RESUMO
The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O2 levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.
Assuntos
Caenorhabditis elegans , Gotículas Lipídicas , Pseudomonas aeruginosa , Humanos , Gotículas Lipídicas/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Células HEK293 , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Relógios Biológicos/genética , Evolução Biológica , Metabolismo dos Lipídeos/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologiaRESUMO
This study aimed to compare the digestibility of tropical grasses by horses by the in vivo method using mobile nylon bags with the in vitro digestibility method using horse feces as a source of inoculum. Five horses were used in a 2 × 5 factorial design with randomized blocks featuring two methods (in vivo and in vitro) and five grasses: Tifton 85 hay (Cynodon spp.), sixweeks threeawn grass (Aristida adsencionis, Linn), Alexandergrass (Brachiaria plantaginea (Link) Hitchc.), capim-de-raiz (Chloris orthonoton, Doell), and Sabi grass (Urochloa mosambicensis). No difference (P>0.05) was found between the in vivo and in vitro methods regarding nutrient digestibility of Sabi grass and sixweeks threeawn. Tifton 85 was the only grass that showed differences (P<0.05) between the two methods concerning the apparent digestibility of all nutrients. Alexandergrass, Tifton 85, and capim-de-raiz exhibited the best digestibility of dry matter, neutral detergent fiber, acid detergent fiber, and organic matter by the mobile bag method compared to the in vitro method. Tifton 85 and capim-de-raiz had higher crude protein digestibility by the mobile bag method than by the in vitro method. The mean retention time of the mobile bags in the digestive tract of the horses was 43.69 h. The bags with samples of sixweeks threeawn and Sabi grass had shorter retention times than capim-de-raiz and Alexandergrass (P<0.0001). It is concluded that, for sixweeks threeawn and Sabi grass, digestibility in horses can be assessed using the in vitro method in place of the mobile nylon bag method.
Assuntos
Ração Animal , Digestão , Poaceae , Animais , Cavalos/metabolismo , Poaceae/química , Digestão/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária , Fezes/química , MasculinoRESUMO
The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/tratamento farmacológico , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Piridinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citosol/metabolismo , Citosol/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Pirimidinas/farmacologia , Movimento Celular/efeitos dos fármacos , Relógios Circadianos/efeitos dos fármacos , Relógios Circadianos/fisiologia , Proteínas CLOCK/metabolismo , Proteínas CLOCK/genética , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
The organophosphate insecticide chlorpyrifos (CPF), an acetylcholinesterase inhibitor, has raised serious concerns about human safety. Apart from inducing synaptic acetylcholine accumulation, CPF could also act at nicotinic acetylcholine receptors, like the α7-isoform (α7-nAChR), which could potentially be harmful to developing brains. Our aims were to use molecular docking to assess the binding interactions between CPF and α7-nAChR through, to test the neurocytotoxic and oxidative effects of very low concentrations of CPF on SH-SY5Y cells, and to hypothesize about the potential mediation of α7-nAChR. Docking analysis showed a significant binding affinity of CPH for the E fragment of the α7-nAChR (ΔGibbs: -5.63 to -6.85 Kcal/mol). According to the MTT- and Trypan Blue-based viability assays, commercial CPF showed concentration- and time-dependent neurotoxic effects at a concentration range (2.5-20 µM), ten-folds lower than those reported to have crucial effects for sheer CPF. A rise of the production of radical oxygen species (ROS) was seen at even lower concentrations (1-2.5 µM) of CPF after 24h. Notably, our docking analysis supports the antagonistic actions of CPF on α7-nAChR that were recently published. In conclusion, while α7-nAChR is responsible for neuronal survival and neurodevelopmental processes, its activity may also mediate the neurotoxicity of CPF.
