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We introduce Ultra-Flexible Tentacle Electrodes (UFTEs), packing many independent fibers with the smallest possible footprint without limitation in recording depth using a combination of mechanical and chemical tethering for insertion. We demonstrate a scheme to implant UFTEs simultaneously into many brain areas at arbitrary locations without angle-of-insertion limitations, and a 512-channel wireless logger. Immunostaining reveals no detectable chronic tissue damage even after several months. Mean spike signal-to-noise ratios are 1.5-3x compared to the state-of-the-art, while the highest signal-to-noise ratios reach 89, and average cortical unit yields are ~1.75/channel. UFTEs can track the same neurons across sessions for at least 10 months (longest duration tested). We tracked inter- and intra-areal neuronal ensembles (neurons repeatedly co-activated within 25 ms) simultaneously from hippocampus, retrosplenial cortex, and medial prefrontal cortex in freely moving rodents. Average ensemble lifetimes were shorter than the durations over which we can track individual neurons. We identify two distinct classes of ensembles. Those tuned to sharp-wave ripples display the shortest lifetimes, and the ensemble members are mostly hippocampal. Yet, inter-areal ensembles with members from both hippocampus and cortex have weak tuning to sharp wave ripples, and some have unusual months-long lifetimes. Such inter-areal ensembles occasionally remain inactive for weeks before re-emerging.
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Encéfalo , Electrodos Implantados , Hipocampo , Neuronas , Animales , Neuronas/fisiología , Encéfalo/fisiología , Encéfalo/citología , Hipocampo/fisiología , Hipocampo/citología , Masculino , Ratas , Relación Señal-Ruido , Potenciales de Acción/fisiología , Ratones , Corteza Prefrontal/fisiología , Corteza Prefrontal/citologíaAsunto(s)
Cardiomiopatía Hipertrófica , Ablación por Catéter , Ablación por Radiofrecuencia , Tabique Interventricular , Humanos , Resultado del Tratamiento , Ablación por Catéter/efectos adversos , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/terapia , Cardiomiopatía Hipertrófica/cirugíaRESUMEN
Background: Reports show that the left ventricular myocardial work index (LVMWI) is a novel parameter for evaluating cardiac function. Decompensated heart failure leads to a high rate of early mortality in advanced patients with light-chain cardiac amyloidosis (AL-CA) and prevents them from a relatively delayed response to chemotherapy. This study aimed to assess the association of the LVMWI with short-term outcomes and to construct a simple model for risk stratification. Methods: A total of 79 patients with an initial diagnosis of AL-CA were included in this retrospective cohort study. LVMWI was calculated by integrating brachial artery cuff blood pressure and left ventricular longitudinal strain (LVLS). The short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. Results: The median follow-up time was 21 months (3-36 months), and 23 (29%) patients died in the first 6 months. The time-dependent ROC and the area under the curve (AUC) showed that the LVMWI had the best predictive potential at the 6-month time point [AUC =0.805; 95% confidence interval (CI): 0.690-0.920]. A bivariate prognostic model based on the LVMWI was constructed, and D-dimer showed a synergistic effect with optimum predicted potential (AUC =0.877; 95% CI: 0.791-0.964). Kaplan-Meier analysis demonstrated that patients with two, one, and none of the variates beyond the cut-off value bore a different risk of 6-month all-cause mortality (accumulated mortality was 86%, 30%, 3%, respectively; log-rank, P<0.001). Multivariate nested logistic regression showed that the level of D-dimer provided an incremental prognostic value (Δχ2=10.3; P=0.001) to the value determined from New York Heart Association (NYHA) classification and the LVMWI. Conclusions: The LVMWI is associated with the short-term outcome of patients with AL-CA. The D-dimer test provides additional prognostic information for the LVMWI.
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PURPOSE: This study compared the effectiveness of sacubitril/valsartan (SV) vs. valsartan (V) for treating persistent atrial fibrillation (AF) after radio-frequency catheter ablation (RFCA). METHODS: Patients with persistent AF who received RFCA were randomly assigned to the SV or V treatment group with the intervention lasting for 12 months. The primary outcome included any atrial arrhythmia episode lasting ≥ 30 s after a 3-month blanking period. The secondary outcome included any atrial arrhythmia episode lasting ≥ 24 h or requiring cardioversion after a 3-month blanking period. The H2FPEF score was used to assess the possibility of patients suffering from heart failure with preserved ejection fraction. RESULTS: A total of 143 patients with persistent AF who received RFCA were randomized for the study, with 5 patients failing to follow-up. Among them, 29 (42%) out of 69 patients receiving V and 15 (21.7%) out of 69 patients receiving SV reached the primary endpoint (P < 0.001). A total of 26 (37.7%) out of 69 patients receiving V and 7 (10.1%) out of 69 patients receiving SV reached the secondary endpoint (P < 0.001). A decrease in the H2FPEF score after a 1-year follow-up seemed to be related to the recurrence of AF (OR, 0.065; 95% CI: 0.018-0.238, P < 0.001). CONCLUSIONS: SV can decrease AF recurrence after catheter ablation in patients with persistent AF at the 1-year follow-up. The mechanism for this process may be related to the reduction in the H2FPEF score in patients with preserved ejection fraction heart failure.
