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The study was designed to assess whether repeated administration of diazepam (Valium®, Roche)-a benzodiazepine exerting an agonist action on GABAA receptors-may alleviate both the short (1 week, 1W) and long-term (6 weeks, 6W) deleterious effects of alcohol withdrawal occurring after chronic alcohol consumption (6 months; 12% v/v) in C57/BL6 male mice. More pointedly, we first evidenced that 1W and 6W alcohol-withdrawn mice exhibited working memory deficits in a sequential alternation task, associated with sustained exaggerated corticosterone rise and decreased pCREB levels in the prefrontal cortex (PFC). In a subsequent experiment, diazepam was administered i.p. for 9 consecutive days (1 injection/day) during the alcohol withdrawal period at decreasing doses ranging from 1.0 mg/kg to 0.25 mg/kg. Diazepam was not detected in the blood of withdrawn mice at the time of memory testing, occurring 24 hours after the last diazepam injection. Repeated diazepam administration significantly improved alternation rates and normalized levels of glucocorticoids and pCREB activity in the PFC in 1W but not in 6W withdrawn mice. Thus, repeated diazepam administration during the alcohol-withdrawal period only transitorily canceled out the working memory impairments and glucocorticoid alterations in the PFC of alcohol-withdrawn animals.
Assuntos
Alcoolismo/tratamento farmacológico , Diazepam/farmacologia , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Alcoolismo/complicações , Alcoolismo/metabolismo , Alcoolismo/psicologia , Animais , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Ansiedade/metabolismo , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Diazepam/sangue , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/sangue , Agonistas de Receptores de GABA-A/sangue , Agonistas de Receptores de GABA-A/farmacologia , Glucocorticoides/metabolismo , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Nootrópicos/sangue , Córtex Pré-Frontal/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologia , Fatores de TempoRESUMO
Surface plasmons are collective oscillations of electrons in metals or semiconductors that enable confinement and control of electromagnetic energy at subwavelength scales. Rapid progress in plasmonics has largely relied on advances in device nano-fabrication, whereas less attention has been paid to the tunable properties of plasmonic media. One such medium--graphene--is amenable to convenient tuning of its electronic and optical properties by varying the applied voltage. Here, using infrared nano-imaging, we show that common graphene/SiO(2)/Si back-gated structures support propagating surface plasmons. The wavelength of graphene plasmons is of the order of 200 nanometres at technologically relevant infrared frequencies, and they can propagate several times this distance. We have succeeded in altering both the amplitude and the wavelength of these plasmons by varying the gate voltage. Using plasmon interferometry, we investigated losses in graphene by exploring real-space profiles of plasmon standing waves formed between the tip of our nano-probe and the edges of the samples. Plasmon dissipation quantified through this analysis is linked to the exotic electrodynamics of graphene. Standard plasmonic figures of merit of our tunable graphene devices surpass those of common metal-based structures.
Assuntos
Campos Eletromagnéticos , Grafite/química , Raios Infravermelhos , Nanotecnologia/métodos , Microscopia de Força Atômica , Eletricidade Estática , Propriedades de SuperfícieRESUMO
Predicting the localization of a protein has become a useful practice for inferring its function. Most of the reported methods to predict subcellular localizations in Gram-negative bacterial proteins make use of standard protein representations that generally do not take into account the distribution of the amino acids and the structural information of the proteins. Here, we propose a protein representation based on the structural information contained in the pairwise statistical contact potentials. The wavelet transform decodes the information contained in the primary structure of the proteins, allowing the identification of patterns along the proteins, which are used to characterize the subcellular localizations. Then, a support vector machine classifier is trained to categorize them. Cellular compartments like periplasm and extracellular medium are difficult to predict, having a high false negative rate. The wavelet-based method achieves an overall high performance while maintaining a low false negative rate, particularly, on "periplasm" and "extracellular medium". Our results suggest the proposed protein characterization is a useful alternative to representing and predicting protein sequences over the classical and cutting edge protein depictions.
