Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.059
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
PLoS Biol ; 21(12): e3002416, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38048319

RESUMO

Phages are one of the key ecological drivers of microbial community dynamics, function, and evolution. Despite their importance in bacterial ecology and evolutionary processes, phage genes are poorly characterized, hampering their usage in a variety of biotechnological applications. Methods to characterize such genes, even those critical to the phage life cycle, are labor intensive and are generally phage specific. Here, we develop a systematic gene essentiality mapping method scalable to new phage-host combinations that facilitate the identification of nonessential genes. As a proof of concept, we use an arrayed genome-wide CRISPR interference (CRISPRi) assay to map gene essentiality landscape in the canonical coliphages λ and P1. Results from a single panel of CRISPRi probes largely recapitulate the essential gene roster determined from decades of genetic analysis for lambda and provide new insights into essential and nonessential loci in P1. We present evidence of how CRISPRi polarity can lead to false positive gene essentiality assignments and recommend caution towards interpreting CRISPRi data on gene essentiality when applied to less studied phages. Finally, we show that we can engineer phages by inserting DNA barcodes into newly identified inessential regions, which will empower processes of identification, quantification, and tracking of phages in diverse applications.


Assuntos
Bacteriófagos , Bacteriófagos/genética , DNA , Genes Essenciais/genética
2.
Brain ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167538

RESUMO

The development and maintenance of chronic pain involves the reorganization of spinal nociceptive circuits. The mechanistic target of rapamycin complex 2 (mTORC2), a central signaling hub that modulates both actin-dependent structural changes and mTORC1-dependent mRNA translation, plays key roles in hippocampal synaptic plasticity and memory formation. However, its function in spinal plasticity and chronic pain is poorly understood. Here we show that pharmacological activation of spinal mTORC2 induces pain hypersensitivity, whereas its inhibition, using downregulation of the mTORC2-defining component Rictor, alleviates both inflammatory and neuropathic pain. Cell-type-specific deletion of Rictor showed that the selective inhibition of mTORC2 in a subset of excitatory neurons impairs spinal synaptic potentiation and alleviates inflammation-induced mechanical and thermal hypersensitivity, and nerve injury-induced heat hyperalgesia. The ablation of mTORC2 in inhibitory interneurons strongly alleviated nerve injury-induced mechanical hypersensitivity. Our findings reveal the role of mTORC2 in chronic pain and highlight its cell-type-specific functions in mediating pain hypersensitivity in response to peripheral inflammation and nerve injury.

3.
Nano Lett ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356872

RESUMO

Nonlinear optical materials of atomic thickness, such as non-centrosymmetric 2H transition metal dichalcogenide monolayers, have a second-order nonlinear susceptibility (χ(2)) whose intensity can be tuned by strain. However, whether χ(2) is enhanced or reduced by tensile strain is a subject of conflicting reports. Here, we grow high-quality MoSe2 monolayers under controlled biaxial strain created by two different substrates and study their linear and nonlinear optical responses with a combination of experimental and theoretical approaches. Up to a 15-fold overall enhancement in second-harmonic generation (SHG) intensity is observed from MoSe2 monolayers grown on SiO2 when compared to its value on a Si3N4 substrate. By considering an interference contribution from different dielectrics and their thicknesses, a factor of 2 enhancement of χ(2) was attributed to the biaxial strain: substrate interference and strain are independent handles to engineer the SHG strength of non-centrosymmetric 2D materials.

4.
Gut ; 2024 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-39461739

RESUMO

BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

5.
J Am Chem Soc ; 146(33): 22970-22981, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39120593

RESUMO

Mixed tin-lead (Sn-Pb) halide perovskites stand out as promising materials for next-generation photovoltaics and near-infrared optoelectronics. However, their sensitivity to oxidative degradation remains a major hurdle toward their widespread deployment. A holistic understanding of their oxidation processes considering all their constituent ions is therefore essential to stabilize these materials. Herein, we reveal that A-site cation choice plays an inconspicuous yet crucial role in determining Sn-Pb perovskite stability toward oxidation. Comparing typical A-site compositions, we show that thin films and solar cells containing cesium are more resistant to oxidative stress relative to their methylammonium analogs. We identify degradation in these compositions to be closely linked to the presence of triiodide, a harmful species evolving from native I2 oxidants. We find that hydrogen bonding between methylammonium and I2 promotes triiodide formation, while the strong polarizing character of cesium limits this process by capturing I2. Inspired from these findings, we design two strategies to boost stability of sensitive methylammonium-based Sn-Pb perovskite films and devices against oxidation. Specifically, we modulate the polarizing character of surface A-sites in perovskite via CsI and RbI coatings, and we incorporate Na2S2O3 as an I2 scavenging additive. These crucial mechanistic insights will pave the way for the design of highly efficient and stable Sn-Pb perovskite optoelectronics.

