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OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.
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Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Reproducibilidad de los Resultados , Voluntarios Sanos , Electroencefalografía/métodos , Biomarcadores , Potenciales Evocados Auditivos/fisiologíaRESUMEN
We search for the dark photon dark matter (DPDM) using a cryogenic millimeter-wave receiver. DPDM has a kinetic coupling with electromagnetic fields with a coupling constant of χ and is converted into ordinary photons at the surface of a metal plate. We search for signal of this conversion in the frequency range 18-26.5 GHz, which corresponds to the mass range 74-110 µeV/c^{2}. We observed no significant signal excess, allowing us to set an upper bound of χ<(0.3-2.0)×10^{-10} at 95% confidence level. This is the most stringent constraint to date and tighter than cosmological constraints. Improvements from previous studies are obtained by employing a cryogenic optical path and a fast spectrometer.
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OBJECTIVES: The aim of the present study was to verify the associations between dysphagia as screened by the Eating Assessment Tool-10 (EAT-10) and indicators in the 100-mL water swallowing test (WST) or medical history among community-dwelling older people. STUDY DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: The study participants were 202 community-dwelling older Japanese adults aged ≥65 years. MEASUREMENTS: We investigated the participants' basic attributes, including age, sex, body mass index, medical history (cerebrovascular disease, respiratory disease: chronic obstructive pulmonary disease [COPD], and history of pneumonia within the previous year), and number of prescribed medications. Dysphagia assessment was performed using the EAT-10 and the 100-mL WST as subjective and objective examinations, respectively. The 100-mL WST used four indicators (SC: swallowing capacity, VS: volume per swallow, TS: time per swallow, and choking signs). Patients with and without dysphagia according to the EAT-10 were divided into two groups according to a cutoff score of 3, and the two groups were then compared in terms of their characteristics including medical history and 100-mL WST indicators. A multiple logistic regression model was used to determine whether the indicators of the 100-mL WST or medical history were independently associated with dysphagia in the EAT-10. RESULTS: The multiple logistic regression analysis revealed that dysphagia in the EAT-10 was independently associated with male sex (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 0.98-7.90), COPD (OR = 14.68; 95% CI = 3.14-68.85), and VS and TS in the 100-mL WST (OR = 0.85; 95% CI = 0.80-0.90 and OR = 3.03; 95% CI = 1.78-5.16, respectively). CONCLUSIONS: Our results revealed that the EAT-10 was independently associated with the 100-mL WST and respiratory disease. We propose that swallowing rehabilitation incorporating respiratory training could be effective for older people screened using the EAT-10.
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Trastornos de Deglución/diagnóstico , Trastornos de Deglución/fisiopatología , Deglución/fisiología , Enfermedades Respiratorias/fisiopatología , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios Transversales , Femenino , Fragilidad , Humanos , Vida Independiente , Japón , Masculino , Oportunidad Relativa , Autoinforme , Factores SexualesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Participatory research can help to broaden the understanding of medical systems and beliefs of traditional communities. An ethnopharmacological survey in collaboration with local people focused on plants used in quilombos located in Southeast Region in Brazil identified cultural factors that influence plant and recipe choice. AIM OF THE STUDY: To investigate the factors related to the therapeutic efficiency of medicinal plants from the perspective of Quilombo da Fazenda residents. MATERIALS AND METHODS: University researchers collaborated with community residents for both aims and methods of the study. The local partners were trained in the gathering of ethnopharmacological data and then selected and interviewed the residents considered experts on the use of medicinal plants. Data on the use of each species were supported by voucher specimens collected by the local partners and university researchers. Participant observations and field diaries by the university researchers supplemented the data. RESULTS: Eight interviewees mentioned 92 medicinal species with 60 therapeutic uses, applied in 208 recipes or remedies. Asteraceae (13 species), Lamiaceae (5) and Urticaceae (5) contributed most medicinal plant species. Of the 12 etic categories of use, the circulatory system category had the highest number of plants mentioned. Decoction was the most commonly used preparation method (66.8%), and most remedies were administered orally (76.4%). Eighty-six recipes included more than one plant species and/or the addition of other components, such as sugar, salt or animal products. Several cultural factors influence medicinal plant use. Popular beliefs on the quality of blood or the humoral properties of plants and illnesses, characteristics of the plants and other factors determine which plant is used and why. CONCLUSIONS: The participatory method identified a large number of factors that influence medicinal plant use: the patient's blood type; the condition of the plant and the disease (hot-cold system); the route of administration and dosage; the preventive uses of the plants; and the influence of other factors, such as the sun, the moon and dew. The participatory approach is useful for gaining insight on the decision processes of medicinal plant use in traditional societies, and also for those communities wanting to document their knowledge with or without the participation of the academy.