Assuntos
Algoritmos , Proteínas de Bactérias/metabolismo , Bactérias Gram-Negativas/metabolismo , Estatística como Assunto , Análise de Ondaletas , Motivos de Aminoácidos , Bases de Dados de Proteínas , Estrutura Terciária de Proteína , Transporte Proteico , Curva ROC , Frações Subcelulares/metabolismo , Máquina de Vetores de SuporteRESUMO
OBJECTIVE: To compare the accuracy of Kane, Barrett Universal II, Haigis, and SRK-T formulas in eyes with average keratometry greater than 46 diopters (D). METHODS: A retrospective analysis was conducted on 101 eyes of 101 patients with average keratometry greater than 46 D. The absolute prediction error (EA) was obtained for each patient one month after surgery. The mean absolute prediction error (MEA), median absolute prediction error (MedEA) and the percentage of patients with absolute refractive error less than 0.25 D, 0.50 D, and 1.00 D were calculated for each formula analyzed. RESULTS: The Kane formula achieved the lowest MEA (0.53 ± 0.43) and the lowest MedEA (0.41), followed by Barrett Universal II (MEA: 0.56 ± 0.42, MedEA: 0.49), SRK-T (MEA: 0.59 ± 0.44, MedEA: 0.54), and Haigis (MEA: 0.77 ± 0.47, MedEA: 0.69), showing a significant difference in the results. It was also observed that the Kane formula was the most accurate, with the highest percentage of patients, with EA less than 0.25 D, 0.50 D, and 1.00 D (30.7%, 54.4%, and 86.1%, respectively), while the Haigis formula was the least accurate (12.9%, 33.7%, and 69.3%, respectively). CONCLUSION: In eyes with corneas having average keratometry greater than 46 D, the Kane formula proves to be a useful tool in intraocular lens (IOL) power calculation and demonstrates higher precision compared to the Barrett Universal II, SRK-T, and Haigis formulas.
Assuntos
Lentes Intraoculares , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Córnea/anatomia & histologia , Córnea/patologia , Óptica e Fotônica , Refração Ocular/fisiologia , Reprodutibilidade dos Testes , Biometria/métodosRESUMO
Our results demonstrate that the addition of cisplatin after paclitaxel-induced mitotic arrest was more effective than individual treatment on gastric adenocarcinoma cells (MKN45). However, the treatment did not induce benefits in cells derived from lymph node metastasis (ST2957). Time-lapse microscopy revealed that cell death was caused by mitotic catastrophe and apoptosis induction, as the use of the caspase inhibitor z-VAD-fmk decreased cell death. We propose that the molecular mechanism mediating this cell fate is a slippage suffered by these cells, given that our Western blot (WB) analysis revealed premature cyclin B degradation. This resulted in the cell exiting from mitosis without undergoing DNA damage repair, as demonstrated by the strong phosphorylation of H2AX. A comet assay indicated that DNA repair was impaired, and Western blotting showed that the Chk2 protein was degraded after sequential treatment (paclitaxel-cisplatin). Based on these results, the modulation of cell death during mitosis may be an effective strategy for gastric cancer therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Mitose/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Clorometilcetonas de Aminoácidos/farmacologia , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2 , Cisplatino/uso terapêutico , Ciclina B/metabolismo , Humanos , Metástase Linfática/patologia , Paclitaxel , Proteínas Serina-Treonina Quinases/metabolismo , Taxoides/uso terapêuticoRESUMO
The debate of life on Mars centers around the source of the globular, micrometer-sized mineral carbonates in the ALH84001 meteorite; consequently, the identification of Martian processes that form carbonates is critical. This paper reports a previously undescribed carbonate formation process that occurs on Earth and, likely, on Mars. We identified micrometer-sized carbonates in terrestrial aerosols that possess excess (17)O (0.4-3.9). The unique O-isotopic composition mechanistically describes the atmospheric heterogeneous chemical reaction on aerosol surfaces. Concomitant laboratory experiments define the transfer of ozone isotopic anomaly to carbonates via hydrogen peroxide formation when O(3) reacts with surface adsorbed water. This previously unidentified chemical reaction scenario provides an explanation for production of the isotopically anomalous carbonates found in the SNC (shergottites, nakhlaites, chassignites) Martian meteorites and terrestrial atmospheric carbonates. The anomalous hydrogen peroxide formed on the aerosol surfaces may transfer its O-isotopic signature to the water reservoir, thus producing mass independently fractionated secondary mineral evaporites. The formation of peroxide via heterogeneous chemistry on aerosol surfaces also reveals a previously undescribed oxidative process of utility in understanding ozone and oxygen chemistry, both on Mars and Earth.
