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1.
Artigo em Inglês | MEDLINE | ID: mdl-32734299

RESUMO

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. One-hundred forty-three PD patients (71 smokers) and 178 healthy controls (HC) (62 smokers) participated in a multicenter MRI study. T1-weightened images were used to examine brain structural alterations using voxel based morphometry in a priori defined regions of the defensive system network. PD was associated with grey matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.

2.
Neuroimage Clin ; 27: 102268, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32361414

RESUMO

Neuronal nitric oxide synthase (NOS-I) impacts on fear/anxiety-like behavior in animals. In humans, the short (S) allele of a functional promotor polymorphism of NOS1 (NOS1 ex1f-VNTR) has been shown to be associated with higher anxiety and altered fear conditioning in healthy subjects in the amygdala and hippocampus (AMY/HIPP). Here, we explore the role of NOS1 ex1f-VNTR as a pathophysiological correlate of panic disorder and agoraphobia (PD/AG). In a sub-sample of a multicenter cognitive behavioral therapy (CBT) randomized controlled trial in patients with PD/AG (n = 48: S/S-genotype n=15, S/L-genotype n=21, L/L-genotype n=12) and healthy control subjects, HS (n = 34: S/S-genotype n=7, S/L-genotype n=17, L/L-genotype=10), a differential fear conditioning and extinction fMRI-paradigm was used to investigate how NOS1 ex1f-VNTR genotypes are associated with differential neural activation in AMY/HIPP. Prior to CBT, L/L-allele carriers showed higher activation than S/S-allele carriers in AMY/HIPP. A genotype × diagnosis interaction revealed that the S-allele in HS was associated with a pronounced deactivation in AMY/HIPP, while patients showed contrary effects. The interaction of genotype × stimulus type (CS+, conditioned stimulus associated with an aversive stimulus vs. CS-, unassociated) showed effects on differential learning in AMY/HIPP. All effects were predominately found during extinction. Genotype associated effects in patients were not altered after CBT. Low statistical power due to small sample size in each subgroup is a major limitation. However, our findings provide first preliminary evidence for dysfunctional neural fear conditioning/extinction associated with NOS1 ex1f-VNTR genotype in the context of PD/AG, shedding new light on the complex interaction between genetic risk, current psychopathology and treatment-related effects.

3.
Transl Psychiatry ; 10(1): 110, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317621

RESUMO

Extinction learning is suggested to be a central mechanism during exposure-based cognitive behavioral psychotherapy. A positive association between the patients' pretreatment extinction learning performance and treatment outcome would corroborate the hypothesis. Indeed, there is first correlational evidence between reduced extinction learning and therapy efficacy. However, the results of these association studies may be hampered by extinction-training protocols that do not match treatment procedures. Therefore, we developed an extinction-training protocol highly tailored to the procedure of exposure therapy and tested it in two samples of 46 subjects in total. By using instructed fear acquisition training, including a consolidation period overnight, we wanted to ensure that the conditioned fear response was well established prior to extinction training, which is the case in patients with anxiety disorders prior to treatment. Moreover, the extinction learning process was analyzed on multiple response levels, comprising unconditioned stimulus (US) expectancy ratings, autonomic responses, defensive brain stem reflexes, and neural activation using functional magnetic resonance imaging. Using this protocol, we found robust fear conditioning and slow-speed extinction learning. We also observed within-group heterogeneity in extinction learning, albeit a stable fear response at the beginning of the extinction training. Finally, we found discordance between different response systems, suggesting that multiple processes are involved in extinction learning. The paradigm presented here might help to ameliorate the association between extinction learning performance assessed in the laboratory and therapy outcomes and thus facilitate translational science in anxiety disorders.

4.
Am J Psychiatry ; 177(3): 254-264, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838872

RESUMO

OBJECTIVE: Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder. METHODS: An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment. RESULTS: At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs. CONCLUSIONS: The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions.


