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1.
BMC Geriatr ; 24(1): 284, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532326

RESUMO

BACKGROUND: Dyadic coping resources have been considered a potential explanatory mechanism of spousal interdependence in health, but the mediation of spousal collaboration for the relationship between self-rated health and depressive symptoms has yet to be examined. This study aimed to investigate the within- (actor effect) and between-partner effects of self-rated health on depressive symptoms in community-dwelling older couples facing physical functioning limitations and to examine the role of spousal collaboration in mediating the actor and cross-partner effects of self-rated health on depressive symptoms. METHOD: Data from 185 community-dwelling older Chinese married couples were analyzed using the actor-partner interdependence mediation model (APIMeM). Couples were interviewed through trained research assistants using the 5-item common dyadic coping subscale of the Dyadic Coping Inventory (DCI), the Visual Analog Scale (VAS) of the QoL questionnaire EQ-5D and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Husbands' self-rated health had an actor effect on their own depressive symptoms and a partner effect on their wives' depressive symptoms. Wives' self-rated health had an actor effect on their own depressive symptoms. The actor effects between self-rated health and depressive symptoms were partially mediated by their own perception of spousal collaboration. Furthermore, husbands' self-rated health not only affects wives' depressive symptoms directly but also indirectly by influencing wives' perceptions of spousal collaboration. DISCUSSION: The findings from this study underscored the importance of viewing couples' coping processes from a dyadic and gender-specific perspective, since more (perceived) collaborative efforts have beneficial effects on both partners' mental health outcomes.


Assuntos
Depressão , Qualidade de Vida , Humanos , Depressão/psicologia , Cônjuges/psicologia , Inquéritos e Questionários , China
2.
Eur J Neurol ; 30(5): 1346-1351, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36773004

RESUMO

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Seguimentos , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/epidemiologia , Nicotina , Fatores de Risco , Hemorragia Cerebral/etiologia , Imageamento por Ressonância Magnética
3.
Eur J Neurol ; 30(1): 144-149, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181703

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Estudos Transversais , Tronco Encefálico , Fatores de Risco , Imageamento por Ressonância Magnética
4.
Stroke ; 53(3): 817-824, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34706565

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. METHODS: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. RESULTS: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15-8.63]; P=0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04-5.86]; P=0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18-8.99]; P=0.022 and odds ratio, 2.53 [95% CI, 1.07-5.98]; P=0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80-110.39]; P=0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%-23.6%) for the entire cohort, 30.2% (20.2%-42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%-51.1%) for children with brain stem CCM. CONCLUSIONS: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.


Assuntos
Hemorragia Cerebral , Hemangioma Cavernoso do Sistema Nervoso Central , Imageamento por Ressonância Magnética , Adolescente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/cirurgia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/mortalidade , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Masculino , Fatores de Risco , Taxa de Sobrevida
5.
Artigo em Inglês | MEDLINE | ID: mdl-35477890

RESUMO

Somatic gain-of-function (GOF) mutations in phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), the catalytic subunit of phosphoinositide 3-kinase (PI3K), have been recently discovered in cerebral cavernous malformations (CCMs), raising the possibility that the activation of PI3K pathways is a possible universal regulator of vascular morphogenesis. However, there have been contradicting data presented among various groups and studies. To enhance the current understanding of vascular anomalies, it is essential to explore this possible relationship between altered PI3K signalling pathways and its influence on the pathogenesis of CCMs. GOF PIK3CA-mutants have been linked to overgrowth syndromes, allowing this group of disorders, resulting from somatic activating mutations in PIK3CA, to be collectively named as PIK3CA-related overgrowth spectrum disorders. This paper reviews and attempts to conceptualise the relationships and differences among clinical presentations, genotypic and phenotypic correlations and possible coexistence of PIK3CA and CCM mutations/phenotypes in CCM lesions. Finally, we present a model reflecting our hypothetical understanding of CCM pathogenesis based on a systematic review and conceptualisation of data obtained from other studies.