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Medicina Tradicional , Plantas Medicinales , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Etnofarmacología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Magnoliopsida , Masculino , Persona de Mediana Edad , Fitoterapia , Encuestas y CuestionariosRESUMEN
Essentials Acquired Glanzmann thrombasthenia (aGT) is generally caused by function-blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbß3 with anti-αIIbß3 Abs. The anti-αIIbß3 Abs of the patient did not inhibit platelet function but reduced surface αIIbß3. Internalization of αIIbß3 induced by the Abs binding may be responsible for the phenotype. SUMMARY: Background Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-αIIbß3 autoantibodies. Aim We characterize an unusual case of aGT caused by marked reduction of surface αIIbß3 with non-function-blocking anti-αIIbß3 antibodies (Abs). Methods A 72-year-old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of αIIbß3 expression and genetic analysis were performed. We also analyzed effects of anti-αIIbß3 Abs of the patient on platelet function and αIIbß3 expression. Results Surface αIIbß3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbß3 to the amount of 40-50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface αIIbß3 expression caused a GT phenotype, and active internalization of αIIbß3 was suggested. Anti-αIIbß3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC-1 binding, indicating that the Abs were non-function-blocking. Surface αIIbß3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface αIIbß3 expression was recovered to 20% of normal with reduction of anti-αIIbß3 Abs. Conclusion We demonstrated a unique aGT phenotype due to marked reduction of surface αIIbß3. Internalization induced by anti-αIIbß3 Abs may be responsible in part for the phenotype.
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Autoanticuerpos/inmunología , Plaquetas/inmunología , Integrina alfa2/inmunología , Integrina beta3/inmunología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/inmunología , Trombastenia/inmunología , Anciano , Plaquetas/metabolismo , Células Cultivadas , Epistaxis/sangre , Epistaxis/inmunología , Hemorragia Gastrointestinal/sangre , Hemorragia Gastrointestinal/inmunología , Humanos , Integrina alfa2/sangre , Integrina beta3/sangre , Masculino , Fenotipo , Pruebas de Función Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Trombastenia/sangre , Trombastenia/diagnósticoRESUMEN
OBJECTIVE: To examine the relationship between the living location and outcomes of physical activity level and physical and psychological functioning in older women. The specific aim was to understand the association between living in a sloped versus non-sloped environment and these outcomes. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 108 older women aged 65 years or older who resided in Nagasaki prefecture participated. MEASUREMENTS: Physical activity, lung function, muscle strength (hand grip and quadriceps force) and depressive symptoms were assessed objectively. RESULTS: In logistic regression, activity counts per day (OR 0.779, 95%CI 0.715-0.841, p<0.01), activity times per day (OR 0.821, 95%CI 0.801-0.913, p<0.01), hand grip force (OR 0.666, 95%CI 0.558-0.796, p<0.001), and depressed (Center for Epidemiological Studies Depression Scale score ≥16) (OR 1.093, 95%CI 1.019-1.427, p<0.05) showed statistically significant inverse associations with living in a sloped ground. CONCLUSIONS: Since dwelling on sloped ground was associated with negative (lower physical activity levels, lower grip strength, and more depression) outcomes, a comprehensive geriatric assessment, related to all aspects of older women, is recommended. Planning of home exercise programs for the elderly should take such environmental factors into consideration.
