the maintenance of grasslands, their protected habitats and species and forage production. Rainfall irregularity explains part of the variation of these parameters. To verify these hypotheses, we conduct a comprehensive, multi-scale, multi-taxa study over a ten-year period in a Mediterranean protected area. At the regional scale, experimental plots in which this joint management was implemented are representative of residual managed grasslands of the protected area. At the mesoscale, rainfall irregularity is the main factor explaining inter-annual differences in the biomass of open landscapes, while fauna depends on management, tree cover and trophic resources. At the local scale, in a representative experimental plot, clearing had an immediate negative impact on plant richness and bird and positive on forage. Over a decade, plant biodiversity increased while forage, specialist plants and bird maintained, despite the regrowth of bush. Drought had a negative impact on richness, plant and forage abundance and phenological asynchrony on butterflies. In conclusion, joint management has positive, neutral and negative impacts to be considered before implementing this strategy. This long-term monitoring study draws important lessons for designing a sustainable management of grasslands under abandonment and irregular climate, that should be applied in temperate and Mediterranean regions that are increasingly vulnerable to these trends.


Assuntos
Borboletas , Pradaria , Animais , Humanos , Fazendeiros , Biodiversidade , Ecossistema , Plantas
6.
Ther Apher Dial ; 28(1): 3-8, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37731171

RESUMO

Nowadays, chronic kidney disease (CKD) prevalence keeps increasing worldwide. The management of these patients usually requires renal replacement therapy (RRT). However, the complexity of patients' profiles comprises a great challenge to overcome. During the last decades, CKD units have been developed to offer multidisciplinary and coordinated attention to patients, helping in the decision-making of the RRT. Nevertheless, there is a huge variability in the performance and organization of care practice, implying an existing necessity to homogenize the RRT modality chosen. We propose a test composed of two parts: one to be completed by the medical staff (to evaluate contraindications for the different RRT techniques) and another by the patient or nursing staff (to consider patients' preferences). In this sense, it would be possible to have a common and useful tool to complement patient education in RRT, as well as sharing decision-making in the ACKD units taking into account patient preferences.


Assuntos
Terapia de Substituição Renal Contínua , Insuficiência Renal Crônica , Humanos , Diálise Renal/métodos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal/métodos , Prevalência
7.
Ophthalmology ; 131(3): 277-287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37802392

RESUMO

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Ceratite por Acanthamoeba , Benzamidinas , Biguanidas , Humanos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Produção de Droga sem Interesse Comercial , Estudos Prospectivos
8.
J Exp Zool B Mol Dev Evol ; 342(4): 350-367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38155515

RESUMO

In anurans, the vertebral column diverges widely from that of other tetrapods; yet the molecular mechanisms underlying its morphogenesis remain largely unexplored. In this study, we investigate the role of the homeologous uncx.L and uncx.S genes in the vertebral column morphogenesis of the allotetraploid frog Xenopus laevis. We initiated our study by cloning the uncx orthologous genes in the anuran Xenopus and determining their spatial expression patterns using in situ hybridization. Additionally, we employed gain-of-function and loss-of-function approaches through dexamethasone-inducible uncx constructs and antisense morpholino oligonucleotides, respectively. Comparative analysis of the messenger RNA sequences of homeologous uncx genes revealed that the uncx.L variant lacks the eh1-like repressor domain. Our spatial expression analysis indicated that in the presomitic mesoderm and somites, the transcripts of uncx.L and uncx.S are located in overlapping domains. Alterations in the function of uncx genes significantly impact the development and differentiation of the sclerotome and myotome, resulting in axial skeleton malformations. Our findings suggest a scenario where the homeologous genes uncx.L and uncx.S exhibit antagonistic functions during somitogenesis. Specifically, uncx.S appears to be crucial for sclerotome development and differentiation, while uncx.L primarily influences myotome development. Postallotetraploidization, the uncx.L gene in X. laevis evolved to lose its eh1-like repressor domain, transforming into a "native dominant negative" variant that potentially competes with uncx.S for the same target genes. Finally, the histological analysis revealed that uncx.S expression is necessary for the correct formation of pedicles and neural arch of the vertebrae, and uncx.L is required for trunk muscle development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Xenopus , Xenopus laevis , Animais , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Coluna Vertebral/metabolismo , Evolução Biológica , Somitos/metabolismo
9.
United European Gastroenterol J ; 11(10): 1010-1020, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38015591

RESUMO

BACKGROUND: Preliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis. OBJECTIVE: We aimed to investigate the prevalence of significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population-based cohort from the same region. METHODS: This was a single-center, cross-sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013-February 2017. These patients were propensity score matched (ratio 1:4) with a population-based cohort from the same region (PREVHEP-ETHON study; NCT02749864; N = 5988). RESULTS: Of 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP-ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p = 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts. CONCLUSIONS: Our findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver-related causes of fibrosis.


