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Varying coefficient models (VCMs) are commonly used for their high degree of flexibility in modeling complex systems. Many applications in fisheries utilize VCMs to capture spatial variation in populations of marine fishes. All of these applications use the penalized least squares method for estimation. However, this approach is known to be sensitive to non-normal distributions and outliers, a common feature of ecological data. Robust estimation methods are more appropriate for handling noisy and non-normal data. We present the application of a signed-rank-based procedure for obtaining robust estimates in VCMs on a fisheries dataset from the North Pacific Ocean. We demonstrates that the signed-rank-based estimation method provides better fit and improved prediction in comparison to the classical likelihood VCM fits in both simulations and the real data application, particularly when the distributions are non-normal and may be misspecified. Rank-based estimation of VCMs is therefore valuable for modeling ecological data and obtaining useful inferences where non-normality and outliers are common.
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5 fluorouracil (5FU), an antineoplastic drug, is often utilized in the therapeutic regimen for several types of cancer, including the hepatoblastoma in children. The effects of 5FU on the population of ovarian preantral follicles, which is the largest oocyte reservoir, is still poorly understood. The integrity of the ovarian preantral follicle pool is important for lifelong fertility. The better understanding of such effects may favor intervention strategies to protect fertility in 5FU-treated children and women coping with cancer. To analyze the effects of 5FU on isolated murine secondary follicles in vitro, ovaries were collected from young mice (28-30 days old), and secondary follicles were isolated and cultured for 12 days in basic culture medium, with or without 5FU at concentrations of 0.3 mM, 1 mM, 3 mM, 10 mM, and 30 mM. In the in vitro study, we analyzed the percentage of morphologically normal follicles, antrum formation, follicular diameter, and hormone production. On day 12, oocytes were recovered for in vitro maturation. 5FU treatment did not alter the percentage of morphologically normal follicles. On day 12, only 1, 10, and 30 mM 5FU significantly reduced the percentage of antrum. From day 4 onwards, 5FU treatments significantly reduced follicle diameter. The meiosis resumption rate was significantly lower in all 5FU treatments. 5FU concentrations ≥3 mM reduced estradiol levels. In conclusion, 5FU does not affect follicular morphology. However, 5FU deleteriously affects follicular growth, estradiol production, and oocyte maturation in isolated ovarian follicles.
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Antineoplásicos , Fluorouracilo , Animales , Femenino , Fluorouracilo/farmacología , Meiosis , Ratones , Oocitos , Folículo OváricoRESUMEN
This study investigated: 1) the kinetics of oocyte chromatin configuration during in vitro maturation (IVM) of caprine and bovine oocytes; and 2) the effect of in vitro pre-maturation (IVPM) with cilostamide with or without association of the follicular wall (FW) on the same parameters. In experiment I, cumulus-oocyte complexes (COCs) were cultured in vitro in a standard maturation medium for 6, 12, 18 or 30â¯h. For experiment II, the COCs were cultured for 30â¯h, either in a standard IVM medium or in IVPM containing cilostamide (10 or 20⯵M) and FW alone or in combination, for 6 or 12â¯h before the onset of maturation. The MII rate was similar (Pâ¯>â¯.05) between 18 and 30â¯h of maturation, both of which were higher (Pâ¯<â¯.05) than 6 and 12â¯h IVM in both species (Experiment I). Contrary to caprine, all IVPM treatments presented a higher (Pâ¯<â¯.05) percentage of bovine oocytes arrested at the GV stage than the control treatment after 6â¯h of culture. The percentage of MII oocytes after 30â¯h (IVPM+IVM) of culture in bovine oocytes treated with 10⯵M cilostamide associated with FW and FW alone cultured for 6â¯h presented MII percentages similar to the control. However, in caprine, these treatments significantly reduced the percentages of MII in relation to the control treatment (Experiment II). In conclusion, the combination of concentration-exposure time to cilostamide during IVPM delayed meiotic progression in bovine after 6 and 12â¯h of culture. However, overall the culture period (IVPM+IVM) influenced the oocyte chromatin configuration and kinetics in both species.
