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This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.
Assuntos
Materiais Revestidos Biocompatíveis , Macrófagos , Teste de Materiais , Células-Tronco Mesenquimais , Osteogênese , Aço Inoxidável , Propriedades de Superfície , Titânio , Titânio/química , Aço Inoxidável/química , Animais , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Macrófagos/metabolismo , Osteogênese/efeitos dos fármacos , Diferenciação Celular , Próteses e Implantes , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Biofilmes , Staphylococcus epidermidis/efeitos dos fármacos , Aderência Bacteriana , MolhabilidadeRESUMO
New World porcupines (Erethizontinae) originated in South America and dispersed into North America as part of the Great American Biotic Interchange (GABI) 3-4 million years ago.1 Extant prehensile-tailed porcupines (Coendou) today live in tropical forests of Central and South America.2,3 In contrast, North American porcupines (Erethizon dorsatum) are thought to be ecologically adapted to higher-latitude temperate forests, with a larger body, shorter tail, and diet that includes bark.4,5,6,7 Limited fossils8,9,10,11,12,13 have hindered our understanding of the timing of this ecological differentiation relative to intercontinental dispersal during the GABI and expansion into temperate habitats.14,15,16,17,18 Here, we describe functionally important features of the skeleton of the extinct Erethizon poyeri, the oldest nearly complete porcupine skeleton documented from North America, found in the early Pleistocene of Florida. It differs from extant E. dorsatum in having a long, prehensile tail, grasping foot, and lacking dental specializations for bark gnawing, similar to tropical Coendou. Results from phylogenetic analysis suggest that the more arboreal characteristics found in E. poyeri are ancestral for erethizontines. Only after it expanded into temperate, Nearctic habitats did Erethizon acquire the characteristic features that it is known for today. When combined with molecular estimates of divergence times, results suggest that Erethizon was ecologically similar to a larger species of Coendou when it crossed the Isthmus of Panama by the early Pleistocene. It is likely that the range of this more tropically adapted form was limited to a continuous forested biome that extended from South America through the Gulf Coast.
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Fósseis , Porcos-Espinhos , Porcos-Espinhos/anatomia & histologia , Animais , Fósseis/anatomia & histologia , América do Sul , Cauda/anatomia & histologia , Extinção Biológica , América do Norte , Evolução Biológica , EcossistemaRESUMO
The objective of this study was to quantify the prevalence of and identify the factors associated with dental pain among elementary- and middle-school students in Mexico. An ecological study was carried out with data from the 2008 National School-based Student-Health Survey. Information on dental pain from schoolchildren (aged 5 to 16 years) was collected from public schools across the 32 states of Mexico. In the original study, a questionnaire was used to explore various factors that affect the oral and dental health status of schoolchildren. The outcome variable was the prevalence rate (for dental pain) reported at state level. Various contextual socioeconomic variables were included, in addition to dental caries. Analyses were performed using Stata software. 52.9% of interviewees were girls; 26.9% of male and female schoolchildren in Mexico experienced gum or dental pain during the period analyzed (95% Confidence Interval = 26.02, 27.77%); according to the Spearman correlation results, self-reported dental pain was unrelated (p > 0.05) to the socioeconomic and sociodemographic variables that make up the Gross Domestic Product (GDP) and the Human Development (HDI), as well as the marginalization and the Gini indices. However, the estimated percentages of self-reported dental pain and caries were positively correlated in the elementary- (r = 0.8958, p < 0.0001), middle-school (r = 0.8958, p < 0.0001) and total populations (r = 0.8542, p < 0.0001). Prevalence of self-reported dental pain was 28%, or about one in three, of the Mexican children and adolescents in the study sample. The state-level sociodemographic and socioeconomic risk indicators were not associated with the prevalence of dental pain. Self-reported caries was positively correlated with self-reported dental pain.
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Autorrelato , Odontalgia , Humanos , México/epidemiologia , Criança , Feminino , Masculino , Adolescente , Odontalgia/epidemiologia , Prevalência , Pré-Escolar , Cárie Dentária/epidemiologia , Fatores SocioeconômicosRESUMO
BACKGROUND: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). METHODS: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. RESULTS: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. CONCLUSIONS: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.
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Abstract The objective of this research is to present a comparative analysis using various lengths of time windows (TW) during emotion recognition, employing machine learning techniques and the portable wireless sensing device EPOC+. In this study, entropy will be utilized as a feature to evaluate the performance of different classifier models across various TW lengths, based on a dataset of EEG signals extracted from individuals during emotional stimulation. Two types of analyses were conducted: between-subjects and within-subjects. Performance measures such as accuracy, area under the curve, and Cohen's Kappa coefficient were compared among five supervised classifier models: K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), and Decision Trees (DT). The results indicate that, in both analyses, all five models exhibit higher performance in TW ranging from 2 to 15 seconds, with the 10 seconds TW particularly standing out for between-subjects analysis and the 5-second TW for within-subjects; furthermore, TW exceeding 20 seconds are not recommended. These findings provide valuable guidance for selecting TW in EEG signal analysis when studying emotions.
