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1.
Rev Sci Instrum ; 93(12): 124901, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586892

RESUMO

We demonstrate multiplexed readout of 43 transition edge sensor (TES) bolometers operating at 90 mK using a frequency division multiplexing (FDM) readout chain with bias frequencies ranging from 1 to 3.5 MHz and a typical frequency spacing of 32 kHz. We improve the previously reported performance of our FDM system by two important steps. First, we replace the coplanar wires with microstrip wires, which minimize the cross talk from mutual inductance. From the measured electrical cross talk (ECT) map, the ECT of all pixels is carrier leakage dominated. Only five pixels show an ECT level higher than 1%. Second, we reduce the thermal response speed of the TES detectors by a factor of 20 by increasing the heat capacity of the TES, which allows us to bias all TES detectors below 50% in transition without oscillations. We compare the current-voltage curves and noise spectra of the TESs measured in single-pixel mode and multiplexing mode. We also compare the noise equivalent power (NEP) and the saturation power of the bolometers in both modes, where 38 pixels show less than 10% difference in NEP and 5% difference in saturation power when measured in the two different modes. The measured noise spectrum is in good agreement with the simulated noise based on measured parameters from an impedance measurement, confirming that our TES is dominated by phonon noise.

2.
Rev Sci Instrum ; 92(3): 033103, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33820098

RESUMO

In the frequency-domain multiplexing (FDM) scheme, transition-edge sensors (TESs) are individually coupled to superconducting LC filters and AC biased at MHz frequencies through a common readout line. To make efficient use of the available readout bandwidth and to minimize the effect of non-linearities, the LC resonators are usually designed to be on a regular grid. The lithographic processes, however, pose a limit on the accuracy of the effective filter resonance frequencies. Off-resonance bias carriers could be used to suppress the impact of intermodulation distortions, which, nonetheless, would significantly affect the effective bias circuit and the detector spectral performance. In this paper, we present a frequency shift algorithm (FSA) to allow off-resonance readout of TESs, while preserving the on-resonance bias circuit and spectral performance, demonstrating its application to the FDM readout of an x-ray TES microcalorimeter array. We discuss the benefits in terms of mitigation of the impact of intermodulation distortions at the cost of increased bias voltage and the scalability of the algorithm to multi-pixel FDM readout. We show that with FSA, in the multi-pixel and frequencies shifted on-grid, the line noises due to intermodulation distortion are placed away from the sensitive region in the TES response and the x-ray performance is consistent with the single-pixel, on-resonance level.

3.
Rev Sci Instrum ; 92(1): 014710, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33514257

RESUMO

We have characterized and mapped the electrical cross talk (ECT) of a frequency division multiplexing (FDM) system with a transition edge sensor (TES) bolometer array, which is intended for space applications. By adding a small modulation at 120 Hz to the AC bias voltage of one bolometer and measuring the cross talk response in the current noise spectra of the others simultaneously, we have for the first time mapped the ECT level of 61 pixels with a nominal frequency spacing of 32 kHz in a 61 × 61 matrix and a carrier frequency ranging from 1 MHz to 4 MHz. We find that about 94% of the pixels show an ECT level of less than 0.4%. Only the adjacent pixels reach this level, and the ECT for the rest of the pixels is less than 0.1%. We also observe higher ECT levels, up to 10%, between some of the pixels, which have bundled long, parallel coplanar wires connecting TES bolometers to inductor-capacitor filters. In this case, the high mutual inductances dominate. To mitigate this source of ECT, the coplanar wires should be replaced by microstrip wires in the array. Our study suggests that an FDM system can have a relatively low ECT level, e.g., around 0.4% if the frequency spacing is 30 kHz. Our results successfully demonstrate a low electrical cross talk for a space FDM technology.

4.
Sci Rep ; 10(1): 2798, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071379

RESUMO

Usutu virus (USUV) is a mosquito-borne flavivirus circulating in Western Europe that causes die-offs of mainly common blackbirds (Turdus merula). In the Netherlands, USUV was first detected in 2016, when it was identified as the likely cause of an outbreak in birds. In this study, dead blackbirds were collected, screened for the presence of USUV and submitted to Nanopore-based sequencing. Genomic sequences of 112 USUV were obtained and phylogenetic analysis showed that most viruses identified belonged to the USUV Africa 3 lineage, and molecular clock analysis evaluated their most recent common ancestor to 10 to 4 years before first detection of USUV in the Netherlands. USUV Europe 3 lineage, commonly found in Germany, was less frequently detected. This analyses further suggest some extent of circulation of USUV between the Netherlands, Germany and Belgium, as well as likely overwintering of USUV in the Netherlands.