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Bovinos , Cabras , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/efectos de los fármacos , Quinolonas/farmacología , Animales , Femenino , Técnicas de Maduración In Vitro de los Oocitos/métodos , Cinética , Meiosis , Oocitos/fisiologíaRESUMEN
In the original publication of the article, two of the author names "L. A. Schröder, F. Metzner" and email address of the authors "J. Devine, J. Moon, A. C. Haller" were missed out. The correct author group with affiliations are provided in this correction.
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PURPOSE: The Patient-Reported Outcome Measurement Information System (PROMIS®) is a National Institutes of Health (NIH)-funded initiative to develop reliable, valid, and normed item banks to measure health. We describe the first large-scale translation and cross-cultural adaptation effort to German and Spanish of eight pediatric PROMIS item banks: Physical activity (PAC), subjective well-being (SWB), experiences of stress (EOS), and family relations (FAM). METHODS: We utilized methods outlined in the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Translation Task Force recommendations. Ten professional translators performed a translatability assessment and generated forward translations. Forward Translations were compared within a country and cross-culturally to identify problems and to produce a consensus-derived version, which was then back translated, evaluated, and revised where necessary. Reconciled versions were evaluated in cognitive interviews with 126 children before finalization. RESULTS: Eight resulting pediatric PROMIS® item banks were translated: Two PAC banks (22 total items), three SWB banks (125 total items), two EOS banks (45 total items), and one FAM bank (47 total items). Up to 92% of all items raised no or only minor translation difficulties, 0-5.6% were difficult to translate. Up to 20% item revisions were necessary to ensure conceptual equivalence and comprehensibility. Cognitive interviews indicated that 91-94% of the final items were appropriate for children (8-17 years). CONCLUSIONS: German and Spanish translations of eight PROMIS Pediatric item banks were created for clinical trials and routine pediatric health care. Initial translatability assessment and rigorous translation methodology helped to ensure conceptual equivalence and comprehensibility. Next steps include cross-cultural validation and adaptation studies.
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Evaluación de Resultado en la Atención de Salud/métodos , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Traducción , Traducciones , Adolescente , Niño , Comparación Transcultural , Ejercicio Físico/fisiología , Femenino , Hispánicos o Latinos , Humanos , Sistemas de Información , Masculino , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Estrés Psicológico/psicologíaRESUMEN
The aim of this study was to investigate the effect of three concentrations of anethole (30, 300, and 2000 µg/mL) on survival, antrum formation, follicular diameter, and oocyte maturation in the caprine species. The study also evaluated the effects of anethole on transcripts of ICAM-1, CAV-1, TIMP-2, and PAI-1 genes and levels of reactive oxygen species (ROS) in isolated goat preantral ovarian follicles before and after in vitro culture for 18 days. Preantral follicles were isolated from goat ovaries and individually cultured in alpha minimum essential medium modified (α-MEM+), defined as the control treatment, α-MEM+ supplemented with ascorbic acid at a concentration of 100 µg/mL (AA), or α-MEM+ supplemented with three different concentrations of anethole (30, 300, 2000 µg/mL) for a period of 18 days. Treatments were named as α-MEM+, AA, AN30, AN300, and AN2000, respectively. After culture, the follicles were opened, the cumulus oocytes complex (COCs) were removed and matured in vitro. The walls of the follicles were used for the quantitation of mRNA by quantitative real-time polymerase chain reaction. Finally, the medium collected at the end of culture was used for the measurements of ROS. After 18 days of culture, the AA treatment showed the percentage of intact follicles and follicular diameter significantly higher compared with the other treatments. However, daily growth rate, antrum formation, and also oocyte diameter were similar among the treatments. In addition, compared with AA, the rate of oocytes for in vitro maturation (diameter ≥ 110 µm) and the meiosis resumption rate were significantly higher in the treatments AN30 and AN2000, respectively. When assessing gene related to remodeling of the basement membrane, significant differences in mRNA levels for ICAM-1, CAV-1, TIMP-2, and PAI-1 were observed in comparison with Day 0, i.e., in the noncultured control. In addition, the ROS from Day 12, all treatments with the addition of anethole have significantly lower values of ROS than α-MEM+ and AA. In conclusion, the addition of anethole to the in vitro culture medium was able to improve the development of goat preantral follicles by reducing concentrations of ROS and increasing the percentage of oocytes able to resume meiosis.
