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1.
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1553824

RESUMO

Introdução: Acidentes ofídicos são doenças negligenciadas e constituem uma parcela importante da morbidade de pessoas em idade produtiva que vivem em zonas rurais. A maior parte dos seus efeitos a curto prazo é amplamente conhecida, especialmente aqueles de natureza clínica; no entanto, ainda se observa lacuna importante do conhecimento das consequências a longo prazo de tais agravos, notadamente as de ordem psíquica. Este artigo relata um caso de adoecimento mental subsequente a um acidente crotálico e gera reflexões de âmbito cultural e fisiopatológico a respeito das sequelas de tais eventos. Apresentação do caso: Trata-se de adolescente residente no interior baiano que foi vítima de mordedura por cascavel e teve necessidade de hospitalização em unidade de terapia intensiva. Observou-se que, mesmo após melhora clínica, iniciou com sintomas psicóticos prodrômicos e progrediu para piora mental grave, que culminou em internação psiquiátrica e diagnóstico de esquizofrenia no decorrer dos meses seguintes. Conclusões: Nota-se, neste caso, correlação direta entre esses dois eventos; mas, em razão da escassez de trabalhos científicos que abordem tais questões, depreende-se que é preciso investigar e estudar com maior profundidade possíveis associações entre acidentes crotálicos e psicoses.


Introduction: Snakebites are neglected diseases and constitute an important part of the morbidity of working-age people who live in rural areas. Most of their short-term effects are widely known, especially those of a clinical nature; however, there is still an important gap in the knowledge of the long-term consequences of such injuries, notably those of a psychotic nature. This article aims to report a case of mental illness subsequent to a rattlesnake bite accident and generate cultural and pathophysiological reflections regarding the consequences of such events. Case presentation: An adolescent residing in the interior of the state of Bahia was bitten by a rattlesnake and required hospitalization in an intensive care unit. It was observed that even after clinical improvement, the case started with prodromal psychotic symptoms and progressed to severe mental deterioration that culminated in psychiatric hospitalization and diagnosis of schizophrenia over the following months. Conclusions: In this case, there was a direct correlation between these two events, but because of the scarcity of scientific works that address such issues, it is necessary to investigate and study in greater depth possible associations between snakebite accidents and psychoses.


Introducción: Las mordeduras de serpientes son enfermedades desatendidas y constituyen una parte importante de la morbilidad de las personas en edad laboral que viven en zonas rurales. La mayoría de sus efectos a corto plazo son ampliamente conocidos, especialmente los de carácter clínico; sin embargo, todavía existe un importante vacío en el conocimiento de las consecuencias a largo plazo de este tipo de lesiones, en particular las de carácter psíquico. Este artículo tiene como objetivo informar un caso de enfermedad mental posterior a un accidente crotálico y generar reflexiones culturales y fisiopatológicas sobre las consecuencias de tales eventos. Presentación del caso: Se trata de un adolescente residente en el interior de Bahía que fue mordido por una serpiente cascabel y requirió hospitalización en unidad de cuidados intensivos. Se observó que, aún después de la mejoría clínica, comenzó con síntomas psicóticos prodrómicos y progresó a un deterioro mental severo que culminó con hospitalización psiquiátrica y diagnóstico de esquizofrenia en los meses siguientes. Conclusiones: En este caso, existe una correlación directa entre estos dos eventos pero, debido a la escasez de trabajos científicos que aborden tales cuestiones, parece necesario investigar y estudiar con mayor profundidad posibles asociaciones entre accidentes crotálicos y psicosis.

2.
J Neurosci Methods ; 409: 110194, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866205

RESUMO

BACKGROUND: Measurement of the efficacy of the networks of attention is a frequent component of research in cognitive and clinical neuroscience. Developed in 2002, the Attention Network Test (ANT), has become the most widely used tool for this purpose. NEW METHOD: In 2017 a more engaging, game-like tool based on the ANT, called the AttentionTrip was described. The network scores from five studies which used AttentionTrip are shown to be robust. NEWER METHOD: That version of AttentionTrip required a steering wheel and desk-top computer. Here we describe a new, portable version of the AttentionTrip that is administered using a hand-held tablet (iPad) RESULTS: Three samples of participants (total = 44) completed the portable version of AttentionTrip. The network scores generated using the portable AttentionTrip were also robust. Effect sizes compare favourably with those generated by the ANT and the desktop version. CONCLUSIONS: The findings support the use of the portable AttentionTrip as an alternative to the ANT when user engagement is important, such as when participants are prone to boredom, and when repeated administrations are required.