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Trastorno Depresivo/patología , Ejercicio Físico/fisiología , Fuerza Muscular/fisiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ambiente , Femenino , Evaluación Geriátrica , HumanosRESUMEN
The neuropeptide kisspeptin and its receptor play an essential role in reproduction as a potent modulator of the gonadotrophin-releasing hormone (GnRH) neurone. In addition to its reproductive function, kisspeptin signalling is also involved in extra-hypothalamic-pituitary-gonadal (HPG) axis systems, including oxytocin and arginine vasopressin (AVP) secretion. By contrast to the accumulating information for kisspeptin neurones and kisspeptin fibres, the histological distribution and function of the kisspeptin receptor in the rat brain remain poorly characterised. Using in situ hybridisation combined with immunofluorescence, the present study aimed to determine the whole brain map of Kiss1r mRNA (encoding the kisspeptin receptor), and to examine whether oxytocin or AVP neurones express Kiss1r. Neurones with strong Kiss1r expression were observed in several rostral brain areas, including the olfactory bulb, medial septum, diagonal band of Broca and throughout the preoptic area, with the most concentrated population being around 0.5 mm rostral to the bregma. Co-immunofluorescence staining revealed that, in these rostral brain areas, the vast majority of the Kiss1r-expressing neurones co-expressed GnRH. Moderate levels of Kiss1r mRNA were also noted in the rostral periventricular area, paraventricular nucleus (PVN), and throughout the arcuate nucleus. Relatively weak Kiss1r expression was observed in the supraoptic nucleus and supramammillary nuclei. Moderate to weak expression of Kiss1r was also observed in several regions in the midbrain, including the periaqueductal gray and dorsal raphe nucleus. We also examined whether oxytocin and AVP neurones in the PVN co-express Kiss1r. Immunofluorescence revealed the co-expression of Kiss1r in a subset of the oxytocin neurones but not in the AVP neurones in the PVN. The present study provides a fundamental anatomical basis for further examination of the kisspeptin signalling system in the extra-HPG axis, as well as in reproductive function.
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Imagen Molecular , Oxitocina/análisis , Núcleo Hipotalámico Paraventricular/metabolismo , Receptores de Kisspeptina-1/análisis , Receptores de Kisspeptina-1/genética , Animales , Arginina Vasopresina/biosíntesis , Arginina Vasopresina/genética , Femenino , Hormona Liberadora de Gonadotropina/biosíntesis , Neuronas/metabolismo , Oxitocina/metabolismo , Ratas , Ratas TransgénicasRESUMEN
OBJECTIVES: The purpose of this study is to describe the effects of the three main interventions and identify the individual and community determinants of full vaccination coverage among children aged 12-59 months in Nyanza province, Kenya. STUDY DESIGN: Cross-sectional study. METHODS: We utilized three datasets. One is the Nyanza Province County-based Multiple Indicator Cluster Survey 2011. The other two datasets are the lists of community units and health facilities in Nyanza Province, Kenya. A three-level multilevel logistic regression analysis was performed. RESULTS: In the final model, the highest wealth quintile (AOR: 2.49; 95% CI: 1.333-4.642; P = 0.004), the community with high coverage of media devices (AOR: 1.50; 95% CI: 1.029-2.198; P = 0.035), the participation of mass immunization campaigns (AOR: 1.63; 95% CI: 1.153-2.303; P = 0.006) were the significant determinants of complete child vaccination. CONCLUSIONS: In conclusion, further implementation of mass immunization campaigns is the recommended intervention to increase the uptake of required vaccinations among children. In addition, further attention to the poor and the low coverage of media devices is necessary, since they are the most vulnerable population in terms of accessibility of vaccination services. Implementation community based activity, such as community health workers, would have a positive impact on vaccination coverage, if their performance is continuously high.
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Promoción de la Salud/métodos , Esquemas de Inmunización , Vacunación/estadística & datos numéricos , Niño , Preescolar , Centros Comunitarios de Salud , Estudios Transversales , Encuestas de Atención de la Salud , Accesibilidad a los Servicios de Salud , Humanos , Lactante , Kenia , Modelos Logísticos , Vacunación Masiva/estadística & datos numéricos , Análisis MultinivelRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Urban Ethnoveterinary should be further explored because of its value as it resists conventional medical care. In addition, the comparison between the resources used by Ethnoveterinary and Ethnopharmacology should be investigated in depth, increasing the availability of new bioactive potential in human and veterinary medicines. This project aimed to determine whether plants are used in the health care of dogs and/or cats in urban area and to compare its uses with other ethnoveterinary and ethnopharmacological data. MATERIALS AND METHODS: Three veterinary clinics from east area of São Paulo city were selected, in order to record the offering of plants to pets by their owners. Individual interviews were conducted from May to November 2012 and consisted of application of semi-structured interviews and questionnaires. A literature search was performed to compare our findings with other ethnopharmacological and ethnoveterinarian data from the literature. RESULTS: A total of 273 people were interviewed and 46 (16.84%) of them utilize medicinal plants for their pets. Most plant species are exclusively home grown (57.9%). The plants most cited were Plectranthus barbatus Andrews, Matricaria chamomilla L. and Foeniculum vulgare Mill. The most frequent route of administration, part utilized and mode of preparation was oral (80.35%), leaves (89.47%) and infusion (61.90%), respectively. From 19 cited plants, 14 (73.7%) are mentioned in ethnoveterinary literature, whereas 11 (57.9%) are used for the same purposes. All plants reported in our study have at least one common use with ethnopharmacology. CONCLUSION: The survey provided evidence of ethnoveterinary use of medicinal plants for dogs and/or cats in urban area of São Paulo, complementarily with the official veterinary, and showed that the plants used in pets are also used in humans with the same purposes and routes of administration, as well as in other animals.
