RESUMO
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive dementia, and amnestic mild cognitive impairment (aMCI) has been defined as a transitional stage between normal aging and AD. Accumulating evidence has shown that altered functional connectivity (FC) and structural connectivity (SC) in the default mode network (DMN) is the prominent hallmarks of AD. However, the relationship between the changes in SC and FC of the DMN is not yet clear. In the present study, we derived the FC and SC matrices of the DMN with functional magnetic resonance imaging (fMRI) and diffusion-weighted imaging (DWI) data and further assessed FC and SC abnormalities within a discovery dataset of 120 participants (39 normal controls, 34 patients with aMCI and 47 patients with AD), as well as a replication dataset of 122 participants (43 normal controls, 37 patients with aMCI and 42 patients with AD). Disrupted SC and FC were found among DMN components (e.g., the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), and hippocampus) in patients in the aMCI and AD groups in the discovery dataset; most of the disrupted connections were also identified in the replication dataset. More importantly, some SC and FC elements were significantly correlated with the cognitive ability of patients with aMCI and AD. In addition, we found structural-functional decoupling between the PCC and the right hippocampus in patients in the aMCI and AD groups. These findings of the alteration of DMN connectivity in neurodegenerative cohorts deepen our understanding of the pathophysiological mechanisms of AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Rede de Modo Padrão , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagemRESUMO
Findings on the effect of social status on corruption perception are mixed. To make sense of the mixed results, three studies were conducted to examine whether meritocracy moderates this effect. In Study 1, we measured all variables using a questionnaire-based correlational design. In the preregistered Study 2, we adopted an experimental design in which we manipulated social status using a false feedback paradigm and measured corruption perception and meritocracy. In Study 3, we manipulated meritocracy using a scrambled sentence task and measured its effect on the relationship between social status and corruption perception. The results consistently demonstrated that meritocracy could moderate the influence of social status on corruption perception. Specifically, social status was negatively associated with corruption perception when meritocracy was weak, whereas the association was not significant when meritocracy was strong. Our results suggest that meritocracy critically affects acknowledgment of the pervasiveness of social injustice and even deters the disadvantaged from fighting against corruption.
Assuntos
Crime/psicologia , Classe Social , Justiça Social , Adulto , Feminino , Humanos , Masculino , Percepção , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Hypertension patients often suffered from insomnia problems which lowered the quality of life. Studies have shown that acupuncture is effective to treat perimenopausal and cancer-related insomnia. However, there is a lack of randomized controlled trials to support the effectiveness of acupuncture on insomnia of hypertension patients. METHODS AND ANALYSIS: This study is a randomized, double-blind (patients and evaluators), and placebo-controlled clinical trial to investigate the effect of acupuncture in hypertension patients' insomnia management. We will recruit 158 hypertension patients suffering from insomnia in Bao'an People's Hospital, Shenzhen and randomly assign them into treatment group (antihypertensive drugsâ+âacupuncture) and control group (antihypertensive drugsâ+âsham acupuncture) in a 1:1 ratio. The patients will receive acupuncture 3 times a week for 12âweeks, and then a 6-months follow-up will be conducted after the treatment. The primary outcome is the Pittsburgh Sleep Quality Index. The secondary outcomes include sleep parameters, blood pressure dropping, sleeping pill dosage, Rating Depression Scale score, and Self-Rating Anxiety Scale score. The primary outcome will be evaluated at baseline, 4, 8, and 12âweeks, and 1, 3, and 6âmonths following the end of treatment. The secondary outcomes will be assessed at baseline and 12âweeks of the treatment period.
Assuntos
Terapia por Acupuntura , Hipertensão , Distúrbios do Início e da Manutenção do Sono , Anti-Hipertensivos , Humanos , Hipertensão/complicações , Hipertensão/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/terapia , Qualidade do Sono , Resultado do TratamentoRESUMO
Vascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that are insufficient to confirm a diagnosis of dementia. The default mode network (DMN) is a large-scale brain network of interacting brain regions involved in attention, working memory and executive function. The role of DMN white matter integrity in cognitive deficits of VCIND patients is unclear. Using diffusion tensor imaging (DTI), this study was carried out to investigate white matter microstructural changes in the DMN in VCIND patients and their contributions to cognitive deficits. Thirty-one patients with subcortical VCIND and twenty-two healthy elderly subjects were recruited. All patients underwent neuropsychological assessments and DTI examination. Voxel-based analyses were performed to extract fractional anisotropy (FA) and mean diffusivity (MD) measures in the DMN. Compared with the healthy elderly subjects, patients diagnosed with subcortical VCIND presented with abnormal white matter integrity in several key hubs of the DMN. The severity of damage in the white matter microstructure in the DMN significantly correlated with cognitive dysfunction. Mediation analyses demonstrated that DTI values could account for attention, executive and language impairments, and partly mediated global cognitive dysfunction in the subcortical VCIND patients. DMN integrity is significantly impaired in subcortical VCIND patients. The disrupted DMN connectivity could explain the attention, language and executive dysfunction, which indicates that the white matter integrity of the DMN may be a neuroimaging marker for VCIND.
