Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

Alexa,let's train now!——A systematic review and classification approach to digital and home-based physical training interventions aiming to support healthy cognitive aging

Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions.In this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention programs.Thus,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance.Methods:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults.The systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered relevant.Two reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older adults.Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence(≤85%)and monitoring of the level of regular physical activity in the control group.Conclusion:The current state of evidence concerning the effectiveness of digital and home-based physical training interventions is mixed overall,though there is limited evidence that specific types of digital and home-based physical training interventions(e.g.,online classes and step-based exergames)can be an effective strategy for improving cognitive performance in older adults.However,due to the limited number of available studies,future high-quality studies are needed to buttress this assumption empirically and to allow for more solid and nuanced conclusions.

Genetic testing in congenital heart disease:A clinical approach

Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.

Feasibility and safety of cryoballoon ablation for atrial fibrillation inpatients with congenital heart disease

BACKGROUND The prevalence of atrial fibrillation (AF) is on the rise in the aging population with congenital heart disease (CHD). A few case series have described the feasibility and early outcomes associated with radiofrequency catheter ablation of AF centered on electrically isolating pulmonary veins (PV) in patients with CHD. In contrast, cryoballoon ablation has not previously been studied in this patient population despite its theoretical advantages, which include a favorable safety profile and shorter procedural time. AIM To assess the safety and feasibility of cryoballoon ablation for AF in an initial cohort of patients with CHD. METHODS The study population consisted of consecutive patients with CHD and cryoballoon ablation for AF at the Montreal Heart Institute between December 2012 and June 2017. Procedural complications, acute success, and 1-year freedom from recurrent AF after a single procedure with or without antiarrhythmic drugs were assessed. Procedures were performed under conscious sedation. Left atrial access was obtained via a single transseptal puncture or through an existing atrial septal defect (ASD). Cryoballoon occlusion was assessed by distal injection of 50% diluted contrast into the pulmonary vein. At least one 240-second cryothermal application was performed upon obtaining complete pulmonary vein occlusion. Following ablation, patients were routinely followed at outpatient visits at 1, 3, 6, and 12 mo, and then annually. RESULTS Ten patients, median age 57.9 (interquartile range 48.2-61.7) years, 60% female, met inclusion criteria and were followed for 2.8 (interquartile range 1.4-4.5) years.Two had moderately complex CHD (sinus venosus ASD with partial anomalous pulmonary venous return;aortic coarctation with a persistent left superior vena cava), with the remainder having simple defects. AF was paroxysmal in 8 (80.0%) and persistent in 2 (20.0%) patients. The pulmonary vein anatomy was normal in 6 (60.0%) patients. Four had left common PV (n = 3) and/or 3 right PV (n = 2). Electrical pulmonary vein isolation (PVI) was acutely successful in all. One patient had transient phrenic nerve palsy that recovered during the intervention. No major complication occurred. One year after a single ablation procedure, 6 (60%) patients remained free from AF. One patient with recurrent AF had recovered pulmonary vein conduction and underwent a second PVI procedure. A second patient had ablation of an extra-pulmonary vein trigger for AF. CONCLUSION Cryoballoon ablation for AF is feasible and safe in patients with simple and moderate forms of CHD, with an excellent acute success rate and modest 1-year freedom from recurrent AF.

一种有效记录成骨细胞L型钙通道电流的穿孔全细胞膜片钳方法

目的:探讨一种有效记录成骨细胞L型钙通道电流的穿孔全细胞膜片钳方法。此方法使玻璃电极与细胞内液保持电化学连续性,使细胞内环境保持稳定,改善常规全细胞膜片钳破膜造成的破膜难和封接不稳,以及常规全细胞膜片钳破膜后造成的封接不稳。方法:以成骨细胞为研究对象,采用β-七叶素穿孔全细胞膜片钳技术,记录骨细胞L型钙通道电流。结果:采用这种穿孔全细胞膜片钳技术,能有效记录到成骨细胞上L型钙通道电流。结论:穿孔膜片钳技术是一种简便而有效的记录全细胞电流的实验方法,该方法的建立为今后更深入的研究疾病中成骨细胞的病理生理机制提供实验基础。