Assuntos
Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Transtorno de Pânico/terapia , Adulto , Terapia Cognitivo-Comportamental , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/psicologia , Resultado do Tratamento , Adulto Jovem
5.
Eur Neuropsychopharmacol ; 29(10): 1138-1151, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444036

RESUMO

The gene coding for glycine receptor ß subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk¼) in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

6.
Int Urol Nephrol ; 51(4): 627-632, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30810883

RESUMO

OBJECTIVE: To explore the feasibility and safety of the Tsinghua PINS Remote Tech to facilitate sacral neuromodulation programming procedure. METHOD: For 22 patients who had previously participated in the phase III clinical trial for treating overactive bladder with the Tsinghua PINS sacral neuromodulation system during several Hospital, PINS Remote Tech was applied to perform postoperative parameter adjustment in order to evaluate the safety and reliability of this new technique. Telephone surveys on Remote Tech-related questionnaires were also conducted. RESULTS: 17/22 patients underwent 26 parameter adjustments, average adjustment frequency was 1.53 times per person; the average adjustment time was 23.4 ± 5.1 min (15-32 min). The total effective rate of the Remote control was 14/17 (82.3%). 7/17 (41.1%) patients' symptoms recurrence due to not knowing how to handle patient controller, these patients were instructed on how to use it correctly through Remote Tech even without reprogramming it. Other 10 patients received reprogramming. There was no discomfort during and after parameter adjustment. The questionnaire survey showed that the remote technology saved patients' time and lowered financial costs, significantly improved patient satisfaction. All patients expressed their willingness to recommend it to other patients. CONCLUSION: The PINS Remote Tech can significantly reduce the financial cost and provide a remote reprogram control service that is as safe and reliable as outpatient program control.


Assuntos
Terapia por Estimulação Elétrica/métodos , Internet , Bexiga Urinária Hiperativa/terapia , Adulto , Terapia por Estimulação Elétrica/economia , Eletrodos Implantados , Estudos de Viabilidade , Feminino , Humanos , Plexo Lombossacral , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Satisfação do Paciente , Inquéritos e Questionários , Telemedicina
8.
J Cell Biochem ; 120(3): 4687-4693, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30537032

RESUMO

FAM83H-AS1, also known as oncogenic long noncoding RNA (lncRNA)-3, is a novel lncRNA that has been suggested to be dysregulated in a variety of human cancers. However, the expression status and function of FAM83H-AS1 in bladder cancer are still unknown. The object of our study is to explore the clinical value of FAM83H-AS1 in patients with bladder cancer and the biological function of FAM83H-AS1 in bladder cancer cells. In our results, the expression of FAM83H-AS1 was obviously elevated in bladder cancer tissue samples and bladder cancer cell lines compared with adjacent normal tissue samples and normal bladder epithelial cell lines, respectively. In addition, high expression of FAM83H-AS1 was associated with advanced clinical stage and the presence of muscularis invasion and served as an independent poor prognostic factor for overall survival in patients with bladder cancer. The loss-of-function study showed that silencing FAM83H-AS1 expression suppressed cell proliferation, migration, and invasion and induced cycle arrest at G0/G1 phase. In conclusion, FAM83H-AS1 is involved in the progression of bladder cancer and serves as a prognostic biomarker and potential therapeutic target for patients with bladder cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Movimento Celular , Pontos de Checagem da Fase G1 do Ciclo Celular , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Fase de Repouso do Ciclo Celular , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
9.
J Affect Disord ; 245: 451-460, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30428445

RESUMO

BACKGROUND: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT. METHODS: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns. RESULTS: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT. LIMITATIONS: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed. CONCLUSIONS: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity.


Assuntos
Agorafobia/fisiopatologia , Transtorno Depressivo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Plasticidade Neuronal , Transtorno de Pânico/fisiopatologia , Adulto , Agorafobia/diagnóstico por imagem , Agorafobia/psicologia , Agorafobia/terapia , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Cognição , Terapia Cognitivo-Comportamental , Comorbidade , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/psicologia , Medo/psicologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/psicologia , Transtorno de Pânico/terapia
10.
Sci Rep ; 7(1): 8495, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819118

RESUMO

The sorption mechanism of nickel (Ni) at the illite/water interface was investigated using batch, sorption modelling, extended X-ray absorption fine structure (EXAFS), and extraction approaches. The results showed that Ni(II) sorption on illite was strongly dependent on pH, contact time, temperature, and initial Ni(II) concentration. At a low initial Ni(II) concentration, the ion exchange species of ≡X2Ni° and the inner-sphere complexes including ≡SsONi+, ≡SwONi+ and ≡SwONiOH° species are observed on the sorption edges of Ni(II) on illite. As the initial Ni(II) concentration increased to 1.7 × 10-3 mol/L, precipitates including surface-induced precipitation of s-Ni(OH)2 and amorphous Ni(OH)2 became more significant, especially under neutral to alkaline conditions. EXAFS analysis confirmed that Ni-Al layered double hydroxide (LDH) can gradually form with an increase in the contact time. At pH 7.0, α-Ni(OH)2 was produced in the initial stage and then transformed to the more stable form of Ni-Al LDH with increasing contact time because of the increased Al3+ dissolution. With an increase in temperatures, α-Ni(OH)2 phase on illite transformed to Ni-Al LDH phase, indicating a lower thermodynamic stability compared to Ni-Al LDH phase. These results are important to understand the geochemical behaviors to effectively remediate soil contaminated with Ni(II).

