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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
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.
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Formigas , Clima Tropical , Animais , Mudança Climática , Florestas , Masculino , Chuva , Estações do Ano , ÁrvoresRESUMO
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.
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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
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.
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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
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
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
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
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
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
TP73 is a member of the TP53 family whose expression has been observed altered in most human cancers and associated with the prognosis. TP73 translates into a complex number of isoforms with both oncogenic and tumour-suppressor functions and presents a complex cross-talk with other members of the family (TP53 and TP63). In this revision, we focus on the evidence that may support TP73 variants as prognostic markers in cancer. Nowadays, most publications in this topic highlight the association between overexpression of the oncogenic variants and failure to respond to chemotherapy and/or shorter survival. In addition, we comment on the putative possibilities that the detection through a liquid biopsy of TP73 variants may provide, and finally, the significance of determining the value of the combined alteration of the TP53 family members in the clinical setting.
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Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/patologia , Proteína Tumoral p73/genética , Animais , Humanos , Isoformas de ProteínasRESUMO
Amphotericin B (AmB) is still the most effective drug for the treatment of systemic fungal infections in humans. Despite significant theoretical and experimental efforts trying to understand its molecular mechanism of action, the answer has remained elusive. In this work, we present a computational methodology to test the current membrane related hypotheses, namely, transmembrane ion channel, adsorption, and sterol sponge. We use a thermodynamic approach in which we represent the membrane by a multiphase solvation model with atomic detail (MMPSM) and calculate the free energy of transferring the drug between phases with different dielectric properties. Furthermore, we compare AmB to a chemical analogue with increased safety, an l-histidine methyl ester of AmB. Our findings reveal that both drugs dimerize in all solvents studied here. Also, it is energetically unfavorable for the drugs to penetrate into the hydrophobic core of the membrane, unless their concentration is high. Finally, it is thermodynamically possible that the sterols migrate from the membrane into a drug droplet adsorbed at the surface of the bilayer. In light of our results, several effects could take place in the complex antibiotic process. We suggest a molecular mechanism that connects all three hypotheses through a drug concentration dependence and propose that the drug promotes the formation of membrane toroidal pores. Because MMPSM is of general interest, we made it available at http://tripplab.com/tools/mmpsm .
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Anfotericina B/química , Bicamadas Lipídicas/química , Solventes/química , Anfotericina B/metabolismo , Colesterol/química , Colesterol/metabolismo , Dimerização , Ergosterol/química , Ergosterol/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/metabolismo , TermodinâmicaRESUMO
Resumen: ANTECEDENTES: la inducción del trabajo de parto es un procedimiento que se indica cuando existe riesgo de continuar el embarazo, en lugar de interrumpirlo. Esta maniobra enfrenta nuevas presiones, por lo que es necesario mantener actualizado el conocimiento sobre su indicación. En los últimos años se han desarrollado protocolos clínicos de mayor eficacia y seguridad, que han hecho más accesible este procedimiento. OBJETIVO: emitir un consenso actualizado y analizar los diferentes aspectos de la práctica cotidiana relacionada con la inducción del trabajo de parto. MATERIALES Y MÉTODOS: se integró un grupo de especialistas de trece instituciones nacionales para analizar diferentes aspectos de la práctica cotidiana de la inducción del trabajo de parto. Se siguió una metodología tipo Delphi de cuatro etapas, con bibliografía de normas clínicas internacionales de apoyo. CONCLUSIONES: la inducción del trabajo de parto considera los siguientes criterios: establecer con certeza que el procedimiento ofrece el mejor desenlace para la madre y el feto, confirmar la edad gestacional, realizar la evaluación obstétrica completa y contar con infraestructura para enfrentar las posibles complicaciones. Existen diferentes opciones para la inducción del trabajo de parto; sin embargo, en los últimos años se ha generalizado la prescripción de análogos de prostaglandinas (misoprostol) en todo el mundo. El especialista debe efectuar la evaluación individualizada de la paciente y el feto, con la finalidad de descartar situaciones que comprometan la salud de ambos. La complicación más común de la inducción del trabajo de parto es la taquisistolia, que puede asociarse con desprendimiento prematuro de placenta, rotura uterina y sufrimiento fetal agudo. Los óvulos vaginales de liberación controlada representan la única opción para retirar el estímulo con dinoprostona o misoprostol ante efectos adversos.