6.
Eur J Neurol ; 29(3): 865-872, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34762327

RESUMO

BACKGROUND AND PURPOSE: This study aimed to assess the occurrence and significance of postoperative neuropathic pain (NP) in patients with surgically treated brainstem cavernous malformations (BSCMs). METHODS: Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. The relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL) and life satisfaction was evaluated. RESULTS: Six out of 74 patients (8%) suffered from NP. The Leeds Assessment of Neuropathic Symptoms and Signs scores ranged from 12 to 16 (mean 14.28 ± 1.6). Visual analog scale pain was 5.2 ± 2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (life satisfaction) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient- and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of six patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results. CONCLUSION: Our findings may help to raise awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Neuralgia , Tronco Encefálico/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Neuralgia/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Qualidade de Vida , Resultado do Tratamento
7.
Eur J Neurol ; 29(5): 1427-1434, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35060255

RESUMO

BACKGROUND AND PURPOSE: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. METHODS: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. RESULTS: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. CONCLUSIONS: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Humanos , Imageamento por Ressonância Magnética
8.
Acta Pharmacol Sin ; 43(2): 342-353, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34811512

RESUMO

Panax notoginseng, a traditional Chinese medicine, exerts beneficial effect on diabetic kidney disease (DKD), but its mechanism is not well clarified. In this study we investigated the effects of ginsenoside Rb1 (Rb1), the main active ingredients of Panax notoginseng, in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms. In cultured mouse podocyte cells, Rb1 (10 µM) significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury. Furthermore, Rb1 treatment reversed high glucose-induced increases in Cyto c, Caspase 9 and mitochondrial regulatory protein NOX4, but did not affect the upregulated expression of aldose reductase (AR). Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity. We compared the effects of Rb1 with eparestat, a known aldose reductase inhibitor, in high glucose-treated podocytes, and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage, and Rb1 was more effective in inhibiting apoptosis. In AR-overexpressing podocytes, Rb1 (10 µM) inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury. In streptozotocin-induced DKD mice, administration of Rb1 (40 mg·kg-1·d-1, ig, for 7 weeks) significantly mitigated diabetic-induced glomerular injuries, such as glomerular hypertrophy and mesangial matrix expansion, and reduced the expression of apoptotic proteins. Collectively, Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage, and effectively mitigates the progression of diabetic kidney disease.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Nefropatias Diabéticas/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Podócitos/efeitos dos fármacos , Albuminúria/metabolismo , Animais , Apoptose/efeitos dos fármacos , Glicemia/análise , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/patologia , Citometria de Fluxo , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Podócitos/enzimologia
9.
J Integr Plant Biol ; 64(5): 965-978, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35249253

RESUMO

Auxin and auxin-mediated signaling pathways are known to regulate lateral root development. Although exocytic vesicle trafficking plays an important role in recycling the PIN-FORMED (PIN) auxin efflux carriers and in polar auxin transport during lateral root formation, the mechanistic details of these processes are not well understood. Here, we demonstrate that BYPASS1-LIKE (B1L) regulates lateral root initiation via exocytic vesicular trafficking-mediated PIN recycling in Arabidopsis thaliana. b1l mutants contained significantly more lateral roots than the wild type, primarily due to increased lateral root primordium initiation. Furthermore, the auxin signal was stronger in stage I lateral root primordia of b1l than in those of the wild type. Treatment with exogenous auxin and an auxin transport inhibitor indicated that the lateral root phenotype of b1l could be attributed to higher auxin levels and that B1L regulates auxin efflux. Indeed, compared to the wild type, C-terminally green fluorescent protein-tagged PIN1 and PIN3 accumulated at higher levels in b1l lateral root primordia. B1L interacted with the exocyst, and b1l showed defective PIN exocytosis. These observations indicate that B1L interacts with the exocyst to regulate PIN-mediated polar auxin transport and lateral root initiation in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/metabolismo
10.
Stroke ; 52(4): 1259-1264, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33588600