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Hospitales Veterinarios , Plantas Medicinales , Drogas Veterinarias , Adulto , Animales , Brasil , Gatos , Perros , Etnofarmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Encuestas y CuestionariosRESUMEN
Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Femenino , Humanos , Japón , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/terapia , Linfocitos/patología , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
Serotonin (5-HT) and norepinephrine (NE) have been implicated in the mediation of endogenous analgesic mechanisms via the descending inhibitory pain pathway in the brain, and dysfunction in both the 5-HT and NE systems has been suggested as an etiology of fibromyalgia (FM). Given that 5-HT reuptake inhibition in the brain appears to be associated with pain reduction, this mechanism might exert an analgesic effect also on pain associated with FM. In this case, it would be of interest to investigate the correlation of 5-HT transporter (SERT) occupancy with in vivo analgesic effect on pain associated with FM. Here, we investigated the relationship between SERT occupancies and the analgesic effects of AS1069562, the (+)-isomer of indeloxazine, and duloxetine, which are both 5-HT and NE reuptake inhibitors (SNRIs), on muscular pain in reserpine-induced myalgia (RIM) rats, an animal model of FM-like chronic pain. We also investigated the SERT occupancy level necessary for AS1069562 and duloxetine to exert analgesic effects on muscular pain. AS1069562 and duloxetine attenuated muscular hyperalgesia in RIM rats, representing the first findings to be reported regarding the analgesic effect of AS1069562 on pain associated with FM. SERT occupancy levels of AS1069562 and duloxetine increased in both dose- and plasma and brain concentration-dependent manners. SERT occupancy levels of AS1069562 and duloxetine were significantly correlated with efficacy on muscular pain thresholds in RIM rats. This finding concerning the precise correlation of SERT occupancy with in vivo analgesic effect on pain associated with FM is reported here for the first time. SERT occupancy level above 70% was necessary for AS1069562 and duloxetine to exert significant analgesic effects on muscular pain. These results suggest that SERT occupancy level is useful in determining appropriate analgesic doses of AS1069562 and duloxetine for treating pain symptoms in FM patients.
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Analgésicos/farmacología , Morfolinas/farmacología , Mialgia/tratamiento farmacológico , Mialgia/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Analgésicos/farmacocinética , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Clorhidrato de Duloxetina/farmacocinética , Clorhidrato de Duloxetina/farmacología , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Masculino , Morfolinas/farmacocinética , Umbral del Dolor/efectos de los fármacos , Presión , Ratas Sprague-Dawley , Reserpina , Resultado del TratamientoRESUMEN
Numerical simulations of structure formation in the early universe predict the formation of some fraction of stars with several hundred solar masses. No clear evidence of supernovae from such very massive stars has, however, yet been found in the chemical compositions of Milky Way stars. We report on an analysis of a very metal-poor star SDSS J001820.5-093939.2, which possesses elemental-abundance ratios that differ significantly from any previously known star. This star exhibits low [α-element Fe] ratios and large contrasts between the abundances of odd and even element pairs, such as scandium/titanium and cobalt/nickel. Such features have been predicted by nucleosynthesis models for supernovae of stars more than 140 times as massive as the Sun, suggesting that the mass distribution of first-generation stars might extend to 100 solar masses or larger.
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UNLABELLED: We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain. INTRODUCTION: Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan. METHODS: Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren-Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain. RESULTS: Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5-6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0--0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1-2.9), independent of other covariates including age and deformities. CONCLUSION: Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.