11.
Sci Rep ; 7: 46744, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28440287

RESUMO

The sorption of Ni(II) on a calcareous aridisol (CA) soil, one of the major soil types in northwestern China, was investigated using batch and extended X-ray absorption fine structure (EXAFS) approaches in a 0.01 mol/L NaClO4 solution at different pH values (6.0-10.0), temperatures (25-60 °C) and contact times (2-15 days). Under alkaline conditions, EXAFS analysis showed that the interatomic distances between Ni and O atoms (RNi-O) were approximately 2.04 Å with a typical coordination number (CN) of ~6.0 O atoms in the contact time range from 2 to 15 days. The RNi-Ni (~3.07 Å) suggested that the structure of the Ni(II) adsorbed on the CA soil was basically the same as that of Ni(OH)2(s), while the Ni-Al shell (RNi-Al ~3.16 Å) gradually formed and grew with the increasing contact time. Under weakly acidic conditions, the sorption mechanism of Ni(II) on the CA soil possibly included at least two processes: (i) a fast accumulation dominated by ion exchange and surface complexation and (ii) the formation of a Ni-Al LDH phase over the long term. A high temperature is beneficial to the fixation of Ni(II) on the CA soil and the formation of a Ni-Al LDH.

12.
Artigo em Inglês | MEDLINE | ID: mdl-28322476

RESUMO

Exposure-based psychological interventions currently represent the empirically best established first line form of cognitive-behavioural therapy for all types of anxiety disorders. Although shown to be highly effective in both randomized clinical and other studies, there are important deficits: (1) the core mechanisms of action are still under debate, (2) it is not known whether such treatments work equally well in all forms of anxiety disorders, including comorbid diagnoses like depression, (3) it is not known whether an intensified treatment with more frequent sessions in a shorter period of time provides better outcome than distributed sessions over longer time intervals. This paper reports the methods and design of a large-scale multicentre randomized clinical trial (RCT) involving up to 700 patients designed to answer these questions. Based on substantial advances in basic research we regard extinction as the putative core candidate model to explain the mechanism of action of exposure-based treatments. The RCT is flanked by four add-on projects that apply experimental neurophysiological and psychophysiological, (epi)genetic and ecological momentary assessment methods to examine extinction and its potential moderators. Beyond the focus on extinction we also involve stakeholders and routine psychotherapists in preparation for more effective dissemination into clinical practice.


Assuntos
Transtornos de Ansiedade/reabilitação , Terapia Comportamental/métodos , Extinção Psicológica , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neurofisiologia , Psicofísica , Resultado do Tratamento , Adulto Jovem
13.
Nano Lett ; 16(12): 7974-7981, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960450

RESUMO

One-dimensional nanoscale epitaxial arrays serve as a great model in studying fundamental physics and for emerging applications. With an increasing focus laid on the Cs-based inorganic halide perovskite out of its outstanding material stability, we have applied vapor phase epitaxy to grow well aligned horizontal CsPbX3 (X: Cl, Br, or I or their mixed) nanowire arrays in large scale on mica substrate. The as-grown nanowire features a triangular prism morphology with typical length ranging from a few tens of micrometers to a few millimeters. Structural analysis reveals that the wire arrays follow the symmetry of mica substrate through incommensurate epitaxy, paving a way for a universally applicable method to grow a broad family of halide perovskite materials. The unique photon transport in the one-dimensional structure has been studied in the all-inorganic Cs-based perovskite wires via temperature dependent and spatially resolved photoluminescence. Epitaxy of well oriented wire arrays in halide perovskite would be a promising direction for enabling the circuit-level applications of halide perovskite in high-performance electro-optics and optoelectronics.