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Anisoles/farmacología , Cabras/fisiología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Folículo Ovárico/crecimiento & desarrollo , Derivados de Alilbenceno , Animales , Femenino , Técnicas de Maduración In Vitro de los Oocitos/métodos , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The aim of the present study was to evaluate the effect of anti-Müllerian hormone (AMH), with and without FSH, on the in vitro development of isolated caprine preantral follicles, as well as follicular steroid production and mRNA levels of AMH, hormone receptors (AMH and FSH), CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1), CYP17 (cytochrome P450, family 17, subfamily A, polypeptide 1), HSD3B (3-beta-hydroxysteroid dehydrogenase) and Myc (myelocytomatosis oncogene). Isolated secondary follicles were cultured in minimum essential medium alpha (α-MEM+) alone or supplemented with 50ng mL-1 AMH and/or 100ng mL-1 FSH added sequentially on different days of culture. Follicles were cultured for a total of 18 days, with different media during the first (Days 0-9) and second (Days 10-18) halves of the culture period, resulting in six treatment groups, as follows: α-MEM+/α-MEM+, FSH/FSH, AMH/AMH, AMH+FSH/AMH+FSH, AMH/FSH, and FSH/AMH. Follicle development was evaluated on the basis of follicular growth, oocyte maturation and steroid secretion. There was a decrease in follicular growth rate in the AMH, AMH+FSH and AMH/FSH treatment groups compared with α-MEM+ and FSH treatment groups (P<0.05). However, the different culture conditions had no effect on rates of meiotic resumption and steroid secretion (P>0.05). Moreover, follicles cultured in the presence of FSH had lower levels of AMH receptor type II (AMHRII) mRNA compared with non-cultured control (freshly isolated follicles), and the AMH and AMH/FSH treatment groups. In conclusion, AMH reduces the follicular growth rate of isolated goat preantral follicles in vitro without affecting follicular survival.
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Hormona Antimülleriana/metabolismo , Hormona Folículo Estimulante/metabolismo , Regulación del Desarrollo de la Expresión Génica , Oogénesis , Folículo Ovárico/metabolismo , Receptores de HFE/agonistas , Receptores de Péptidos/agonistas , Receptores de Factores de Crecimiento Transformadores beta/agonistas , Mataderos , Animales , Hormona Antimülleriana/genética , Hormona Antimülleriana/farmacología , Brasil , Bovinos , Proliferación Celular/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cruzamientos Genéticos , Estradiol/metabolismo , Femenino , Hormona Folículo Estimulante/genética , Hormona Folículo Estimulante/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Cabras , Humanos , Oogénesis/efectos de los fármacos , Folículo Ovárico/citología , Folículo Ovárico/efectos de los fármacos , Progesterona/metabolismo , Receptores de HFE/genética , Receptores de HFE/metabolismo , Receptores de Péptidos/genética , Receptores de Péptidos/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Testosterona/metabolismo , Técnicas de Cultivo de TejidosRESUMEN
The deleterious effect of heat stress (HS) on competence of oocytes from antral follicles is well recognized, but there is a lack of data regarding its impact on the viability and growth of preantral follicles. In this study, we used in vitro preantral follicle cultures to investigate the effects of HS on the following parameters: survival and development of primordial follicles after in vitro culture of ovarian fragments (experiment I); growth and antrum formation of isolated advanced secondary follicles (experiment II); and maturation rates after in vitro maturation (IVM) of cumulus-oocyte complexes (COCs) from antral follicles (>2-6 mm) grown in vivo (experiment III). Furthermore, the following end points were evaluated in all experiments: follicle/oocyte survival, reactive oxygen species (ROS), estradiol (E2) and progesterone (P4) production, as well as mRNA expression for select genes related to stress (HSP70) and apoptosis (MCL1 and BAX). In all experiments, HS consisted of exposing the structures (ovarian fragments, isolated preantral follicles and COCs) to 41 °C for 12 hours and then to 38.5 °C until the end of the culture (7 days for experiments I and II and 24 hours for experiment III). The temperature for the control group was held at 38.5 °C for the entire culture period. Heat stress increased (P < 0.05) the percentage of developing follicles (intermediate, primary, and secondary follicles) at 12 hours and increased levels of ROS at all evaluated time points (12, 24 hours, and D7), when compared to the control (experiment I). Heat stress did not affect (P > 0.05) any identified end points when preantral follicles were cultured in their isolated form (experiment II). However, in experiment III, HS decreased (P < 0.05) both the rates of metaphase II after 24 hours and E2 production at 12 hours of IVM. Moreover, HS increased (P < 0.0001) levels of P4 after IVM and ROS production at every evaluated time point, compared with the control (12 and 24 hours). In conclusion, HS caused: (1) early activation of primordial follicles; (2) an increase in ROS production by early preantral follicles enclosed in ovarian tissue and by COCs; (3) a short-term reduction of E2 production by COCs; and (4) an increase in P4 secretion from COCs. However, HS did not affect in vitro culture of advanced isolated secondary follicles. Experimental evidence indicates that preantral follicles are less sensitive to HS than COC.