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Dolor de Espalda/etiología , Osteoartritis de la Columna Vertebral/complicaciones , Fracturas Osteoporóticas/complicaciones , Curvaturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/complicaciones , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Dolor de Espalda/epidemiología , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Vértebras Lumbares/patología , Persona de Mediana Edad , Osteoartritis de la Columna Vertebral/epidemiología , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/epidemiología , Curvaturas de la Columna Vertebral/epidemiología , Curvaturas de la Columna Vertebral/patología , Fracturas de la Columna Vertebral/epidemiología , Vértebras Torácicas/patologíaRESUMEN
Neurosteroidal oestrogen has been proposed to play important roles in a variety of reproductive behaviours. Aromatase, a key enzyme in oestrogen synthesis, is localised in neural nuclei of specific brain regions and is developmentally regulated, with a transient expression peak at the perinatal period. The brain-specific promoter of the aromatase gene was analysed aiming to determine the transcriptional control mechanisms that could help explain the spatiotemporal expression. We previously reported that a 202-bp sequence, which is upstream from the transcriptional initiation site, is essential for the basal transcriptional activity. The 202-bp upstream region of brain-specific exon 1 comprises at least three types of cis-acting elements: aro-AI (Arom-Aα), aro-AII (Arom-Aß) and aro-B (Arom-B). To identify the binding proteins for the cis-acting elements, a yeast one-hybrid screen was performed with these cis-element sequences using a mouse foetal cDNA library. Lhx2, a LIM-homeodomain protein, was identified as one of the aro-B binding proteins. The identification was further confirmed using the gel shift assay, which demonstrated binding competition of nuclear proteins to the aro-B element with a typical Lhx2-binding element. In addition, a chromatin immunoprecipitation assay with an anti-Lhx2 antibody demonstrated that Lhx2 bound to the aro-B site in vivo. A reporter assay of the brain-specific promoter demonstrated increased Lhx2-dependent promoter activity. Furthermore, the time-dependent increase in aromatase mRNA in primary cultured foetal neurones was suppressed by an small-interfering RNA-mediated knockdown of Lhx2 expression. These results show that Lhx2 is involved in the transcriptional regulation of aromatase in the rodent brain.
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Aromatasa/genética , Encéfalo/metabolismo , Proteínas con Homeodominio LIM/fisiología , Regiones Promotoras Genéticas , Factores de Transcripción/fisiología , Animales , Aromatasa/metabolismo , Secuencia de Bases , Encéfalo/enzimología , Células COS , Células Cultivadas , Chlorocebus aethiops , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica/genética , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Datos de Secuencia Molecular , Especificidad de Órganos/genética , Regiones Promotoras Genéticas/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
An indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes is extremely rare in pediatrics. The present report describes the very rare case of a 1-month-old girl with an irreducible indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes, and the successful surgical treatment of simple herniorraphy. We review the literature on this type of relationship between indirect inguinal hernia and hernial visceras of the uterus, ovaries, and Fallopian tubes and discuss the clinical features of this complication. Furthermore, the possible cause of indirect inguinal hernia containing the uterus, ovaries, and Fallopian tubes was explored.
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Trompas Uterinas/diagnóstico por imagen , Hernia Inguinal/diagnóstico por imagen , Ovario/diagnóstico por imagen , Útero/diagnóstico por imagen , Femenino , Hernia Inguinal/complicaciones , Hernia Inguinal/cirugía , Herniorrafia , Humanos , Lactante , UltrasonografíaRESUMEN
Strongyloides ratti (Nagoya strain) is unique in that a portion of adults parasitizing the small intestine withstands 'worm expulsion', which starts at around day 8 post-infection (p.i.) by host immunity, and establishes in the large intestine after day 19 p.i. To investigate the mechanism, adults obtained from the small intestine at day 7 or 19 p.i. were transplanted into the colon of infection-primed immune rats. Adults obtained at day 7 p.i. were rejected quickly, whereas those obtained at day 19 p.i. could establish infection. Moreover, the body length and the number of intrauterine eggs increased in the large intestine. In a separate experiment, large intestinal parasitism was abolished by the treatment of host rats with an anti-oxidant, butylated hydroxyanisole. These results indicate that small intestinal adults between days 7 and 19 p.i. acquired the ability to parasitize the large intestine of immune rats, and that free radicals produced by the host may have played a significant role in the process.