14.
Soc Cogn Affect Neurosci ; 11(8): 1245-54, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26969863

RESUMO

Individuals with high anxiety sensitivity (AS) have an increased risk of developing anxiety disorders and are more biased in how they process fear-related stimuli. This study investigates the neural correlates of fear-related words and word associations in high- and low-AS individuals. We used a semantic priming paradigm during functional magnetic resonance imaging in which three types of target words (fear symptoms, e.g. 'dizziness'; neutral, e.g. 'drink'; and pseudowords, e.g. 'salkom') were preceded by two types of prime words (fear-triggers, e.g. 'elevator'; and neutral, e.g. 'bottle'). Subjects with high AS rated fear-symptom words (vs neutral words) as more unpleasant than low-AS individuals; they also related these words more strongly to fear-triggers and showed prolonged reaction times. During the processing of fear-symptom words, greater activation in the left anterior insula was observed in high-AS subjects than in low-AS subjects. Lower activation in the left inferior frontal gyrus, angular gyrus, fusiform gyrus and bilateral amygdalae was found in high-AS subjects when fear-symptom words were preceded by fear-trigger words. The findings suggest that cognitive biases and the anterior insula play a crucial role in high-AS individuals. Furthermore, semantic processes may contribute to high AS and the risk of developing anxiety disorders.


Assuntos
Ansiedade/fisiopatologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Medo/fisiologia , Individualidade , Adulto , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Priming de Repetição/fisiologia , Semântica , Adulto Jovem
15.
Clin Exp Pharmacol Physiol ; 43(2): 182-92, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26666965

RESUMO

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, effectively reduces plasma cholesterol, but its effect on atherosclerosis is unclear. Foam cell formation has been implicated as a key mediator during the development of atherosclerosis. The purpose of this study was to investigate the effects of ezetimibe on foam cell formation and explore the underlying mechanism. The results presented here show that ezetimibe reduces atherosclerotic lesions in apolipoprotein E deficient (apoE-/-) mice by lowering cholesterol levels. Treatment of macrophages with Chol:MßCD resulted in foam cell formation, which was concentration-dependently inhibited by the presence of ezetimibe. Mechanically, ezetimibe treatment downregulated the expression of CD36 and scavenger receptor class B1 (SR-B1), but upregulated the expression of apoE and caveolin-1 in macrophage-derived foam cells, which kept consistent with our microarray results. Moreover, treatment with ezetimibe abrogated the increase of phospho-extracellular signal regulated kinase (ERK) 1/2 and their nuclear accumulation in foam cells. Inhibition of the MAPK pathway by the MEK inhibitor PD98059 attenuated the inhibitory effect of ezetimibe on the expression of p-ERK1/2 and caveolin-1. Taken together, these results showed that ezetimibe suppressed foam cell formation via the caveolin-1/MAPK signalling pathway, suggesting that inhibition of foam cell formation might be a novel mechanism underlying the anti-atherosclerotic effect of ezetimibe.


Assuntos
Caveolina 1/metabolismo , Ezetimiba/farmacologia , Células Espumosas/citologia , Células Espumosas/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Antígenos CD36/genética , Caveolina 1/genética , Linhagem Celular , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Ezetimiba/uso terapêutico , Humanos , Masculino , Camundongos , Regulação para Cima/efeitos dos fármacos
17.
J Affect Disord ; 184: 182-92, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26093832

RESUMO

BACKGROUND: Depression is frequent in panic disorder (PD); yet, little is known about its influence on the neural substrates of PD. Difficulties in fear inhibition during safety signal processing have been reported as a pathophysiological feature of PD that is attenuated by depression. We investigated the impact of comorbid depression in PD with agoraphobia (AG) on the neural correlates of fear conditioning and the potential of machine learning to predict comorbidity status on the individual patient level based on neural characteristics. METHODS: Fifty-nine PD/AG patients including 26 (44%) with a comorbid depressive disorder (PD/AG+DEP) underwent functional magnetic resonance imaging (fMRI). Comorbidity status was predicted using a random undersampling tree ensemble in a leave-one-out cross-validation framework. RESULTS: PD/AG-DEP patients showed altered neural activation during safety signal processing, while +DEP patients exhibited generally decreased dorsolateral prefrontal and insular activation. Comorbidity status was correctly predicted in 79% of patients (sensitivity: 73%; specificity: 85%) based on brain activation during fear conditioning (corrected for potential confounders: accuracy: 73%; sensitivity: 77%; specificity: 70%). LIMITATIONS: No primary depressed patients were available; only medication-free patients were included. Major depression and dysthymia were collapsed (power considerations). CONCLUSIONS: Neurofunctional activation during safety signal processing differed between patients with or without comorbid depression, a finding which may explain heterogeneous results across previous studies. These findings demonstrate the relevance of comorbidity when investigating neurofunctional substrates of anxiety disorders. Predicting individual comorbidity status may translate neurofunctional data into clinically relevant information which might aid in planning individualized treatment. The study was registered with the ISRCTN: ISRCTN80046034.