Assuntos
Atmosfera/química , Carbonatos/química , Marte , Meteoroides , Isótopos de Oxigênio/análise , Exobiologia , Peróxido de Hidrogênio/química , Nanopartículas/análise , Ozônio/químicaRESUMO
A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank » 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P » 0.029) and with poorly differentiated tumors (P » 0.039) and tended to have shorter overall survival than patients with low levels (P » 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.
Assuntos
Neoplasias Colorretais/sangue , Exossomos/metabolismo , Biomarcadores Tumorais , Antígeno Carcinoembrionário/biossíntese , Antígeno Carcinoembrionário/sangue , Proteínas de Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Exossomos/genética , Feminino , Genes p53 , Células HCT116 , Humanos , Masculino , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Oxirredutases , Prognóstico , RNA Mensageiro/biossíntese , Vesículas Secretórias/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVES: The use of magnets in transumbilical cholecystectomy improves triangulation and achieves optimal critical view. However, the attraction between magnets can cause collisions and their management complicates the procedure, and this will become more important in children. In order to simplify the technique, we have developed a hybrid model with a single magnet. MATERIAL AND METHODS: Retrospective review of cholecystectomies performed in our department between June 2011 and July 2012. The technique combines the use of a magnet and a curved grasper. Through transumbilical incision, a 12 mm trocar and another flexible 5 mm are placed. Laparoscope with working channel uses the 12 mm trocar. The magnet is introduced to the abdominal cavity using the working channel to provide cephalad retraction of gallbladder fundus. Curved grasper is run by the assistant to mobilize the infundibulum across flexible trocar. The surgeon operates through the working channel of the laparoscope. RESULTS: Twenty-six patients were operated on with this technique. Mean age was 14 years (4-17) and weight 50 kg (18-90). 65% were girls. The mean operative time was 62 minutes (50-70) and the critical view of safety was achieved in all cases. Instrumental collision or hands crossing were not seen. There were no intraoperative or postoperative complications. The hospital stay was 1.4 +/- 0.6 days and the median follow-up 201 days (42-429). CONCLUSIONS: The hybrid technique, combining magnet and a curved grasper, simplifies transumbilical surgery. It seems a feasible and safe for transumbilical cholecystectomy and potentially reproducible.
Assuntos
Colecistectomia Laparoscópica/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , UmbigoRESUMO
Tropical forests sustain many ant species whose mating events often involve conspicuous flying swarms of winged gynes and males. The success of these reproductive flights depends on environmental variables and determines the maintenance of local ant diversity. However, we lack a strong understanding of the role of environmental variables in shaping the phenology of these flights. Using a combination of community-level analyses and a time-series model on male abundance, we studied male ant phenology in a seasonally wet lowland rainforest in the Panama Canal. The male flights of 161 ant species, sampled with 10 Malaise traps during 58 consecutive weeks (from August 2014 to September 2015), varied widely in number (mean = 9.8 weeks, median = 4, range = 1 to 58). Those species abundant enough for analysis (n = 97) flew mainly towards the end of the dry season and at the start of the rainy season. While litterfall, rain, temperature, and air humidity explained community composition, the time-series model estimators elucidated more complex patterns of reproductive investment across the entire year. For example, male abundance increased in weeks when maximum daily temperature increased and in wet weeks during the dry season. On the contrary, male abundance decreased in periods when rain receded (e.g., at the start of the dry season), in periods when rain fell daily (e.g., right after the beginning of the wet season), or when there was an increase in the short-term rate of litterfall (e.g., at the end of the dry season). Together, these results suggest that the BCI ant community is adapted to the dry/wet transition as the best timing of reproductive investment. We hypothesize that current climate change scenarios for tropical regions with higher average temperature, but lower rainfall, may generate phenological mismatches between reproductive flights and the adequate conditions needed for a successful start of the colony.