疑似或已确诊为冠状动脉疾病的患者其静息心率的长期预后预测价值

Heart rate reduction is the cornerstone of the treatment of angina. The purpose of this study was to explore the prognostic value of heart rate in patients with stable coronary artery disease(CAD). Methods and results: We assessed the relationship between resting heart rate at baseline and cardiovascular mortality/ morbidity, while adjusting for risk factors. A total of 24 913 patients with suspected or proven CAD from the Coronary Artery Surgery Study registry were studied for a median followup of 14.7 years. All-cause and cardiovascular mortality and cardiovascular rehospitalizations were increased with increasing heart rate(P< 0.0001). Patients with resting heart rate ≥ 83 bpm at baseline had a significantly higher risk for total mortality[hazard ratio(HR)=1.32, CI 1.19- 1.47, P< 0.0001]- and cardiovascular mortality(HR=1.31, CI 1.15- 1.48, P< 0.0001) after adjustment for multiple clinical variables when compared with the reference group. When comparing patients with heart rates between 77- 82 and ≥ 83 bpm with patients with a heart rate ≤ 62 bpm, the HR values for time to first cardiovascular rehospitalization were 1.11 and 1.14, respectively(P< 0.001 for both). Conclusion: Resting heart rate is a simple measurement with prognostic implications. High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with CAD.

极高强度他汀治疗对冠状动脉粥样硬化消退的影响——ASTEROID试验

背景：以前的血管内超声（intravascular ultrasound，IVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格的评价病变进展和消退的IVUS测量指标。 目标：评价极高强度他汀治疗是否能逆转IVUS确定的冠状动脉粥样硬化。 设计和地点：于美国、加拿大、欧洲和澳大利亚53个社区和3级保健中心进行前瞻性开标盲法终点试验（A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden，ASTEROID）。应用马达驱动回撤IVUS评价基线和治疗24个月时冠状动脉粥样斑块负荷。每对基线和随访IVUS测量结果均进行盲法分析。 病例：从2002年11月到2003年10月，507例患者有基线IVUS检查结果，并接受至少1个剂量的研究药物。在24个月后，349例患者具有可用于评估的系列IVUS检查结果。 干预：所有患者均接受瑞舒伐他汀40ms／d强化治疗。 主要观测指标：预先设定了两个一级疗效指标：PAV变化和基线最严重病变10min节段动脉粥样斑块体积变化。二级疗效指标为整个动脉标准化总斑块体积的变化。结果：平均（SD）LDL—C水平由基线时的130．4（34．3）ms／dL降至60．8（20．0）ms／扎，平均下降了53．2％（P〈0．001）。平均（SD）HDL-C水平从基线时的43．1（11．1）ms／dL升至49．0（12．6）ms／dL，平均增加了14．7％（P〈0．001）。整个血管PAV平均（SD）变化为-0．98％（3．15％），中位数为-0．79％（97．5％CI，-1．21％～-0．53％）（与基线比较，P〈0．001）。最严重病变10min节段斑块体积平均（SD）变化为-6．1（10．1）mm^3，中位数为-5．6mm^3（97．5％CI，-6．8～-4．0mm^3）（与基线比较，P〈0．001）。总斑块体积变化中位数降低了6．8％，平均减少了-14．7（25．7）mm^3，中位数为-12．5mm^3（95％CI，-15．1～-10．5mm^3）（与基线比较，P〈0．001）。不良事件少见，与其他他汀试验相似。 结论：应用瑞舒伐他汀40ms／d进行极高强度他汀治疗可使LDL-C平均水平达到60．8ms／dL，使HDL—C增加14．7％。这导致所有3个预先设定的IVUS斑块负荷指标均显示动脉粥样硬化消退。因此，将LDL-C降至低于目前指南规定的水平，同时显著提高HDL-C，可以使冠心病患者动脉粥样硬化斑块消退。这些变化对临床预后的影响尚需进一步研究确定。

