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1.
Nurs Health Sci ; 26(1): e13104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413495

RESUMO

Visceral adipose tissue accumulation is strongly linked with numerous chronic diseases; however, the accessibility for visceral adipose tissue measurement is limited. This study employed a cross-sectional design to determine the optimal strongest predictor of high visceral adipose tissue in each sex and identified the optimal cutoff value thereof. Purposive sampling was used to recruit 94 men and 326 women aged ≥40 years in southern Taiwan. Receiver operating characteristic curve analysis was used to explore the optimal predictor of high visceral adipose tissue (defined as ≥135 cm2 for men and ≥100 cm2 for women) in each sex. The waist-to-hip ratio was the strongest predictor for men, with a cutoff value of 0.96 yielding the maximum sensitivity (94.29%) and specificity (93.22%). By contrast, body mass index was the strongest predictor for women, with a cutoff value of 25.45 kg/m2 yielding the maximum sensitivity (87.18%) and specificity (87.55%). The results may serve as a reference for health policy-makers in screening for high visceral adipose tissue to identify individuals at high risk of developing chronic diseases for health promotion.


Assuntos
Tecido Adiposo , Gordura Intra-Abdominal , Masculino , Humanos , Feminino , Estudos Transversais , Taiwan , Índice de Massa Corporal , Curva ROC , Doença Crônica , Fatores de Risco , Circunferência da Cintura
2.
Addict Biol ; 28(1): e13253, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36577735

RESUMO

Use of prescription opioids, particularly oxycodone, is an initiating factor driving the current opioid epidemic. There are several challenges with modelling oxycodone abuse. First, prescription opioids including oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl, which have been more commonly used in rodent research. This oral route of administration determines the pharmacokinetic profile, which then influences the establishment of drug-reinforcement associations in animals. Moreover, the pattern of intake and the environment in which addictive drugs are self-administered are critical determinants of the levels of drug intake, of behavioural sensitization and of propensity to relapse behaviour. These are all important considerations when modelling prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we designed an oral, homecage-based oxycodone self-administration paradigm. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and the majority exhibit preference for oxycodone, escalation of intake, physical signs of dependence and reinstatement of seeking after withdrawal. In addition, a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model is therefore translationally relevant and useful for studying the neurobiological substrates of prescription opioid abuse.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Oxicodona , Masculino , Camundongos , Feminino , Animais , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Fentanila , Reforço Psicológico
3.
Cancer Sci ; 113(4): 1182-1194, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35133065

RESUMO

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated phenomenon characterized by clonal expansion of blood cells harboring somatic mutations in hematopoietic genes, including DNMT3A, TET2, and ASXL1. Clinical evidence suggests that CHIP is highly prevalent and associated with poor prognosis in solid-tumor patients. However, whether blood cells with CHIP mutations play a causal role in promoting the development of solid tumors remained unclear. Using conditional knock-in mice that express CHIP-associated mutant Asxl1 (Asxl1-MT), we showed that expression of Asxl1-MT in T cells, but not in myeloid cells, promoted solid-tumor progression in syngeneic transplantation models. We also demonstrated that Asxl1-MT-expressing blood cells accelerated the development of spontaneous mammary tumors induced by MMTV-PyMT. Intratumor analysis of the mammary tumors revealed the reduced T-cell infiltration at tumor sites and programmed death receptor-1 (PD-1) upregulation in CD8+ T cells in MMTV-PyMT/Asxl1-MT mice. In addition, we found that Asxl1-MT induced T-cell dysregulation, including aberrant intrathymic T-cell development, decreased CD4/CD8 ratio, and naïve-memory imbalance in peripheral T cells. These results indicate that Asxl1-MT perturbs T-cell development and function, which contributes to creating a protumor microenvironment for solid tumors. Thus, our findings raise the possibility that ASXL1-mutated blood cells exacerbate solid-tumor progression in ASXL1-CHIP carriers.