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Bovinos/fisiología , Células del Cúmulo/fisiología , Calor , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/fisiología , Folículo Ovárico/fisiología , Animales , Femenino , Estrés FisiológicoRESUMEN
The aim of this study was to evaluate the effect of different combinations of insulin and FSH concentrations in culture media containing GH on the in vitro follicle morphology, antrum formation, growth rates, estradiol (E2) production, oocyte viability and maturation as well as gene expression for FSHR, GHR, INSR, CYP19A1, CYP17, 3ßHSD. Secondary follicles were individually cultured for 18 days in a basic medium containing 50ng/mL GH supplemented with low insulin concentration (INS-LW: 10ng/mL) or high insulin concentration (INS-HG: 10µg/mL) alone or with a fixed FSH concentration (FSH100: 100ng/mL) or with increasing FSH concentrations (FSH-SEQ: 100ng/mL, days 0-6; 500ng/mL, days 6-12; 1000ng/mL days 12-18). In the INS-LW treatment was observed a higher (P<0.05) incidence of normal follicles at day 18 of culture. However, overall higher (P<0.05) follicular growth, oocyte diameter and meiotic resumption rates were obtained using INS-HG+FSH 100. The INS-HG and INS-HG+FSH100 treatments showed higher E2 production and mRNA levels for CYP19A1, CYP17, 3ßHSD when compared to INS-LW and INS-LW+FSH100. However, the addition of increasing FSH concentration, regardless of insulin concentration, did not improve the follicular growth, meotic resumption, E2 production or gene expression of steroidogenic enzymes when compared with INS-HG+FSH100. In conclusion, in presence of GH, a basic medium supplemented with 10µg/mL insulin and 100µg/mL FSH throughout the culture period, improves follicular and oocyte growth, oocyte meiotic resumption and E2 production from isolated preantral caprine follicles cultured in vitro.
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Medios de Cultivo/química , Hormona Folículo Estimulante/farmacología , Cabras/fisiología , Hormona del Crecimiento/farmacología , Insulina/farmacología , Folículo Ovárico/metabolismo , Animales , Medios de Cultivo/farmacología , ADN Complementario/genética , ADN Complementario/metabolismo , Estrógenos/metabolismo , Femenino , Hormona Folículo Estimulante/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Técnicas de Maduración In Vitro de los Oocitos/métodos , Insulina/administración & dosificación , ARN/genética , ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Técnicas de Cultivo de Tejidos/veterinariaRESUMEN
INTRODUCTION: The quality of life in neurological disorders (Neuro-QoL) measurement system is a 470-item compilation of health-related quality of life domains for adults and children with neurological disorders. It was developed and cognitively debriefed in English and Spanish, with general population and clinical samples in the USA. This paper describes the Spanish translation and linguistic validation process. METHODS: The translation methodology combined forward and back-translations, multiple reviews, and cognitive debriefing with 30 adult and 30 pediatric Spanish-speaking respondents in the USA. The adult Fatigue bank was later also tested in Spain and Argentina. A universal approach to translation was adopted to produce a Spanish version that can be used in various countries. Translators from several countries were involved in the process. RESULTS: Cognitive debriefing results indicated that most of the 470 Spanish items were well understood. Translations were revised as needed where difficulty was reported or where participants' comments revealed misunderstanding of an item's intended meaning. Additional testing of the universal Spanish adult Fatigue item bank in Spain and Argentina confirmed good understanding of the items and that no country-specific word changes were necessary. CONCLUSION: All the adult and pediatric Neuro-QoL measures have been linguistically validated with Spanish speakers in the USA. Instruments are available for use at www.assessmentcenter.net.