Assuntos
Transtorno Depressivo/diagnóstico , Transtorno de Pânico/diagnóstico , Adulto , Agorafobia/complicações , Agorafobia/psicologia , Comorbidade , Condicionamento Psicológico , Transtorno Depressivo/patologia , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Extinção Psicológica , Medo/psicologia , Feminino , Humanos , Aprendizado de Máquina , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Transtorno de Pânico/complicações , Transtorno de Pânico/patologia , Transtorno de Pânico/psicologia , Valor Preditivo dos Testes
18.
Kidney Int ; 87(2): 396-408, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25207880

RESUMO

Cytokines and chemokines produced by tubular epithelial and infiltrating cells are critical to inflammation in renal ischemia-reperfusion injury. IL-37, a newly described IL-1 family member, inhibits IL-18-dependent pro-inflammatory cytokine production by its binding to IL-18 receptors and IL-18 binding protein. The potential role of IL-37 in renal ischemia-reperfusion injury is unknown. Here we found that exposure of tubular epithelial cells to exogenous IL-37 downregulated hypoxia and the IL-18-induced expression of TNFα, IL-6, and IL-1ß. Importantly, human PT-2 tubular epithelial cells have inducible expression of IL-37. Moreover, pro-inflammatory cytokine expression was augmented in IL-37 mRNA-silenced tubular epithelial cells and inhibited by transfection with pCMV6-XL5-IL-37. In a mouse ischemic injury model, transgenic expression of human IL-37 inhibited kidney expression of TNFα, IL-6, and IL-1ß and improved mononuclear cell infiltration, kidney injury, and function. Thus, human tubular epithelial cells express the IL-18 contra-regulatory protein IL-37 as an endogenous control mechanism to reduce inflammation. Augmenting kidney IL-37 may represent a novel strategy to suppress renal injury responses and promote kidney function after renal ischemic injury and transplantation.


Assuntos
Citocinas/genética , Interleucina-18/metabolismo , Interleucina-1/metabolismo , Rim/imunologia , Rim/lesões , Traumatismo por Reperfusão/imunologia , Animais , Linhagem Celular , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1/antagonistas & inibidores , Interleucina-1/genética , Rim/irrigação sanguínea , Túbulos Renais/imunologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Receptores de Interleucina-18/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia
19.
Acta Pharmacol Sin ; 35(9): 1129-36, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25087996

RESUMO

AIM: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro. METHODS: VSMCs of SD rats were cultured in the presence of Chol:MßCD (10 µg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence. RESULTS: Treatment with Chol:MßCD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:MßCD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 µmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 µmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did. CONCLUSION: Ezetimibe suppresses cholesterol accumulation in rat VSMCs in vitro by regulating SREBP-1 and caveolin-1 expression, possibly via the MAPK signaling pathway.


Assuntos
Azetidinas/farmacologia , Colesterol/metabolismo , Lipídeos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Ezetimiba , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Behav Res Ther ; 62: 88-96, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25124776

RESUMO

Cognitive behavioral therapy (CBT) is an evidence-based treatment for mental disorders. Several meta-analytical reviews supported its efficacy and effectiveness in the treatment of panic disorder with agoraphobia (PD/AG). Recently, it has been shown that neurobiological changes are associated with the process and outcome of CBT. However, the general and specific neurobiological effects of CBT are still widely unknown. Therefore, the potential of applying neuroscience to clinical practice and optimizing CBT is still limited. The current review summarizes recent findings about the neural correlates of CBT in PD/AG measured with fMRI. Furthermore, the current review will focus on neural activation patterns predicting and moderating therapeutic success of CBT, due to its potential application in personalized treatment in the future. Finally, we will discuss some future perspectives of the neurosciences in CBT research.


Assuntos
Agorafobia/terapia , Encéfalo/fisiopatologia , Terapia Cognitivo-Comportamental , Terapia Implosiva , Transtorno de Pânico/terapia , Agorafobia/fisiopatologia , Agorafobia/psicologia , Humanos , Imagem por Ressonância Magnética , Transtorno de Pânico/fisiopatologia , Transtorno de Pânico/psicologia , Resultado do Tratamento
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