Assuntos
Hematopoiese Clonal , Neoplasias , Proteínas Repressoras , Animais , Linfócitos T CD8-Positivos/metabolismo , Hematopoiese Clonal/genética , Hematopoese/genética , Camundongos , Mutação , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Microambiente Tumoral
4.
Int J Legal Med ; 136(2): 397-404, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34718845

RESUMO

Identification of semen and spermatozoa is crucial in the forensic investigation of alleged sexual assault cases. In cases of alleged sexual assault where there is a long time gap between the incident and sample collection, or in cases of low sperm count, current methods have limitations of specificity, in the case of presumptive tests for semen, or the problem of recording spermatozoa by microscopy if they are few in number. A 3-plex MSRE-PCR (methylation-sensitive restriction enzyme-PCR) assay using a spermatozoa-specific DNA methylated marker to identify spermatozoa has been reported previously by our laboratory. A key advantage over current methods is the increased sensitivity and specificity. A transition from a research tool to operational use requires blind trial testing and inter-laboratory trials. We report on a collaborative exercise where reagents of the 3-plex MSRE-PCR were sent to six participating laboratories. Each laboratory used their own equipment, consumables, and the presumptive reagents conventionally for body fluid (such as acid phosphatase or PSA), DNA extraction, and quantification in practical casework. The reagents and protocol for the 3-plex MSRE-PCR assay and 9 samples were provided by the organizing laboratory. The participating laboratories were requested to fill in the questionnaire after testing. The reported results from all the six participating laboratories were concordant and the expected correct results for the presence of spermatozoa. These outcomes verified the reproducibility and feasibility of the 3-plex MSRE-PCR assay. The results also indicated that the 3-plex MSRE-PCR assay was readily accessible to forensic laboratories for integrating it into current forensic casework processes.


Assuntos
Sêmen , Espermatozoides , Metilação de DNA , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes
5.
Int J Obes (Lond) ; 45(5): 982-997, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33558643

RESUMO

BACKGROUND: Visceral adipose tissue (VAT) are deleterious fat deposits in the human body and can be effectively reduced by exercise intervention. Despite well-established exercise prescriptions are available, the effective dosage of exercise for reducing VAT requires verification. OBJECTIVES: The aims of this systematic review and meta-analysis were to determine the most effective exercise dosage (modality, intensity, duration, and amount) for decreasing VAT. METHODS: Nine databases (EMBASE, Medline, Cochrane Central Register of Controlled Trial, PubMed, CINAHL, Scopus, Web of Science, Airiti Library, and PerioPath) were systematically searched for randomized controlled trials that objectively assessed VAT. The arms of included studies covered with different exercise modalities and dosage. Relevant databases were searched through February 2020. RESULTS: Of the 34 studies (n = 1962) included in systematic review, 32 (n = 1900) were pooled for pairwise or network meta-analysis. The results indicated that high-intensity interval training (SMD -0.39, 95% CI -0.60 to -0.18) and aerobic exercise (SMD -0.26, 95% CI -0.38 to -0.13) of at least moderate intensity were beneficial for reducing VAT. By contrast, resistance exercise, aerobic exercise combined with resistance exercise, and sprint interval training had no significant effects. No difference in VAT reduction was observed between exercising more or less than 150 min per week. Meta-regression revealed that the effect of VAT reduction was not significantly influenced by an increase in the duration of or amount of exercise in an exercise program. The effective dosage of exercise for reducing VAT was three times per week for 12 to 16 weeks, while duration per session for aerobic exercise was 30-60 min, and either less than 30 min or 30-60 min of high-intensity interval training accomplished sufficient energy expenditure to impact VAT. CONCLUSIONS: These results can inform exercise prescriptions given to the general population for improving health by reducing VAT.


Assuntos
Terapia por Exercício/métodos , Exercício Físico , Gordura Intra-Abdominal , Obesidade Abdominal/terapia , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Magn Reson Imaging ; 53(1): 305-318, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32798280

RESUMO

BACKGROUND: Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression-free survival (PFS) and overall survival (OS) merit further investigation. PURPOSE: To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer. STUDY TYPE: Prospective cohort study. POPULATION: In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis. FIELD STRENGTH/SEQUENCE: 3.0T integrated PET/MRI including diffusion-weighted echo-planar imaging (b = 50 and 1000 s/mm2 ) and [18F]fluorodeoxyglucose PET. ASSESSMENT: Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. STATISTICAL TESTS: A Mann-Whitney U-test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival. RESULTS: In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin , and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio [HR] = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008). DATA CONCLUSION: PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 3.