3.
Pharmaceutics ; 16(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38931825

RESUMO

Skin lesions are an important health concern, exposing the body to infection risks. Utilizing natural products containing chamomile (Chamomilla recutita L.) holds promise for curative purposes. Additionally, hyaluronic acid (HA), an active ingredient known for its tissue regeneration capacity, can expedite healing. In this study, we prepared and characterized an extract of C. recutita and integrated it into a nanoemulsion system stabilized with HA, aiming at harnessing its healing potential. We assessed the impact of alcoholic strength on flavonoid extraction and chemically characterized the extract using UHPLC/MS while quantifying its antioxidant and antimicrobial capacity. We developed a nanoemulsion loaded with C. recutita extract and evaluated the effect of HA stabilization on pH, droplet size, polydispersity index (PDI), zeta potential, and viscosity. Results indicated that 70% hydroalcoholic extraction yielded a higher flavonoid content. The extract exhibited antioxidant capacity in vitro, a desirable trait for skin regeneration, and demonstrated efficacy against key microbial strains (Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa) associated with skin colonization and infections. Flavonoids spireoside and apiin emerged as the most abundant bioactives. The addition of HA led to increased viscosity while maintaining a suitable pH for topical application. Zeta potential, droplet size, and PDI met acceptable criteria. Moreover, incorporating C. recutita extract into the nanoemulsion enhanced its antimicrobial effect. Hence, the nanoemulsion system loaded with C. recutita and HA stabilization exhibits favorable characteristics for topical application, showing promise in aiding the healing processes.

4.
Molecules ; 29(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38930806

RESUMO

Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO2 after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO2 were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 µg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.


Assuntos
Dióxido de Carbono , Cromatografia com Fluido Supercrítico , Cumarínicos , Extratos Vegetais , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Dióxido de Carbono/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Humanos , Cromatografia com Fluido Supercrítico/métodos , Componentes Aéreos da Planta/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação
5.
J Forensic Sci ; 69(4): 1449-1455, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38706115

RESUMO

Highways, the lifeline of the Brazilian economy, transport approximately 75% of the country's economic activity, highlighting its importance. However, professional drivers, accustomed to long daily journeys, make use of tablets widely available in Gas Station, which are known as "Rebites," which could contain a mixture of legal and illegal compounds. Thus, this study aims at the chemical characterization of these through different analytical methods. Initially, we performed a comprehensive screening of compounds present in seven samples collected across the country using high-resolution mass spectrometry (HRMS). The findings revealed caffeine as the main compound, alongside theophylline, lidocaine, and clobenzorex, among others. In the next step, we employ quantitative nuclear magnetic resonance (qNMR) to quantify the caffeine content in the tablets. The results indicated a caffeine concentration ranging between 14% and 31% (m/m), which may imply a daily overdose of this compound from around four tablets. In summary, this investigation provides a chemical characterization of real samples of "Rebites" freely obtained along Brazilian highways. Caffeine emerged as the predominant active compound, with its concentration determined by qNMR analysis. The notable presence of caffeine, combined with other stimulants, depressants, and hallucinogens, underscores the need for strict quality control measures regarding "Rebites" to safeguard public health.


Assuntos
Cafeína , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Brasil , Humanos , Cafeína/análise , Comprimidos , Drogas Ilícitas/análise , Drogas Ilícitas/química , Veículos Automotores , Caminhoneiros
6.
bioRxiv ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38766026

RESUMO

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce Activity Quantification and Analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine learning techniques. It decomposes complex live imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, and imaging modalities. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, and distinct sensorimotor signal propagation patterns in the mouse spinal cord.