Assuntos
Disfunção Cognitiva , Substância Branca , Idoso , Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Rede de Modo Padrão , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Substância Branca/diagnóstico por imagemRESUMO
Purpose: To investigate the protective effects of dexmedetomidine (Dex) on post cardiopulmonary bypass (CPB) lung injury in rats and to explore the possibility of underlying mechanisms involving phosphatidylinositol 3-kinase (PI3K)/Akt. Materials and Methods: Forty healthy male Sprague-Dawley rats were randomly divided into five groups (n = 8 for each). A left lung ischemia-reperfusion injury model of CPB was established in all five groups. Rats were given saline, dexmedetomidine (Dex), dimethyl sulfoxide (DMSO), wortmannin (Wtm), and Dex plus Wtm during the CPB process, in Group Saline, Dex, DMSO, Wtm, and Dex + Wtm, respectively. Mean arterial pressure, oxygenation index (OI), and respiratory index (RI) were measured at the following three timepoints: before CPB (T1), at the onset of opening of the left hilus pulmonis (T2), and at the end of the CPB process (T3). At T3, hematoxylin and eosin (H&E) staining was conducted to evaluate pathology of lung injury. The rate of lung tissue apoptosis was determined by flow-cytometry. The expression of Akt, p-Akt, caspase-3, and caspase-9 was assessed by Western blot. Results: Dex treatment during CPB protected rat lungs from post-CPB lung injury, manifested by improved lung function, mitigated pathological damage, and reduced lung tissue apoptosis. The expression and phosphorylation of Akt was significantly enhanced by Dex treatment compared to the saline/DMSO-treated group. Wtm, a recognized PI3K inhibitor, abolished the protective effect of Dex. The levels of caspase-3 and caspase-9 were also significantly elevated in the Wtm-treated group. Conclusions: Dex reduces post-CPB lung injury in rats, at least partially, by activating the PI3K/Akt pathway and inhibiting lung tissue apoptosis.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Ponte Cardiopulmonar/efeitos adversos , Dexmedetomidina/farmacologia , Lesão Pulmonar/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Apoptose , Dexmedetomidina/uso terapêutico , Modelos Animais de Doenças , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Wortmanina/administração & dosagemRESUMO
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive dementia. Diffusion tensor imaging (DTI) has been widely used to show structural integrity and delineate white matter (WM) degeneration in AD. The automated fiber quantification (AFQ) method is a fully automated approach that can rapidly and reliably identify major WM fiber tracts and evaluate WM properties. The main aim of this study was to assess WM integrity and abnormities in a cohort of patients with amnestic mild cognitive impairment (aMCI) and AD as well as normal controls (NCs). For this purpose, we first used AFQ to identify 20 major WM tracts and assessed WM integrity and abnormalities in a cohort of 120 subjects (39 NCs, 34 aMCI patients and 47 AD patients) in a discovery dataset and 122 subjects (43 NCs, 37 aMCI patients and 42 AD patients) in a replicated dataset. Pointwise differences along WM tracts were identified in the discovery dataset and simultaneously confirmed in the replicated dataset. Next, we investigated the utility of DTI measures along WM tracts as features to distinguish patients with AD from NCs via multilevel cross validation using a support vector machine. Correlation analysis revealed the identified microstructural WM alterations and classification output to be highly associated with cognitive ability in the patient groups, suggesting that they may be a robust biomarker of AD. This systematic study provides a pipeline to examine WM integrity and its potential clinical application in AD and may be useful for studying other neurological and psychiatric disorders.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Substância Branca , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Testes Neuropsicológicos , Substância Branca/diagnóstico por imagemRESUMO
Objective: To summarize the effectiveness of Ilizarov technique in the correction of flexion contracture deformity of the knee after burn. Methods: Between April 2012 and July 2017, Ilizarov technique was used to treat 14 cases (17 knees) of knee flexion contracture patients. There were 11 males (13 knees) and 3 females (4 knees), with an age of 20-48 years (mean, 37 years). The duration of scar formation was 8 months to 24 years (mean, 5 years). The scar ranged from the upper part of the thigh, down to the middle part of the leg, from both sides to the inside and outside of the popliteal fossa, without ulceration. The area after scar contracture was 12 cm×10 cm to 30 cm×22 cm. Preoperative total activity of motion (TAM) was 30-115° (mean, 69°). There were 4 cases in wheelchair, 5 cases walking with double crutches, 3 cases with limp, and 2 cases with half squat walking. According to the knee function evaluation criteria by QIN Sihe, the preoperative knee function was fair in 3 knees, poor in 5 knees, and very poor in 9 knees. Results: All patients were followed up 6 months to 5 years (mean, 2 years). No local skin necrosis, needle tract infection, limb numbness, and other complications occurred. Knee flexion deformities were all corrected. The postoperative TAM was 70-145° (mean, 125°). All patients were able to walk with plantar weight-bearing, and their gait improved when compared with that before operation. Five cases could walk without a crutch and only slightly claudication after operation. At last follow-up, according to the knee function evaluation criteria, the results were excellent in 9 knees, good in 5 knees, and fair in 3 knees, all were significantly improved when compared with that before operation ( Z=-3.677, P=0.000). Conclusion: Ilizarov technique has the advantages of minimally invasive, safe, and easy to operate for the treatment of flexion contracture deformity of the knee after burn.