Assuntos
Fluordesoxiglucose F18 , Neoplasias do Colo do Útero , Biomarcadores , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico por imagem
7.
FASEB J ; 34(7): 9678-9693, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32469121

RESUMO

Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células , Exercício Físico , Fibronectinas/farmacologia , Glioma/tratamento farmacológico , Neuropeptídeos/farmacologia , Animais , Apoptose , Ciclo Celular , Movimento Celular , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Soft Matter ; 17(47): 10628-10639, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34755754

RESUMO

Four representative bisurea molecules (HDI-BA, MDI-BA, TDI-BA, and IPDI-BA) were synthesized and dispersed simultaneously by reacting benzylamine (BA) with various types of diisocyanates in a polyester/ortho-xylene resin medium to produce bisurea-loaded resins (BLRs) for anti-sagging application with paints and coating materials. These bisurea molecules are symmetric and differ only in the central spacer unit, thereby presenting an ideal and simplest model system to delve into the structure-performance relationship. The multiscale structural features arising from self-assembly in each of the BLRs were scrutinized using the combination of multi-angular dynamic light scattering (DLS), small-angle light/X-ray scattering (SALS/SAXS), rheology, and scanning electron/optical microscopy (SEM/OM) characterization. All four BLRs were revealed to foster micron-sized, mostly sphere-like agglomerates, with distinct hierarchical structures that correlate well with their thixotropic and anti-sagging performances. Three BLRs (HDI-BA, MDI-BA, and TDI-BA) produce similar rod-like packing units (10 × 1 × 1 nm3), with only one exception (IPDI-BA) that produces a spherical packing unit (2 nm in diameter). However, the bulk feature of the agglomeration state, which dictates the thixotropic and anti-sagging properties, cannot be readily foreseen from the chemical structure or elementary packing unit of a bisurea. The present findings, while confirming the importance of optimum molecular design that controls the early-stage self-assembly behavior of a bisurea in resin media, highlight the necessity of resolving detailed (multiscale) structural features in order to establish the full structure-performance relationship imperatively needed for like material systems and applications.

9.
Epilepsia ; 60(8): 1627-1638, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31297795

RESUMO

OBJECTIVE: To identify neuroimaging and clinical biomarkers associated with a language-impaired phenotype in refractory temporal lobe epilepsy (TLE). METHODS: Eighty-five patients with TLE were characterized as language-impaired (TLE-LI) or non-language-impaired (TLE-NLI) based on comprehensive neuropsychological testing. Structural magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) were obtained in patients and 47 healthy controls (HC). fMRI activations and cortical thickness were calculated within language regions of interest, and fractional anisotropy (FA) was calculated within deep white matter tracts associated with language. Analyses of variance were performed to test for differences among the groups in imaging measures. Receiver operator characteristic curves were used to determine how well different clinical versus imaging measures discriminated TLE-LI from TLE-NLI. RESULTS: TLE-LI patients showed significantly less activation within left superior temporal cortex compared to HC and TLE-NLI, regardless of side of seizure onset. TLE-LI also showed decreased FA in the inferior longitudinal fasciculus and arcuate fasciculus compared to HC. Cortical thickness did not differ between groups in any region. A model that included language-related fMRI activations within the superior temporal gyrus, age at onset, and demographic variables was the most predictive of language impairment (area under the curve = 0.80). SIGNIFICANCE: These findings demonstrate a unique imaging signature associated with a language-impaired phenotype in TLE, characterized by functional and microstructural alterations within the language network. Reduced left superior temporal activation combined with compromise to language association tracts underlies this phenotype, extending our previous work on cognitive phenotypes that could have implications for treatment-planning or cognitive progression in TLE.


Assuntos
Epilepsia do Lobo Temporal/complicações , Transtornos da Linguagem/etiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Transtornos da Linguagem/diagnóstico por imagem , Transtornos da Linguagem/fisiopatologia , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Fenótipo
10.
Epilepsia ; 60(5): 935-947, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31020649

RESUMO

OBJECTIVES: Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated. RESULTS: Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment.