Abstract: BACKGROUND: Induction of labor is a maneuver indicated when there is a greater risk of continuing the pregnancy, than interrupting it. The induction of labor faces new pressures that make it necessary for the doctor to be permanently updated. In recent years, clinical protocols of greater efficiency and safety have been developed, which have made this procedure more accessible. OBJECTIVE: To present an updated consensus and to analyze the different aspects related to the labor induction. MATERIAL AND METHODS: A Delphi-type of consensus was conducted with participation of active obstetricians and gynecologists specialists from thirteen national institutions. Major clinical-oriented topics of induction of labor were addressed. CONCLUSIONS: To induce labor, it is necessary that at least the following situations coexist: to establish with certainty that the procedure offers the best outcome for the mother and her child, to confirm the gestational age, to make a complete obstetric evaluation and to have the infrastructure Necessary to deal with possible complications. There are several options to induce labor, although in recent years the indication of prostaglandin analogues (misoprostol) has become the most common option worldwide. The specialist must make an individualized evaluation of the patient and the fetus, in order to rule out situations that may endanger the health of any of them. The most common complication of labor induction is tachysystole, which can be complicated by premature placental abruption, uterine rupture and acute fetal distress, requiring urgent attention. Controlled-release vaginal ovules are the only option available to withdraw the stimulus with dinoprostone or misoprostol in the presence of adverse effects.
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We studied the participation of GABA neurotransmission in the medial preoptic area (mPOA) with respect to the onset of the pup retrieval response and nest building. Pregnant female rats were implanted with bilateral cannulae in the mPOA on day 12 of pregnancy and, on day 16, the females were hysterectomised and ovariectomised and given 200 µg/kg of oestradiol benzoate. Two days later, the females received one of the following intracerebral drug treatments: GABAB agonist baclofen (200 ng); GABAB antagonist phaclofen (1 µg); GABAA antagonist bicuculline (60 ng); or physiological saline. Five minutes after intracerebral infusion, three foster pups were introduced into the females' home cage. The subjects were observed for pup grouping (retrieval) during 15 min, after which the pups were left with the female. During the next 12 h, an observation was made every 1 h to determine whether the pups had been grouped (retrieved) or not. The GABAB agonist baclofen reduced the proportion of females retrieving pups from 4 to 8 h following pup introduction. By contrast, both the GABAA antagonist bicuculline and the GABAB antagonist phaclofen enhanced the proportion of females retrieving pups during the first 3 h of observation. The latency to pup retrieval in subjects treated with the GABAB agonist baclofen was significantly longer than that in subjects given any of the antagonists. All females built a nest but baclofen reduced nest quality. These data show that activation of GABAB receptors in the mPOA has an inhibitory effect on basic maternal behaviours, whereas blockade of either the GABAA or GABAB receptor facilitates pup retrieval. It is possible that reduced GABAergic tone in the mPOA is a key element in the initiation of maternal behaviours in postparturient rats.
Assuntos
Estradiol/fisiologia , Comportamento Materno , Área Pré-Óptica/fisiologia , Receptores de GABA-A/fisiologia , Receptores de GABA-B/fisiologia , Animais , Baclofeno/administração & dosagem , Baclofeno/análogos & derivados , Bicuculina/administração & dosagem , Feminino , Antagonistas de Receptores de GABA-A/administração & dosagem , Agonistas dos Receptores de GABA-B/administração & dosagem , Antagonistas de Receptores de GABA-B/administração & dosagem , Histerectomia , Comportamento Materno/efeitos dos fármacos , Comportamento de Nidação/efeitos dos fármacos , Ovariectomia , Gravidez , Área Pré-Óptica/efeitos dos fármacos , Ratos WistarRESUMO
We present a novel iterative regularized algorithm (IRA) for neural activity reconstruction that explicitly includes spatiotemporal constraints, performing a trade-off between space and time resolutions. For improving the spatial accuracy provided by electroencephalography (EEG) signals, we explore a basis set that describes the smooth, localized areas of potentially active brain regions. In turn, we enhance the time resolution by adding the Markovian assumption for brain activity estimation at each time period. Moreover, to deal with applications that have either distributed or localized neural activity, the spatiotemporal constraints are expressed through [Formula: see text] and [Formula: see text] norms, respectively. For the purpose of validation, we estimate the neural reconstruction performance in time and space separately. Experimental testing is carried out on artificial data, simulating stationary and non-stationary EEG signals. Also, validation is accomplished on two real-world databases, one holding Evoked Potentials and another with EEG data of focal epilepsy. Moreover, responses of functional magnetic resonance imaging for the former EEG data have been measured in advance, allowing to contrast our findings. Obtained results show that the [Formula: see text]-based IRA produces a spatial resolution that is comparable to the one achieved by some widely used sparse-based estimators of brain activity. At the same time, the [Formula: see text]-based IRA outperforms other similar smooth solutions, providing a spatial resolution that is lower than the sparse [Formula: see text]-based solution. As a result, the proposed IRA is a promising method for improving the accuracy of brain activity reconstruction.