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Fibrilación Atrial , Ablación por Catéter , Insuficiencia Cardíaca , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Recurrencia , Ablación por Catéter/efectos adversos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Valsartán/efectos adversos , Resultado del TratamientoRESUMEN
Background: Surgery for isolated functional tricuspid regurgitation (TR) poses a high risk. Several transcatheter approaches are being evaluated for the treatment of such patients. The K-Clip system is a percutaneous approach designed for functional TR; however, its utility remains unknown. Objectives: This study aimed to report the 30-day echocardiographic and clinical outcomes with the K-Clip system for severe TR, including changes in TR severity and NYHA functional class. Methods: Transcatheter tricuspid valve annuloplasty was performed in 39 patients with intermediate or high surgical risk who underwent the K-Clip system. The right internal jugular vein procedure was performed with annuloplasty guided by fluoroscopy and echocardiography. The primary outcomes were clinical success and all-cause mortality at the 30-day follow-up. Results: The K-Clip was successfully implanted in all cases, with 1 to 3 devices deployed. At the 30-day follow-up, none of the patients had died. TR severity was reduced by at least one grade in all patients. There were no severe procedural or 30-day adverse events, except for 1 new pacemaker implantation. The proportion of NYHA class III-IV patients decreased from 79.5% to 5.1%, and the ascites disappeared. The 6-minute walk distance increased by 78 m (P < 0.05), and the Kansas City Cardiomyopathy Questionnaire score improved by 11 points (P < 0.05). Conclusions: The K-Clip device is practical, safe, and effective for patients with severe TR. A 30-day reduction in TR and enhanced cardiac function and quality of life were associated with transcatheter tricuspid annuloplasty using the K-Clip device, according to short-term follow-up studies. (Confirmatory Clinical Study of Treating Tricuspid Regurgitation With K-Clip TM Transcatheter Annuloplasty System [TriStar]; NCT05173233).
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BACKGROUND: Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. METHODS: Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses was utilized to verify the prognostic potential of CA125. RESULTS: The mean age was 61±8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e' and left ventricular ejection fraction showed acceptable prognostic potential (C-index= 0.829, 95%CI 0.749 to 0.909). CA125 remained an independent prognostic factor (HR=1.018, 95%CI 1.005 to 1.031, P=0.008) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs 0.784, P=0.037). CONCLUSIONS: Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.
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BACKGROUND: Left ventricular hypertrophy (LVH) is an independent prognostic factor for cardiovascular events and it can be detected by echocardiography in the early stage. In this study, we aim to develop a semi-automatic diagnostic network based on deep learning algorithms to detect LVH. METHODS: We retrospectively collected 1610 transthoracic echocardiograms, included 724 patients [189 hypertensive heart disease (HHD), 218 hypertrophic cardiomyopathy (HCM), and 58 cardiac amyloidosis (CA), along with 259 controls]. The diagnosis of LVH was defined by two experienced clinicians. For the deep learning architecture, we introduced ResNet and U-net++ to complete classification and segmentation tasks respectively. The models were trained and validated independently. Then, we connected the best-performing models to form the final framework and tested its capabilities. RESULTS: In terms of individual networks, the view classification model produced AUC = 1.0. The AUC of the LVH detection model was 0.98 (95% CI 0.94-0.99), with corresponding sensitivity and specificity of 94.0% (95% CI 85.3-98.7%) and 91.6% (95% CI 84.6-96.1%) respectively. For etiology identification, the independent model yielded good results with AUC = 0.90 (95% CI 0.82-0.95) for HCM, AUC = 0.94 (95% CI 0.88-0.98) for CA, and AUC = 0.88 (95% CI 0.80-0.93) for HHD. Finally, our final integrated framework automatically classified four conditions (Normal, HCM, CA, and HHD), which achieved an average of AUC 0.91, with an average sensitivity and specificity of 83.7% and 90.0%. CONCLUSION: Deep learning architecture has the ability to detect LVH and even distinguish the latent etiology of LVH.