Assuntos
Epilepsia do Lobo Temporal/patologia , Transtornos da Memória/diagnóstico por imagem , Imagem Multimodal/métodos , Neuroimagem , Aprendizagem Verbal , Adulto , Mapeamento Encefálico , Imagem de Tensor de Difusão , Epilepsia do Lobo Temporal/complicações , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão , Sensibilidade e Especificidade , Aprendizagem Verbal/fisiologia , Substância Branca/patologia , Adulto Jovem
11.
Eur Radiol ; 29(2): 628-635, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29974220

RESUMO

OBJECTIVES: The aim of this study was to compare single and tandem ureteral stenting in the management of malignant ureteral obstruction (MUO). METHODS: Our hospital's institutional review board approved this prospective study. Between November 2014 and June 2017, single ureteral stenting was performed in 56 patients (94 renal units) and tandem ureteral stenting in 48 patients (63 renal units) for MUO. A comparative analysis of the technical success rate, patient survival, stent patency, and complications was performed. RESULTS: Similar demographic data were observed in patients receiving either single or tandem ureteral stenting. The technical success rate was 93.6% (88/94) for single ureteral stenting and 95.2% (60/63) for tandem ureteral stenting. There was no difference in overall survival between patients receiving single or tandem ureteral stenting (p = 0.41), but the duration of stent patency in tandem ureteral stenting was significantly longer (p = 0.022). The mean patency time was 176.7 ± 21.3 days for single ureteral stenting, and 214.7 ± 21.0 days for tandem ureteral stenting. The complications of ureteral stenting were urinary tract infection (n = 18), lower urinary tract symptoms (n = 5), haematuria (n = 3), and stent migration (n = 1). CONCLUSIONS: Tandem ureteral stenting is a safe and feasible treatment for MUO, and had better efficacy compared to single ureteral stenting. KEY POINTS: • Ureteral stenting is an established treatment for the management of malignant ureteral obstruction (MUO) • Prospective single-centre study showed that tandem ureteral stenting is a safe and feasible treatment for MUO • Tandem ureteral stenting provides longer stent patency compared to single ureteral stenting in patient with MUO.


Assuntos
Stents , Obstrução Ureteral/terapia , Adulto , Idoso , Feminino , Hematúria/etiologia , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Cuidados Paliativos/métodos , Estudos Prospectivos , Stents/efeitos adversos , Ultrassonografia de Intervenção/métodos , Ureter , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/etiologia , Infecções Urinárias/etiologia
12.
Anal Bioanal Chem ; 411(17): 3871-3880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31209551

RESUMO

Polymerase chain reaction (PCR) is a powerful technique for the detection and quantification of nucleic acids and has enormous applications to research in molecular biology. Certain inherited diseases, caused by single nucleotide mutations, however, are difficult to identify by PCR, using DNA primers and probes, in a situation where a false diagnosis may lead to incorrect or delayed treatment. With the aim of enhancing the specificity of PCR, we used novel chemically synthesized oligonucleotides containing site-specific methyl phosphotriester (MPTE) inter-nucleoside linkage(s) as primers and probes. The methyl phosphotriester linkages carry no charge, so the reduction in the electrostatic repulsion of an MPTE-DNA/DNA duplex shows stronger hybridization affinity compared to a DNA/DNA duplex. However, the electrosteric effects introduced by the methyl group may result in instability of the double-stranded DNA (dsDNA) formed. With the use of specific MPTE modification sites and optimization of the number of MPTE modifications, greater delta melting temperature (ΔTm) may be obtained, in concert with adjustment of PCR operating conditions, especially with respect to the annealing temperature, to achieve more discriminatory results between the target template and the perfectly matched primer and the mismatched primer. In single nucleotide polymorphism (SNP) genotyping, the results demonstrated that MPTE-modified probes can improve specificity. In summary, MPTE-modified oligonucleotides are a promising DNA analog applied to PCR primers and probes to enhance the specificity and to provide more precise detection results for various applications, such as for genetic diagnosis. In summary, two common DNA polymerases we tested could successfully recognize the MPTE-modified primers and probes. Under the optimal operating conditions, MPTE modification has the ability to improve the discrimination of single nucleotide polymorphism by increasing the ΔTm of the perfect match and mismatch sequences and to provide more precise detection results for various applications, such as genetic diagnosis.