Assuntos
Hepatopatias , Trombofilia , Humanos , Estudos Transversais , Cirrose Hepática/diagnóstico , Hepatopatias/complicações , Trombofilia/complicações , Trombofilia/epidemiologia , Trombofilia/genética
10.
Nat Commun ; 14(1): 7738, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007553

RESUMO

Bottom-up grown nanomaterials play an integral role in the development of quantum technologies but are often challenging to characterise on large scales. Here, we harness selective area growth of semiconductor nanowires to demonstrate large-scale integrated circuits and characterisation of large numbers of quantum devices. The circuit consisted of 512 quantum devices embedded within multiplexer/demultiplexer pairs, incorporating thousands of interconnected selective area growth nanowires operating under deep cryogenic conditions. Multiplexers enable a range of new strategies in quantum device research and scaling by increasing the device count while limiting the number of connections between room-temperature control electronics and the cryogenic samples. As an example of this potential we perform a statistical characterization of large arrays of identical quantum dots thus establishing the feasibility of applying cross-bar gating strategies for efficient scaling of future selective area growth quantum circuits. More broadly, the ability to systematically characterise large numbers of devices provides new levels of statistical certainty to materials/device development.

11.
Small ; : e2306045, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009519

RESUMO

Plexcitonic nanoparticles exhibit strong light-matter interactions, mediated by localized surface plasmon resonances, and thereby promise potential applications in fields such as photonics, solar cells, and sensing, among others. Herein, these light-matter interactions are investigated by UV-visible and surface-enhanced Raman scattering (SERS) spectroscopies, supported by finite-difference time-domain (FDTD) calculations. Our results reveal the importance of combining plasmonic nanomaterials and J-aggregates with near-zero-refractive index. As plexcitonic nanostructures nanorattles are employed, based on J-aggregates of the cyanine dye 5,5,6,6-tetrachloro-1,1-diethyl-3,3-bis(4-sulfobutyl)benzimidazolocarbocyanine (TDBC) and plasmonic silver-coated gold nanorods, confined within mesoporous silica shells, which facilitate the adsorption of the J-aggregates onto the metallic nanorod surface, while providing high colloidal stability. Electromagnetic simulations show that the electromagnetic field is strongly confined inside the J-aggregate layer, at wavelengths near the upper plexcitonic mode, but it is damped toward the J-aggregate/water interface at the lower plexcitonic mode. This behavior is ascribed to the sharp variation of dielectric properties of the J-aggregate shell close to the plasmon resonance, which leads to a high opposite refractive index contrast between water and the TDBC shell, at the upper and the lower plexcitonic modes. This behavior is responsible for the high SERS efficiency of the plexcitonic nanorattles under both 633 nm and 532 nm laser illumination. SERS analysis showed a detection sensitivity down to the single-nanoparticle level and, therefore, an exceptionally high average SERS intensity per particle. These findings may open new opportunities for ultrasensitive biosensing and bioimaging, as superbright and highly stable optical labels based on the strong coupling effect.

12.
Cell Rep ; 42(10): 113244, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37838947

RESUMO

Anomalous aggregation of α-synuclein (α-Syn) is a pathological hallmark of many degenerative synucleinopathies including Lewy body dementia (LBD) and Parkinson's disease (PD). Despite its strong link to disease, the precise molecular mechanisms that link α-Syn aggregation to neurodegeneration have yet to be elucidated. Here, we find that elevated α-Syn leads to an increase in the plasma membrane (PM) phosphoinositide PI(4,5)P2, which precipitates α-Syn aggregation and drives toxic increases in mitochondrial Ca2+ and reactive oxygen species leading to neuronal death. Upstream of this toxic signaling pathway is PIP5K1γ, whose abundance and localization is enhanced at the PM by α-Syn-dependent increases in ARF6. Selective inhibition of PIP5K1γ or knockout of ARF6 in neurons rescues α-Syn aggregation and cellular phenotypes of toxicity. Collectively, our data suggest that modulation of phosphoinositide metabolism may be a therapeutic target to slow neurodegeneration for PD and other related neurodegenerative disorders.


