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Exposure to commonly used pesticides poses significant health risks to humans and wildlife. Hence, accurate and sensitive pesticide residue testing methods are imperative to minimize potential health hazards. In this study, we report a method to detect several pesticide residues at trace levels utilizing colloidal gold nanoparticles and surface-enhanced Raman spectroscopy (SERS). Gold nanoparticles suspended in water have been found to enhance Raman scattering from 21 pesticides, including fungicides and insecticides, such as neonicotinoids and organothiophosphates. Measured limits of detection ranged from 0.001 to 10 parts per million (ppm). Furthermore, simultaneous detection of two pesticides, phosmet and thiram, in both a mixture solution and on apple skin, was performed using the SERS method and principal component analysis. The results presented here indicate that SERS coupled with colloidal gold nanoparticles is a potential useful tool for identifying pesticides at trace levels for food safety applications.
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Ouro/química , Nanopartículas Metálicas/química , Resíduos de Praguicidas/química , Análise Espectral Raman/métodos , Contaminação de Alimentos/análise , Frutas/química , Limite de Detecção , Malus/química , Análise Espectral Raman/instrumentaçãoRESUMO
In order to optimize outcomes in the face of uncertainty, one must recall past experiences and extrapolate to the future by assigning values to different choice outcomes. This behavior requires an interplay between memory and reward valuation, necessitating communication across many brain regions. At the anatomical nexus of this interplay is the perirhinal cortex (PRC). The PRC is densely connected to the amygdala and orbital frontal cortex, regions that have been implicated in reward-based decision making, as well as the hippocampus. Thus, the PRC could serve as a hub for integrating memory, reward, and prediction. The PRC's role in value-based decision making, however, has not been empirically examined. Therefore, we tested the role of the PRC in a spatial delay discounting task, which allows rats to choose between a 1-s delay for a small food reward and a variable delay for a large food reward, with the delay to the large reward increasing after choice of each large reward and decreasing after each small reward. The rat can therefore adjust the delay by consecutively choosing the same reward or stabilize the delay by alternating between sides. The latter has been shown to occur once the 'temporal cost' of the large reward is established and is a decision-making process termed 'exploitation'. When the PRC was bilaterally inactivated with the GABA(A) agonist muscimol, rats spent fewer trials successfully exploiting to maintain a fixed delay compared to the vehicle control condition. Moreover, PRC inactivation resulted in an increased number of vicarious trial and error (VTE) events at the choice point, where rats had to decide between the two rewards. These behavioral patterns suggest that the PRC is critical for maintaining stability in linking a choice to a reward outcome in the face of a variable cost.
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Comportamento de Escolha/fisiologia , Desvalorização pelo Atraso/fisiologia , Córtex Perirrinal/fisiologia , Comportamento Espacial/fisiologia , Animais , Comportamento de Escolha/efeitos dos fármacos , Desvalorização pelo Atraso/efeitos dos fármacos , Agonistas de Receptores de GABA-A/farmacologia , Masculino , Muscimol/farmacologia , Córtex Perirrinal/efeitos dos fármacos , Ratos , Comportamento Espacial/efeitos dos fármacos , Fatores de TempoRESUMO
Surface-induced thrombosis and lack of endothelialization are major drawbacks that hamper the widespread application of polyurethanes for the fabrication of implantable cardiovascular devices. Endothelialization of the blood-contacting surfaces of these devices may avoid thrombus formation and may be implemented by strategies that introduce micro and submicron patterns that favor adhesion and growth of endothelial cells. In this study, we used laser radiation to directly introduce topographical patterns in the low micrometer range on castor oil-based polyurethane, which is currently employed to fabricate cardiovascular devices. We have investigated cell adhesion, proliferation, morphology and alignment in response to these topographies. Reported results show that line-like and pillar-like patterns improved adhesion and proliferation rate of cultured endothelial cells. The line-like pattern with 1 µm groove periodicity was the most efficient to enhance cell adhesion and induced marked polarization and alignment. Our study suggests the viability of using laser radiation to functionalize PU-based implants by the introduction of specific microtopography to facilitate the development of a functional endothelium on target surfaces.