RESUMO

BACKGROUND AND PURPOSE: This study aims to assess the influence of modifiable cardiovascular risk factors on hemorrhage risk of sporadic cerebral cavernous malformations (CCMs). METHODS: From 1219 consecutive CCM patients (2003-2018), adult subjects with sporadic CCM and complete magnetic resonance imaging were included. We evaluated presence of intracerebral hemorrhage (ICH) as mode of presentation, occurrence of ICH during follow-up and risk factors arterial hypertension, diabetes, hyperlipidemia, nicotine abuse, and obesity (body mass index >30 kg/m2). Impact of risk factors on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. We performed Kaplan-Meier and Cox regression to analyze cumulative 5-year risk for (re)bleeding. RESULTS: We included 682 patients with CCM. The univariate logistic regression showed a significant relationship (odds ratio=1.938 [95% CI, 1.120-3.353], P=0.018) between obesity and ICH as mode of presentation. Multivariate adjusted logistic regression confirmed significant correlation with odds ratio=1.902 (95% CI, 1.024-3.532, P=0.042). Cox regression did not identify predictors for occurrence of (re)hemorrhage (P>0.05; hazard ratios: arterial hypertension 1.112 [95% CI, 0.622-1.990], diabetes 0.850 [95% CI, 0.208-3.482], hyperlipidemia 0.719 [95% CI, 0.261-1.981], nicotine abuse 1.123 [95% CI, 0.591-2.134], and obesity 0.928 [95% CI, 0.416-2.070]). CONCLUSIONS: This study provides evidence that obesity may be a risk factor for CCM hemorrhage. It was significantly associated with ICH as mode of presentation. Other risk factors (arterial hypertension, diabetes, hyperlipidemia, and current nicotine abuse) showed no such effect. None of the factors showed to be independent predictors for cumulative 5-year risk of (re)bleeding.


Assuntos
Neoplasias Encefálicas/complicações , Hemorragia Cerebral/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Obesidade/complicações , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
11.
Eur J Neurol ; 28(6): 2000-2005, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33738912

RESUMO

BACKGROUND: To determine the prevalence of cardiovascular comorbidities and allergic diseases in patients with cavernous malformations of the central nervous system compared to the normal population. METHODS: Clinical and magnetic resonance imaging data of 1352 patients with cerebral cavernous malformations (CCM) from an observational, cross-sectional, single-institutional study were analyzed and compared to an age-and-gender stratified and matched sample from a population-based, epidemiological study assessing cardiovascular risk factors in the local normal population of the same area (RECALL study). RESULTS: Of 1352 patients, 810 (60%) were female. Mean age was 40.4 ± 16 years. 221 patients (16%) suffered from familial disease. Presence of cardiovascular risk factors and intake of certain drugs in the overall cohort was mostly equal to the normal population reference sample (n = 786). The prevalence of allergic diseases was found to be significantly higher in all CCM patients compared to the normal population (30% vs. 20%, odds ratio [OR] 1.35 [1.12-1.63]) and in sporadic CCM cases compared to the normal population and familial cases (32% vs. 20% (OR 1.46 [1.19-1.78], p = 0.0001) and 22% vs. 20%, respectively). CONCLUSIONS: We present novel data on CCM using a large single-institution and population-based setup. The study elaborates disease characteristics of CCM patients in detail. For the first time, evidence for an unexplained high prevalence of allergic diseases in this patient population is described (differing between sporadic and familial cases), supporting the hypothesis that immune response is involved in the pathogenesis of CCM.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
12.
Stroke ; 51(8): 2505-2513, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32646326

RESUMO

BACKGROUND AND PURPOSE: The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H2, which, in turn, is isomerized to prostaglandin E2. In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI. METHODS: The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm. RESULTS: Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size (P=0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs (P=0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression (P=0.022). CONCLUSIONS: Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/metabolismo , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/metabolismo , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Estudos de Coortes , Ciclo-Oxigenase 2/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Aneurisma Intracraniano/genética , Masculino , Pessoa de Meia-Idade
13.
BMC Plant Biol ; 20(1): 332, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664862