Assuntos
Formigas , Clima Tropical , Animais , Mudança Climática , Florestas , Masculino , Chuva , Estações do Ano , ÁrvoresRESUMO
The identification of tumour biomarkers that detect the presence of disease using noninvasive diagnostic procedures is a key part of cancer research. We determined in plasma the vesicle-related microRNA (miRNA) expression profile of nonsmall cell lung cancer (NSCLC) and evaluate whether plasma miRNAs can be both discriminating (between patients and healthy controls) and prognostic markers. 365 human miRNAs were analysed by Taqman® low-density arrays (Applied Biosystems, Foster City, CA, USA) in the plasma from 28 NSCLC patients and 20 controls. Five selected miRNAs (let-7f, miR-20b, miR-30e-3p, miR-223 and miR-301) were validated independently by real-time PCR in plasma from 78 NSCLC and 48 controls and correlated with pathologic parameters and survival. Levels of let-7f, miR-20b and miR-30e-3p were decreased in plasma vesicles of NSCLC patients. Moreover, levels of let-7f and miR-30e-3p distinguished between two groups of patients for stage of disease and therefore possibility of surgery. Plasma levels of miR-30e-3p and let-7f were associated with short disease-free survival and overall survival, respectively. NSCLC patients and healthy controls differ in vesicle-related miRNAs in plasma. Levels of let-7f and miR-30e-3p in NSCLC patients are associated with poor outcome. Thus, plasma vesicle-related miRNAs obtained by noninvasive methods could serve as circulating tumour biomarkers of discriminating and prognostic value.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , Intervalo Livre de Doença , Reações Falso-Positivas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , PrognósticoRESUMO
BACKGROUND: The role of digoxin in the prognosis of patients with heart failure (HF) remains unclear. AIMS: To evaluate the relationship of commencing treatment with digoxin (CTDig) with the mortality and the morbidity of patients with HF. METHODS: Prospective study over 8 years on 4467 patients with HF. Main outcomes were all-cause and cardiovascular mortality, hospitalisations and visits. We analyse the independent relationship of CTDig, with the mortality and the morbidity, stratifying patients for cardiovascular comorbidity, after propensity score-matching for potential confounders (1421 patients who CTDig vs. another 1421 patients non-exposed to digoxin). RESULTS: During a median follow up of 46.1 months, 1872 patients (65.9%) died, and 2203 (77.5%) were hospitalised. CTDig was associated with a lower all-cause mortality (HR = 0.90 [95% CI, 0.84-0.97]), and cardiovascular mortality (HR = 0.87 [0.81-0.96]), hospitalisation (HR = 0.91 [0.86-0.97]), 30-day readmission for HF (HR = 0.88 [0.79-0.95]), and visits (HR = 0.94 [0.90-0.98]) (p < 0.001 in all cases), after adjustment for the propensity to take digoxin, other medications, and other potential confounders. These effects of digoxin were independent of gender, or type of HF (systolic or non-systolic). CONCLUSION: The data suggest that therapy with digoxin is associated with an improved mortality and morbidity of HF, including women and patients with non-systolic HF.
Assuntos
Cardiotônicos/uso terapêutico , Digoxina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pontuação de Propensão , Estudos Prospectivos , Resultado do TratamentoRESUMO
The objective of this study was to evaluate the association between progesterone concentration on Days 4 and 9 of the estrus cycle and endometrial transcriptome at Day 9 in lactating grazing dairy cows. Blood samples were obtained on Days 0, 4, and 9 for progesterone measurement by chemiluminescence. Cows were assigned to one of the following groups (n = 3 per group): cows with low physiological progesterone on Day 4, cows in anestrous, cows with high physiological progesterone on Day 4, and superovulated cows. Endometrial biopsy samples were obtained on Day 9 for RNA sequencing. Quality control and determination of differentially expressed genes (false discovery rate <0.05) were determined using the edgeR package for R software. We identified 3,042 differentially expressed genes among the 4 groups. Cows having high physiological progesterone and superovulated cows showed high similarities and clustered apart from those in anestrus or having low physiological progesterone. Functional analysis using Database for Annotation, Visualization, and Integrated Discovery revealed that endometrial genes upregulated by low progesterone concentration are enriched genes involved in the immune system and inflammatory response. Conversely, cows with high physiological progesterone concentration presented an endometrial transcriptome with similarities to cows with good genetic merit for fertility, showing upregulation of genes related to uterine relaxation-contraction, focal adhesion, GnRH signaling pathway, and epidermal growth factor-like related terms, suggesting a favorable embryo environment. In conclusion, our results support the concept that there is a threshold of progesterone concentration at the beginning of the luteal phase associated with endometrial expression of critical genes involved in the preparation of the uterine environment for embryo implantation.