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Óleo de Rícino/química , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endotélio Vascular/citologia , Terapia a Laser/métodos , Poliuretanos/farmacologia , Adesão Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/efeitos da radiação , Humanos , Especificidade por SubstratoRESUMO
PURPOSE: This retrospective study was performed to determine the effectiveness of preventing recurrent dislocation following primary cemented Endo-MarkIII/SP2 total hip replacement using a posterior lip augmentation device (PLAD). METHODS: Between January 2003 and Dezember 2006, 27 PLADs were used in the treatment of recurrent hip dislocation in 27 patients who had received a cemented primary total hip arthroplasty using Endo-MarkIII/SP2 (Waldemar LINK, Hamburg, Germany) components. The mean number of dislocations prior to stabilization with this specific device was 2.6 (range 2-4, SD ± 0.4) with a mean time to revision surgery of 10 months (IQR 13). The mean age of the patients at time of revision surgery was 81.5 years (range 70-94, SD ± 6.9). The control group evaluating the clinical outcome using the Harris Hip Score (HHS) also received a cemented primary total hip arthroplasty using the same implants. A retrospective clinical and radiological review was carried out at a mean follow-up of 68.5 months (range 30-103, SD ± 17.7). RESULTS: Of the 27 patients, 6 had died at the time of the latest review, with the posterior lip augmentation device still in situ and without reported further dislocation after PLAD application. In 2 of the remaining 21 patients recurrent dislocation occurred, thus a subsequent revision of respective implants had to be performed to achieve persistent joint stability. At latest follow-up no deep infection or implant loosening occurred. CONCLUSION: Surgical treatment of recurrent dislocation following primary cemented Endo-MarkIII/SP2 total hip replacement using a posterior lip augmentation device is a safe and effective procedure which can lead to a secondary stabilization of the total hip arthroplasty in about 90 % of the patients.
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Artroplastia de Quadril , Luxação do Quadril/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Próteses e Implantes , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Feminino , Seguimentos , Luxação do Quadril/etiologia , Prótese de Quadril , Humanos , Masculino , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The aim of this study was to assess the role of synovial C-reactive protein (CRP) in the diagnosis of chronic periprosthetic hip infection. We prospectively collected synovial fluid from 89 patients undergoing revision hip arthroplasty and measured synovial CRP, serum CRP, erythrocyte sedimentation rate (ESR), synovial white blood cell (WBC) count and synovial percentages of polymorphonuclear neutrophils (PMN). Patients were classified as septic or aseptic by means of clinical, microbiological, serum and synovial fluid findings. The high viscosity of the synovial fluid precluded the analyses in nine patients permitting the results in 80 patients to be studied. There was a significant difference in synovial CRP levels between the septic (n = 21) and the aseptic (n = 59) cohort. According to the receiver operating characteristic curve, a synovial CRP threshold of 2.5 mg/l had a sensitivity of 95.5% and specificity of 93.3%. The area under the curve was 0.96. Compared with serum CRP and ESR, synovial CRP showed a high diagnostic value. According to these preliminary results, synovial CRP may be a useful parameter in diagnosing chronic periprosthetic hip infection.
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Proteína C-Reativa/análise , Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Líquido Sinovial/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Artroplastia de Quadril , Sedimentação Sanguínea , Doença Crônica , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Sensibilidade e EspecificidadeRESUMO
We demonstrate that a seismic analysis of stars in their earliest evolutionary phases is a powerful method with which to identify young stars and distinguish their evolutionary states. The early star that is born from the gravitational collapse of a molecular cloud reaches at some point sufficient temperature, mass, and luminosity to be detected. Accretion stops, and the pre-main sequence star that emerges is nearly fully convective and chemically homogeneous. It will continue to contract gravitationally until the density and temperature in the core are high enough to start nuclear burning of hydrogen. We show that there is a relationship for a sample of young stars between detected pulsation properties and their evolutionary status, illustrating the potential of asteroseismology for the early evolutionary phases.