Assuntos
Doenças das Aves/virologia , Surtos de Doenças/veterinária , Infecções por Flavivirus/veterinária , Flavivirus/genética , Aves Canoras/virologia , Animais , Doenças das Aves/epidemiologia , Flavivirus/isolamento & purificação , Infecções por Flavivirus/epidemiologia , Infecções por Flavivirus/virologia , Países Baixos/epidemiologia
5.
Acta Chir Belg ; 120(5): 329-333, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31203729

RESUMO

Background: Weight loss failure or weight regain occurs in up to 25% of patients with a Roux-en-Y gastric bypass (RYGB). Post-operative anatomical changes, like pouch or stoma dilatation, might contribute. Aim of this study is to assess reliability and usefulness of upper gastro intestinal (UGI) contrast studies to detect pouch dilatation.Methods: Retrospective case-control study of patients with weight loss failure between 2010 and 2015 (failure group, n = 101) and a control group (n = 101) with adequate weight loss. Pouch dilatation was systematically reassessed. Clinical parameters were extracted from the electronic patient records.Results: Systematic reassessment showed 23/101 (23%) pouch dilatation in the failure group, compared to 11/101 (11%) in the control group (p = .024). Revision surgery was performed in 43/101 patients in the failure group. After this surgery, only 8% of patients with pouch dilatation achieved adequate weight loss, whereas 39% of patients without pouch dilatation achieved adequate weight loss (p = .07). There was no difference in return to adequate weight loss between patients treated surgically and conservatively (30% vs 28%).Conclusion: Systematic reassessment of UGI contrast studies showed 23% pouch dilatation in patients with weight loss failure after RYGB. However, low interobserver agreement and discrepancy in success rate of revision surgery greatly questions the reliability and usefulness of this diagnostic modality.


Assuntos
Derivação Gástrica/efeitos adversos , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Trato Gastrointestinal Superior/diagnóstico por imagem , Adulto , Idoso , Meios de Contraste , Dilatação Patológica , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Falha de Tratamento , Redução de Peso , Adulto Jovem
6.
Infect Genet Evol ; 73: 49-54, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31014969

RESUMO

Recently, protocols for amplicon based whole genome sequencing using Nanopore technology have been described for Ebola virus, Zika virus, yellow fever virus and West Nile virus. However, there is some debate regarding reliability of sequencing using this technology, which is important for applications beyond diagnosis such as linking lineages to outbreaks, tracking transmission pathways and pockets of circulation, or mapping specific markers. To our knowledge, no in depth analyses of the required read coverage to compensate for the error profile in Nanopore sequencing have been described. Here, we describe the validation of a protocol for whole genome sequencing of USUV using Nanopore sequencing by direct comparison to Illumina sequencing. To that point we selected brain tissue samples with high viral loads, typical for birds which died from USUV infection. We conclude that the low-cost MinION Nanopore sequencing platform can be used for characterization and tracking of Usutu virus outbreaks.


Assuntos
Doenças das Aves/epidemiologia , Doenças das Aves/virologia , Infecções por Flavivirus/veterinária , Flavivirus/genética , Genoma Viral , Genômica , Estrigiformes/virologia , Animais , Surtos de Doenças , Genômica/métodos , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Sequenciamento Completo do Genoma
7.
Animal ; 13(4): 868-878, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30369338

RESUMO

LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle) is a generic, mechanistic model designed to quantify potential and feed-limited growth, which provides insight in the biophysical scope to increase beef production (i.e. yield gap). Furthermore, it enables identification of the bio-physical factors that define and limit growth, which provides insight in management strategies to mitigate yield gaps. The aim of this paper, third in a series of three, is to evaluate the performance of LiGAPS-Beef with independent experimental data. After model calibration, independent data were used from six experiments in Australia, one in Uruguay and one in the Netherlands. Experiments represented three cattle breeds, and a wide range of climates, feeding strategies and cattle growth rates. The mean difference between simulated and measured average daily gains (ADGs) was 137 g/day across all experiments, which equals 20.1% of the measured ADGs. The root mean square error was 170 g/day, which equals 25.0% of the measured ADGs. LiGAPS-Beef successfully simulated the factors that defined and limited growth during the experiments on a daily basis (genotype, heat stress, digestion capacity, energy deficiency and protein deficiency). The simulated factors complied well to the reported occurrence of heat stress, energy deficiency and protein deficiency at specific periods during the experiments. We conclude that the level of accuracy of LiGAPS-Beef is acceptable, and provides a good basis for acquiring insight in the potential and feed-limited production of cattle in different beef production systems across the world. Furthermore, its capacity to identify factors that define or limit growth and production provides scope to use the model for yield gap analysis.