Assuntos
Clorpirifos , Neuroblastoma , Receptores Nicotínicos , Humanos , Clorpirifos/toxicidade , Simulação de Acoplamento Molecular , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Acetilcolinesterase/metabolismo , Receptores Nicotínicos/metabolismoRESUMO
The short-tail yellownose skate, Zearaja brevicaudata, occurs off southern Brazil and along the Argentine continental shelf, including waters surrounding the Islas Malvinas and the upper slope, and is very frequently caught by trawl fisheries throughout its range. The age, growth, and maturity of Z. brevicaudata were investigated using 204 individuals collected by commercial fishing vessels from northern Argentina, between March 2016 and September 2019. Age was determined on a sample comprising vertebrae from 151 individuals, 60 males, ranging in size from 391 to 956 mm total length (TL), and 91 females, ranging in size from 324 to 1060 mm TL. Maximum ages determined for males and females were 22 and 29 years, respectively. A Bayesian framework was employed with a set of three candidate models to estimate growth parameters (von Bertalanffy, Gompertz, and Logistic). The von Bertalanffy model had the best fit, and the sexes showed undistinguishable growth parameters. For sexes combined, derived growth mean parameters (± S.D.) were L∞ = 1081 mm ± 64.34 mm, k = 0.09 ± 0.01 years-1, and L0 = 248 mm ± 23.52 mm. The age at maturity was estimated at 13.15 and 14.66 years for males and females, respectively.
Assuntos
Rajidae , Animais , Rajidae/crescimento & desenvolvimento , Masculino , Feminino , Argentina , Características de História de Vida , Pesqueiros , Teorema de Bayes , Brasil , Maturidade Sexual , Tamanho CorporalRESUMO
Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking. Additionally, NNI effects were analyzed in neuroblastoma SH-SY5Y cells, as they naturally express α-7 nAChRs. Functional studies included proliferative/cytotoxic effects (MTT test) in undifferentiated SH-SY-5Y cells and indirect measurements of [Ca2+]i transients in retinoic acid-differentiated SH-SY-5Y cells loaded with Fluo-4 AM. Docking analysis showed that the binding of IMI and ACE occurred at the same aromatic cage that the specific α-7 nAChR agonist EVP-6124. IMI showed a better docking strength than ACE. According to the MTT assays, low doses (10-50 µM) of IMI better than ACE stimulated neuroblastoma cell proliferation. At higher doses (250-500 µM), IMI also prevailed over ACE and dose-dependently triggered more abrupt fluorescence changes due to [Ca2+]i mobilization in differentiated SH-SY5Y neurons. Indeed, only IMI blunted nicotine-evoked intracellular fluorescence stimulation (i.e., nicotine cross-desensitization). Summarizing, IMI demonstrated a superior docking strength and more robust cellular responses compared to ACE, which were likely associated with a stronger activity at α-7nAChRs. Through the interaction with α-7nAChRs, IMI would demonstrate its high neurotoxic potential for humans. More research is needed for investigating the proliferative effects of IMI in neuroblastoma cells.
Assuntos
Inseticidas , Neuroblastoma , Nitrocompostos , Receptores Nicotínicos , Humanos , Cálcio , Inseticidas/toxicidade , Simulação de Acoplamento Molecular , Nicotina/farmacologia , Neonicotinoides/toxicidadeRESUMO
Objective: The performance of the platelet times neutrophil-to-lymphocyte ratio, namely systemic immune inflammation (SII) index, is an inflammatory index that shows controversial results as a predicting indicator of the poor outcomes of COVID-19. In this study, this indicator was analyzed in 3280 patients admitted at a COVID-19 reference hospital in Quito (Ecuador). Methods: The Receiver Operating Characteristic (ROC) curve analysis was conducted on SII values upon admission to identify the most appropriate cut-off values in discriminating COVID-19 severity and in-hospital mortality. Results: SII was higher in both severe patients and in those who finally died (cut-off points of 757.3 and 808.5 respectively). However, the AUC-ROC analysis (0.60-0.67) demonstrated a modest discriminating performance of SII for COVID-19 severity (61.2% sensitivity and 61.5% specificity), which sensibly improved for COVID-19 mortality (AUC-ROC: 0.73-0.83, sensitivity: 80.6% specificity; 63.6%). Conclusion: SII index may well be an indicator of inflammatory conditions secondary to COVID-19 leading to a higher mortality, rather than a predictor of severe forms of the disease.