Resumen El objetivo de esta investigación es presentar un análisis comparativo empleando diversas longitudes de ventanas de tiempo (VT) durante el reconocimiento de emociones, utilizando técnicas de aprendizaje automático y el dispositivo de sensado inalámbrico portátil EPOC+. En este estudio, se utilizará la entropía como característica para evaluar el rendimiento de diferentes modelos clasificadores en diferentes longitudes de VT, basándose en un conjunto de datos de señales EEG extraídas de individuos durante la estimulación de emociones. Se llevaron a cabo dos tipos de análisis: entre sujetos e intra-sujetos. Se compararon las medidas de rendimiento, tales como la exactitud, el área bajo la curva y el coeficiente de Cohen's Kappa, de cinco modelos clasificadores supervisados: K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF) y Decision Trees (DT). Los resultados indican que, en ambos análisis, los cinco modelos presentan un mayor rendimiento en VT de 2 a 15 segundos, destacándose especialmente la VT de 10 segundos para el análisis entre los sujetos y 5 segundos intrasujetos; además, no se recomienda utilizar VT superiores a 20 segundos. Estos hallazgos ofrecen una orientación valiosa para la elección de las VT en el análisis de señales EEG al estudiar las emociones.
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ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.
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Síndromes do Olho Seco , Doença Enxerto-Hospedeiro , Humanos , Síndromes do Olho Seco/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.
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Helicobacter pylori , Helicobacter pylori/metabolismo , Urease/metabolismo , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Ureia/farmacologiaRESUMO
PURPOSE: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. METHODS: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. RESULTS: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. CONCLUSION: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.
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Braquiterapia , Radioterapia de Intensidade Modulada , Humanos , Braquiterapia/métodos , Espanha , Radioterapia de Intensidade Modulada/métodos , Pescoço , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem RadioterapêuticaRESUMO
Zika virus infection affects the development of the nervous system. This study describes the cognitive, adaptative, communicative, social and motor neurodevelopment of children exposed to Zika virus in utero. We used the Batelle scale to assess neurodevelopment three years after birth. Thirty children were included, who had a mean age at evaluation of 37.5 (IQR: 35.7-39.2) months. We found the following equivalent ages in months for each area: motor 25.8 (SD: 7.8), adaptive 26.7 (SD: 5.8), communicative 30.2 (SD: 6.9), social personal 33.5 (SD: 8.3) and cognitive 35.6 (SD: 5.9). Children showed development delay for their chronological age, 25 children were delayed in one of the five areas assessed. A high rate of children exposed to Zika virus during gestation presented delayed developmental age, mainly regarding the adaptive and motor areas.
El virus del Zika produce desenlaces adversos para el desarrollo del sistema nervioso. Este estudio describe el neurodesarrollo cognitivo, adaptativo, comunicativo, social y motor de niños expuestos intrauterinamente al virus del Zika y hace una evaluación del neurodesarrollo con la escala de Battelle a los tres años después del nacimiento. Participaron 30 niños con una media de edad al momento de la evaluación de 37,5 (RIC: 35,7-39,2) meses. Se halló una edad equivalente en meses en las áreas: motora 25,8 (DE: 7,8), adaptativa 26,7 (DE: 5,8), comunicativa 30,2 (DE: 6,9), personal social 33,5 (DE: 8,3) y cognitiva 35,6 (DE: 5,9). Los niños presentaron retraso en el desarrollo para la edad cronológica, 25 niños presentaban retraso en una de las cinco áreas evaluadas. Una alta proporción de niños expuestos al virus del Zika durante la gestación presentaron retraso en el desarrollo, principalmente en el dominio adaptativo y motor.
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Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Pré-Escolar , Feminino , Humanos , Gravidez , Aclimatação , Desenvolvimento Infantil , Estudos Transversais , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologiaRESUMO
Metabolic syndrome (MetS) predisposes individuals to chronic non-communicable diseases (NCDs) like type 2 diabetes (T2D), non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular disorders caused by systemic inflammation, intestinal dysbiosis, and diminished antioxidant ability, leading to oxidative stress and compromised insulin sensitivity across vital organs. NCDs present a global health challenge characterized by lengthy and costly pharmacological treatments. Complementary and alternative medicine using herbal therapies has gained popularity. Approximately 350,000 plant species are considered medicinal, with 80% of the world's population opting for traditional remedies; however, only 21,000 plants are scientifically confirmed by the WHO. The Rubiaceae family is promissory for preventing and treating MetS and associated NCDs due to its rich content of metabolites renowned for their antioxidative, anti-inflammatory, and metabolic regulatory properties. These compounds influence transcription factors and mitigate chronic low-grade inflammation, liver lipotoxicity, oxidative stress, and insulin resistance, making them a cost-effective non-pharmacological approach for MetS prevention and treatment. This review aims to collect and update data that validate the traditional uses of the Rubiaceae family for treating MetS and associated NCDs from experimental models and human subjects, highlighting the mechanisms through which their extracts and metabolites modulate glucose and lipid metabolism at the molecular, biochemical, and physiological levels.