RESUMO

BACKGROUND: Cold stress inhibits normal physiological metabolism in plants, thereby seriously affecting plant development. Meanwhile, plants also actively adjust their metabolism and development to adapt to changing environments. Several cold tolerance regulators have been found to participate in the regulation of plant development. Previously, we reported that BYPASS1-LIKE (B1L), a DUF793 family protein, participates in the regulation of cold tolerance, at least partly through stabilizing C-REPEAT BINDING FACTORS (CBFs). In this study, we found that B1L interacts with TRANSTHYRETIN-LIKE (TTL) protein, which is involved in brassinosteroid (BR)-mediated plant growth and catalyses the synthesis of S-allantoin, and both proteins participate in modulating plant growth and cold tolerance. RESULTS: The results obtained with yeast two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that B1L directly interacted with TTL. Similar to the ttl-1 and ttl-2 mutants, the b1l mutant displayed a longer hypocotyl and greater fresh weight than wild type, whereas B1L-overexpressing lines exhibited a shorter hypocotyl and reduced fresh weight. Moreover, ttl-1 displayed freezing tolerance to cold treatment compared with WT, whereas the b1l mutant and TTL-overexpressing lines were freezing-sensitive. The b1l ttl double mutant had a developmental phenotype and freezing tolerance that were highly similar to those of ttl-1 compared to b1l, indicating that TTL is important for B1L function. Although low concentrations of brassinolide (0.1 or 1 nM) displayed similarly promoted hypocotyl elongation of WT and b1l under normal temperature, it showed less effect to the hypocotyl elongation of b1l than to that of WT under cold conditions. In addition, the b1l mutant also contained less amount of allantoin than Col-0. CONCLUSION: Our results indicate that B1L and TTL co-regulate development and cold tolerance in Arabidopsis, and BR and allantoin may participate in these processes through B1L and TTL.


Assuntos
Alantoína/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Brassinosteroides/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Temperatura Baixa , Congelamento , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Mutação , Pré-Albumina/genética , Pré-Albumina/metabolismo , Estresse Fisiológico , Técnicas do Sistema de Duplo-Híbrido
14.
Int J Mol Sci ; 21(5)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121259

RESUMO

Heat stress can particularly affect the kidney because of its high rate of adenosine triphosphate consumption. Competition between apoptosis and autophagy-mediated survival always exists in damaged tissue. And Hsp90 can enhance cellular protection to resist heat stress. However, the relationship between Hsp90 and the above competition and its underlying mechanism in the kidney are unclear. The present study found that heat stress induced obvious histopathological and oxidative injury, which was connected with cellular apoptosis and autophagy in the kidney and was associated with the levels of Hsp90 expression or function. The data showed that during heat stress, Hsp90 activated the PKM2-Akt signaling pathway to exert antiapoptotic effects and induce Hsp70 expression regulated by HSF-1, stimulated autophagy-mediated survival through the HIF-1α-BNIP3/BNIP3L pathway, and finally protected the kidney from heat-stress injury. Moreover, the nuclear translocation of PKM2, (p-) Akt, HSF-1, and HIF-1α was enhanced by heat stress, but only intranuclear p-Akt and HSF-1 were specifically influenced by Hsp90, contributing to regulate the cellular ability of resisting heat-stress damage. Our study provided new insights regarding the molecular mechanism of Hsp90 in the kidney in response to heat-stress injury, possibly contributing to finding new targets for the pharmacological regulation of human or animal acute kidney injury from heat stress in future research.


Assuntos
Apoptose , Autofagia , Proteínas de Choque Térmico HSP90/metabolismo , Resposta ao Choque Térmico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piruvato Quinase/metabolismo , Animais , Antioxidantes/metabolismo , Sobrevivência Celular , Proteínas de Choque Térmico HSP70/metabolismo , Rim/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , Oxirredução , Fosforilação , Transdução de Sinais
15.
Hum Brain Mapp ; 40(14): 4287-4295, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31264324

RESUMO

Type 2 diabetes (T2D) is associated with an accelerated episodic memory decline, but the underlying pathophysiological mechanisms are not well understood. Hallmarks of T2D comprise impairment of insulin secretion and insulin sensitivity. Insulin signaling modulates cerebral neurotransmitter activity, including the excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) systems. Here we tested the hypothesis that the glutamate and GABA systems are altered in T2D patients and this relates to memory decline and insulin resistance. Using 1 H-magnetic resonance spectroscopy (MRS), we examined glutamate and GABA concentrations in episodic memory relevant brain regions (medial prefrontal cortex and precuneus) of T2D patients and matched controls. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps and memory performance was assessed using a face-profession associations test. T2D patients exhibited peripheral insulin resistance and had a decreased memory for face-profession associations as well as elevated GABA concentration in the medial prefrontal cortex but not precuneus. In addition, medial prefrontal cortex GABA concentration was negatively associated with memory performance suggesting that abnormal GABA levels in the medial prefrontal cortex are linked to the episodic memory decline that occurs in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Transtornos da Memória/metabolismo , Memória Episódica , Córtex Pré-Frontal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adulto , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Ácido gama-Aminobutírico/análise
16.
Magn Reson Med ; 82(5): 1859-1875, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31199013