Assuntos
Doença de Parkinson , Fosfatidilinositol 4,5-Difosfato , Fosfotransferases (Aceptor do Grupo Álcool) , Agregação Patológica de Proteínas , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Neurônios/metabolismo , Doença de Parkinson/patologia , Fosfatidilinositol 4,5-Difosfato/metabolismo , Agregação Patológica de Proteínas/metabolismo , Transdução de Sinais , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
14.
J Pathol ; 261(4): 427-441, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37776271

RESUMO

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+ -adenosine triphosphatase 2a pump (SERCA2a ) and ryanodine receptor (RyR2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Injúria Renal Aguda , Cálcio , Humanos , Camundongos , Animais , Cálcio/metabolismo , Receptor de TWEAK/metabolismo , Estudos Retrospectivos , Citocina TWEAK/metabolismo , Fatores de Necrose Tumoral/metabolismo , Miócitos Cardíacos/metabolismo , Injúria Renal Aguda/metabolismo
15.
ACS Nano ; 17(17): 16943-16951, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37602824

RESUMO

Rhodium-platinum core-shell nanoparticles on a carbon support (Rh@Pt/C NPs) are promising candidates as anode catalysts for polymer electrolyte membrane fuel cells. However, their electrochemical stability needs to be further explored for successful application in commercial fuel cells. Here we employ identical location scanning transmission electron microscopy to track the morphological and compositional changes of Rh@Pt/C NPs during potential cycling (10 000 cycles, 0.06-0.8 VRHE, 0.5 H2SO4) down to the atomic level, which are then used for understanding the current evolution occurring during the potential cycles. Our results reveal a high stability of the Rh@Pt/C system and point toward particle detachment from the carbon support as the main degradation mechanism.

16.
Front Plant Sci ; 14: 1225775, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521929

RESUMO

Polyploidy is common among grasses (Poaceae) and poses challenges for conventional breeding. Genome editing technology circumvents crossing and selfing, enabling targeted modifications to multiple gene copies in a single generation while maintaining the heterozygous context of many polyploid genomes. Bahiagrass (Paspalum notatum Flüggé; 2n=4x=40) is an apomictic, tetraploid C4 species that is widely grown in the southeastern United States as forage in beef cattle production and utility turf. The chlorophyll biosynthesis gene magnesium chelatase (MgCh) was selected as a rapid readout target for establishing genome editing in tetraploid bahiagrass. Vectors containing sgRNAs, Cas9 and nptII were delivered to callus cultures by biolistics. Edited plants were characterized through PCR-based assays and DNA sequencing, and mutagenesis frequencies as high as 99% of Illumina reads were observed. Sequencing of wild type (WT) bahiagrass revealed a high level of sequence variation in MgCh likely due to the presence of at least two copies with possibly eight different alleles, including pseudogenes. MgCh mutants exhibited visible chlorophyll depletion with up to 82% reductions in leaf greenness. Two lines displayed progression of editing over time which was linked to somatic editing. Apomictic progeny of a chimeric MgCh editing event were obtained and allowed identification of uniformly edited progeny plants among a range of chlorophyll depletion phenotypes. Sanger sequencing of a highly edited mutant revealed elevated frequency of a WT allele, probably due to frequent homology-directed repair (HDR). To our knowledge these experiments comprise the first report of genome editing applied in perennial, warm-season turf or forage grasses. This technology will accelerate bahiagrass cultivar development.