Assuntos
COVID-19 , Humanos , Mortalidade Hospitalar , Plaquetas , Linfócitos , Eritrócitos , Estudos Retrospectivos , Curva ROCRESUMO
Neonicotinoids are effective insecticides with specificity for invertebrate nicotinic acetylcholine receptors. Neonicotinoids are chemically stable and tend to remain in the environment for long so concerns about their neurotoxicity in humans do nothing but increase. Herein, we evaluated the chronic toxic effects of acetamiprid- and imidacloprid-based insecticides over the differentiation of human neuroblastoma SH-SY5Y cells, which were exposed to these insecticides at a concentration range similar to that applied to crop fields (0.01-0.5 mM). Both insecticides did not have acute cytotoxic effects in both non-differentiated and in staurosporine-differentiated SH-SY5Y cells cytotoxicity as measured by the MTT and vital-dye exclusion tests. However, after a chronic (7-day) treatment, only imidacloprid dose-dependently decreased the viability of SH-SY5Y cells (F(4,39) = 43.05, P < 0.001), largely when administered-during cell differentiation (F(4,39) = 51.86, P < 0.001). A well-defined dose-response curve was constructed for imidacloprid on day 4 (R2 = 0.945, EC50 = 0.14 mM). During differentiation, either imidacloprid or acetamiprid dose-dependently caused neurite branch retraction on day 3, likely because of oxidative stress, to the extent that cells turned into spheres without neurites after 7-day treatment. Despite their apparent safety, the neurodevelopmental vulnerability of SH-SY5Y neurons to the chronic exposure to imidacloprid and to a lesser extent to acetamiprid points to a neurotoxic risk for humans.
RESUMO
BACKGROUND: Potentially inappropriate prescription (PIP) constitutes a risk for the development of adverse effects of a drug that outweigh its benefits, which can be considered inappropriate medication use. OBJECTIVE: To describe the prevalence of PIP in geriatric patients hospitalized at the internal medicine department of a referral hospital in Mexico. MATERIAL AND METHODS: Cross-sectional, descriptive design, with simple allocation of medical records from patients older than 65 years hospitalized between January 2016 and August 2017. The STOPP/START criteria were applied to identify the number of PIPs, the number of prescribed medications, number and type of comorbidities, as well as days of hospital stay. RESULTS: A prevalence of PIP of 73.3% was identified, with main comorbidities being hypertension and type 2 diabetes mellitus. A total of 1,885 prescribed medications were quantified; mean hospital stay was 6.3 days. CONCLUSIONS: A high prevalence of PIP was identified in hospitalized geriatric patients, hence the importance of applying the STOPP/START criteria and of the role of the pharmacist for validating the prescription prior to drug administration.
ANTECEDENTES: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. OBJETIVO: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. MATERIAL Y MÉTODOS: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. RESULTADOS: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. CONCLUSIONES: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.
Assuntos
Diabetes Mellitus Tipo 2 , Prescrição Inadequada , Humanos , Idoso , Estudos Transversais , México , Hospitais , Encaminhamento e ConsultaRESUMO
Resumen Antecedentes: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. Objetivo: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. Material y métodos: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. Resultados: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. Conclusiones: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.