6.
Br J Cancer ; 130(1): 63-72, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37973956

RESUMO

BACKGROUND: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. METHODS: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. RESULTS: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). CONCLUSION: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. TRIAL REGISTRATION: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estudos Prospectivos , Vesículas Extracelulares/metabolismo , Biópsia Líquida , Biomarcadores Tumorais/genética
7.
Am J Gastroenterol ; 119(4): 646-654, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983769

RESUMO

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Metronidazol/uso terapêutico , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto/uso terapêutico , Amoxicilina/uso terapêutico , Tinidazol , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos
8.
Clin Chem ; 70(1): 81-89, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175586

RESUMO

BACKGROUND: Metastasis is the leading cause of cancer-related deaths. Most studies have focused on the primary tumor or on overt metastatic lesions, leaving a significant knowledge gap concerning blood-borne cancer cell dissemination, a major step in the metastatic cascade. Circulating tumor cells (CTCs) in the blood of patients with solid cancer can now be enumerated and investigated at the molecular level, giving unexpected information on the biology of the metastatic cascade. CONTENT: Here, we reviewed recent advances in basic and translational/clinical research on CTCs as key elements in the metastatic cascade. SUMMARY: Findings from translational studies on CTCs have elucidated the complexity of the metastatic process. Fully understanding this process will open new potential avenues for cancer therapeutic and diagnostic strategies to propose precision medicine to all cancer patients.


Assuntos
Células Neoplásicas Circulantes , Humanos , Pesquisa Translacional Biomédica , Conhecimento , Medicina de Precisão
9.
New Phytol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238145

RESUMO

Arsenic poses a global threat to living organisms, compromising crop security and yield. Limited understanding of the transcriptional network integrating arsenic-tolerance mechanisms with plant developmental responses hinders the development of strategies against this toxic metalloid. Here, we conducted a high-throughput yeast one-hybrid assay using as baits the promoter region from the arsenic-inducible genes ARQ1 and ASK18 from Arabidopsis thaliana, coupled with a transcriptomic analysis, to uncover novel transcriptional regulators of the arsenic response. We identified the GLABRA2 (GL2) transcription factor as a novel regulator of arsenic tolerance, revealing a wider regulatory role beyond its established function as a repressor of root hair formation. Furthermore, we found that ANTHOCYANINLESS2 (ANL2), a GL2 subfamily member, acts redundantly with this transcription factor in the regulation of arsenic signaling. Both transcription factors act as repressors of arsenic response. gl2 and anl2 mutants exhibit enhanced tolerance and reduced arsenic accumulation. Transcriptional analysis in the gl2 mutant unveils potential regulators of arsenic tolerance. These findings highlight GL2 and ANL2 as novel integrators of the arsenic response with developmental outcomes, offering insights for developing safer crops with reduced arsenic content and increased tolerance to this hazardous metalloid.

10.
PLoS Comput Biol ; 19(11): e1011208, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37983271

RESUMO

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioma/tratamento farmacológico , Glioma/patologia , Temozolomida/farmacologia , Temozolomida/uso terapêutico
11.
Helicobacter ; 29(4): e13111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39001621

RESUMO

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento
12.
Environ Res ; 252(Pt 3): 118913, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38643821

RESUMO

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.


Assuntos
Exposição Ambiental , Expossoma , Humanos , Colômbia/epidemiologia , Pré-Escolar , Feminino , Exposição Ambiental/análise , Masculino , Poluentes Atmosféricos/análise , Gravidez , Poluição do Ar/análise , Estudos de Coortes
13.
World J Surg ; 48(7): 1730-1738, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38725097

RESUMO

BACKGROUND: Gallstone-related conditions affect a significant portion of the population, with varying prevalence among different ethnic groups. Complications such as pancreatitis and cholangitis are associated with the presence of common bile duct (CBD) stones. Existing guidelines for diagnosing choledocholithiasis lack precision, leading to excessive use of invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A prospective study was conducted at Hospital Central "Dr. Ignacio Morones Prieto," involving 374 patients in the development cohort and 154 patients in the validation cohort. Patients meeting inclusion criteria underwent biochemical testing and ultrasonography. A predictive scoring system was developed using logistic regression and validated in an independent cohort. Clinical and laboratory variables were collected, and model performance was assessed using receiver-operator characteristic (ROC) curves. RESULTS: The predictive model incorporated variables such as age, pancreatitis, cholangitis, bilirubin levels, and CBD stone presence on ultrasound. The model demonstrated an area under the ROC curve (AUC) of 93.81% in the validation dataset. By adjusting the threshold defining high-risk probability to 40%, the model improved specificity and sensitivity compared to existing guidelines. Notably, the model reclassified patients, leading to a more accurate risk assessment. CONCLUSIONS: The developed algorithm accurately predicts choledocholithiasis non-invasively in patients with symptomatic gallstones. This tool has the potential to reduce reliance on costly or invasive procedures like magnetic resonance cholangiopancreatography and ERCP, offering a more efficient and cost-effective approach to patient management. The user-friendly calculator developed in this study could streamline diagnostic procedures, particularly in resource-limited healthcare settings, ultimately improving patient care.