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Enfermedades del Sistema Nervioso/psicología , Calidad de Vida/psicología , Traducciones , Adolescente , Adulto , Esclerosis Amiotrófica Lateral/psicología , Argentina , Niño , Comprensión , Epilepsia/psicología , Fatiga , Femenino , Hispánicos o Latinos , Humanos , Lenguaje , Lingüística , Masculino , Esclerosis Múltiple/psicología , Distrofias Musculares/psicología , Enfermedad de Parkinson/psicología , España , Accidente Cerebrovascular/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS(®)) is a new, state-of-the-art assessment system for measuring patient-reported health and well-being of adults and children that has the potential to be more valid, reliable and responsive than existing PROMs. The PROMIS items can be administered in short forms or, more efficiently, through computerized adaptive testing. This paper describes the translation of 563 items from 17 PROMIS item banks (domains) for adults from the English source into Dutch-Flemish. METHODS: The translation was performed by FACITtrans using standardized methodology and approved by the PROMIS Statistical Center. The translation included four forward translations, two back-translations, three to five independent reviews (at least two Dutch, one Flemish) and pre-testing in 70 adults (age range 20-77) from the Netherlands and Flanders. RESULTS: A small number of items required separate translations for Dutch and Flemish: physical function (five items), pain behaviour (two items), pain interference (one item), social isolation (one item) and global health (one item). Challenges faced in the translation process included: scarcity or overabundance of possible translations, unclear item descriptions, constructs broader/smaller in the target language, difficulties in rank ordering items, differences in unit of measurement, irrelevant items or differences in performance of activities. By addressing these challenges, acceptable translations were obtained for all items. CONCLUSION: The methodology used and experience gained in this study can be used as an example for researchers in other countries interested in translating PROMIS. The Dutch-Flemish PROMIS items are linguistically equivalent. Short forms will soon be available for use and entire item banks are ready for cross-cultural validation in the Netherlands and Flanders.
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Estado de Salud , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida , Encuestas y Cuestionarios/normas , Traducción , Adulto , Anciano , Bélgica , Comparación Transcultural , Femenino , Humanos , Sistemas de Información , Masculino , Persona de Mediana Edad , Países Bajos , Reproducibilidad de los Resultados , Semántica , Adulto JovenRESUMEN
PURPOSE: Impairment of cognitive function, a common complaint in patients receiving chemotherapy, is usually measured through neuropsychological tests. Patient self-evaluation of cognitive difficulties is an important complement to those tests. The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report questionnaire with potential to be used in standard clinical practice as a tool for evaluating patient's cognitive function before, during, and after chemotherapy. The purpose of our study was to conduct linguistic validation of the French version of the FACT-Cog. METHODS: Both qualitative and quantitative methods were used in this study. After undergoing a rigorous translation methodology, the French FACT-Cog version was pretested in France with 35 cancer patients undergoing chemotherapy treatment. Interviews were conducted with all patients to ascertain their understanding of each item. The validation of the final version was conducted among 63 cancer patients, and sociodemographic information was collected as well as brief measure of cognitive function and depression score. RESULTS: Patient comments obtained through the cognitive debriefing interviews indicated that patients understand the French FACT-Cog items as they are intended and that the measure is culturally appropriate. Internal consistency reliability of the subscales, evaluated using Cronbach's coefficient alpha, was high for all four subscales: Perceived Cognitive Impairments = 0.93, Impact On QOL = 0.85, Comments From Others = 0.70, and Perceived Cognitive Abilities = 0.89. All item-total correlations for each subscale were greater than 0.20, and most were greater than 0.50. CONCLUSIONS: Results from this study effectively demonstrate that the French FACT-Cog is a reliable instrument for the self-reporting of cognitive abilities in patients undergoing chemotherapy.