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BACKGROUND: With an increased number of surgical procedures involving the mitral annular region, the risk of mitral valve prolapse (MVP) has also increased. Previous studies have reported that worsening of MVP occurred early after radiofrequency catheter ablation (RFCA) at papillary muscles in ventricular tachycardia (VT) patients with preoperative MVP. CASE SUMMARY: We report a case where MVP and papillary muscle rupture occurred 2 wk after RFCA in a papillary muscle originated VT patient without mitral valve regurgitation or prolapse before. The patient then underwent mitral valve replacement with no premature ventricular contraction or VT. During the surgery, a papillary muscle rupture was identified. Pathological examination showed necrosis of the papillary muscle. The patient recovered after mitral valve replacement. CONCLUSION: Too many ablation procedures and energy should be avoided.
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A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-NTM) mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze (EPM) and showed reduced social preference in a three-chamber social interaction test. Following EPM tests, c-Fos expression levels indicated that the nucleus accumbens (NAc) was associated with risk-avoidance behavior in DISC1-NTM mice. In addition, in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons (FS) in the NAc were significantly lower in DISC1-NTM mice than in wild-type (WT) mice. In addition, in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-NTM mice than in WT controls. The impairment of risk avoidance in DISC1-NTM mice was rescued using optogenetic tools that activated NAcPV neurons. Finally, inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-NTM mice during tests on the elevated zero maze. Taken together, our findings confirm an impairment in risk avoidance in DISC1-NTM mice and suggest that reduced excitability of NAcPV neurons is responsible.
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Núcleo Accumbens , Parvalbúminas , Animales , Interneuronas/metabolismo , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Núcleo Accumbens/metabolismo , Parvalbúminas/metabolismoRESUMEN
Left atrial sphericity index (LASI) is one significant geometric remodeling parameter to evaluate the prognosis of atrial fibrillation (AF). We aimed to determine whether transthoracic echocardiography (TTE)-derived LASI may help predict the outcomes following AF radiofrequency catheter ablation (RFCA). This prospective study enrolled 190 consecutive AF patients who underwent TTE 24 h before RFCA. LASI was calculated as the ratio of left atrial maximum volume to spherical volume. After 1-year follow-up, 56 patients (29.5%) relapsed. Multivariate Cox regression showed that LASI (hazard ratio = 1.48, 95% Cl 1.15-1.92, P = 0.003) was an independent predictor of AF recurrence. Stratifying patients into four subgroups with different LAVI showed that high LASI value indicated a high risk of recurrence, especially in patients with mildly and moderately enlarged atria (the recurrence rate was 0% vs. 26.3%, P = 0.049; 9.5% vs. 40.9%, P = 0.018, respectively). In conclusion, TTE-derived LASI may be useful to predict AF recurrence after RFCA.
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Fibrilación Atrial , Ablación por Catéter , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Humanos , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Circulating long noncoding RNA (lncRNA) plays a vital role in clinical disease diagnosis and prognosis. Here, we evaluate the role of a lncRNA, named growth arrest specific 5 (GAS5), in atrial fibrillation (AF). METHODS: Expression of GAS5 was measured by qRT-PCR. Diagnostic and prognostic values of GAS5 were assessed by the receiver operating characteristics curve (ROC), Kaplan-Meier (KM) and Cox regression analyses. RESULTS: A total of 173 participants were enrolled in this study. Circulating GAS5 expression was significantly down-regulated in AF patients. This change occurred prior to enlargement of the left atrial volume and was strongly associated with AF progression, which demonstrates the potential use of GAS5 as an early biomarker. The area under the ROC curve (AUC) was 0.858 (95% CI 0.789-0.926, P < .001). Seventy of the 85 AF patients received radiofrequency catheter ablation (RFCA), and 22 (31.4%) had relapsed by the 1-year follow-up. The KM analysis (log-rank test, P = .031) and multivariable Cox analysis (HR = 0.127, 95% CI 0.026-0.616; P = .01) revealed that GAS5 has a role in predicting recurrence after RFCA. CONCLUSION: Circulating lncRNA GAS5 is a potential biomarker for AF diagnosis and prognosis. Down-regulation of GAS5 occurs prior to left atrial enlargement and can be used for the prognosis of AF progression and recurrence.