Assuntos
Primers do DNA/química , Fosfatos/química , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sondas de DNA , DNA Polimerase Dirigida por DNA/metabolismo , Genótipo , Metilação , Técnicas de Diagnóstico Molecular
13.
Neurobiol Learn Mem ; 148: 30-37, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29294382

RESUMO

Obsessive-compulsive disorder (OCD) is usually accompanied with hyperactivity of the orbitofrontal cortex (OFC). OCD patients have anxiety issues, and there is high comorbidity of OCD and post-traumatic stress disorder (PTSD). One of the leading factors of PTSD is the failure of fear extinction. In this study, we examined whether hyperactivity of the OFC interfered with extinction processes. The lateral OFC (lOFC) was pharmacologically activated with N-methyl-d-aspartate (NMDA) in behaving rats during encoding, consolidation, and retrieval, of Pavlovian fear extinction. We found that when we brought the lOFC on-line before extinction training or retrieval test, there was a general initial suppression of fear expression regardless behavioral history, which was followed by development of nonspecific fear response. Moreover, pre-extinction activation of the lOFC impaired the encoding of extinction demonstrated by a general up-shift of fear levels during retrieval test compared to controls. We also found that regardless of whether the lOFC was activated or not, immediate post-extinction manipulation interfered extinction consolidation in general. To conclude, activation of the lOFC altered expression of learned fear and negatively impaired extinction outcome. Our results provided a new angle to study the etiology of comorbid OCD and PTSD.


Assuntos
Comportamento Animal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , N-Metilaspartato/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Long-Evans
14.
Epilepsia ; 59(5): 1037-1047, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29658987

RESUMO

OBJECTIVE: Bilingual healthy adults have been shown to exhibit an advantage in executive functioning (EF) that is associated with microstructural changes in white matter (WM) networks. Patients with temporal lobe epilepsy (TLE) often show EF deficits that are associated with WM compromise. In this study, we investigate whether bilingualism can increase cognitive reserve and/or brain reserve in bilingual patients with TLE, mitigating EF impairment and WM compromise. METHODS: Diffusion tensor imaging was obtained in 19 bilingual and 26 monolingual patients with TLE, 12 bilingual healthy controls (HC), and 21 monolingual HC. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for the uncinate fasciculus (Unc) and cingulum (Cing), superior frontostriatal tract (SFS), and inferior frontostriatal tract (IFS). Measures of EF included Trail Making Test-B (TMT-B) and Delis-Kaplan Executive Function System Color-Word Inhibition/Switching. Analyses of covariance were conducted to compare FA and MD of the Unc, Cing, SFS, and IFS and EF performance across groups. RESULTS: In bilingual patients, FA was lower in the ipsilateral Cing and Unc compared to all other groups. For both patient groups, MD of the ipsilateral Unc was higher relative to HC. Despite more pronounced reductions in WM integrity, bilingual patients performed similarly to monolingual TLE and both HC groups on EF measures. By contrast, monolingual patients performed worse than HC on TMT-B. In addition, differences in group means between bilingual and monolingual patients on TMT-B approached significance when controlling for the extent of WM damage (P = .071; d = 0.62), suggesting a tendency toward higher performance for bilingual patients. SIGNIFICANCE: Despite poorer integrity of regional frontal lobe WM, bilingual patients performed similarly to monolingual patients and HC on EF measures. These findings align with studies suggesting that bilingualism may provide a protective factor for individuals with neurological disease, potentially through reorganization of EF networks that promote greater cognitive reserve.