Assuntos
Doenças dos Bovinos/metabolismo , Endometrite/veterinária , Endométrio/metabolismo , Ciclo Estral/fisiologia , Inflamação/veterinária , Progesterona/metabolismo , Animais , Bovinos , Regulação para Baixo , Endometrite/metabolismo , Feminino , Fertilidade/fisiologia , Regulação da Expressão Gênica/fisiologia , Inflamação/metabolismo , RNA/genética , RNA/metabolismo , Regulação para CimaRESUMO
The development of high-throughput technologies such as next-generation sequencing for DNA sequencing together with the decrease in their cost has led to the progressive introduction of genomic profiling in our daily practice in oncology. Nowadays, genomic profiling is part of genetic counseling, cancer diagnosis, molecular characterization, and as a biomarker of prognosis and response to treatment. Furthermore, germline or somatic genomic characterization of the tumor may provide new treatment opportunities for patients with cancer. In this review, we will summarize the clinical applications and limitations of genomic profiling in oncology clinical practice, focusing on next-generation sequencing.
Assuntos
Biomarcadores Tumorais/genética , Mutação , Neoplasias/genética , Aconselhamento Genético/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Oncologia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Medicina de Precisão/métodos , PrognósticoRESUMO
Electromagnetic source imaging (ESI) techniques have become one of the most common alternatives for understanding cognitive processes in the human brain and for guiding possible therapies for neurological diseases. However, ESI accuracy strongly depends on the forward model capabilities to accurately describe the subject's head anatomy from the available structural data. Attempting to improve the ESI performance, we enhance the brain structure model within the individual-defined forward problem formulation, combining the head geometry complexity of the modeled tissue compartments and the prior knowledge of the brain tissue morphology. We validate the proposed methodology using 25 subjects, from which a set of magnetic-resonance imaging scans is acquired, extracting the anatomical priors and an electroencephalography signal set needed for validating the ESI scenarios. Obtained results confirm that incorporating patient-specific head models enhances the performed accuracy and improves the localization of focal and deep sources.
Assuntos
Eletroencefalografia/métodos , Cabeça/anatomia & histologia , Cabeça/diagnóstico por imagem , Modelagem Computacional Específica para o Paciente/estatística & dados numéricos , Adolescente , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Mapeamento Encefálico/estatística & dados numéricos , Criança , Pré-Escolar , Biologia Computacional , Eletroencefalografia/estatística & dados numéricos , Fenômenos Eletromagnéticos , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Modelos Neurológicos , Neuroimagem/estatística & dados numéricosRESUMO
This study was conducted to compare efficacy of treatments with EB or GnRH and different quantities of exogenous progesterone (P4) for synchronization of time of ovulation on follicular growth and pregnancy in lactating dairy cows. In Experiment 1, 40 cows were treated with EB or GnRH and 1.9 or 3.0 g of P4 via progesterone-containing intravaginal devices (IVPD; D0), two doses of PGF2α on D7, GnRH on D9, and TAI on D10. In Experiment 2, 1,440 cows were treated with EB or GnRH and 1 g IVPD on D0, cloprostenol, eCG and EB on D7. Cows in estrus by 48 h were AIDE, and non-estrous cows were administered GnRH and TAI 60 h after IVPD removal. Non-estrous cows were AIDE 72 h after IVPD removal. In Experiment 1, P4 was greater on D7 for cows treated with GnRH than those treated with EB. The dominant follicle was larger for cows treated with GnRH than those treated with EB. In Experiment 2, for estrous cows, pregnancy per AI was greater in cows AI at 48 h compared to 60 h after IVPD removal for cows treated with GnRH, and greater with AI at 60 h after IVPD removal compared to 48 h in EB-treated cows. In non-estrous cows, there was no effect on pregnancy. In conclusion, treatment with GnRH compared with EB resulted in increased P4 regardless of amount of exogenous P4, and there were differential proportions of estrous cows pregnant depending on time of AI after IVPD removal.