Assuntos
Coledocolitíase , Humanos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/diagnóstico , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Curva ROC , Valor Preditivo dos Testes , Ultrassonografia , Modelos Logísticos
14.
Pediatr Exerc Sci ; 36(4): 201-210, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39069282

RESUMO

BACKGROUND: Phase angle (PhA) is an indicator of cellular health, function, and integrity. PhA has been considered an indicator of nutritional and health status, but it is uncertain whether it could be used as a fitness or athletic performance indicator. OBJECTIVE: To analyze the relationship between PhA and the fitness and athletic performance of adolescent boxers and to know whether this association is independent of body composition. METHODS: Thirty-seven trained youth boxers (15-18 y old) participated in the study. Participants underwent anthropometry and bioelectrical impedance assessments. The following tests were conducted: Fitness-Gram battery; speed, agility, and quickness; ball throws; punch impact force; bench press maximal strength; and vertical and horizontal jumps. Linear regression models were estimated and adjusted by covariates. RESULTS: The PhA was related to upper-limb strength. Nevertheless, in linear regression models, after adjusting models by body composition, only PhA remained as a predictor of relative maximal strength. The PhA was not a predictor of speed, agility, and quickness; cardiorespiratory fitness; or lower-limb power, in which adiposity was the main predictor of fitness. CONCLUSIONS: In adolescent boxers, PhA can predict upper-limb maximal strength independently of bioelectrical impedance analysis premises. However, compared with mucle mass, PhA is not a better predictor of upper-limb maximal strength.


Assuntos
Desempenho Atlético , Composição Corporal , Boxe , Impedância Elétrica , Força Muscular , Humanos , Adolescente , Desempenho Atlético/fisiologia , Masculino , Força Muscular/fisiologia , Boxe/fisiologia , Aptidão Física/fisiologia , Feminino , Antropometria , Aptidão Cardiorrespiratória/fisiologia , Teste de Esforço , Modelos Lineares , Extremidade Superior/fisiologia
15.
Sensors (Basel) ; 24(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400500

RESUMO

One of the main lines of research in distributed learning in recent years is the one related to Federated Learning (FL). In this work, a decentralized Federated Learning algorithm based on consensus (CoL) is applied to Wireless Ad-hoc Networks (WANETs), where the agents communicate with other agents to share their learning model as they are available to the wireless connection range. When deploying a set of agents, it is essential to study whether all the WANET agents will be reachable before the deployment. The paper proposes to explore it by generating a simulation close to the real world using a framework (FIVE) that allows the easy development and modification of simulations based on Unity and SPADE agents. A fruit orchard with autonomous tractors is presented as a case study. The paper also presents how and why the concept of artifact has been included in the above-mentioned framework as a way to highlight the importance of some devices used in the environment that have to be located in specific places to ensure the full connection of the system. This inclusion is the first step to allow Digital Twins to be modeled with this framework, now allowing a Digital Shadow of those devices.

16.
Int J Mol Sci ; 25(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38397077

RESUMO

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.


Assuntos
Antioxidantes , Envelhecimento da Pele , Humanos , Antioxidantes/farmacologia , Raios Ultravioleta/efeitos adversos , Pele/metabolismo , Estresse Oxidativo
17.
Molecules ; 29(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39339496

RESUMO

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. The current antichagasic drugs nifurtimox and benznidazole have inconveniences of toxicity; therefore, the search for alternative therapeutic strategies is necessary. The present study reports the synthesis, drug-likeness predictions, and in vitro anti-trypanosome activity of a series of 14 quinazoline 2,4,6-triamine derivatives. All compounds were tested against T. cruzi (epimastigotes and trypomastigotes) and in HFF1 human foreskin fibroblasts. The bioassays showed that compounds 2-4 containing nitrobenzoyl substituents at 6-position of the quinazoline 2,4,6-triamine nucleus were the most potent on its antiprotozoal activity. The effect was observed at 24 h and it was preserved for at least 5 days. Also, compounds 2-4 were not toxic to the human control cells, showing high selectivity index. The quinazoline nitro derivatives have potential use as antichagasic agents.