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Algoritmos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Eletroencefalografia/métodos , Simulação por Computador , Bases de Dados Factuais , Humanos , Imageamento por Ressonância Magnética/métodos , Cadeias de Markov , Modelos Neurológicos , Processamento de Sinais Assistido por Computador , Fatores de TempoRESUMO
Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiopatologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Alcoolismo/metabolismo , Alcoolismo/fisiopatologia , Animais , Transtornos Cognitivos/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Córtex Pré-Frontal/metabolismo , Transdução de Sinais/fisiologia , Síndrome de Abstinência a Substâncias/metabolismoRESUMO
OBJECTIVE: Thyroid disorders may affect blood pressure and renal function modifying factors of the plasmatic and kidney renin-angiotensin system such as aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We investigated the expression of AP A in the kidney, as well as its enzymatic activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male rats. METHODS: Hyperthyroidism was induced by daily subcutaneous injections of tetraiodothyronine. Hypothyroid rats were obtained by administration of methimazole in drinking water. Expression of AP A was determined by Western blot analysis. Plasma AP A activity was measured fluorometrically using glutamyl-ß-naphthylamide as substrate. RESULTS: While hyperthyroid rats exhibited lower levels of plasma AP A activity than controls, the kidney of hyperthyroid animals expressed significantly higher AP A than controls and hypothyroid animals. CONCLUSIONS: A discrepancy between the high expression of AP A in kidney of hyperthyroid rats and the low activity of AP A measured in plasma and kidney of hyperthyroid animals was found. The posttranslational influence of environmental biochemical factors may be in part responsible for that divergence.
Assuntos
Glutamil Aminopeptidase/metabolismo , Bócio Nodular/enzimologia , Hipertireoidismo/enzimologia , Hipotireoidismo/enzimologia , Rim/enzimologia , Animais , Modelos Animais de Doenças , Ativação Enzimática , Glutamil Aminopeptidase/sangue , Bócio Nodular/sangue , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Masculino , Ratos , Ratos WistarRESUMO
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
Phytosterol (PS) intake may be used for hypercholesterolaemia in some groups although the presence of non-responders is well known. Carotenoids and PS/cholesterol may compete for the same transporters during absorption. As part of a randomized, double-blind, crossover, multiple-dose supplementation study with ß-cryptoxanthin (ß-Cx) and PS, single and combined, polymorphisms of ABCG8 (A632V) and NCPL1 (L272L) were determined in 19 post-menopausal women. Subjects carrying CC polymorphism for NCP1L1 (L272L) showed a net increase in total cholesterol and LDL after PS intake but, interestingly, displayed a decrease in both lipid fractions after consuming PS plus ß-Cx. For the ABCG8 (A632V) gene, CT/TT carriers consuming PS also displayed an increase in total cholesterol and LDL, but this increment was much lower after the intake of PS plus ß-Cx. Additionally, in CC carriers for ABCG8 (A632V), a greater decrease in total cholesterol and LDL was found after the intake of PS plus ß-Cx compared to that observed after PS alone. Overall, our results suggest that ß-Cx improves the response to PS in individuals carrying specific genetic polymorphisms (i.e. non-responders), opening the possibility to modulate the response to PS by food technology. (ClinicalTrials.gov NCT01074723).