Assuntos
Ração Animal , Simulação por Computador , Modelos Econômicos , Carne Vermelha/economia , Animais , Austrália , Cruzamento , Bovinos , Clima , França , Genótipo , Aumento de Peso
8.
Animal ; 13(4): 856-867, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29996955

RESUMO

The model LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle) has been developed to assess potential and feed-limited growth and production of beef cattle in different areas of the world and to identify the processes responsible for the yield gap. Sensitivity analysis and evaluation of model results with experimental data are important steps after model development. The first aim of this paper, therefore, is to identify which parameters affect the output of LiGAPS-Beef most by conducting sensitivity analyses. The second aim is to evaluate the accuracy of the thermoregulation sub-model and the feed intake and digestion sub-model with experimental data. Sensitivity analysis was conducted using a one-at-a-time approach. The upper critical temperature (UCT) simulated with the thermoregulation sub-model was most affected by the body core temperature and parameters affecting latent heat release from the skin. The lower critical temperature (LCT) and UCT were considerably affected by weather variables, especially ambient temperature and wind speed. Sensitivity analysis for the feed intake and digestion sub-model showed that the digested protein per kg feed intake was affected to a larger extent than the metabolisable energy (ME) content. Sensitivity analysis for LiGAPS-Beef was conducted for ¾ Brahman×» Shorthorn cattle in Australia and Hereford cattle in Uruguay. Body core temperature, conversion of digestible energy to ME, net energy requirements for maintenance, and several parameters associated with heat release affected feed efficiency at the herd level most. Sensitivity analyses have contributed, therefore, to insight which parameters are to be investigated in more detail when applying LiGAPS-Beef. Model evaluation was conducted by comparing model simulations with independent data from experiments. Measured heat production in experiments corresponded fairly well to the heat production simulated with the thermoregulation sub-model. Measured ME contents from two data sets corresponded well to the ME contents simulated with the feed intake and digestion sub-model. The relative mean absolute errors were 9.3% and 6.4% of the measured ME contents for the two data sets. In conclusion, model evaluation indicates the thermoregulation sub-model can deal with a wide range of weather conditions, and the feed intake and digestion sub-model with a variety of feeds, which corresponds to the aim of LiGAPS-Beef to simulate cattle in different beef production systems across the world.


Assuntos
Ração Animal , Simulação por Computador , Modelos Econômicos , Carne Vermelha/economia , Animais , Austrália , Cruzamento , Bovinos , Clima , França , Genótipo , Aumento de Peso
9.
Animal ; 13(4): 845-855, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29996958

RESUMO

The expected increase in the global demand for livestock products calls for insight in the scope to increase actual production levels across the world. This insight can be obtained by using theoretical concepts of production ecology. These concepts distinguish three production levels for livestock: potential (i.e. theoretical maximum) production, which is defined by genotype and climate only; feed-limited production, which is limited by feed quantity and quality; and actual production. The difference between the potential or limited production and the actual production is the yield gap. The objective of this paper, the first in a series of three, is to present a mechanistic, dynamic model simulating potential and feed-limited production for beef cattle, which can be used to assess yield gaps. A novelty of this model, named LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle), is the identification of the defining factors (genotype and climate) and limiting factors (feed quality and available feed quantity) for cattle growth by integrating sub-models on thermoregulation, feed intake and digestion, and energy and protein utilisation. Growth of beef cattle is simulated at the animal and herd level. The model is designed to be applicable to different beef production systems across the world. Main model inputs are breed-specific parameters, daily weather data, information about housing, and data on feed quality and quantity. Main model outputs are live weight gain, feed intake and feed efficiency (FE) at the animal and herd level. Here, the model is presented, and its use is illustrated for Charolais and Brahman × Shorthorn cattle in France and Australia. Potential and feed-limited production were assessed successfully, and we show that FE of herds is highest for breeds most adapted to the local climate conditions. LiGAPS-Beef also identified the factors that define and limit growth and production of cattle. Hence, we argue the model has scope to be used as a tool for the assessment and analysis of yield gaps in beef production systems.


Assuntos
Ração Animal , Simulação por Computador , Modelos Econômicos , Carne Vermelha/economia , Animais , Austrália , Cruzamento , Bovinos , Clima , França , Genótipo , Aumento de Peso
10.
Radiat Prot Dosimetry ; 177(4): 440-449, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29272884

RESUMO

X-ray radiography is a commonly used diagnostic method for premature neonates. However, because of higher radiosensitivity and young age, premature neonates are more sensitive to the detrimental effects of ionising radiation. Therefore, it is important to monitor and optimise radiation doses at the neonatal intensive care unit (NICU). The number of x-ray examinations, dose-area product (DAP) and effective doses are evaluated for three Dutch NICUs using digital flat panel detectors. Thorax, thorax-abdomen and abdomen protocols are included in this study. Median number of examinations is equal to 1 for all three hospitals. Median DAP ranges between 0.05 and 1.02 µGy m2 for different examination types and different weight categories. These examinations result in mean effective doses between 4 ± 4 and 30 ± 10 µSv per examination. Substantial differences in protocols and doses can be observed between hospitals. This emphasises the need for up-to-date reference levels formulated specifically for premature neonates.


Assuntos
Doenças do Recém-Nascido/diagnóstico por imagem , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Radiografia Abdominal , Radiografia Torácica , Humanos , Recém-Nascido , Método de Monte Carlo , Países Baixos , Doses de Radiação , Estudos Retrospectivos , Raios X
11.
Sci Rep ; 7(1): 13563, 2017 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-29051552

RESUMO

Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive neuroscience and has become a valuable tool in the study of auditory processing in zebra finches, a well-established model of learned vocal communication. Due to its sensitivity to head motion, most fMRI studies in animals are performed in anaesthetized conditions, which might significantly impact neural activity evoked by stimuli and cognitive tasks. In this study, we (1) demonstrate the feasibility of fMRI in awake zebra finches and (2) explore how light anaesthesia regimes affect auditory-evoked BOLD responses to biologically relevant songs. After an acclimation procedure, we show that fMRI can be successfully performed during wakefulness, enabling the detection of reproducible BOLD responses to sound. Additionally, two light anaesthesia protocols were tested (isoflurane and a combination of medetomidine and isoflurane), of which isoflurane alone appeared to be the most promising given the high success rate, non-invasive induction, and quick recovery. By comparing auditory evoked BOLD responses in awake versus lightly anaesthetized conditions, we observed overall effects of anaesthetics on cerebrovascular reactivity as reflected in the extent of positive and negative BOLD responses. Further, our results indicate that light anaesthesia has limited effects on selective BOLD responses to natural versus synthetic sounds.


Assuntos
Anestésicos/farmacologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Vigília/efeitos dos fármacos , Estimulação Acústica , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Tentilhões , Cabeça/fisiologia , Isoflurano/farmacologia , Imageamento por Ressonância Magnética , Masculino
13.
Mol Neurobiol ; 53(8): 5796-806, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27544234

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world and is characterized by a progressive loss of cognitive functions leading to dementia. One major histopathological hallmark of AD is the formation of amyloid-beta plaques, which is reproduced in numerous transgenic animal models overexpressing pathogenic forms of amyloid precursor protein (APP). In human AD and in transgenic amyloid plaque mouse models, several studies report altered rates of adult neurogenesis, i.e. the formation of new neurons from neural stem and progenitor cells, and impaired neurogenesis has also been attributed to contribute to the cognitive decline in AD. So far, changes in neurogenesis have largely been considered to be a consequence of the plaque pathology. Therefore, possible alterations in neurogenesis before plaque formation or in prodromal AD have been largely ignored. Here, we analysed adult hippocampal neurogenesis in amyloidogenic mouse models of AD at different points before and during plaque progression. We found prominent alterations of hippocampal neurogenesis before plaque formation. Survival of newly generated cells and the production of new neurons were already compromised at this stage. Moreover and surprisingly, proliferation of doublecortin (DCX) expressing neuroblasts was significantly and specifically elevated during the pre-plaque stage in the APP-PS1 model, while the Nestin-expressing stem cell population was unaffected. In summary, changes in neurogenesis are evident already before plaque deposition and might contribute to well-known early hippocampal dysfunctions in prodromal AD such as hippocampal overactivity.


Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Neurogênese , Doença de Alzheimer/metabolismo , Animais , Contagem de Células , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Giro Denteado/patologia , Modelos Animais de Doenças , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Feminino , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Neuropeptídeos/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patologia
14.
Breast ; 29: 8-13, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27376887

RESUMO

BACKGROUND: To achieve radical tumour excision in non-palpable breast cancer accurate tumour localization is essential. Historically, this has been achieved by wire localization (WL). Recently, new techniques like Iodine-125 seeds (IL) have become available. The aim of this study was to determine whether the results in case of IL are better than when WL is used. METHOD: A consecutive series of patients operated on because of non-palpable breast cancer was analysed. Between January 2007 and April 2011 WL was method of choice. From April 2011 till January 2013 IL was introduced and became the standard procedure. PRIMARY OUTCOMES WERE: success rate of (peri-) operative localization and radicality of the excision. Secondary outcomes were duration of operation and volumes of the excised tissue specimen. RESULTS: A total of 236 women were included; 149 women underwent WL and 87 women IL. The overall success rate for WL was 93.3%. In 10 patients (6.7%) WL failed because of peri-operative dislocation of the wire compared to only one failure to locate the seed in de postoperative specimen in the IL-group (1.1%, p = 0.098). Radical resection was obtained in 126/149 (84.6%) of the WL-patients, in comparison with 81/87 (93.1%) in the IL-group (p = 0.054). Median operation time and volume of the specimen was not significantly different between both groups. CONCLUSION: Localization of non-palpable breast cancer using Iodine-125 seeds is, at least, as good as the standard wire localization procedure.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Marcadores Fiduciais , Radioisótopos do Iodo , Mamografia/métodos , Compostos Radiofarmacêuticos , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica , Duração da Cirurgia , Estudos Prospectivos , Carga Tumoral
15.
Neuroimage ; 125: 363-377, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26525654

RESUMO

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, the MK, the RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Doenças Desmielinizantes/patologia , Imagem de Tensor de Difusão/métodos , Substância Branca/patologia , Animais , Córtex Cerebral/patologia , Quelantes/toxicidade , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL
16.
Curr Alzheimer Res ; 12(10): 941-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26502821

RESUMO

The corpus callosum is the largest commissural fiber connecting left and right hemisphere of the brain. Emerging evidence suggests that a variety of abnormalities detected in the microstructure of this white matter fiber can be an early event in Alzheimer's disease (AD) pathology. However, little is known about tissue characteristics of these abnormalities and how these abnormalities evolve during AD progression. In this study, we measured in vivo magnetic resonance transverse relaxation times (T2) to longitudinally monitor changes in tissue integrity and abnormalities related to myelination and demyelination processes in corpus callosum of AD mouse models. The most striking finding of our study was a significant elongation of T2 values in the corpus callosum at 10, 14, 16 and 18 months of age compared to age-matched wild-type mice. In contrast, the gray matter regions surrounding the corpus callosum, such as the cortex and hippocampus, showed a significant T2 decrease compared to wild-type mice. Histological analyses clearly revealed demyelination, gliosis and amyloid-plaque deposition in the corpus callosum. Our results suggest that demyelinating and inflammatory pathology may result in prolonged relaxation time during AD progression. To our knowledge, this is the first in vivo T2 study assessing the microstructural changes with age in the corpus callosum of the Tg2576 mouse model and it demonstrates the application of T2 measurement to noninvasively detect tissue integrity of the corpus callosum, which can be an early event in disease progression.


Assuntos
Doença de Alzheimer/patologia , Corpo Caloso/patologia , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Astrócitos/patologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Corpo Caloso/fisiopatologia , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Imunofluorescência , Hipocampo/patologia , Hipocampo/fisiopatologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tálamo/patologia , Tálamo/fisiopatologia
17.
Neth J Med ; 72(7): 345-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25178767

RESUMO

BACKGROUND: Advanced imaging techniques as magnetic resonance imaging (MRI) are increasingly performed in the diagnostic workup of patients. Incidentally, diffuse signal alterations of the bone marrow are detected because MRI visualises various components of the bone marrow. The clinical significance of these signal alterations is unknown. OBJECTIVE: The main goal of this study was to determine the diagnostic value of a bone marrow biopsy in patients with incidentally found diffuse signal alterations of the bone marrow. METHODS: We retrospectively examined all bone marrow biopsies performed from 1 January 2007 to 31 December 2013 (n = 1947). Patients were included when the biopsy was obtained following an MRI with a diffuse abnormal bone marrow signal. Patients who underwent MRI for suspected malignancy were excluded. Histological and cytological results of the bone marrow examinations were analysed. RESULTS: 15 of the 1947 bone marrow biopsies (0.77%) were performed because of diffuse signal alterations on MRI. In seven of these 15 bone marrow biopsies (47%) a clinically important haematological disorder was found. Eight patients had a normal bone marrow evaluation. CONCLUSION: Based on this retrospective study, a bone marrow examination in patients with incidentally detected diffuse signal alterations should be considered to exclude haematological pathology. Prospective studies have to be performed to further investigate the best diagnostic strategy.