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PURPOSE: Double-bundle ACL reconstruction has been demonstrated to be at least as effective as single-bundle reconstruction in terms of restoring knee rotational and translational stability. Until now, the influence on knees with hyperextension has not been evaluated. It was the purpose of this study to evaluate whether double-bundle ACL reconstruction restricts extension in hyperextendable knees. METHODS: Hamstring tendon reconstructions of 10 human cadaveric knees with the ability of hyperextension (age: 48 ± 14 years) were performed as single bundle (SB) on one side and double bundle (DB) on the other side. A surgical navigation system (BrainLab, Germany) was used to assess the kinematics of each knee at the intact and reconstructed state. A difference with regard to the anterior-to-posterior translation (AP) and rotational stability at 30° of knee flexion, 90° of flexion and the hyperextension capability of each specimen was analysed. RESULTS: The difference in AP translation before and after the reconstruction was not significantly different in 30° and 90° of flexion (n.s). Both single- and double-bundle reconstructions restored the preoperative kinematics at 30° and 90° of knee flexion (n.s). The knee extension was 4° ± 1.8° with the intact ACL and 4° ± 1.7° after reconstruction in the SB group (n.s). The knee extension was 5° of hyperextension ± 1.1° with the intact ACL and 0° ± 0.4° after reconstruction in the DB group; the limitation of the extension was significantly larger in this group (p = 0.013). CONCLUSION: Both single- and double-bundle ACL reconstruction techniques are capable of restoring knee anteroposterior and rotational stability. Double-bundle reconstructions significantly reduce knee extension in knees with hyperextension capability. Care must be taken when using double-bundle techniques in patients with knee hyperextension as this procedure may limit the knee extension after double-bundle ACL reconstruction.
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Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Traumatismos do Joelho/fisiopatologia , Articulação do Joelho/fisiopatologia , Amplitude de Movimento Articular , Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior/métodos , Humanos , Traumatismos do Joelho/cirurgia , Período Pós-OperatórioRESUMO
Establishment of the saltcedar leaf beetle (Diorhabda spp.) has been unpredictable when caged or released in the field for saltcedar (Tamarix spp.) biocontrol. It has been observed that one caged tree might be voraciously fed upon by beetles while an adjacent tree in the cage is left untouched. We hypothesized that differences in the nutrient content of individual trees may explain this behavior. We evaluated survival, development rate, and egg production of beetles fed in the laboratory on saltcedar foliage from trees that had been grown under a range of fertilizer treatments. Tissue samples from the experimental trees and from the field were analyzed for percent nitrogen, phosphorus, and potassium. There was essentially no survival of beetle larvae fed foliage from saltcedar trees at nitrogen levels below 2.0%. At levels above 2.0% N, beetle larvae had corresponding increased survival rates and shorter development times. Multiple regression analyses indicated that nitrogen and phosphorus are important for larval survival and faster development rates. Higher levels of potassium were important for increased egg cluster production. The plant tissue analysis showed that the percentage of nitrogen in the experimental trees reflected the range of trees in the field and also that there is high variability within trees in the field. Our research indicates that if beetles are released on trees with poor nutrient quality, the larvae will not survive.
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Besouros/fisiologia , Controle Biológico de Vetores , Tamaricaceae/fisiologia , Animais , Besouros/crescimento & desenvolvimento , Aptidão Genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , New Mexico , Oviposição , Folhas de Planta/fisiologia , Análise de RegressãoRESUMO
We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.
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Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Tolerância Imunológica , Transplante de Rim/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Hipersensibilidade Tardia , Suínos , Porco Miniatura , Transplante HomólogoRESUMO
It is well known that interferon-gamma (IFN-gamma) not only plays a critical role in antigen-dependent but also in antigen-independent tissue injury; however, it is not clear how tolerance induction affects the actions of IFN-gamma in the transplant setting. To address this question, we compared the effects of IFN-gamma on porcine recipients of near-syngeneic, rejecting, and tolerant heart transplants. IFN-gamma was infused continuously into the left anterior descending artery of hearts transplanted into 3 groups of major histocompatibility complex (MHC) inbred miniature swine, each treated with a 12-day course of cyclosporine A (CyA). Group 1 recipients received a MHC class I disparate heart, group 2 recipients received a near-syngeneic heart, and group 3 recipients were cotransplanted with a MHC class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional group of animals was not transplanted but received intracoronary IFN-gamma infusion into their native hearts. IFN-gamma perfusion not only accelerated the acute rejection of MHC class I disparate hearts (mean survival time = 19 +/- 7.21 vs 38 +/- 8.19 days, P = .025), but caused near-syngeneic heart transplants, which otherwise survive indefinitely, to reject within 35 days (n = 3). In contrast, IFN-gamma perfusion had no demonstrable effects on interstitial rejection, the development of vascular lesions, or graft survival in tolerant heart plus kidney allograft recipients (n = 4) or in autologous hearts (n = 2). These results suggest that tolerance induction mitigates the damaging effects of IFN-gamma itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury.