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Antioxidantes/farmacología , Hidroxianisol Butilado/farmacología , Colon/parasitología , Intestino Delgado/parasitología , Strongyloides ratti/patogenicidad , Estrongiloidiasis/parasitología , Animales , Tamaño Corporal , Heces/parasitología , Interacciones Huésped-Parásitos , Masculino , Recuento de Huevos de Parásitos , Ratas , Ratas Wistar , Strongyloides ratti/efectos de los fármacos , Factores de TiempoRESUMEN
BACKGROUND: Thromboxane A(2) receptor (TXA(2)R) abnormality appears to dominantly disturb platelet function. OBJECTIVES: To reveal a molecular genetic defect in a patient with TXA(2)R abnormality and investigate the mechanism for the impaired response to TXA(2). PATIENT: The proband (OSP-2, PT) was a 7-year-old Japanese girl, suffering from repeated mucocutaneous bleeding. METHODS AND RESULTS: U46619 (2.5 and 10 µm)-induced platelet aggregation was remarkably impaired in the proband and her father. Immunoblots showed that TXA(2)R expression levels in their platelets were approximately 50% of controls, and nucleotide sequence analysis revealed that they were heterozygous for a novel mutation, c.167dupG in the TXA(2)R cDNA. Expression studies using Chinese hamster ovary (CHO) cells indicated that the mutation is responsible for the expression defect in TXA(2)R. We then examined α(IIb)ß(3) activation by employing an initial velocity analysis and revealed that U46619 failed to induce a sustained α(IIb)ß(3) and Rap1B activation in the proband. In addition, platelet secretion as monitored by P-selectin expression was markedly impaired in response to U46619 but not to ADP. The interaction between secreted ADP and P2Y(12) has been shown to play a critical role in the sustained α(IIb)ß(3) activation (Kamae et al. J Thromb Haemost 2006; 4: 1379). As expected, small amounts of exogenous ADP (0.5 µm) partially restored the sustained α(IIb)ß(3) activation induced by U46619. CONCLUSION: Our present data strongly suggest that the impaired platelet activation in response to U46619 in the heterozygous subject for the TXA(2)R mutation is, at least in part, as a result of the decrease in ADP secretion.
Asunto(s)
Mutación , Receptores de Tromboxano A2 y Prostaglandina H2/genética , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , Plaquetas/metabolismo , Células CHO , Niño , Cricetinae , Cricetulus , Femenino , Hemorragia , Heterocigoto , Humanos , Masculino , Padres , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Receptores Acoplados a Proteínas G/genéticaRESUMEN
UNLABELLED: We evaluated the ability of heel quantitative ultrasound (QUS) and metacarpal radiographic absorptiometry (RA) to identify subjects with vertebral deformities in Japanese women aged ≥40. Both QUS and RA were associated with vertebral deformities, and the estimated prevalence at each T-score widely varied with age. INTRODUCTION: Heel QUS and metacarpal RA have been used for screening patients to evaluate risk of osteoporotic fractures. The aim of this study was to evaluate the ability of QUS and RA to identify women with vertebral deformities in 570 Japanese women aged ≥40, and to estimate the prevalence of vertebral deformity at each T-score. METHODS: Calcaneal QUS and metacarpal RA were performed. Radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. RESULTS: The receiver operating characteristic analysis showed that both calcaneal stiffness index (SI) and metacarpal bone mineral density (BMD) were associated with vertebral deformities. Using the T-score of -2.5 as a cutoff value, the specificity and sensitivity for identifying individuals with vertebral deformities was 65% and 83% for calcaneal SI, and 40% and 88% for metacarpal BMD, respectively. The prevalence of vertebral deformity was estimated using age-adjusted logistic regression models. Women with calcaneal SI T-score of -2.5 had a 2% estimated probability of vertebral deformity at age 40, and 22% at age 80. For metacarpal BMD T-score of -2.5, estimated probability was less than 1% at age 40, and 27% at age 80. CONCLUSION: Both calcaneal SI and metacarpal BMD were associated with prevalence of vertebral deformity. Furthermore, the prevalence widely varied with age at any given bone value.