Assuntos
Bovinos/fisiologia , Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/farmacologia , Lactação/fisiologia , Folículo Ovariano/efeitos dos fármacos , Progesterona/farmacologia , Administração Intravaginal , Animais , Estradiol/administração & dosagem , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Inseminação Artificial/veterinária , Paridade , Gravidez , Progesterona/administração & dosagemRESUMO
Interpretation of brain activity responses using motor imagery (MI) paradigms is vital for medical diagnosis and monitoring. Assessed by machine learning techniques, identification of imagined actions is hindered by substantial intra- and inter-subject variability. Here, we develop an architecture of Convolutional Neural Networks (CNN) with an enhanced interpretation of the spatial brain neural patterns that mainly contribute to the classification of MI tasks. Two methods of 2D-feature extraction from EEG data are contrasted: Power Spectral Density and Continuous Wavelet Transform. For preserving the spatial interpretation of extracting EEG patterns, we project the multi-channel data using a topographic interpolation. Besides, we include a spatial dropping algorithm to remove the learned weights that reflect the localities not engaged with the elicited brain response. We evaluate two labeled scenarios of MI tasks: bi-class and three-class. Obtained results in an MI database show that the thresholding strategy combined with Continuous Wavelet Transform improves the accuracy and enhances the interpretability of CNN architecture, showing that the highest contribution clusters over the sensorimotor cortex with a differentiated behavior of rhythms [Formula: see text] and [Formula: see text].
RESUMO
The early detection of Alzheimer's disease and quantification of its progression poses multiple difficulties for machine learning algorithms. Two of the most relevant issues are related to missing data and results interpretability. To deal with both issues, we introduce a methodology to predict conversion of mild cognitive impairment patients to Alzheimer's from structural brain MRI volumes. First, we use morphological measures of each brain structure to build an instance-based feature mapping that copes with missed follow-up visits. Then, the extracted multiple feature mappings are combined into a single representation through the convex combination of reproducing kernels. The weighting parameters per structure are tuned based on the maximization of the centered-kernel alignment criterion. We evaluate the proposed methodology on a couple of well-known classification machines employing the ADNI database devoted to assessing the combined prognostic value of several AD biomarkers. The obtained experimental results show that our proposed method of Instance-based representation using multiple kernel learning enables detecting mild cognitive impairment as well as predicting conversion to Alzheimers disease within three years from the initial screening. Besides, the brain structures with larger combination weights are directly related to memory and cognitive functions.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , PrognósticoRESUMO
INTRODUCTION: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3-0.9% of the appendectomies, 35-58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis. MATERIALS AND METHODS: We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer. RESULTS: Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively. CONCLUSION: Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series.
Assuntos
Adenocarcinoma/química , Neoplasias do Apêndice/química , Biomarcadores Tumorais/análise , Células Caliciformes/química , Neoplasias Ovarianas/química , Neoplasias Peritoneais/química , Proteína Tumoral p73/análise , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Colo/química , Neoplasias do Colo/química , Procedimentos Cirúrgicos de Citorredução , Regulação para Baixo , Feminino , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Peritônio/químicaRESUMO
In the recent past, estimating brain activity with magneto/electroencephalography (M/EEG) has been increasingly employed as a noninvasive technique for understanding the brain functions and neural dynamics. However, one of the main open problems when dealing with M/EEG data is its non-Gaussian and nonstationary structure. In this paper, we introduce a methodology for enhancing the data covariance estimation using a weighted combination of multiple Gaussian kernels, termed WM-MK, that relies on the Kullback-Leibler divergence for associating each kernel weight to its relevance. From the obtained results of validation on nonstationary and non-Gaussian brain activity (simulated and real-world EEG data), WM-MK proves that the accuracy of the source estimation raises by more effectively exploiting the measured nonlinear structures with high time and space complexity.
Assuntos
Eletroencefalografia/estatística & dados numéricos , Magnetoencefalografia/métodos , Magnetoencefalografia/estatística & dados numéricos , Modelos Estatísticos , Simulação por Computador , Eletroencefalografia/métodos , HumanosRESUMO
OBJECTIVE: To associate serologic response to Helicobacter pylori (Hp) among seropositive university students and their families in western Mexico. METHODS: We conducted a comparative transversal study, and randomized 30 nuclear families of 14 Hp-seropositive university students and 14 Hp-seronegative university students. We carried out seropositivity measurements (IgG) to Hp using the ELISA method. An analysis was performed utilizing the chi-squared and Mann-Whitney U tests, with the aid of EPI INFO 2000 and SIGMA STAT 3.2 software. RESULTS: Global seropositivity in the families of infected students was 57 vs. 13% of the relatives of non-infected students (p = 0.000002). In families of Hp-positive students we found the following frequencies: parental (father and mother) 70%; mother 71%, and siblings 42%, while for seronegative individuals incidences were: parental 17% (p = 0.00005), mother 12% (p = 0.001), and siblings 10% (p = 0.0076). CONCLUSIONS: There is a greater prevalence of antibodies against Hp in the relatives of seropositive students.