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Transplante de Coração/imunologia , Tolerância Imunológica , Interferon gama/farmacologia , Transplante Homólogo/imunologia , Animais , Rejeição de Enxerto/prevenção & controle , SuínosRESUMO
UNLABELLED: Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. METHODS: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.
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Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Complexo Principal de Histocompatibilidade , Modelos Animais , Suínos , Porco MiniaturaRESUMO
OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level = 35-50 ng/mL) as their only immunosuppression. RESULTS: All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (>497, >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis. CONCLUSIONS: We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class II disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction.
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Antígenos de Histocompatibilidade Classe II/imunologia , Tolerância Imunológica , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/patologia , Transplante de Pulmão/patologia , Complexo Principal de Histocompatibilidade , Modelos Animais , Suínos , Porco Miniatura , Transplante Homólogo/imunologiaRESUMO
OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. Using a strategy to induce tolerance across strong allogeneic barriers, we have employed a brief, intensive course of immunosuppression to determine whether the induction of donor-specific hyporesponsiveness would prevent allograft rejection in a preclinical model of lung transplantation using MHC-inbred miniature swine. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate donors. The recipients received a 12-day postoperative course of cyclosporine (n = 6) or a 12-day postoperative course of high-dose tacrolimus (n = 3) as their only immunosuppression. Control animals received no immunosuppression (n = 3). RESULTS: Cyclosporine-treated recipients exhibited graft survival ranging from 67 to >605 days. All six animals developed acute cellular rejection between postoperative days (PODs) 27 and 108. Two animals lost their grafts on PODs 67 and 69, before developing obliterative bronchiolitis (OB). The other four recipients developed OB between PODs 119 and 238. In contrast, all tacrolimus-treated recipients maintained their grafts long term, without developing chronic rejection (>339, >308, and >231). These recipients also exhibited donor-specific hyporesponsiveness in assays of cell-mediated lymphocytotoxity. All untreated control animals lost their grafts to acute rejection by POD 11. CONCLUSIONS: This study demonstrates the ability of a brief course of high-dose tacrolimus to induce long-term graft acceptance with donor-specific hyporesponsiveness in a class I-disparate preclinical lung transplant model.
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Sobrevivência de Enxerto/imunologia , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Pulmão/patologia , Suínos , Porco Miniatura , Tacrolimo/uso terapêutico , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
The current status of experimental and clinical applications for functional MR imaging of pulmonary ventilation using hyperpolarized noble gases are reviewed. 3-helium (3He) and 129-xenon (129Xe) can be hyperpolarized by optical pumping techniques such as spin exchange or metastability exchange in sufficient amounts. This process leads to an artificial, non-equilibrium increase of the density of excited nuclei which represents the source of the MR signal. Those hyperpolarized gases are administered mostly via inhalation, and will fill airways and airspaces allowing for ventilation imaging. Recent human studies concentrate on imaging the airways and airspaces with high spatial resolution. Normal ventilation is reflected by an almost complete and homogeneous distribution of the hyperpolarized gas represented by the signal detected. Loss of signal or inhomogeneous signal distribution represent mass effects and ventilatory abnormalities. Even healthy subjects with seasonal allergies without pulmonary symptoms have been observed to exhibit transient ventilation defects. Real-time imaging of ventilation has become feasible for 3He MR imaging and allows for assessment of ventilation-distribution. Furthermore, functional oxygen-sensitive 3He MR imaging opens the field of non-invasive assessment of regional intrapulmonary oxygen concentrations in vivo. Knowing that the diffusion of gas is affected by the geometry and nature of its environment, diffusion measurements are under investigation as a sensitive marker of diseases that involve structural changes of lung parenchyma, such as emphysema and fibrosis. Whereas 3He is not absorbed and is restricted to the airspaces, 129Xe is soluble in blood and lipid-rich tissue. This presents the opportunity for additional dissolved-phase imaging, providing a step towards simultaneous ventilation-perfusion studies.
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Hélio , Pulmão/fisiologia , Imageamento por Ressonância Magnética , Ventilação Pulmonar , Isótopos de Xenônio , Humanos , Isótopos , Pulmão/anatomia & histologia , Capacidade de Difusão Pulmonar , Relação Ventilação-PerfusãoRESUMO
MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests.