17.
Intern Emerg Med ; 18(8): 2385-2395, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37493862

RESUMO

The aim was to evaluate the ability of six risk scores (4C, CURB65, SEIMC, mCHOSEN, QuickCSI, and NEWS2) to predict the outcome of patients with COVID-19 during the sixth pandemic wave in Spain. A retrospective observational study was performed to review the electronic medical records in patients ≥ 18 years of age who consulted consecutively in an emergency department with COVID-19 diagnosis throughout 2 months during the sixth pandemic wave. Clinical-epidemiological variables, comorbidities, and their respective outcomes, such as 30-day in-hospital mortality and clinical deterioration risk (a combined outcome considering: mechanical ventilation, intensive care unit admission, and/or 30-day in-hospital mortality), were calculated. The area under the curve for each risk score was calculated, and the resulting curves were compared by the Delong test, concluding with a decision curve analysis. A total of 626 patients (median age 79 years; 49.8% female) fulfilled the inclusion criteria. Two hundred and ninety-three patients (46.8%) had two or more comorbidities. Clinical deterioration risk criteria were present in 10.1% (63 cases), with a 30-day in-hospital mortality rate of 6.2% (39 cases). Comparison of the results showed that score 4C presented the best results for both outcome variables, with areas under the curve for mortality and clinical deterioration risk of 0.931 (95% CI 0.904-0.957) and 0.871 (95% CI 0.833-0.910) (both p < 0.001). The 4C Mortality Score proved to be the best score for predicting mortality or clinical deterioration risk among patients with COVID-19 attended in the emergency department in the following 30 days.


Assuntos
COVID-19 , Deterioração Clínica , Humanos , Feminino , Idoso , Lactente , Masculino , COVID-19/epidemiologia , Teste para COVID-19 , Mortalidade Hospitalar , Serviço Hospitalar de Emergência , Estudos Retrospectivos , Curva ROC
18.
Nat Metab ; 5(8): 1290-1302, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37460843

RESUMO

Having direct access to brain vasculature, astrocytes can take up available blood nutrients and metabolize them to fulfil their own energy needs and deliver metabolic intermediates to local synapses1,2. These glial cells should be, therefore, metabolically adaptable to swap different substrates. However, in vitro and in vivo studies consistently show that astrocytes are primarily glycolytic3-7, suggesting glucose is their main metabolic precursor. Notably, transcriptomic data8,9 and in vitro10 studies reveal that mouse astrocytes are capable of mitochondrially oxidizing fatty acids and that they can detoxify excess neuronal-derived fatty acids in disease models11,12. Still, the factual metabolic advantage of fatty acid use by astrocytes and its physiological impact on higher-order cerebral functions remain unknown. Here, we show that knockout of carnitine-palmitoyl transferase-1A (CPT1A)-a key enzyme of mitochondrial fatty acid oxidation-in adult mouse astrocytes causes cognitive impairment. Mechanistically, decreased fatty acid oxidation rewired astrocytic pyruvate metabolism to facilitate electron flux through a super-assembled mitochondrial respiratory chain, resulting in attenuation of reactive oxygen species formation. Thus, astrocytes naturally metabolize fatty acids to preserve the mitochondrial respiratory chain in an energetically inefficient disassembled conformation that secures signalling reactive oxygen species and sustains cognitive performance.


Assuntos
Astrócitos , Encéfalo , Camundongos , Animais , Astrócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Encéfalo/metabolismo , Cognição , Ácidos Graxos/metabolismo
19.
ACS Nano ; 17(12): 11794-11804, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37317984

RESUMO

Hybrid semiconductor-superconductor nanowires constitute a pervasive platform for studying gate-tunable superconductivity and the emergence of topological behavior. Their low dimensionality and crystal structure flexibility facilitate unique heterostructure growth and efficient material optimization, crucial prerequisites for accurately constructing complex multicomponent quantum materials. Here, we present an extensive study of Sn growth on InSb, InAsSb, and InAs nanowires and demonstrate how the crystal structure of the nanowires drives the formation of either semimetallic α-Sn or superconducting ß-Sn. For InAs nanowires, we observe phase-pure superconducting ß-Sn shells. However, for InSb and InAsSb nanowires, an initial epitaxial α-Sn phase evolves into a polycrystalline shell of coexisting α and ß phases, where the ß/α volume ratio increases with Sn shell thickness. Whether these nanowires exhibit superconductivity or not critically relies on the ß-Sn content. Therefore, this work provides key insights into Sn phases on a variety of semiconductors with consequences for the yield of superconducting hybrids suitable for generating topological systems.

20.
Biomed Pharmacother ; 164: 114997, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37311279

RESUMO

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and ß coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-ß-cyclodextrin (HßCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HßCD and U18666A, yet only HßCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, ß-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. ß-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to ß-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of ß-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.


Assuntos
COVID-19 , Fármacos Dermatológicos , beta-Ciclodextrinas , Humanos , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
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