Asunto(s)
Osteoporosis Posmenopáusica/diagnóstico , Fracturas Osteoporóticas/diagnóstico , Curvaturas de la Columna Vertebral/diagnóstico , Fracturas de la Columna Vertebral/diagnóstico , Absorciometría de Fotón/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Calcáneo/diagnóstico por imagen , Femenino , Humanos , Huesos del Metacarpo/diagnóstico por imagen , Persona de Mediana Edad , Osteoporosis Posmenopáusica/diagnóstico por imagen , Curvaturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/etiología , UltrasonografíaRESUMEN
Protective-layer-coated single-walled carbon nanotubes (SWNTs) with palladium nanoparticle decoration (Pd-SiO(2)-SWNTs) were fabricated and their sensing properties for hydrogen (H(2)) were investigated. SWNTs were coated with a 3-4 nm thick SiO(2) layer by pulsed laser deposition and subsequently decorated with Pd nanoparticles by electron beam evaporation. Even though the SWNTs were completely surrounded by a protective layer, Pd-SiO(2)-SWNTs responded to H(2) down to a concentration of 1 part per million. Compared with the Pd nanoparticle-decorated SWNTs without a protective layer (Pd-SWNTs), Pd-SiO(2)-SWNTs exhibited highly stable sensor responses with variations of less than 20%; Pd-SWNTs showed a variation of 80%. The density of the Pd-SWNTs significantly decreased after the sensing test, while that of the Pd-SiO(2)-SWNTs with the netlike structure remained unchanged. The hydrogen sensing mechanism of the Pd-SiO(2)-SWNTs was attributed to the chemical gating effect on the SWNTs due to dipole layer formation by hydrogen atoms trapped at the Pd-SiO(2) interface. Moreover, the relationship between H(2) concentration and sensor response can be described by the Langmuir isotherm for dissociative adsorption.
RESUMEN
O objetivo deste trabalho foi determinar o número de coliformes totais, termotolerantes, Staphylococcus coagulase positivo e a presença de bactéria do gênero Salmonella no músculo, no tecido superficial, no trato gastrintestinal de peixes e na água de cultivo de pesque-pagues situados na microbacia do Córrego Rico, SP. Não foi detectado Staphylococcus coagulase positivo em nenhuma amostra de água e peixe. O número mais provável (NMP) de coliformes totais no peixe variou de 2,0 x 10 a >1,1 x 104 NMP.100 mL-1, na água de cultivo variou de 4,2 x 104 a > 2,4 x 105 NMP.100 mL-1. A contagem de coliformes termotolerantes no peixe variou de < 3 a 5,1 x 103 NMP.g-1, na água de cultivo variou de 3,8 x 102 a 2,0 x 104 NMP.100 mL-1. Não houve diferença estatística (P > 0,05) entre as populações de micro-organismos pesquisados na água, pele e trato gastrintestinal, o que reflete uma relação entre a presença dos micro-organismos na água e nesses dois locais analisados. Foi isolada Salmonella sp. em uma amostra de músculo e em duas amostras de trato gastrintestinal. O pescado pode ser veículo de contaminação cruzada, tendo como fonte dos micro-organismos a pele e o trato gastrintestinal para sua própria musculatura. Portanto, o monitoramento da qualidade da água é de suma importância para garantir a produção de peixes com boa qualidade.
The objective of this study was to determine the number of total and thermotolerant coliforms, coagulase-positive Staphylococcus, and the presence of bacteria of the genus Salmonella in the muscle, surface tissue, and gastrointestinal tract of fish, and in the pond water of fee-fishing establishments located in the Córrego Rico microwatershed in the state of São Paulo, Brazil. Coagulase-positive Staphylococcus was not detected in any sample of pond water or fish. The most probable number (MPN) of total coliforms in fish ranged from 2.0 x 10 to > 1.1 x 104 NMP.100 mL-1, while in pond water it ranged from 4.2 x 104 to > 2.4 x 105 NMP.100 mL-1. The count of thermotolerant coliforms in fish ranged from < 3 to 5.1 x 103 NMP.g-1, while in pond water it ranged from 3.8 x 102 to 2.0 x 104 NMP.100 mL-1. There was no statistical difference (P > 0.05) among the studied populations of microorganisms in pond water, surface tissue and gastrointestinal tract, which reflects a relationship between the presence of microorganisms in the water and in the two tissues analyzed. Salmonella sp. was isolated in one sample of muscle and in two samples of gastrointestinal tract. The fish can be a vehicle for cross contamination, having the gastrointestinal tract and the surface tissue as a source of microorganisms for its muscles. Therefore, monitoring the water quality is important to ensure the production of fish with good quality.