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Medidas de Volume Pulmonar/métodos , Pulmão/fisiologia , Imageamento por Ressonância Magnética/métodos , Fumar/fisiopatologia , Adulto , Hélio/farmacocinética , Humanos , Isótopos , Pulmão/fisiopatologiaRESUMO
Helioseismology offers, for the first time, an opportunity to probe in detail the deep interior of a star (our Sun). The results will have a profound impact on our understanding not only of the solar interior, but also neutrino physics, stellar evolution theory, and stellar population studies in astrophysics.
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Association studies with the DRD2 Taq1A marker have been variable in implicating DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse. Given that the Taq1A marker is not functionally significant, second-generation studies on the DRD2 receptor to identify functional variants and evaluate their effect on the phenotype are the logical step towards confirming and extending the DRD2 hypothesis. This article discusses the implications and process of progress made in these directions. The new findings are the description of structural variants in the D2 receptor, the demonstration that one of these, Ser311Cys, largely prevents signal transduction following receptor activation and the use of Ser311Cys in a large association and sib-pair linkage anlysis in an American Indian isolate. In this particular population, the Cys311 variant is far more abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2 intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and 15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism, substance use disorders, or schizophrenia. The implication is that a DRD2 variant that dramatically impairs receptor function was not sufficient to significantly alter alcoholism vulnerability in a relatively large and also genetically and environmentally homogeneous sample.
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Alcoolismo/genética , Ligação Genética , Variação Genética/genética , Receptores de Dopamina D2/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Sequência de Aminoácidos , Humanos , Indígenas Norte-Americanos/genéticaRESUMO
Alcoholism is one of a group of common psychiatric diseases which are well-defined clinically and strongly influenced genetically, but which are likely to be highly heterogeneous in causation, genetically and otherwise. Dopamine is a key neurotransmitter in drug-mediated reinforcement. Based on association studies with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to be the "Reward Deficiency Syndrome Gene." Ser311Cys, a naturally occurring variant which largely inactivates transduction after D2 receptor activation, was abundant (0.16) in a Southwestern American Indian population we studied. Therefore, we were able to provide a critical test of the D2 hypothesis of vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs, from large families. The result is that neither alcoholism, substance use disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when the 15 Cys311/Cys311 homozygous individuals are compared to others. Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder.
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Alcoolismo/genética , Indígenas Norte-Americanos/genética , Mutação Puntual , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Alcoolismo/etnologia , Alelos , Arizona/epidemiologia , Suscetibilidade a Doenças , Etnicidade/genética , Variação Genética , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Núcleo Familiar , Recompensa , Esquizofrenia/etnologia , Transtornos Relacionados ao Uso de Substâncias/etnologiaRESUMO
The aim of this report is to demonstrate the correlation between an extremely short time acting but strong force leading to incomplete rupture of the ponto-medullary junction (PMJ) accompanied by rupture of the basilar artery. Potential mechanisms involved in a combined hyperextension and axial torsion of the head followed by characteristic lesions at the PMJ are discussed. A 33-year-old male suffered a blunt head injury following a blow to the head, i.e. a head-butt. Resuscitation was performed for 45 min without success. At post mortem, there was a superficial periorbital haematoma on the right and a deep soft tissue bruise in the right fronto-parieto-temporal area, but no evidence of skull or dens axis fracture. A deep tear at the ponto-medullary junction was identified with rupture of the basilar artery, whereas at the tip of the tear, i.e. the floor of the IVth ventricle, only a thin tissue layer of about 2 mm remained intact. In contrast to the severity of these lesions, only mild subarachnoid hemorrhage was observed, but the ventricular system was filled with blood clot resulting from the retrograde flow of subarachnoid hemorrhage.
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Artéria Basilar/lesões , Bulbo/lesões , Ponte/lesões , Ferimentos não Penetrantes/patologia , Adulto , Cocaína/análogos & derivados , Cocaína/sangue , Cocaína/urina , Etanol/sangue , Etanol/urina , Medicina Legal , Humanos , Masculino , Bulbo/patologia , Ponte/patologia , RupturaRESUMO
PIP: Migrations trends from East to West Germany during the period from the end of World War II to 1990 are reviewed. Migrants' demographic characteristics and preferred destinations are described. Patterns since 1990 are also discussed. (SUMMARY IN ENG AND FRE)^ieng