RESUMO

PURPOSE: To evaluate radiofrequency (RF) induced tissue heating around aneurysm clips during a 7T head MR examination and to determine the decoupling distance between multiple implanted clips. METHODS: A total of 120 RF exposure scenarios of clinical relevance were studied using specific absorption rate and temperature simulations. Variations between scenarios included 2 clips (18.8 and 51.5 mm length), 2 MR-operating modes, 2 head models, and 3 thermoregulation models. Furthermore, a conservative approach was developed to allow for safe scans of patients with aneurysm clips even if detailed information on the implanted clip is unknown. A dedicated simulation-based approach was applied to determine the decoupling distance between multiple implanted clips. RESULTS: For all 60 clinical scenarios with the 18.8-mm-long clip, the absolute tissue temperature remained below regulatory limits. For 15 of 60 scenarios with the 51.5-mm-long clip, limits were slightly exceeded (less than 1°C). The conservative approach led to a maximum time-averaged input power of the RF coil of 3.3W. The corresponding B1+ is 1.32 µT. A decoupling distance of 35 mm allows the aneurysm clips to be treated as uncoupled from one other. CONCLUSION: Safe scanning conditions with respect to RF-induced heating can be applied for single or decoupled aneurysm clips in a 7T ultra-high field MRI setting. Multiple aneurysm clips separated by less than 35 mm need further investigations.


Assuntos
Imageamento por Ressonância Magnética/instrumentação , Instrumentos Cirúrgicos/efeitos adversos , Segurança de Equipamentos , Temperatura Alta , Humanos , Aneurisma Intracraniano/cirurgia , Imagens de Fantasmas , Desenho de Prótese , Ondas de Rádio
17.
Magn Reson Med ; 79(1): 568-581, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28266079

RESUMO

PURPOSE: To examine radiofrequency-induced tissue heating around intracranial aneurysm clips during a 7 Tesla (T) head MR examination. METHODS: Radiofrequency (RF), temperature simulations, and RF measurements were employed to investigate the effects of polarization and clip length on the electric field (E-field) and temperature. Heating in body models was studied using both a conservative approach and realistic exposure scenarios. RESULTS: Worst-case orientation was found for clips aligned parallel to the E-field polarization. Absolute tissue temperature remained below International Electrotechnical Commission regulatory limits for 44 of 50 clinical scenarios. No significant effect on heating was determined for clip lengths below 18.8 mm, and worst-case heating was found for clip length 51.5 mm. The conservative approach led to a maximum permissible E-field of 72 V/m corresponding to B1+ of 1.2 µT, and an accepted power of 4.6 W for the considered RF head coil instead of 38.5 W without clip. CONCLUSION: Safe scanning conditions with respect to RF-induced heating can be applied depending on the information about the clip gained during screening interviews. However, force and torque measurements in the MR system shall be conducted to give a final statement on the MR safety of aneurysm clips at 7T. Magn Reson Med 79:568-581, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Hipertermia Induzida , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética , Instrumentos Cirúrgicos , Simulação por Computador , Temperatura Alta , Humanos , Lactente , Imagens de Fantasmas , Ondas de Rádio , Estresse Mecânico , Torque
18.
Eur Radiol ; 27(1): 354-364, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26993650

RESUMO

PURPOSE: To prospectively evaluate non-contrast-enhanced 7-Tesla (T) MRA for delineation of unruptured intracranial aneurysms (UIAs) in comparison with DSA. MATERIAL AND METHODS: Forty patients with single or multiple UIAs were enrolled in this IRB-approved trial. Sequences acquired at 7 T were TOF MRA and non-contrast-enhanced MPRAGE. All patients additionally underwent 3D rotational DSA. Two neuroradiologists individually analysed the following aneurysm and image features on a five-point scale in 2D and 3D image reconstructions: delineation of parent vessel, dome and neck; overall image quality; presence of artefacts. Interobserver accordance was assessed by the kappa coefficient. RESULTS: A total of 64 UIAs were detected in DSA and in all 2D and 3D MRA image reconstructions. Ratings showed comparable results for DSA and 7-T MRA when considering all image reconstructions. Highest ratings for individual image reconstructions were given for 2D MPRAGE and 3D TOF MRA. Interobserver accordance was almost perfect for the majority of ratings. CONCLUSION: This study demonstrates excellent delineation of UIAs using 7-T MRA within a clinical setting comparable to the gold standard, DSA. The combination of 7-T non-enhanced MPRAGE and TOF MRA for assessment of untreated UIAs is a promising clinical application of ultra-high-field MRA. KEY POINTS: • Non-enhanced 7-T MRA allowed excellent delineation of unruptured intracranial aneurysms (UIAs). • Image quality at 7-T was comparable with DSA considering both sequences. • Assessment of UIAs is a promising clinical application of ultra-high-field MRA.