Assuntos
Queimaduras/complicações , Cicatriz/cirurgia , Contratura/cirurgia , Técnica de Ilizarov , Articulação do Joelho/cirurgia , Adulto , Artroplastia do Joelho , Contratura/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Apoptosis is a cellular mechanism contributing to cardiac surgery using cardiopulmonary bypass (CPB)-induced lung injury. The ubiquitous PI3K/Akt pathway regulates proliferation, apoptosis and differentiation by controlling a broad range of target proteins including NF-κB and GSK-3ß. The roles of the PI3K/Akt/NF-κB and PI3K/Akt/GSK-3ß pathways in CPB-related lung injury are unclear. METHODS: Seventy-two male Sprague-Dawley rats were assigned into sham, CPB, Wortmannin (Wtn) and insulin-like growth factor-I (IGF-I) groups (nâ¯=â¯18, each). Six subjects per group were evaluated at each of three time points: Prior to CPB (T1); opening of the left hilus pulmonis (T2); and 90â¯min after CPB (T3). Arterial blood specimens were obtained at each time point to test respiratory and oxygenation indices. Left lung tissues were processed for H&E and TUNEL staining. Western blot was employed to evaluate protein levels and activities of Akt, phospho-Akt (p-Akt), GSK-3ß, phospho-GSK-3ß (p-GSK-3ß) and nuclear NF-κB. RESULTS: Lung ischemia/reperfusion and CPB caused notable lung injury, as evidenced by lung functional decline and pathological deterioration, accompanied by increases in apoptosis and expression levels of p-Akt, p-GSK-3ß and nuclear NF-κB in lungs (all P < 0.05 vs. Sham). At T3, Wtn-treated CPB subjects showed worsened lung function and pathological lung structures, as well as apoptosis in lungs (all P < 0.05 vs. CPB); additionally, Wtn inhibited Akt phosphorylation and slightly, but significantly increased expression of nuclear NF-κB (both P < 0.001 vs. CPB). Conversely, treatment of subjects with IGF-I increased Akt phosphorylation (P < 0.001 vs. CPB), inhibited expression of nuclear NF-κB (P = 0.008 vs. CPB), improved lung function and tissue morphology (both P < 0.05 vs. CPB), and reduced apoptosis in lungs (P < 0.001 vs. CPB). Neither Wtn nor IGF-I did alter GSK-3ß phosphorylation levels (Pâ¯=⯠0.836 and Pâ¯=⯠0.669 vs. CPB, respectively). CONCLUSION: The PI3K/Akt/NF-κB pathway played a role in CPB-related lung injury, possibly through mediating apoptosis in lungs. GSK-3ß, a signaling effector that also participated in CPB-induced apoptosis in lungs, but was not regulated by the PI3K/Akt pathway in this context.
Assuntos
Apoptose , Ponte Cardiopulmonar/efeitos adversos , Glicogênio Sintase Quinase 3 beta/metabolismo , Lesão Pulmonar/enzimologia , Pulmão/enzimologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/patologia , Lesão Pulmonar/fisiopatologia , Lesão Pulmonar/prevenção & controle , Masculino , Fosforilação , Ratos Sprague-Dawley , Respiração , Transdução de Sinais , Fatores de Tempo , Wortmanina/toxicidadeRESUMO
AIMS: Sevoflurane, a widely used inhaled anesthetic, showed valid protective effect against ischemia reperfusion injury in lung, however, the underlying molecular mechanisms has yet to be explained. MATERIALS AND METHODS: Dogs were divided into four groups: control group, cardiopulmonary bypass (CPB) group, sevoflurane postconditioning group and wortmannin group. Arterial blood was obtained from each group to test the respiratory index and oxygenation index and pulmonary tissues were sampled for apoptotic TUNEL stain. Western Blot was performed to check the level of Akt, p-Akt and nuclear factor kappa B (NF-κB), while ELISA was performed to determine the protein concentrations of tumor necrosis factor α (TNF-α). KEY FINDINGS: Pharmacological postconditioning with sevoflurane protected dog lung from I/R injury with CPB, improved pulmonary dysfunction, and decreased pneumonocyte apoptosis. Application of wortmannin, a specific inhibitor of PI3K, abolished the protective effects and anti-apoptotic effects of sevoflurane-postcondition. Wortmannin also inhibited the sevoflurane-postcondition-induced phosphorylation of AKT and up-regulated the level of NF-κB and TNF-α. SIGNIFICANCE: Accordingly, present study demonstrated that PI3K/AKT/NF-κB pathway plays an important role in the protective effect of sevoflurane postconditioning against CPB induced lung injury.