Abstract Background: Potentially inappropriate prescription (PIP) constitutes a risk for the development of adverse effects of a drug that outweigh its benefits, which can be considered inappropriate medication use. Objective: To describe the prevalence of PIP in geriatric patients hospitalized at the internal medicine department of a referral hospital in Mexico. Material and methods: Cross-sectional, descriptive design, with simple allocation of medical records from patients older than 65 years hospitalized between January 2016 and August 2017. The STOPP/START criteria were applied to identify the number of PIPs, the number of prescribed medications, number and type of comorbidities, as well as days of hospital stay. Results: A prevalence of PIP of 73.3% was identified, with main comorbidities being hypertension and type 2 diabetes mellitus. A total of 1,885 prescribed medications were quantified; mean hospital stay was 6.3 days. Conclusions: A high prevalence of PIP was identified in hospitalized geriatric patients, hence the importance of applying the STOPP/START criteria and of the role of the pharmacist for validating the prescription prior to drug administration.
RESUMO
Background: Presurgical three-dimensional (3D) reconstructions allow spatial localization of cerebral lesions and their relationship with adjacent anatomical structures for optimal surgical resolution. The purpose of the present article is to present a method of virtual preoperative planning aiming to enhance 3D comprehension of neurosurgical pathologies using free DICOM image viewers. Case Description: We describe the virtual presurgical planning of a 61-year-old female presenting a cerebral tumor. 3D reconstructions were created with the "Horos®" Digital Imaging and Communications in Medicine viewer, utilizing images obtained from contrast-enhanced brain magnetic resonance imaging and computed tomography. The tumor and adjacent relevant structures were identified and delimited. A sequential virtual simulation of the surgical stages for the approach was performed with the identification of local gyral and vascular patterns of the cerebral surface for posterior intraoperative recognition. Through virtual simulation, an optimal approach was gained. Accurate localization and complete removal of the lesion were achieved during the surgical procedure. Virtual presurgical planning with open-source software can be utilized for supratentorial pathologies in both urgent and elective cases. Virtual recognition of vascular and cerebral gyral patterns is helpful reference points for intraoperative localization of lesions lacking cortical expression, allowing less invasive corticotomies. Conclusion: Digital manipulation of cerebral structures can increase anatomical comprehension of neurosurgical lesions to be treated. 3D interpretation of neurosurgical pathologies and adjacent anatomical structures is essential for developing an effective and safe surgical approach. The described technique is a feasible and accessible option for presurgical planning.
RESUMO
Patients with strokes to the Anterior Communicating Artery (ACoA) pose an important challenge to rehabilitation teams due to a particular mix of cognitive and behavioral impairments (anosognosia, anterograde amnesia, prospective memory problems, and executive dysfunction). These deficits often compromise engagement with rehabilitation, learning and generalization. The goal of this article is to describe the long-term presentation of a patient with an ACoA stroke (Mrs. B, a 60-year-old electric engineer) as well as her rehabilitation needs and the many challenges experienced by the rehabilitation team when attempting to facilitate functional, vocational and psychosocial recovery. Based on this case, and the existing literature, a neuropsychological rehabilitation framework to understand and address the specific problems and needs of this population is proposed. This framework demands rehabilitation teams to consider: the slow pattern of recovery of this population, the interaction between cognitive and behavioral impairments, the relevance of physical and social environments, the value of personal projects and the need to include psychological and relational interventions.
RESUMO
INTRODUCTION: Increased risk of postmenopausal breast cancer associated with anthropometric measures including Body Mass Index (BMI), adult weight gain, and waist circumference has been observed in North American and European populations, but little evidence is available for Hispanic women. Breast cancer is the leading type of cancer, and leading cause of cancer-related deaths among Hispanic women in Puerto Rico (PR). However, compared with the United States, breast cancer incidence rates are lower but increasing more rapidly. PURPOSE: To examine associations between anthropometric characteristics and breast cancer risk in Hispanic women in PR. METHODS: Data from a population-based case-control study in the San Juan metropolitan region (cases = 315; controls = 348) were used to examine associations between anthropometric measures and breast cancer risk, also considering menopausal status and hormone therapy (HT). RESULTS: Among premenopausal participants, there was a significant trend for lower odds of breast cancer with higher BMI and borderline significant with higher waist to height ratio (WHtR). For postmenopausal participants, a significant trend for lower odds of breast cancer was observed with higher WHtR, and waist to hip ratio (WHR), borderline significant with higher BMI, and higher odds with height. Among postmenopausal participants using HT, a significant trend for lower odds of breast cancer was observed with higher waist circumference, WHtR, WHR, and body shape index. CONCLUSION: Our study provides evidence of anthropometric differences in relation to breast cancer risk in PR compared to previous studies. Future studies should include analyses of fat and lean mass distribution, and hormone receptor status to further understand anthropometry and breast cancer risk among Hispanic women.