Assuntos
Reserva Cognitiva/fisiologia , Epilepsia do Lobo Temporal , Função Executiva , Multilinguismo , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos
15.
J Neurooncol ; 139(3): 633-642, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29860714

RESUMO

BACKGROUND: Molecular markers of WHO grade II/III glioma are known to have important prognostic and predictive implications and may be associated with unique imaging phenotypes. The purpose of this study is to determine whether three clinically relevant molecular markers identified in gliomas-IDH, 1p/19q, and MGMT status-show distinct quantitative MRI characteristics on FLAIR imaging. METHODS: Sixty-one patients with grade II/III gliomas who had molecular data and MRI available prior to radiation were included. Quantitative MRI features were extracted that measured tissue heterogeneity (homogeneity and pixel correlation) and FLAIR border distinctiveness (edge contrast; EC). T-tests were conducted to determine whether patients with different genotypes differ across the features. Logistic regression with LASSO regularization was used to determine the optimal combination of MRI and clinical features for predicting molecular subtypes. RESULTS: Patients with IDH wildtype tumors showed greater signal heterogeneity (p = 0.001) and lower EC (p = 0.008) within the FLAIR region compared to IDH mutant tumors. Among patients with IDH mutant tumors, 1p/19q co-deleted tumors had greater signal heterogeneity (p = 0.002) and lower EC (p = 0.005) compared to 1p/19q intact tumors. MGMT methylated tumors showed lower EC (p = 0.03) compared to the unmethylated group. The combination of FLAIR border distinctness, heterogeneity, and pixel correlation optimally classified tumors by IDH status. CONCLUSION: Quantitative imaging characteristics of FLAIR heterogeneity and border pattern in grade II/III gliomas may provide unique information for determining molecular status at time of initial diagnostic imaging, which may then guide subsequent surgical and medical management.


Assuntos
Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/classificação , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Feminino , Glioma/genética , Glioma/patologia , Humanos , Imageamento Tridimensional , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
16.
Epilepsy Behav ; 78: 187-193, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29126704

RESUMO

OBJECTIVE: Executive dysfunction is observed in a sizable number of patients with refractory temporal lobe epilepsy (TLE). The frontostriatal network has been proposed to play a significant role in executive functioning, however, because of the complex architecture of these tracts, it is difficult to generate measures of fiber tract microstructure using standard diffusion tensor imaging. To examine the association between frontostriatal network compromise and executive dysfunction in TLE, we applied an advanced, multishell diffusion model, restriction spectrum imaging (RSI), that isolates measures of intraaxonal diffusion and may provide better estimates of fiber tract compromise in TLE. METHODS: Restriction spectrum imaging scans were obtained from 32 patients with TLE [16 right TLE (RTLE); 16 left TLE (LTLE)] and 24 healthy controls (HC). An RSI-derived measure of intraaxonal anisotropic diffusion (neurite density; ND) was calculated for the inferior frontostriatal tract (IFS) and superior frontostriatal tract (SFS) and compared between patients with TLE and HC. Spearman correlations were performed to evaluate the relationships between ND of each tract and verbal (i.e., D-KEFS Category Switching Accuracy and Color-Word Interference Inhibition/Switching) and visuomotor (Trail Making Test) set-shifting performances in patients with TLE. RESULTS: Patients with TLE demonstrated reductions in ND of the left and right IFS, but not SFS, compared with HC. Reduction in ND of left and right IFS was associated with poorer performance on verbal set-shifting in TLE. Increases in extracellular diffusion (isotropic hindered; IH) were not associated with executive dysfunction in the patient group. SIGNIFICANCE: Restriction spectrum imaging-derived ND revealed microstructural changes within the IFS in patients with TLE, which was associated with poorer executive functioning. This suggests that axonal/myelin loss to fiber networks connecting the striatum to the inferior frontal cortex is likely contributing to executive dysfunction in TLE.


Assuntos
Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Função Executiva , Transtornos Mentais/complicações , Neuritos , Lobo Temporal/diagnóstico por imagem , Adulto , Epilepsia do Lobo Temporal/complicações , Feminino , Lobo Frontal , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Teste de Sequência Alfanumérica
17.
Mem Cognit ; 46(3): 337-348, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29101550

RESUMO

The expertise effect in memory for chess positions is one of the most robust effects in cognitive psychology. One explanation of this effect is that chess recall is based on the recognition of familiar patterns and that experts have learned more and larger patterns. Template theory and its instantiation as a computational model are based on this explanation. An alternative explanation is that the expertise effect is due, in part, to stronger players having better and more conceptual knowledge, with this knowledge facilitating memory performance. Our literature review supports the latter view. In our experiment, a sample of 79 chess players were given a test of memory for chess positions, a test of declarative chess knowledge, a test of fluid intelligence, and a questionnaire concerning the amount of time they had played nontournament chess and the amount of time they had studied chess. We determined the numbers of tournament games the players had played from chess databases. Chess knowledge correlated .67 with chess memory and accounted for 16% of the variance after controlling for chess experience. Fluid intelligence accounted for an additional 13% of the variance. These results support the conclusion that both high-level conceptual processing and low-level recognition of familiar patterns play important roles in memory for chess positions.