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Antineoplásicos/efectos adversos , Trastornos del Conocimiento/diagnóstico , Cognición , Neoplasias , Adulto , Anciano , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Psicometría/instrumentación , Calidad de Vida , Reproducibilidad de los Resultados , Autoinforme , Encuestas y CuestionariosRESUMEN
NMR spectroscopy has been used to study and characterize the interactions in solution between ß-CD and alkyl-α,ω-bis(dodecyldimethyl ammonium bromide) gemini surfactants with the following head-group spacer lengths: 2, 4, 6, 8, and 10. The application of the method of continuous variation gives as a result that 1:1 and 2:1 (ß-cyclodextrin-gemini) complexes are formed; the association stoichiometry is dependent on the spacer chain length, varying from 1.5 (for s=2) to 1.8 (for s=10). Assuming a two-step mechanism, the binding constants have been computed. In general, the overall binding constant slightly increases with an increase of the number of methylene groups in the spacer. The (1)H NMR spectra of the N-(CH(3))(2) groups in ß-cyclodextrin/gemini mixed solutions are split into two peaks for 12-10-12, suggesting that the gemini spacer can thread the ß-cyclodextrin so that the latter is positioned between the gemini head-groups. Inspection of the ROESY spectra allowed the establishment of several spatial proximities between the protons from the ß-CD and the gemini and for a spacer length of 10, the data indeed indicate that complexes are formed with the CD molecule positioned between the two charged head groups with the spacer passing through the CD molecule.
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Compuestos de Amonio Cuaternario/química , Tensoactivos/química , beta-Ciclodextrinas/química , Espectroscopía de Resonancia MagnéticaRESUMEN
One of the factors that limit the efficiency of polymer-based optoelectronic devices, such as photovoltaic solar cells and light emitting diodes, is the exciton diffusion within the polymeric network. Due to the amorphous nature the of polymeric materials, the diffusion of excitons is limited by the energetic and spatial disorder in such systems, which is a consequence not only of the chemical structure of the polymer but also from its morphology at nanoscale. To get a deep understanding on how such effects influence exciton dynamics we performed a quantum molecular dynamics simulations to determine the energetic disorder within the polymer system, and Monte Carlo simulations to study exciton diffusion in three-dimensional (3D) polymer networks that present both spatial and energetic disorder at nanometre scale. Our results show clearly that exciton diffusion in poly(p-phenylenevinylene) (PPV) occurs preferentially in the direction parallel to the electrodes surface for a polymer-based optoelectronic devices with the orientation of the conjugated strands similar to those obtained by the spin-coating technique and the decay of such excitons occurs preferentially in longer strands which allow us to get insight on exciton behaviour in polymeric systems that are not possible to be obtained directly from the experiments.
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A existência de uma mola hidatiforme completa coexistentecom feto vivo, numa gravidez gemelar, é uma entidaderara. A atitude clínica constitui um desafio uma vez que amanutenção da gravidez de modo a alcançar a viabilidadefetal pode associar-se a potenciais complicações fetais e/oumaternas graves, tais como hemorragia vaginal, pré-eclâmpsia,morte fetal, prematuridade e risco aumentado de doençatrofoblástica persistente, condicionando um verdadeirodilema clínico, mãe/feto.Os autores descrevem o caso de uma mulher de 35 anos,admitida às 24 semanas de gestação por hemorragia vaginalpersistente numa gravidez gemelar bicoriónica, com umadas placentas com feto normal e outra placenta prévia total,compatível com mola hidatiforme completa. Apresentava,concomitantemente, hipertiroidismo subclínico. A gravidezfoi vigiada com atitude expectante até às 27 semanas degestação, altura em que após episódio grave de hemorragiavaginal, realizou-se cesariana com extracção de nado vivocom 947 g. Os níveis séricos da subunidade β da hormonagonadotrofina coriónica humana (β-hGC) negativaram nadécima quarta semana após o parto.A clínica, os níveis séricos de β-hGC e as imagens ecográficassugeriram o diagnóstico de mola hidatiforme completa,os quais foram corroborados pelos estudos citogenéticos (AU)