Assuntos
Angiografia Digital/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Eur Radiol ; 26(9): 2908-14, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26601973

RESUMO

OBJECTIVES: To investigate in-vivo microanatomy of the subcallosal artery branching from the anterior communicating artery (ACoA) using time-of-flight (TOF) magnetic resonance angiography (MRA) at 7 Tesla. METHODS: Seventy-five subjects, including 15 healthy volunteers and 60 patients, were included in this prospective study. Three raters characterized branches from ACoA in maximum intensity projections of TOF MRA at 7 Tesla acquired with 0.22 × 0.22 × 0.41 mm(3) resolution. Furthermore, course patterns and anatomical features of the subcallosal artery (maximum diameter, length, and branching angle from ACoA) were measured. RESULTS: Branches from the anterior communicating artery were visualized in 63 of 74 (85.1 %) subjects and were identified as the subcallosal artery (93.7 %) and the accessory anterior cerebral artery (6.3 %). The course of the subcallosal artery was classified into 3 groups; C-shaped (55.9 %), straight (16.9 %), and S-shaped (27.2 %). There was a significant difference between the branching angles of C-shaped and straight (p < 0.0001), between C-shaped and S-shaped (p < 0.0001), as well as between straight and S-shaped (p = 0.0113) course patterns. CONCLUSIONS: High-resolution in-vivo 7 T TOF MRA can delineate the microanatomy of the subcallosal artery. Three main variants of course patterns and branching angles from ACoA could be identified. KEY POINTS: • In-vivo 7 Tesla TOF MRA can delineate the subcallosal artery microanatomy • Three distinct course patterns of the subcallosal artery were identified • Branching angles from ACoA significantly differed between subcallosal artery course patterns.


Assuntos
Artérias Cerebrais/anatomia & histologia , Artérias Cerebrais/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Córtex Pré-Frontal/irrigação sanguínea , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
MAGMA ; 29(3): 389-98, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27026243

RESUMO

OBJECTIVE: This study assesses and quantifies impairment of postoperative magnetic resonance imaging (MRI) at 7 Tesla (T) after implantation of titanium cranial fixation plates (CFPs) for neurosurgical bone flap fixation. MATERIALS AND METHODS: The study group comprised five patients who were intra-individually examined with 3 and 7 T MRI preoperatively and postoperatively (within 72 h/3 months) after implantation of CFPs. Acquired sequences included T1-weighted magnetization-prepared rapid-acquisition gradient-echo (MPRAGE), T2-weighted turbo-spin-echo (TSE) imaging, and susceptibility-weighted imaging (SWI). Two experienced neurosurgeons and a neuroradiologist rated image quality and the presence of artifacts in consensus reading. RESULTS: Minor artifacts occurred around the CFPs in MPRAGE and T2 TSE at both field strengths, with no significant differences between 3 and 7 T. In SWI, artifacts were accentuated in the early postoperative scans at both field strengths due to intracranial air and hemorrhagic remnants. After resorption, the brain tissue directly adjacent to skull bone could still be assessed. Image quality after 3 months was equal to the preoperative examinations at 3 and 7 T. CONCLUSION: Image quality after CFP implantation was not significantly impaired in 7 T MRI, and artifacts were comparable to those in 3 T MRI.


Assuntos
Placas Ósseas , Encéfalo/diagnóstico por imagem , Craniotomia/métodos , Imageamento por Ressonância Magnética , Adulto , Artefatos , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Desenho de Equipamento , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Neurocirurgia , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Crânio/diagnóstico por imagem , Titânio/química , Adulto Jovem
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