Assuntos
Quinazolinas , Tripanossomicidas , Trypanosoma cruzi , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química , Humanos , Trypanosoma cruzi/efeitos dos fármacos , Tripanossomicidas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/química , Relação Estrutura-Atividade , Fibroblastos/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Estrutura Molecular , Linhagem Celular
18.
Gastroenterol Hepatol ; 47(3): 246-252, 2024 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37236304

RESUMO

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.


Assuntos
Duodeno , Mucosa , Humanos , Consenso , Endoscopia do Sistema Digestório
19.
J Infect Dis ; 228(6): 674-683, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37384795

RESUMO

BACKGROUND: Varicella causes a major health burden in many low- to middle-income countries located in tropical regions. Because of the lack of surveillance data, however, the epidemiology of varicella in these regions remains uncharacterized. In this study, based on an extensive dataset of weekly varicella incidence in children ≤10 during 2011-2014 in 25 municipalities, we aimed to delineate the seasonality of varicella across the diverse tropical climates of Colombia. METHODS: We used generalized additive models to estimate varicella seasonality, and we used clustering and matrix correlation methods to assess its correlation with climate. Furthermore, we developed a mathematical model to examine whether including the effect of climate on varicella transmission could reproduce the observed spatiotemporal patterns. RESULTS: Varicella seasonality was markedly bimodal, with latitudinal changes in the peaks' timing and amplitude. This spatial gradient strongly correlated with specific humidity (Mantel statistic = 0.412, P = .001) but not temperature (Mantel statistic = 0.077, P = .225). The mathematical model reproduced the observed patterns not only in Colombia but also México, and it predicted a latitudinal gradient in Central America. CONCLUSIONS: These results demonstrate large variability in varicella seasonality across Colombia and suggest that spatiotemporal humidity fluctuations can explain the calendar of varicella epidemics in Colombia, México, and potentially in Central America.


Assuntos
Varicela , Criança , Humanos , Varicela/epidemiologia , Colômbia/epidemiologia , Clima , Herpesvirus Humano 3 , Umidade , Estações do Ano , Clima Tropical
20.
Biophys J ; 122(11): 2256-2266, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-36641625

RESUMO

Discoidal lipid-protein nanoparticles known as nanodiscs are widely used tools in structural and membrane biology. Amphipathic, synthetic copolymers have recently become an attractive alternative to membrane scaffold proteins for the formation of nanodiscs. Such copolymers can directly intercalate into, and form nanodiscs from, intact membranes without detergents. Although these copolymer nanodiscs can extract native membrane lipids, it remains unclear whether native membrane properties are also retained. To determine the extent to which bilayer lipid packing is retained in nanodiscs, we measured the behavior of packing-sensitive fluorescent dyes in various nanodisc preparations compared with intact lipid bilayers. We analyzed styrene-maleic acid (SMA), diisobutylene-maleic acid (DIBMA), and polymethacrylate (PMA) as nanodisc scaffolds at various copolymer-to-lipid ratios and temperatures. Measurements of Laurdan spectral shifts revealed that dimyristoyl-phosphatidylcholine (DMPC) nanodiscs had increased lipid headgroup packing compared with large unilamellar vesicles (LUVs) above the lipid melting temperature for all three copolymers. Similar effects were observed for DMPC nanodiscs stabilized by membrane scaffolding protein MSP1E1. Increased lipid headgroup packing was also observed when comparing nanodiscs with intact membranes composed of binary mixtures of 1-palmitoyl-2-oleoyl-phosphocholine (POPC) and di-palmitoyl-phosphocholine (DPPC), which show fluid-gel-phase coexistence. Similarly, Laurdan reported increased headgroup packing in nanodiscs for biomimetic mixtures containing cholesterol, most notable for relatively disordered membranes. The magnitudes of these ordering effects were not identical for the various copolymers, with SMA being the most and DIBMA being the least perturbing. Finally, nanodiscs derived from mammalian cell membranes showed similarly increased lipid headgroup packing. We conclude that nanodiscs generally do not completely retain the physical properties of intact membranes.


Assuntos
Dimiristoilfosfatidilcolina , Nanoestruturas , Animais , Fosforilcolina , Bicamadas Lipídicas/química , Maleatos/química , Polímeros/química , Proteínas de Membrana/química , Estireno , Lipossomas Unilamelares , Nanoestruturas/química , Mamíferos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA