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1.
Clin Radiol ; 78(10): 715-723, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37453807

RESUMO

Gadoxetic disodium (Primovist) is a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent with increasing popularity with its unique dual dynamic and excretory properties in focal liver lesion detection and characterisation. In-depth knowledge of its diagnostic utility and pitfalls in hepatocellular carcinoma (HCC) and liver metastases is crucial in facilitating clinical management. The current article reviews the pearls and pitfalls in these aspects with highlights from the latest research evidence. Pearls for common usage of Primovist in HCC includes detection of precursor cancer lesions in cirrhotic patients. Hepatobiliary phase hypointensity precedes arterial phase hyperenhancement (APHE) in hepatocarcinogenesis. Hepatobiliary phase hypointense nodules without APHE can represent early or progressed hepatocellular carcinoma (HCC) and high-grade dysplastic nodules. In addition, Primovist is useful to differentiate HCC from pseudolesions. Pitfalls in diagnosing HCC include transient tachypnoea in the arterial phase, rare hepatobiliary phase hyperintense HCC, and decompensated liver cirrhosis compromising image quality. Primovist is currently the most sensitive technique in diagnosing liver metastases before curative hepatic resection. Other patterns of enhancement of liver metastases, "disappearing" liver metastases are important pitfalls. Radiologists should be aware of the diagnostic utility, limitations, and potential pitfalls for the common usage of hepatobiliary specific contrast agent in liver MRI.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Meios de Contraste , Sensibilidade e Especificidade , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
2.
Hong Kong Med J ; 29(4): 311-321, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37532669

RESUMO

INTRODUCTION: We conducted translation and psychometric validation of a self-administered, 22-item dichotomous response-based questionnaire to identify nocturia aetiologies and co-morbidities in adult patients. METHODS: The Targeting the individual's Aetiology of Nocturia to Guide Outcomes (TANGO) questionnaire was forward- and backward-translated, then finalised using a standardised methodology. The resulting version, a Chinese version of the TANGO [TANGO (CV)], was evaluated for internal consistency, test-retest reliability, content validity, convergent validity, criterion validity, and discriminant validity via responses from 65 participants (46 men and 19 women; mean age, 67 years, range, 50-88), in comparison with other validated questionnaires and a 4-day bladder/sleep diary. RESULTS: Only 0.4% of responses were missing; 3% of participants required assistance with comprehension. The Kuder-Richardson Formula 20 (KR-20) coefficient for the whole tool was 0.711. Kappa values for individual domains and the whole tool varied from 0.871 to 0.866, indicating satisfactory test-retest reliability. There was strong agreement between the sum of positive responses to each domain and the whole tool (intra-class correlation coefficient=0.878-1.000). Modest correlations (ρ=0.4-0.6) were detected between the tool and bladder/sleep diary-based parameters for convergent validity. Criterion validity was confirmed for each domain and the whole tool [ρ=0.287-0.687]. In receiver operating characteristic analysis, the tool could distinguish patients (≥2 nocturia episodes/night) from controls (≤1 nocturia episode/night) [Youden's J statistic=0.453, area under the curve=0.818, 95% confidence interval (CI)=0.683-0.953] and patients with significant nocturia distress from patients with mild nocturia distress (Youden's J statistic=0.398, area under the curve=0.729, 95% CI=0.581-0.878). CONCLUSION: The TANGO (CV) was formally crossculturally adapted and translated. Its psychometric properties (except sensitivity to change) were validated.


Assuntos
Noctúria , Adulto , Masculino , Humanos , Feminino , Idoso , Noctúria/diagnóstico , Noctúria/etiologia , Comparação Transcultural , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
3.
Clin Radiol ; 77(8): e549-e559, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35641340

RESUMO

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck. The head and neck region is the second most frequent anatomical site of extra-nodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. They can present in highly variable appearances in different anatomical subsites in the head and neck. There is little literature on their imaging appearances on different imaging methods including ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and integrated positron-emission tomography (PET)/CT. The review aims to illustrate the presentation of histopathological-proven extra-nodal lymphoma in the head and neck using various imaging methods.


Assuntos
Neoplasias de Cabeça e Pescoço , Linfoma Difuso de Grandes Células B , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imagem Multimodal , Pescoço , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X
4.
Gastroenterology ; 159(1): 81-95, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32251668

RESUMO

BACKGROUND & AIMS: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong. METHODS: We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. RESULTS: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log10 copies per milliliter in patients with diarrhea vs 3.9 log10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1). CONCLUSIONS: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Diarreia/virologia , Fezes/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Carga Viral , Betacoronavirus/genética , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Diarreia/diagnóstico , Diarreia/epidemiologia , Endoscopia Gastrointestinal/normas , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/virologia , Hong Kong/epidemiologia , Humanos , Controle de Infecções/normas , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Prevalência , RNA Viral/isolamento & purificação , SARS-CoV-2
5.
Sensors (Basel) ; 21(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199042

RESUMO

Mechanical ventilation comprises a significant proportion of the total energy consumed in buildings. Sufficient natural ventilation in buildings is critical in reducing the energy consumption of mechanical ventilation while maintaining a comfortable indoor environment for occupants. In this paper, a new computerized framework based on building information modelling (BIM) and machine learning data-driven models is presented to analyze the optimum thermal comfort for indoor environments with the effect of natural ventilation. BIM provides geometrical and semantic information of the built environment, which are leveraged for setting the computational domain and boundary conditions of computational fluid dynamics (CFD) simulation. CFD modelling is conducted to obtain the flow field and temperature distribution, the results of which determine the thermal comfort index in a ventilated environment. BIM-CFD provides spatial data, boundary conditions, indoor environmental parameters, and the thermal comfort index for machine learning to construct robust data-driven models to empower the predictive analysis. In the neural network, the adjacency matrix in the field of graph theory is used to represent the spatial features (such as zone adjacency and connectivity) and incorporate the potential impact of interzonal airflow in thermal comfort analysis. The results of a case study indicate that utilizing natural ventilation can save cooling power consumption, but it may not be sufficient to fulfil all the thermal comfort criteria. The performance of natural ventilation at different seasons should be considered to identify the period when both air conditioning energy use and indoor thermal comfort are achieved. With the proposed new framework, thermal comfort prediction can be examined more efficiently to study different design options, operating scenarios, and changeover strategies between various ventilation modes, such as better spatial HVAC system designs, specific room-based real-time HVAC control, and other potential applications to maximize indoor thermal comfort.


Assuntos
Poluição do Ar em Ambientes Fechados , Ventilação , Ar Condicionado , Simulação por Computador , Estações do Ano , Temperatura
6.
Opt Express ; 27(7): 10079-10086, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045154

RESUMO

A ferroelectric liquid crystal (FLC) cell with continuously alignment structure is realized by a polarization hologram method for fabricating a Pancharatnam-Berry (PB) lens, which is employed as a concave/convex lens. The PB phase can be maintained by the optical axis in-plane switching; meanwhile, its diffraction efficiency can be tuned in a certain range by electrically controlling azimuthal angle and optical biaxiality of the smectic helical structure realized by deformed helix ferroelectric liquid crystals. The measured diffraction efficiency of the fabricated device is up to 87% and the response time can be 300µs with a low electric voltage. The FLC PB lens can have potential applications in existing optical devices and the realization of FLC with continuous alignment structure can be further used for other LC-based optical devices.

8.
J Neurochem ; 144(1): 81-92, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29105065

RESUMO

Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14 C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.


Assuntos
Barreira Hematoencefálica , Transtornos Cognitivos/etiologia , Ácidos Docosa-Hexaenoicos/farmacocinética , Proteínas de Ligação a Ácido Graxo/fisiologia , Proteínas de Neoplasias/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Química Encefálica , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Gorduras na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/deficiência , Proteínas de Escherichia coli , Proteínas de Ligação a Ácido Graxo/biossíntese , Ácidos Graxos Ômega-3/deficiência , Feminino , Humanos , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação de Sentido Incorreto , Proteínas de Neoplasias/biossíntese , Polissacarídeo-Liases , Presenilina-1/genética , Presenilina-1/metabolismo , Reconhecimento Psicológico , Proteínas Recombinantes de Fusão/metabolismo
9.
Anal Biochem ; 544: 98-107, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29305096

RESUMO

With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR. In our platform, real-time RPA (RT-RPA) was integrated on a lab-on-a-disc (LOAD) with on-board power to maintain temperature for DNA amplification. Sputa collected from healthy volunteers were spiked with respective target M. tb samples for testing. A limit of detection of 102 colony-forming unit per millilitre in 15 min was achieved, making early detection and differentiation of M. tb strains highly feasible in extreme POC settings. Our RT-RPA LOAD platform has also been successfully applied in the differentiation of MDR-TB from H37Ra, an attenuated TB strain. In summary, a quantitative RT-RPA on LOAD assay with a high level of sensitivity was developed as a foundation for further developments in medical bedside and POC diagnostics.


Assuntos
Automação , Dispositivos Lab-On-A-Chip , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase , Tuberculose Resistente a Múltiplos Medicamentos/genética , Voluntários Saudáveis , Humanos , Testes Imediatos , Fatores de Tempo
10.
Brain Behav Immun ; 70: 36-47, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29545118

RESUMO

Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain ß-amyloid (Aß) levels, and the brain clearance of Aß is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Aß. The brain clearance of intracerebroventricularly (icv) administered 125I-Aß42 was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300 mg/kg for 21 days). LiCl exhibited a 31% increase in the brain clearance of 125I-Aß42 over 10 min, which was associated with a 1.6-fold increase in brain microvascular expression of the blood-brain barrier efflux transporter low density lipoprotein receptor-related protein 1 (LRP1) and increased cerebrospinal fluid (CSF) bulk-flow. 8-month-old female wild type (WT) and APP/PS1 mice were also administered daily NaCl or LiCl for 21 days, which was followed by cognitive assessment by novel object recognition and water maze, and measurement of soluble Aß42, plaque-associated Aß42, and brain efflux of 125I-Aß42. LiCl treatment restored the long-term spatial memory deficit observed in APP/PS1 mice as assessed by the water maze (back to similar levels of escape latency as WT mice), but the short-term memory deficit remained unaffected by LiCl treatment. While LiCl did not affect plaque-associated Aß42, soluble Aß42 levels were reduced by 49.9% in APP/PS1 mice receiving LiCl. The brain clearance of 125I-Aß42 decreased by 27.8% in APP/PS1 mice, relative to WT mice, however, LiCl treatment restored brain 125I-Aß42 clearance in APP/PS1 mice to a rate similar to that observed in WT mice. These findings suggest that the cognitive benefits and brain Aß42 lowering effects of LiCl are associated with enhanced brain clearance of Aß42, possibly via brain microvascular LRP1 upregulation and increased CSF bulk-flow, identifying a novel mechanism of protection by LiCl for the treatment of AD.


Assuntos
Peptídeos beta-Amiloides/efeitos dos fármacos , Cognição/efeitos dos fármacos , Cloreto de Lítio/uso terapêutico , Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo , Modelos Animais de Doenças , Cloreto de Lítio/farmacologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Placa Amiloide , Presenilina-1 , Receptores de LDL/efeitos dos fármacos , Receptores de LDL/fisiologia , Proteínas Supressoras de Tumor/efeitos dos fármacos , Proteínas Supressoras de Tumor/fisiologia
11.
J Intellect Disabil Res ; 62(2): 140-149, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29349928

RESUMO

BACKGROUND: Problem behaviours (PBs) are a common cause for clinician contact in people with disorders of intellectual development and may be a common cause for the prescription of psychotropic medication. We aimed to use a large, multinational sample to define the prevalence of PBs, the associations with psychotropic medication use, and to assess for any potential 'diagnostic overshadowing' by the label of PBs in a population of people with disorders of intellectual development. METHOD: A multinational, multi-setting, cross-sectional service evaluation and baseline audit was completed. Data were collected from UK hospitals, UK community settings, Sri Lanka and Hong Kong. A semi-structured questionnaire was completed by treating clinicians, capturing demographic details, prevalence rates of intellectual disability and psychotropic medication use, alongside psychiatric co-morbidity. RESULTS: A sample size of 358 was obtained, with 65% of included participants treated in an inpatient setting. Psychotropic use was prevalent (90%) in our sample, particularly antipsychotics (74%). The prevalence of PB was high (83%). There was no statistically significant association between psychotropic prescription and recorded psychiatric co-morbidity, suggesting prevalent 'off-label' use for PBs, or poor recording of psychiatric co-morbidity. There was some evidence of possible diagnostic overshadowing due to the PB classification. A higher dose of psychotropic medication was associated with aggression toward others (P = 0.03). CONCLUSIONS: We found evidence of prevalent potential 'off-label' use for psychotropic medication, which may be due to PBs. We also found evidence of potential diagnostic-overshadowing, where symptoms of psychiatric co-morbidity may have been attributed to PBs. Our findings provide renewed importance, across borders and health systems, for clinicians to consider a holistic approach to treating PBs, and attempting to best understand the precipitants and predisposing factors before psychotropic prescribing.


Assuntos
Sintomas Comportamentais , Deficiência Intelectual , Uso Off-Label , Psicotrópicos/uso terapêutico , Adulto , Antipsicóticos/uso terapêutico , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/tratamento farmacológico , Sintomas Comportamentais/epidemiologia , Sintomas Comportamentais/etiologia , Comorbidade , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Uso Off-Label/estatística & dados numéricos , Prevalência , Comportamento Problema , Sri Lanka/epidemiologia , Reino Unido/epidemiologia
12.
Hong Kong Med J ; 24(2): 158-165, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29622759

RESUMO

INTRODUCTION: Endobronchial one-way valves have been proposed as treatment for persistent air leak complicating spontaneous pneumothorax in which surgical intervention is not feasible. However, published data on efficacy, safety, and factors associated with success are scanty. METHODS: This is a retrospective study of 37 patients at a general hospital from 2008 to 2016. The impact of endobronchial valve implantation on the time to air-leak cessation after bronchoscopy was evaluated. RESULTS: The median patient age was 71 years. The majority of patients were males (92%), were ever-smokers (83%), had at least one co-morbidity (97%), and had secondary spontaneous pneumothorax (89%). Nineteen patients (51%) had a mean of 2.6 endobronchial valves implanted (range, 1-6). The air leak ceased within 72 hours for only eight patients (22% of the complete cohort), with immediate air-leak cessation after completion of endobronchial valve implantation. All six successful cases that had computed tomographic data of the thorax were shown to have bilateral intact interlobar fissures. The median (interquartile range) Charlson co-morbidity index was 1 (0.25-1) and 2 (1-3) for the success group and failure group, respectively (P=0.029). All patients in the no-endobronchial valve group survived, whereas three patients in the endobronchial valve group died within 30 days of endobronchial valve implantation. CONCLUSION: Only a small proportion of cases of endobronchial valve implantation for air leak complicating pneumothorax had unequivocal success. Intact bilateral interlobar fissures appear to be a necessary, though not sufficient, condition for success. Patients with fewer medical co-morbidities and immediate air-leak cessation after endobronchial valve implantation have a higher likelihood of success.


Assuntos
Pneumotórax/cirurgia , Próteses e Implantes , Idoso , Feminino , Humanos , Masculino , Pneumotórax/complicações , Complicações Pós-Operatórias/mortalidade , Próteses e Implantes/efeitos adversos , Estudos Retrospectivos
14.
J Neurosci ; 36(46): 11755-11767, 2016 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852782

RESUMO

Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+ and FABP5-/- mice using a battery of memory paradigms. FABP5-/- mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring 14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+ and FABP5-/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA, 14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5-/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5+/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5-/- mice are associated with reduced CNS access of DHA. SIGNIFICANCE STATEMENT: Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5-/- mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role for FABP5 in the maintenance of cognitive function via regulating the brain uptake of DHA, and suggests that upregulation of FABP5 in neurodegenerative diseases, where brain DHA levels are possibly diminished (e.g., Alzheimer's disease), may provide a novel therapeutic approach for restoring cognitive function.


Assuntos
Barreira Hematoencefálica/metabolismo , Encéfalo/fisiologia , Cognição/fisiologia , Ácidos Docosa-Hexaenoicos/metabolismo , Função Executiva/fisiologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
15.
J Pharmacol Exp Ther ; 359(2): 354-365, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27630144

RESUMO

Current antipsychotics are effective in treating the positive symptoms associated with schizophrenia, but they remain suboptimal in targeting cognitive dysfunction. Recent studies have suggested that positive allosteric modulation of the M1 muscarinic acetylcholine receptor (mAChR) may provide a novel means of improving cognition. However, very little is known about the potential of combination therapies in extending coverage across schizophrenic symptom domains. This study investigated the effect of the M1 mAChR positive allosteric modulator BQCA [1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid], alone or in combination with haloperidol (a first-generation antipsychotic), clozapine (a second-generation atypical antipsychotic), or aripiprazole (a third-generation atypical antipsychotic), in reversing deficits in sensorimotor gating and spatial memory induced by the N-methyl-d-aspartate receptor antagonist, MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine]. Sensorimotor gating and spatial memory induction are two models that represent aspects of schizophrenia modeled in rodents. In prepulse inhibition (an operational measure of sensorimotor gating), BQCA alone had minimal effects but exhibited different levels of efficacy in reversing MK-801-induced prepulse inhibition disruptions when combined with a subeffective dose of each of the three (currently prescribed) antipsychotics. Furthermore, the combined effect of BQCA and clozapine was absent in M1-/- mice. Interestingly, although BQCA alone had no effect in reversing MK-801-induced memory impairments in a Y-maze spatial test, we observed a reversal upon the combination of BQCA with atypical antipsychotics, but not with haloperidol. These findings provide proof of concept that a judicious combination of existing antipsychotics with a selective M1 mAChR positive allosteric modulator can extend antipsychotic efficacy in glutamatergic deficit models of behavior.


Assuntos
Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Glutamatos/metabolismo , Quinolinas/farmacologia , Receptor Muscarínico M1/metabolismo , Acetilcolina/metabolismo , Regulação Alostérica/efeitos dos fármacos , Animais , Células CHO , Cricetinae , Cricetulus , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Inibição Pré-Pulso/efeitos dos fármacos , Receptor Muscarínico M1/química
16.
Opt Express ; 24(6): 5822-8, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27136779

RESUMO

In this article, we disclose a fork grating (FG) based on the photo-aligned ferroelectric liquid crystal (FLC). The Digital Micro-mirror Device based system is used as a dynamic photomask to generated different holograms. Because of controlled anchoring energy, the photo alignment process offers optimal conditions for the multi-domain FLC alignment. Two different electro-optical modes namely DIFF/TRANS and DIFF/OFF switchable modes have been proposed where the diffraction can be switched either to no diffraction or to a completely black state, respectively. The FLC FG shows high diffraction efficiency and fast response time of 50µs that is relatively faster than existing technologies. Thus, the FLC FG may pave a good foundation toward optical vertices generation and manipulation that could find applications in a variety of devices.

17.
J Virol ; 88(18): 10662-72, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24991008

RESUMO

UNLABELLED: Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. IMPORTANCE: This study established a sequencing workflow from EBV DNA capture and sequencing to de novo assembly and contig joining. We reported eight newly sequenced EBV genomes isolated from primary NPC biopsy specimens and revealed the sequence diversity on a whole-genome level among these EBV isolates. At least two lineages of EBV strains are observed, and recombination among these lineages is inferred. Our study has demonstrated the value of, and provided a platform for, genome sequencing of EBV.


Assuntos
Variação Genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Nasofaríngeas/virologia , Adulto , Sequência de Bases , Biópsia , Carcinoma , Feminino , Genoma Viral , Herpesvirus Humano 4/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutagênese Insercional , Carcinoma Nasofaríngeo , Filogenia , Deleção de Sequência , Adulto Jovem
18.
Opt Lett ; 40(13): 2993-6, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26125350

RESUMO

In this Letter, an advanced multilayer photo-aligned liquid crystal polymer (LCP) thin-film structure with multiple optical functions is introduced. Within each LCP layer, a spatially distribution of local optical axes can be controlled by a patterned photo-alignment layer. As an embodiment of the proposed structure, a two-layer structure with pixelated controlled light-propagation directions and polarizations has been studied, which has shown the potential to be used as a photomask for generating multi-domain photo-alignment structures with a single exposure step. The combination of the multilayer structure with patterned photo-alignment technology provides a new perspective of designing optical structures for polarizing photonics applications.

19.
Opt Lett ; 40(8): 1643-6, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25872037

RESUMO

In this Letter, we disclose a fast switchable Fresnel zone lens (FZL) by confining the ferroelectric liquid crystals (FLCs) in multiple microscopically defined photo-aligned alignment domains. The photo-alignment (PA) offers good control on the anchoring energy (W) by mean of irradiation doses (ID) and thus excellent alignment for FLCs. Two operational modes of the FLCFZL, i.e., FOCUS/OFF and FOCUS/DEFOCUS, were demonstrated. The proposed diffracting element provides fast response time, high diffraction efficiency (η), with saturated electro-optical (EO) operations up to high frequency (≈2 kHz). Thus, the proposed FLCFZLs with simple fabrication open several opportunities to improve the quality of existing devices and to find new applications.

20.
Analyst ; 140(13): 4566-4575, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26000345

RESUMO

As in all RNA viruses, influenza viruses change and mutate constantly because their RNA polymerase has no proofreading ability. This poses a serious threat to public health nowadays. In addition, traditional pathogen-based detection methods may not be able to report an infection from an unknown type or a subtype of virus if its nucleotide sequence is not known. Because of these factors, targeting host microRNA signatures may be an alternative to classify infections and distinguish types of pathogens as microRNAs are produced in humans shortly after infection. Although this approach is in its infant stage, there is an urgent need to develop a rapid reporter assay for microRNA for disease control and prevention. As a proof of concept, we report herein for the first time a non-PCR MARS (MicroRNA-RNase-SPR) assay to detect the microRNA miR-29a-3p from human subjects infected with influenza virus H1N1 by surface plasmon resonance (SPR). In our MARS assay, RNase H is employed to specifically hydrolyze the RNA probes immobilized on the gold surface where they hybridize with its cognate target cDNAs miR-29a-3p, where it was formed from reverse transcription with mature miR-29a-3p specific stem-looped primers. After the digestion of the RNA probe by RNase H, the intact cDNA was released from the RNA-DNA hybrid and bound to a new RNA probe for another enzymatic reaction cycle to amplify signals. With assay optimization, the detection limit of our MARS assay for miR-29a-3p was found to be 1 nM, and this new assay could be completed within 1 hour without thermal cycling. This non-PCR assay with high selectivity for mature microRNA provides a new platform for rapid disease diagnosis, quarantine and disease control.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , MicroRNAs/análise , Faringe/virologia , Ribonuclease H/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Sequência de Bases , Biotina/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/genética , Limite de Detecção , MicroRNAs/genética , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase , Estreptavidina/metabolismo , Fatores de Tempo
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