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Fibrilación Atrial , ARN Largo no Codificante/sangre , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/cirugía , Biomarcadores/sangre , Ablación por Catéter , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Tabique Interventricular , Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/diagnóstico por imagen , Carcinoma Corticosuprarrenal/cirugía , Ecocardiografía , Humanos , Tabique Interventricular/diagnóstico por imagen , Tabique Interventricular/cirugíaRESUMEN
BACKGROUND: Takotsubo cardiomyopathy (TTC), a syndrome of acute left ventricular (LV) dysfunction, is characterized by transitory hypokinesis of LV apices with compensatory hyperkinesis of the LV basal region. The symptoms of TTC mimic acute myocardial infarction, without significant coronary stenoses on coronary angiography. Echocardiogram plays a key role in the diagnosis and prognosis of TTC. New indicators from echocardiograms may be helpful in disease evaluation. CASE SUMMARY: A 67-year-old man with a 10-year history of non-small cell lung cancer was admitted to our hospital for emerging facial edema and dry cough. Bronchoscopic lavage, brushing, and biopsy were performed to evaluate tumor progression. During this procedure, he complained of left chest pain, nausea, and vomiting, with elevated troponin levels. Electrocardiogram showed sinus bradycardia with ST-segment elevation in I, AVL, and V4 to V6 leads. Coronary angiography revealed mild stenosis in the right coronary artery. Echocardiography showed hypokinesis of LV apices with compensatory hyperkinesis of the LV basal region. At the 7-d follow-up, echocardiographic pressure-strain analysis showed a normal LV ejection fraction, but partial recovery of LV myocardial work, which fully recovered 5 mo later. CONCLUSION: This is a case of TTC caused by bronchoscopic operation. We strongly recommend noninvasive myocardial work measured by echocardiographic pressure-strain analysis as a necessary supplementary test for the long-term follow-up of TTC.
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Hypertrophic cardiomyopathy (HCM), affecting approximately 1 in 500 in the general population, is the most prominent cause of sudden heart disease-related mortality in the young. Mitochondrial DNA (mtDNA) mutations are among the primary causes of HCM. We previously identified a novel m.2336T>C homoplasmic mutation in the mitochondrial 16S rRNA gene (MT-RNR2) in a Chinese maternally inherited HCM family. However, the molecular mechanisms by which m.2336T>C mutation contributes to HCM remain elusive. Here we generated transferring mitochondria cell lines (cybrids) with a constant nuclear background by transferring mitochondria from immortalized lymphoblastoid cell lines carrying the HCM-associated m.2336T>C mutation into human mtDNA-less (ρ°) cells. Functional assays showed a decreased stability for 16S rRNA and the steady-state levels of its binding proteins in the mutant cybrids. This mutation impaired the mitochondrial translation capacity and resulted in many mitochondrial dysfunctions, including elevation of ROS generation, reduction of ATP production and impairment of mitochondrial membrane potential. Moreover, the mutant cybrids had poor physiological status and decreased survival ability. These results confirm that the m.2336T>C mutation leads to mitochondrial dysfunction and strongly suggest that this mutation may play a role in the pathogenesis of HCM.
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Cardiomiopatía Hipertrófica/genética , ADN Mitocondrial/genética , Mitocondrias/patología , Mutación Puntual , ARN Ribosómico 16S/genética , Supervivencia Celular , Metabolismo Energético , Salud de la Familia , Humanos , Mitocondrias/genética , Biosíntesis de Proteínas , Estabilidad del ARN , ARN Ribosómico 16S/metabolismo , Proteínas de Unión al ARN/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVES: Beta-blockers have improved the prognosis of patients with dilated cardiomyopathy as they improve left ventricular (LV) systolic function and structure, which are crucial for myocardial recovery. However, to date, no accurate methods can predict the effectiveness of ß-blocker therapy. Our goal was to evaluate whether peripheral endothelial function could be a useful predictor for ß-blocker responses and related LV reverse remodeling (LVRR) in patients with idiopathic dilated cardiomyopathy (IDC). METHODS: Fifty-two IDC patients were recruited and underwent brachial artery flow-mediated dilation (FMD). Beta-blockers were titrated to doses tolerable for each patient. LV function and structure were measured by echocardiography. A positive response to ß-blockers was defined as an increase of ≥10% in LV ejection fraction (LVEF). LVRR was defined as an increase of ≥10% in LVEF and a decrease of ≥15% in LV end-systolic volume (LVESV). RESULTS: Baseline FMD was 8.4±3.0% in IDC patients and significantly lower than healthy controls. At three-month follow-up, 54% of patients had a positive ß-blocker response and 40% achieved LVRR. Patients with a positive response to ß-blockers or with LVRR had significantly higher baseline FMD values than those without. FMD was the most significant predictor of changes in LVEF and LVESV. The sensitivity and specificity of baseline FMD to predict ß-blocker responses was 64.3% and 83.3%, respectively, and to predict LVRR was 61.9% and 80.6%, respectively. Beta-blockers themselves did not influence FMD values. CONCLUSIONS: FMD could serve as an independent predictor for monitoring ß-blocker therapy effectiveness in IDC patients.