Assuntos
Biópsia , Medula Óssea/patologia , Doenças Hematológicas/patologia , Achados Incidentais , Imageamento por Ressonância Magnética , Adulto , Idoso , Feminino , Doenças Hematológicas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Psychopharmacology (Berl) ; 227(3): 479-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23354531

RESUMO

BACKGROUND: An effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research. We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI. METHODS: Pharmacological MRI (phMRI) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment. Resting state fMRI (rs-fMRI) and diffusion MRI were used to study the changes in functional connectivity (FC) and ultra-structural tissue integrity before and after subchronic memantine treatment. Further corroborating behavioural evidences were documented. RESULTS: Dose-dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine. Subchronic treatment revealed significant effects in the hippocampus, cingulate, prelimbic and retrosplenial cortices. Decreases in FC amongst the hippocampal and frontal cortical structures (prelimbic, cingulate) were apparent through rs-fMRI investigation, indicating a loss of connectivity. Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes, suggesting ultra-structural changes in the hippocampus and cingulate cortex. Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs. CONCLUSION: Our findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific, noncompetitive NMDA antagonists may lead to functional and ultra-structural alterations, particularly in the hippocampus and cingulate cortex. These changes may underlie the behavioural effects. Furthermore, the present findings underscore the utility and the translational potential of multimodal MR imaging and acute/subchronic memantine model in the search for novel disease-modifying treatments for schizophrenia.


Assuntos
Mapeamento Encefálico , Encéfalo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Imageamento por Ressonância Magnética/métodos , Memantina/farmacologia , Imagem Multimodal/métodos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/farmacocinética , Masculino , Memantina/administração & dosagem , Memantina/farmacocinética , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
19.
Mol Ecol ; 22(2): 397-408, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23205699

RESUMO

There is significant and often heritable variation in cognition and its underlying neural mechanisms, yet specific genetic contributions to such variation are not well characterized. Black-capped chickadees present a good model to investigate the genetic basis of cognition because they exhibit tremendous climate-related variation in memory, hippocampal morphology and neurogenesis rates throughout the North American continent, and these cognitive traits appear to have a heritable basis. We examined the hippocampal transcriptome profiles of laboratory-reared chickadees from the two most divergent populations to test whether differential gene expression in the hippocampus is associated with population differences in spatial memory, hippocampal morphology and adult hippocampal neurogenesis rates. Using high-resolution mRNA sequencing coupled to a de novo transcriptome assembly, we generated 23 295 consensus sequences, which predicted 16 206 protein sequences with 13 982 showing high similarity to known protein sequences or conserved hypothetical proteins in other species. Of these, we identified differential expression in nearly 380 genes, with 47 genes specifically linked to neurogenesis, apoptosis, synaptic function, and learning and memory processes. Many of the other differentially expressed genes, however, may be associated with other functions. Our study presents the first avian hippocampal transcriptome, and it is the first study identifying differential gene expression associated with natural variation in cognition and the hippocampus. Our results provide additional support to the hypothesis that population differences in memory, hippocampal morphology and neurogenesis in chickadees have likely resulted from natural selection that appears to act on memory and its underlying neural mechanisms.


Assuntos
Clima , Comportamento Alimentar , Hipocampo/metabolismo , Memória , Aves Canoras/genética , Transcriptoma , Animais , Hipocampo/anatomia & histologia , Neurogênese , Aves Canoras/anatomia & histologia
20.
Rev Sci Instrum ; 83(8): 084501, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22938317

RESUMO

Investigation of the transport of reactive fluids in porous rocks is an intriguing but challenging task and relevant in several areas of science and engineering such as geology, hydrogeology, and petroleum engineering. We designed and constructed an experimental setup to investigate physical and chemical processes caused by the flow of reactive and volatile fluids such as supercritical CO(2) and/or H(2)S in geological formations. Potential applications are geological sequestration of CO(2) in the frame of carbon capture and storage and acid-gas injection for sulfur disposal and/or enhanced oil recovery. The present paper outlines the design criteria and the realization of reactive transport experiments on the laboratory scale. We focus on the spatial and time evolution of rock and fluid composition as a result of chemical rock fluid interaction and the coupling of chemistry and fluid flow in porous rocks.

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