7.
PhytoKeys ; 242: 69-138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818383

RESUMO

Malpighiaceae has undergone unprecedented changes in its traditional classification in the past two decades due to several phylogenetic studies shedding light on the non-monophyly of all subfamilies and most tribes and genera. Even though morphological characters were used to reconstruct the last molecular generic phylogeny of Malpighiaceae, a new classification system has never been proposed for this family. Based on a comprehensive review of the last twenty years of published studies for this family, we propose a new classification system and provide a taxonomic synopsis for Malpighiaceae based on molecular phylogenetics, morphology, palynology, and chemistry as a baseline for the systematics, conservation, and taxonomy of this family worldwide. Malpighiaceae currently comprises two subfamilies (Byrsonimoideae and Malpighioideae), 12 tribes ( Acmanthereae, Acridocarpeaetrib. nov., Barnebyeaetrib. nov., Bunchosieaetrib. nov., Byrsonimeae, Galphimieae, Gaudichaudieae, Hiptageae, Hiraeeae, Malpighieae, Mcvaughieaetrib. nov., and Ptilochaeteaetrib. nov.), 72 genera (incl. Mamedeagen. nov.), and 1,499 accepted species (715 of which are currently under some kind of extinction threat). We present identification keys for all subfamilies, tribes, and genera, a full morphological description for the proposed new genus, the re-circumscription of ten genera alongside the needed new combinations, the proposition of several new synonyms, the typification of several names, and notes on the taxonomy, distribution, conservation, and ecology up to the genus rank. Morphological plates are also provided to illustrate the immense diversity of morphological traits used in the new classification and synopsis.

8.
Chem Biodivers ; : e202400679, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822223

RESUMO

Banisteriopsis (Malpighiaceae) is an important genus of neotropical savannas with related biological and medicinal activities but under-explored metabolomic profiles. We present a chemometric analysis for discriminating secondary metabolites of three species of Banisteriopsis (B. laevifolia, B. malifolia, and B. stellaris) leaves. Initially, each species was separately extracted with ethanol:water (4:1, v/v) and analysed by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS/MS). The chromatographic profiles were subjected to Global Natural Product Social (GNPS) and Partial Least Squares Discriminant Analysis (PLS-DA). Eighty-nine compounds (cosine ≥ 0.90) were annotated, including flavonoids, phenolics, and acids. The chemometric analysis (VIP Score) showed each species' relative concentration of the more relevant compounds. In addition, four compounds that discriminate the metabolomic profiles of B. laevifolia, B. malifolia, and B. stellaris were identified by PLS-DA.

9.
Food Res Int ; 184: 114241, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609221

RESUMO

This review aimed to critically and comparatively analyze the physicochemical, proximate, nutritional, phytochemical composition, and bioactivities of araticum (Annona crassiflora Mart.) (AAc), a fruit from the Brazilian Cerrado. Additionally, the potential applications of this fruit in the food industry were reviewed. Data and information were collected from the Scopus, Web of Science, and Google Scholar databases. AAc, a fruit mainly studied in the Brazilian regions of Minas Gerais and Goiás, has well-documented physicochemical, proximate, and nutritional characteristics. It is rich in fiber, sugars, vitamins A and C, minerals, and oil, making it attractive to the food industry. However, there are research gaps, such as the impact of climatic conditions on the AAc chemical composition. Additional studies are needed, especially for the peel and seeds, and investigations of pre-treatments effect on the chemical composition are recommended. The application of AAc in food products is mainly limited to pulp, but there is potential for using peels and seeds. AAc is a rich source of phytochemical compounds with various biological properties, such as antioxidants, hepatoprotective, and antimicrobial activities. Future studies should explore other phytochemicals present in the fruit beyond phenolic compounds. The consumption of AAc can contribute to combating food insecurity malnutrition, and promoting the conservation of the Brazilian Cerrado.


Assuntos
Annona , Indústria Alimentícia , Frutas , Sementes , Compostos Fitoquímicos
10.
Front Cell Infect Microbiol ; 14: 1297099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495650

RESUMO

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.


Assuntos
Doença de Chagas , Doenças Transmissíveis , Trypanosoma cruzi , Feminino , Animais , Camundongos , Humanos , Trypanosoma cruzi/metabolismo , Pepsina A/metabolismo , Parasitemia , Modelos Animais de Doenças , Cromatografia Líquida , Espectrometria de Massas em Tandem , Doença de Chagas/parasitologia , Mucinas
11.
Sci Rep ; 14(1): 5000, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424216