Assuntos
Neoplasias da Mama , Adulto , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Hispânico ou Latino , Hormônios , Humanos , Porto Rico/epidemiologia , Fatores de Risco , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
Invasive fungal infections as aspergillosis and candidiasis are well-documented complications in critically ill patients with acute respiratory distress syndrome due to COVID-19. However, invasive infections by other molds are rarely reported. We describe a case of invasive fusariosis in a patient with severe COVID-19 with a fatal outcome.
RESUMO
Availability of highly parallelized immunoassays has renewed interest in the discovery of serology biomarkers for infectious diseases. Protein and peptide microarrays now provide a rapid, high-throughput platform for immunological testing and validation of potential antigens and B-cell epitopes. However, there is still a need for tools to prioritize and select relevant probes when designing these arrays. In this work we describe a computational method called APRANK (Antigenic Protein and Peptide Ranker) which integrates multiple molecular features to prioritize potentially antigenic proteins and peptides in a given pathogen proteome. These features include subcellular localization, presence of repetitive motifs, natively disordered regions, secondary structure, transmembrane spans and predicted interaction with the immune system. We trained and tested this method with a number of bacteria and protozoa causing human diseases: Borrelia burgdorferi (Lyme disease), Brucella melitensis (Brucellosis), Coxiella burnetii (Q fever), Escherichia coli (Gastroenteritis), Francisella tularensis (Tularemia), Leishmania braziliensis (Leishmaniasis), Leptospira interrogans (Leptospirosis), Mycobacterium leprae (Leprae), Mycobacterium tuberculosis (Tuberculosis), Plasmodium falciparum (Malaria), Porphyromonas gingivalis (Periodontal disease), Staphylococcus aureus (Bacteremia), Streptococcus pyogenes (Group A Streptococcal infections), Toxoplasma gondii (Toxoplasmosis) and Trypanosoma cruzi (Chagas Disease). We have evaluated this integrative method using non-parametric ROC-curves and made an unbiased validation using Onchocerca volvulus as an independent data set. We found that APRANK is successful in predicting antigenicity for all pathogen species tested, facilitating the production of antigen-enriched protein subsets. We make APRANK available to facilitate the identification of novel diagnostic antigens in infectious diseases.
Assuntos
Antígenos/análise , Antígenos/imunologia , Simulação por Computador , Infecções/imunologia , Biologia Computacional/métodos , Humanos , ProteomaRESUMO
In the epidemiological COVID-19 research, artificial intelligence is a unique approach to make predictions about disease severity to manage COVID-19 patients. A limitation of artificial intelligence is, however, the high risk of bias. We investigated the skill of data mining and machine learning, two advanced forms of artificial intelligence, to predict severe COVID-19 pneumonia based on routine laboratory tests. A sample of 4009 COVID-19 patients was divided into Severe (PaO2< 60 mmHg, 489 cases) and Non-Severe (PaO2 ≥ 60 mmHg, 3520 cases) groups according to blood hypoxemia on admission and their laboratory datasets analyzed by the R software and WEKA workbench. After curation, data were processed for the selection of the most influential features including hemogram, pCO2, blood acid-base balance, prothrombin time, inflammation biomarkers, and glucose. The best fit of variables was successfully confirmed by either the Multilayer Perceptron, a feedforward neural network algorithm that performed machine recognition of severe COVID-19 with 96.5% precision, or by the C4.5 software, a supervised learning algorithm based on an objective-predefined variable (severity) that generated a decision tree with 89.4% precision. Finally, a complex bivariate Pearson's correlation matrix combined with advanced hierarchical clustering (dendrograms) were conducted for knowledge discovery. The hidden structure of the datasets revealed shift patterns related to the development of COVID-19-induced pneumonia that involved the lymphocyte-to-C-reactive protein and leukocyte-to-C-protein ratios, neutrophil %, pH and pCO2. The data mining approaches to the hematological fluctuations associated with severe COVID-19 pneumonia could not only anticipate adverse clinical outcomes, but also reveal putative therapeutic targets.