Assuntos
Função Executiva/fisiologia , Rememoração Mental/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Resolução de Problemas/fisiologia , Reconhecimento Psicológico/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Conhecimento , Masculino , Pessoa de Meia-Idade , Competência Profissional , Adulto Jovem
19.
Fish Shellfish Immunol ; 55: 690-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27368541

RESUMO

The effect of Spirulina dried powder (SDP) on the immune response of white shrimp Litopenaeus vannamei was studied in vitro and in vivo. Incubating shrimp haemocytes in 0.5 mg ml(-1) SDP caused the degranulation of haemocytes and a reduction in the percentage of large cells within 30 min. Shrimp haemocytes incubated in 1 mg ml(-1) SDP significantly increased their phenoloxidase (PO) activity, serine proteinase activity, and respiratory burst activity (RB, release of superoxide anion). A recombinant protein of lipopolysaccharide and ß-1,3-glucan binding protein (LGBP) of the white shrimp was produced, named rLvLGBP, and examined for its binding with SDP. An ELISA binding assay showed that rLvLGBP binds to SDP with a dissociation constant of 0.0507 µM. In another experiment, shrimp fed diets containing SDP at 0 (control), 30, and 60 g kg(-1) after four weeks were examined for LGBP transcript level and lysozyme activity, as well as phagocytic activity, clearance efficiency, and resistance to Vibrio alginolyticus. These parameters were significantly higher in shrimp receiving diets containing SDP at 60 g kg(-1) or 30 g kg(-1) than in controls. In conclusion, shrimp haemocytes receiving SDP provoked the activation of innate immunity as evidenced by the recognition and binding of LGBP, degranulation of haemocytes, reduction in the percentage of large cells, increases in PO activity, serine proteinase activity, superoxide anion levels, and up-regulated LGBP transcript levels. Shrimp receiving diets containing SDP had increased lysozyme activity and resistance against V. alginolyticus infection. This study showed the mechanism underlying the immunostimulatory action of Spirulina and its immune response in shrimp.


Assuntos
Dieta , Suplementos Nutricionais , Imunidade Inata , Penaeidae/imunologia , Spirulina/química , Vibrio alginolyticus/fisiologia , Ração Animal/análise , Animais , Hemócitos/enzimologia , Hemócitos/imunologia , Hemócitos/metabolismo , Penaeidae/metabolismo , Penaeidae/microbiologia , Fagocitose/efeitos dos fármacos
20.
Am J Psychol ; 129(1): 1-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27029102

RESUMO

The recognition-action theory of chess skill holds that expertise in chess is due primarily to the ability to recognize familiar patterns of pieces. Despite its widespread acclaim, empirical evidence for this theory is indirect. One source of indirect evidence is that there is a high correlation between speed chess and standard chess. Assuming that there is little or no time for calculation in speed chess, this high correlation implies that calculation is not the primary factor in standard chess. Two studies were conducted analyzing 100 games of speed chess. In Study 1, we examined the distributions of move times, and the key finding was that players often spent considerable time on a few moves. Moreover, stronger players were more likely than weaker players to do so. Study 2 examined skill differences in calculation by examining poor moves. The stronger players made proportionally fewer blunders (moves that a 2-ply search would have revealed to be errors). Overall, the poor moves made by the weaker players would have required a less extensive search to be revealed as poor moves than the poor moves made by the stronger players. Apparently, the stronger players are searching deeper and more accurately. These results are difficult to reconcile with the view that speed chess does not allow players time to calculate extensively and call into question the assertion that the high correlation between speed chess and standard chess supports recognition-action theory.


Assuntos
Reconhecimento Visual de Modelos/fisiologia , Resolução de Problemas/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Humanos , Teoria Psicológica , Fatores de Tempo
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