RESUMO

Trypanosoma cruzi is the protozoan that causes Chagas disease (CD), an endemic parasitosis in Latin America distributed around the globe. If CD is not treated in acute phase, the parasite remains silent for years in the host's tissues in a chronic form, which may progress to cardiac, digestive or neurological manifestations. Recently, studies indicated that the gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. During interaction T. cruzi and host cells release extracellular vesicles (EVs) that modulates the immune system and infection, but the dynamics of secretion of host and parasite molecules through these EVs is not understood. Now, we used two cell lines: mouse myoblast cell line C2C12, and human intestinal epithelial cell line Caco-2to simulate the environments found by the parasite in the host. We isolated large EVs (LEVs) from the interaction of T. cruzi CL Brener and Dm28c/C2C12 and Caco-2 cells upon 2 and 24 h of infection. Our data showed that at two hours there is a strong cellular response mediated by EVs, both in the number, variety and enrichment/targeting of proteins found in LEVs for diverse functions. Qualitative and quantitative analysis showed that proteins exported in LEVs of C2C12 and Caco-2 have different patterns. We found a predominance of host proteins at early infection. The parasite-host cell interaction induces a switch in the functionality of proteins carried by LEVs and a heterogeneous response depending on the tissues analyzed. Protein-protein interaction analysis showed that cytoplasmic and mitochondrial homologues of the same parasite protein, tryparedoxin peroxidase, were differentially packaged in LEVs, also impacting the interacting molecule of this protein in the host. These data provide new evidence that the interaction with T. cruzi leads to a rapid tissue response through the release of LEVs, reflecting the enrichment of some proteins that could modulate the infection environment.


Assuntos
Doença de Chagas , Vesículas Extracelulares , Trypanosoma cruzi , Animais , Camundongos , Humanos , Trypanosoma cruzi/metabolismo , Células CACO-2 , Doença de Chagas/parasitologia , Vesículas Extracelulares/metabolismo , Interações Hospedeiro-Parasita
12.
Food Res Int ; 180: 114090, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395563

RESUMO

There is a growing demand for the food industry to find appealing matrices that display a clean and sustainable label capable of replacing animal proteins in the encapsulation market for natural pigments. Therefore, this study evaluated the impact of enzymatic hydrolysis by Flavourzyme protease on the encapsulation properties of rice bran proteins, aiming to protect anthocyanins in grape juice microparticles. To achieve this, rice bran protein hydrolysates (RPH) with low (5%, LRPH), medium (10%, MRPH), and high (15%, HRPH) degrees of hydrolysis (DH) were used combined with maltodextrin as carrier agents for the microencapsulation of grape juice by spray drying. The feed solutions contained 1 g of carrier agents (CA)/g of soluble solids from the juice (SS) and protein: a 15% CA ratio. Non-hydrolyzed rice protein was used as a carrier agent to obtain a control sample to evaluate the effect of enzymatic hydrolysis on the microencapsulation of grape juice. Protein modification increased the surface activity of the protein and its ability to migrate to the surface of the microparticles, forming a protective film, as observed by X-ray photoelectron spectroscopy. Using HRPH as a carrier agent combined with maltodextrin improved the internal and total anthocyanin retention, antioxidant capacity measured by DPPH and ABTS+ assays, and powder recovery compared to the control sample, and increased DH reduced particle size and powder stickiness. These particles were more homogeneous, rough, and without cracks. The microencapsulation efficiency was above 70%. All powders exhibited low values of hygroscopicity and degree of caking. Therefore, enzymatic hydrolysis proves to be a promising alternative for improving rice bran protein's encapsulating properties since using RPH as an encapsulating agent conferred greater protection of anthocyanins in microparticles. Moreover, the HRPH sample exhibited the most favorable outcomes overall, indicating its potential for prospective utilization in the market, supported by its elevated Tg.


Assuntos
Oryza , Vitis , Animais , Antocianinas/química , Oryza/química , Hidrólise , Pós , Estudos Prospectivos
13.
Food Res Int ; 178: 113986, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309886

RESUMO

This study is a bibliometric analysis and literature review on the use of oleogels (OGs), hydrogels (HGs) and hybrid gels (HYGs) in chocolate, compounds and spreads with the aim of reducing the saturated fat in these products. The articles were selected by analyzing titles, keywords and abstracts in the Web of Science (WoS), Scopus and Google Scholar databases. Supplementary documents were obtained from government sources, including patent registrations. The theoretical and practical aspects were critically analyzed, highlighting the main points of agreement and disagreement between the authors. The results revealed a lack of regulations and official guidelines that widely allow the use of OGs, HGs and HYGs in chocolate confectionery products. The type and characteristics of raw materials affect the properties of products. Replacing cocoa butter (CB) with OGs, HGs or HYGs also affects texture, melting point and behavior, and nutritional aspects. These substitutions can result in products with better sensory acceptance and health benefits, such as reducing saturated fat and promoting cardiovascular health. However, it is important to find the ideal combination and proportions of components to obtain the desired properties in the final products.