Assuntos
COVID-19 , Inteligência Artificial , Biomarcadores , Mineração de Dados , Testes Hematológicos , Humanos , Laboratórios , SARS-CoV-2RESUMO
The worldwide spread of carbapenem- and polymyxin-resistant Enterobacterales represents an urgent public-health threat. However, for most countries in the Americas, the available data are limited, although Latin America has been suggested as a silent spreading reservoir for isolates carrying plasmid-mediated polymyxin resistance mechanisms. This work provides an overall update on polymyxin and polymyxin resistance and focuses on uses, availability and susceptibility testing. Moreover, a comprehensive review of the current polymyxin resistance epidemiology in the Americas is provided. We found that reports in the English and Spanish literature show widespread carbapenemase-producing and colistin-resistant Klebsiella pneumoniae in the Americas determined by the clonal expansion of the pandemic clone ST258 and mgrB-mediated colistin resistance. In addition, widespread IncI2 and IncX4 plasmids carrying mcr-1 in Escherichia coli come mainly from human sources; however, plasmid-mediated colistin resistance in the Americas is underreported in the veterinary sector. These findings demonstrate the urgent need for the implementation of polymyxin resistance surveillance in Enterobacterales as well as appropriate regulatory measures for antimicrobial use in veterinary medicine.
Assuntos
Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Polimixinas/farmacologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Humanos , Klebsiella pneumoniae/metabolismo , Proteínas de Membrana/genética , Testes de Sensibilidade Microbiana , América do Norte , Plasmídeos/genética , América do Sul , beta-Lactamases/genéticaRESUMO
BACKGROUND: To demonstrate whether extensive intraoperative peritoneal lavage (EIPL) could yield better results in overall survival and less recurrence, regardless of peritoneal cytology, compared to standard peritoneal lavage (SPL). METHODS: A prospective randomised multicenter study including 94 patients (47 per arm) to detect a 20% difference in 3-year overall survival in patients with locally advanced tumours without peritoneal carcinomatosis. Three samples of peritoneal fluid were obtained (at the beginning, the end of procedure and after the assigned peritoneal lavage). Clinicopathological and surgical data were analysed by group. Postoperative complications, location of recurrence and surgical approach were evaluated. Overall survival was calculated by the Kaplan-Meier method and the uni/multivariate analysis for prognostic factors was carried out using Cox regression analysis. RESULTS: A total of 86 patients were analysed (4 excluded per group). No statistical differences were observed in clinicopathological or surgical data between groups, considering both groups well-balanced for analysis. Overall survival at 3 years was 64.3% for SPL vs. 62.3% for EIPL (p 0.421). Only three patients had at least one positive peritoneal cytology (1:2). There were no differences regarding postoperative complications (SPL: 37.2% vs. EIPL: 32.5%, p 0.65) or between location of recurrence and number of recurrences. The number of recurrences did not differ between surgical approaches, but locoregional and peritoneal recurrences were fewer with the laparoscopic approach (p 0.048). CONCLUSIONS: The regular use of extensive peritoneal lavage in patients with locally advanced gastric cancer, regardless of peritoneal cytology, has not been effective as prophylaxis of peritoneal recurrence or better survival.