A twin pregnancy with a coexisting complete hydatiformmole and a healthy fetus is a rare event. The ma-Casos clínicosMola hidatiforme completa préviacoexistente com feto vivo numagravidez gemelar bicoriónica1 Serviço de Medicina Materno Fetal2 Centro de Diagnóstico Pré-Natal3 Serviço de Anatomia PatológicaMaternidade Dr. Alfredo da CostaLisboa (Portugal)4 Unidade de CitogenéticaDepartamento de Genética HumanaInstituto Nacional de Saúde Dr. Ricardo Jorge, INSA, I.PLisboa (Portugal)T. Sardinha1A. I. Machado1E. Dias1L. Martins2I. Biscaia3H. Correia4F. Serrano1J. Correia2A. Campos1nagement is challenging because although the fetus maybe viable, maintaining the pregnancy is associated withpotentially serious maternal and fetal complications, likevaginal bleeding, pre-eclampsia, preterm delivery, fetaldeath and an increased risk of persistent gestational trophoblasticdisease, which leads us to a clear mother versusfetus clinical dilemma.We describe a case of a 35-year-old woman who wasadmitted for persistent vaginal bleeding in a 24 weeks bichorionictwin pregnancy, one placenta with a normal fetusand the other, a complete placenta praevia,compatible with a complete hydatiform mole. She alsopresented subclinical hyperthyroidism. The pregnancywas managed conservatively until 27 weeks gestationwhen, following an episode of major antepartum haemorrhage,a 947-g live was delivered by Caesarean Section.Serum human chorionic gonadotrophin β-subunit(β-hCG) concentrations returned to baseline fourteen weeksfollowing delivery.The clinical, the serum β-hCG concentrations and theultrasound suggested the diagnosis of a complete hydatiformmole but it was the cytogenetic studies that confirmed it (AU)
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Humanos , Femenino , Embarazo , Adulto , Enfermedades en Gemelos/diagnóstico , Mola Hidatiforme/diagnóstico , Hemorragia Uterina , CesáreaRESUMEN
DNA is a material that has the potential to be used in nanoelectronic devices as an active component. However, the electronic properties of DNA responsible for its conducting behaviour remain controversial. Here we use a self-consistent quantum molecular dynamics method to study the effect of DNA structure and base sequence on the energy involved when electrons are added or removed from isolated molecules and the transfer of the injected charge along the molecular axis when an electric field is applied. Our results show that the addition or removal of an electron from DNA molecules is most exothermic for poly(dC)-poly(dG) in its B-form and poly(dA)-poly(dT) in its A-form, and least exothermic in its Z-form. Additionally, when an electric field is applied to a charged DNA molecule along its axis, there is electron transfer through the molecule, regardless of the number and sign of the injected charge, the molecular structure and the base sequence. Results from these simulations provide useful information that is hard to obtain from experiments and needs to be considered for further modelling aiming to improve charge transport efficiency in nanoelectronic devices based on DNA.
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Given the reports made about dogs detecting cancer on the basis of odour, our hypothesis is that the volatile organic compounds produced by tumours, and detected by dogs, are products of MHC genes. Two lines of evidences support this hypothesis: (1) human body odour is genetically determined by MHC. These antigen molecules (HLA in humans) have soluble and detectable isoforms that are present in body fluids such as blood, urine and sweat; (2) there is a strong association between changes in HLA expression and cancer. Tumour transformation is frequently associated with low classical HLA class I molecules expression, namely HLA-A, HLA-B, and HLA-C. In addition, cancer is associated with high nonclassical HLA class I molecules expression, such as HLA-G and HLA-E. These evidences suggest that these HLA-associated olfactory cues of human cancer could be easily analysed, for example, by the "electronic nose", making possible a very precocious and reliable diagnostic of cancer. Because cancer immunescape mechanism is similar to that observed in the materno-fetal immune tolerance, we propose also that immunomodulatory abortifacients could be a good strategy in cancer treatment.
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Perros/fisiología , Complejo Mayor de Histocompatibilidad , Neoplasias/diagnóstico , Odorantes , Olfato , Animales , HumanosRESUMEN
Sexual dimorphism in the human pelvis is inferentially related to parturition. Investigators disagree about the identification and obstetric significance of pelvic dimorphism. Benefiting from a large sample of complete skeletons from the Coimbra Identified Skeletal Collection, we show that the dimensions of the true pelvis (birth canal) that are most sexually dimorphic (that is, the dimensions of females are greater than males) are those which are related to biparietal deformation, which often leads to the death of the human neonate. These dimensions are: the anteroposterior diameter of the inlet (index of dimorphism = 108.41), the transverse diameter of the bispinous midplane (index of dimorphism = 117.13) and the transverse diameter of the outlet (index of dimorphism = 112.3). Therefore, sexual dimorphism in the human pelvis is a reflection of differential selection on the two sexes. These results may stimulate further studies with a fresh approach regarding the fossil and comparative evidence for when and how the modern pattern of birth has evolved.