Assuntos
Cacau , Chocolate , Chocolate/análise , Hidrogéis , Ácidos Graxos/análise , Compostos Orgânicos
14.
Cell ; 187(4): 814-830.e23, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364788

RESUMO

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.


Assuntos
Bainha de Mielina , Retroelementos , Animais , Expressão Gênica , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Retroelementos/genética , RNA/metabolismo , Peixe-Zebra/genética , Anuros
15.
J Mol Graph Model ; 126: 108627, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37801808

RESUMO

This research investigates the application of Graph Neural Networks (GNNs) to enhance the cost-effectiveness of drug development, addressing the limitations of cost and time. Class imbalances within classification datasets, such as the discrepancy between active and inactive compounds, give rise to difficulties that can be resolved through strategies like oversampling, undersampling, and manipulation of the loss function. A comparison is conducted between three distinct datasets using three different GNN architectures. This benchmarking research can steer future investigations and enhance the efficacy of GNNs in drug discovery and design. Three hundred models for each combination of architecture and dataset were trained using hyperparameter tuning techniques and evaluated using a range of metrics. Notably, the oversampling technique outperforms eight experiments, showcasing its potential. While balancing techniques boost imbalanced dataset models, their efficacy depends on dataset specifics and problem type. Although oversampling aids molecular graph datasets, more research is needed to optimize its usage and explore other class imbalance solutions.


Assuntos
Desenvolvimento de Medicamentos , Descoberta de Drogas , Hidrolases , Redes Neurais de Computação
16.
Coluna/Columna ; 23(1): e279688, 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557649

RESUMO

ABSTRACT Traumatic atlanto-occipital dislocation is a rare, severe, and usually fatal injury. In this paper, we report the case of a 28-year-old patient with multiple trauma, who suffered an atlanto-occipital dislocation (AOD) associated with rotatory dislocation at C1-C2, condyle fracture and traumatic brain injury resulting from a car accident, with a cardiopulmonary arrest at the accident site. The patient had motor and sensory deficits, suffering other complications of clinical severity during hospitalization. After two years of surgical treatment follow-up, the patient had a complete recovery of neuromotor and sensory functions. This case demonstrates that neurological recovery with minimal sequelae is possible, even after an unfavorable prognosis resulting from a severe injury with a high risk of death as this kind of trauma. It is essential for health professionals to have the ability to identify and treat AOD, ensuring improved clinical outcomes, reducing mortality and morbidity, and providing a better life to affected patients. Level of Evidence IV; Cases Series.


Resumo: A luxação traumática atlanto-occipital (LTAO) é uma lesão rara, grave e com alto índice de mortalidade. Neste artigo relatamos o caso de um paciente de 28 anos, politraumatizado, que sofreu uma LTAO associada à luxação rotatória em C1-C2, à avulsão de côndilo e ao traumatismo crânio encefálico decorrente de acidente automobilístico, com relato de uma parada cardiorrespiratória no local do acidente. O paciente deu entrada no serviço com déficit motor e sensitivo, sofrendo outras intercorrências de gravidade clínica durante a internação. Após dois anos do tratamento cirúrgico, o paciente evoluiu favoravelmente com completa recuperação das alterações neuromotoras e sensitivas. O caso apresentado demonstra que é possível a recuperação neurológica com sequelas mínimas, mesmo após um prognóstico desfavorável decorrente de uma lesão grave e o elevado risco de morte decorrente desse tipo de trauma. É essencial que os profissionais de saúde estejam aptos a identificar e tratar a LTAO, garantindo uma melhorar dos resultados clínicos, redução da mortalidade e morbidade, além de proporcionar uma melhor qualidade de vida aos pacientes afetados. Nível de Evidência IV; Série de casos.