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Cardiomiopatía Dilatada , Endotelio Vascular , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Antagonistas Adrenérgicos beta/farmacología , Adulto , Anciano , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/tratamiento farmacológico , Cardiomiopatía Dilatada/fisiopatología , Monitoreo de Drogas/métodos , Ecocardiografía/métodos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/fisiologíaRESUMEN
The ability of animals to respond to life-threatening stimuli is essential for survival. Although vision provides one of the major sensory inputs for detecting threats across animal species, the circuitry underlying defensive responses to visual stimuli remains poorly defined. Here, we investigate the circuitry underlying innate defensive behaviours elicited by predator-like visual stimuli in mice. Our results demonstrate that neurons in the superior colliculus (SC) are essential for a variety of acute and persistent defensive responses to overhead looming stimuli. Optogenetic mapping revealed that SC projections to the lateral posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay, are sufficient to mimic visually evoked fear responses. In vivo electrophysiology experiments identified a di-synaptic circuit from SC through LP to the lateral amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked defensive responses. Our results reveal a novel collicular-thalamic-Amg circuit important for innate defensive responses to visual threats.
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Amígdala del Cerebelo/fisiología , Miedo/fisiología , Instinto , Núcleos Talámicos Laterales/fisiología , Neuronas/fisiología , Colículos Superiores/fisiología , Vías Visuales/fisiología , Percepción Visual/fisiología , Animales , Potenciales Evocados Visuales , Núcleos Talámicos Laterales/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas , Optogenética , Estimulación Luminosa , Colículos Superiores/citología , Tálamo/citología , Tálamo/fisiologíaRESUMEN
BACKGROUND: Patients with metabolic syndrome are at increased risk for cardiovascular disease. Combination lipid-lowering therapy is often needed in patients with metabolic syndrome and mixed dyslipidemia. The aim of this study was to compare the effect of statin combined with a new hypolipidemic agent, coenzyme A (CoA) with moderate-dose statin monotherapy in subjects with metabolic syndrome and mixed dyslipidemia by evaluating data from a subgroup of patients with metabolic syndrome and mixed dyslipidemia from a previously conducted randomized study. METHODS: In the present post hoc analysis, 212 patients were included, receiving statin monotherapy (n = 94) or statin combined with CoA 400 U/day (n = 118) for 8 weeks. The lipoprotein profile was determined at baseline and week 8 visits. Attainment of low-density lipoprotein-cholesterol (LDL-C) < 100 mg/dL, non-high-density lipoprotein-cholesterol (HDL-C) < 130 mg/dL, and the combined goal of these two parameters was also evaluated. RESULTS: The mean percent change was more prominent with CoA plus statin compared with placebo plus statin in triglyceride (TG) (-32.5% vs. -8.7%, respectively; P = 0.0002), total cholesterol (-9.6% vs. -3.6%, P = 0.013), LDL-C (-7.5% vs. 2.1%, P = 0.033), and non-HDL-C (-14.3% vs. -6.4%, P = 0.011). Treatment with CoA plus statin resulted in larger percentages of participants attaining lipid goals for LDL-C (70.3% vs. 56.4%, P = 0.044), non-HDL-C (60.2% vs. 45.7%, P = 0.039), and the combined goal of LDL-C and non-HDL-C (57.6% vs. 42.6%, P = 0.038) than statin monotherapy. CONCLUSION: These results demonstrate that CoA plus statin therapy was more effective in improving lipoprotein parameters than statin alone in patients with metabolic syndrome and mixed hyperlipidemia.
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Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson's disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.
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Astrocitos/citología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Neuronas Dopaminérgicas/patología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Enfermedad de Parkinson/terapia , Trasplante de Células Madre , Animales , Astrocitos/metabolismo , Astrocitos/efectos de la radiación , Astrocitos/trasplante , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Regulación de la Expresión Génica , Humanos , Luz , Ratones , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Neurogénesis/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Ingeniería de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Sustancia Negra/metabolismo , Sustancia Negra/patologíaRESUMEN
BACKGROUND: Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. METHODS: In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). RESULTS: A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. CONCLUSIONS: In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. TRIAL REGISTRATION: Current Controlled Trials ClinicalTrials.gov ID NCT01928342.