Asunto(s)
Fósiles , Huesos Pélvicos/anatomía & histología , Caracteres Sexuales , Femenino , Cabeza/embriología , Humanos , Trabajo de Parto/fisiología , Masculino , Portugal , Embarazo , Factores SexualesRESUMEN
We propose the hypothesis that genes of human intelligence are related with metabolism of thyroid and steroids hormones, which have a crucial role in brain development and function. First, there is evidence to support the idea that during hominid evolution small genetic differences were related with significant endocrine changes in thyroid and steroids hormones. Second, these neuroactive hormones are also related with unique features of human evolution such as body and brain size increase, penis and breast enlargement, pelvic sexual dimorphism, active sexuality, relative lack of hair and higher longevity. Besides underling many of the differences between humans and great apes, steroids hormones promote brain growth and development, are important in the myelination process, explain sexual dimorphisms in brain and intelligence and improve specific cognitive abilities in humans. Supporting our hypothesis, recent studies indicate differences in neuroactive hormones metabolism between humans and non-human primates. Furthermore, a link between X chromosome genes and sex steroids may explain why the frequency of genes affecting intelligence is so high on the X chromosome. This association suggests that, during hominid evolution, there was a positive feedback in both sexes on the same genes responsible for secondary sexual character development and intelligence. This interaction leads to acceleration of development of human brain and intelligence. Finally, we propose that neuroactive hormone therapy may provide significant improvement in some cognitive deficits in all stages of human life and in cases of neurodegenerative diseases. However, further investigation is needed, mainly in the enzymatic machinery, in order to understand the direct role of these hormones in intelligence.
Asunto(s)
Evolución Biológica , Encéfalo/fisiología , Glándulas Endocrinas/fisiología , Evolución Molecular , Hormonas Esteroides Gonadales/genética , Inteligencia , Hormonas Tiroideas/genética , Animales , Ligamiento Genético , Genética de Población/métodos , Humanos , Modelos Genéticos , Selección GenéticaRESUMEN
The present study was undertaken to determine if the antipsychotic drug clozapine (CLZ) in the concentration range 2-50 microM can rescue polymorphonuclear cells (PMNs) from undergoing apoptosis. Our results indicate that 20 microM CLZ can rescue PMNs both from UVB-accelerated (28.0% vs. 45.9% for control without CLZ; P < 0.05) and from spontaneous (35.8% vs. 57.6%; P < 0.05) apoptosis whereas 50 microM CLZ could rescue PMNs from spontaneous (34.3% vs. 57.6%; P < 0.05) apoptosis only. Furthermore, since apoptosis has been reported to involve the impairment of PMN function, we evaluated the effects of CLZ on respiratory burst in UVB-irradiated and in unirradiated PMNs. When 20 or 50 microM CLZ-pretreated PMNs were aged in a culture during 4 h, the luminol-dependent chemiluminescence (CL) response was 3-fold (P < 0.01) and 2.5-fold (P < 0.05) increased, respectively, by subsequent exposure to serum opsonized zymosan (OZ). When 50 microM-pretreated PMNs were either UVB-irradiated or unirradiated, the CL response was 2.6-fold (P < 0.05) and 3.3-fold (P < 0.05) increased, respectively, after subsequent exposure to formyl-methionyl-leucyl-phenylalanine (fMLP). In contrast, the degree of enhancement was negligible upon subsequent exposure to ionomycin or phorbol myristate acetate (PMA). When incubation times were extended up to 22 h, the CL response induced by OZ in 20 microM CLZ-treated PMNs had a 4.9-fold increase (P < 0.001). This priming effect could be reverted when 20 microM CLZ-treated PMNs (aged 4 h in culture) were coincubated for 5 min with the protein tyrosine kinase inhibitor genistein as well as with the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin. These findings suggest that CLZ primes respiratory burst and prevents PMN apoptosis as a consequence of tyrosine phosphorylation- and PI3-K activation-dependent signal transduction pathways.