Resumen: La luxación traumática atlanto-occipital (LTAO) es una lesión grave, poco frecuente y con una elevada tasa de mortalidad. En este artículo presentamos el caso de un paciente politraumatizado de 28 años que sufrió una LTAO asociada a luxación rotatoria en C1-C2, a la avulsión de cóndilos y traumatismo craneoencefálico como consecuencia de un accidente de tráfico, con parada cardiorrespiratoria en el lugar del accidente. El paciente presentaba déficits motores y sensoriales y sufrió otras complicaciones clínicas graves durante su hospitalización. Luego de dos años de tratamiento quirúrgico, el paciente evoluciona favorablemente con recuperación completa de las alteraciones neuromotoras y sensitivas. El caso presentado demuestra que la recuperación neurológica con mínimas secuelas es posible, incluso después de un pronóstico desfavorable debido a una lesión grave y al alto riesgo de muerte derivado de este tipo de traumatismos. Es esencial que los profesionales sanitarios sean capaces de identificar y tratar la LTAO, garantizando mejores resultados clínicos, una reducción de la mortalidad y la morbilidad, y una mejor calidad de vida para los pacientes afectados. Nivel de Evidencia IV; Series de casos.

17.
Nat Commun ; 14(1): 8073, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057349

RESUMO

How long-term changes in surface topography relate to coseismic uplift is key to understanding the creation of high elevations along active mountain fronts, and remains hotly debated. Here we investigate this link by modeling the development of growth strata and the folding of river terraces above the Pishan duplex system in the southern Tarim Basin. We show that synchronous duplex thrusting of two neighboring faults with varying slip rates, associated with in-sequence propagation of the Pishan thrust system, is required to explain the presence of opposite-dipping panels of growth strata on the duplex front, and basinward migration of terrace fold crests. Importantly, this process of synchronous thrusting within the duplex reconciles the discrepancy between the deformation of terrace folds at the 10-1-100 million-year timescale and the maximum coseismic uplift of the 2015 Mw 6.4 Pishan earthquake on the frontal thrust. These results suggest that topography mismatch at different time scales can reflect the long-term kinematic evolution of fault systems. Thus, our study highlights the importance of characterizing complex subsurface fault kinematics for studying topographic growth, and motivates rethinking of the mountain building process in worldwide active fold-and-thrust belts, from short-term to long-term timescales.

18.
Hearts ; 4(4): 97-117, dez.2023. ilus
Artigo em Inglês | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1530621

RESUMO

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy.

19.
Phys Chem Chem Phys ; 25(48): 32922-32930, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38018412

RESUMO

This work delves into the bonding nature of the pentagonal-pyramidal benzene and hexamethylbenzene dications, C6R62+ (R = H and CH3), which contain a hexacoordinate carbon. The study employs a range of methodologies to analyze a series of scalar fields, including electron density, electron localization function, local momentum representation, and the evaluation of the Coulomb hole through information theory-derived functions. The findings unveil that electron density undergoes transfer from the pentagonal ring to the apical group. As a result, the base of the complex accumulates the positive charge. Moreover, an extended electron density domain emerges between the carbon pentagon and the apical carbon atom. This phenomenon is related to the molecular orbitals with a dipolar character aligned with the principal axis of the molecule. The results also indicate an electron density polarization towards the apical carbon, coupled with an exclusion of electron density surrounding both the apical carbon and the lower portion of the pentagonal ring. These provide valuable insights into the complex bonding nature of hexacoordinate carbon and its implications for organic chemistry.

20.
J Evol Biol ; 36(11): 1595-1608, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37885128

RESUMO

Hybridization could be considered part of the evolutionary history of many species. The hybridization among sea turtle species on the Brazilian coast is atypical and occurs where nesting areas and reproductive seasons overlap. Integrated analysis of morphology and genetics is still scarce, and there is no evidence of the parental chromosome set distribution in sea turtle interspecific hybrids. In this study, chromosome markers previously established for pure sea turtle species were combined with morphological and molecular analyses aiming to recognize genetic composition and chromosome sets in possible interspecific hybrids initially identified by mixed morphology. The data showed that one hybrid could be an F2 individual among Caretta caretta × Eretmochelys imbricata × Chelonia mydas, and another is resulting from backcross between C. caretta × Lepidochelys olivacea. Native alleles of different parental lineages were reported in the hybrids, and, despite this, it was verified that the hybrid chromosome sets were still balanced. Thus, how sea turtle hybridism can affect genetic features in the long term is a concern, as the implications of the crossing-over in hybrid chromosomal sets and the effects on genetic function are still unpredictable.


Assuntos
Tartarugas , Animais , Tartarugas/genética , Evolução Biológica , Reprodução , Cromossomos , Análise Citogenética
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