代谢综合征及其各组成部分与冠心病患者远期死亡风险

Background: The metabolic syndrome confers an increased risk of major cardiovascular events in individuals initially free from coronary heart disease(CHD). Presently, approximately 25% of the US population possesses the metabolic syndrome as defined using the National Cholesterol Education Program(NCEP) criteria. We sought to assess the impact of the metabolic syndrome and its individual components on intermediate- term and long- term outcomes in patients with CHD. Methods: The CASS registry represents a database of 24 958 patients with suspected or proven CHD who underwent cardiac catheterization between 1974 and 1979. Mean long- term follow- up was 12.6± 5.1 years. Metabolic syndrome was defined using modified definitions of the NCEP and World Health Organization(WHO) because high- density lipoprotein cholesterol measures were not available. Results: We identified 3279 and 1080 patients with metabolic syndrome using our modified NCEP and WHO definitions, respectively. Adjusted long- term all- cause death was higher in patients with metabolic syndrome(hazard ratio [HR] 1.21, 95% CI 1.14- 1.29; HR 1.56, 95% CI 1.43- 1.70 for NCEP and WHO criteria, respectively). Similarly, long- term adjusted risk of cardiovascular death and intermediate- term risk of morbidity and mortality were higher in patients with the metabolic syndrome. Fasting blood glucose ≥ 110 mg/dL was responsible for most of the increased risk associated with the metabolic syndrome(adjusted HR 1.47, 95% CI 1.39- 1.56). Conclusions: The metabolic syndrome confers a higher risk of long- term death in patients with preexisting CHD, and dysglycemia appears to be responsible for most of the associated risk.

1000例患者接受系统性非体外循环冠状动脉搭桥术后的远期结果

背景:非体外循环冠状动脉搭桥术(OPCAB)目前被用作传统“体外循环”手术外的替代选择,但有关其远期效果的数据很少。本研究旨在回顾应用系统性OPCAB方面的长期经验。方法和结果:1996—2004年间共系统性地实施了1000次OPCAB手术,占同期所有冠状动脉血运重建治疗的95%,其中97%接受了完整随访。患者的平均年龄为64±10岁,778例男性,222例女性。73%的患者有三支血管病变。

High-Fat Diets-Induced Metabolic Alterations Alter the Differentiation Potential of Adipose Tissue-Derived Stem Cells

Background: Adipose tissue-derived stem cells (ASC) possess the ability to differentiate into adipocytes or endothelial cells to help in the adipogenesis, vasculogenesis and vascular repair. This study aims at determining the impact of high-fat diets (HFD)-induced type 2 diabetes (T2D) on the differentiation potential of ASC. Results: C57BL/6J male mice were fed a vegetal (VD) or an animal (AD) HFD. Isolation of ACS from mice showing different levels of metabolic alterations reveals that advanced T2D did not affect the number of cells per gram of tissue. Rather, a higher proportion of inflammatory CD36+ cells was identified in HFD fed mice. Despite a marked decreased expression of adipogenic genes (aP2, C/EBPα and PPARγ2), ASC from HFD groups had a higher adipogenic potential and a lower endothelial differentiation potential in vitro compared to control. ASC from the VD group had enhanced cyclin B1 expression and had more adipogenic potential compared to AD group. Conclusion: Our results demonstrate that the metabolic modifications, linked to the nature of fatty acids in diets, modulate the differentiation potential of ASC with increased adipogenesis to the detriment of the endothelial pathway. Results highlight the importance of evaluating the ASC differentiation behavior in a context of autologous cell-based therapy for the repair of vascular tissues in diabetic patients.

An early proof-of-concept of cardiac resynchronization therapy

Almost 50 years ago,we published detailed hemodynamic findings in a patient with heart failure and intermittent left bundle branch block.Delayed intraventricular conduction was consistently accompanied by an increased duration of left ventricular(LV)isometric contraction,a drop in systolic blood pressure,a rise in heart rate,and a drop in cardiac output.To our knowledge,this observation provided the first ever evidence that delayed mechanical LV contraction was associated with deterioration,and return to a normal pre-ejection phase with improvement in LV function.

Immersible ergocycle prescription as a function of relative exercise intensity

Purpose: The purpose of this study was to establish the relationship between various expressions of relative exercise intensity percentage of maximal oxygen uptake(%VO_(2max)), percentage of maximal heart rate(%HR_(max)), %VO_2 reserve(%VO_2R), and %HR reserve(%HRR)) in order to obtain the more appropriate method for exercise intensity prescription when using an immersible ergocycle(IE) and to propose a prediction equation to estimate oxygen consumption(VO_2) based on IE pedaling rate(rpm) for an individualized exercise training prescription.Methods: Thirty-three healthy participants performed incremental exercise tests on IE and dryland ergocycle(DE) at equal external power output(Pext). Exercise on IE began at 40 rpm and was increased by 10 rpm until exhaustion. Exercise on DE began with an initial load of 25 W and increased by 25 W/min until exhaustion. VO_2 was measured with a portable gas analyzer(COSMED K4b^2) during both incremental tests. On IE and DE, %VO_2R, %HRmax, and %HRR at equal Pext did not differ(p > 0.05).Results: The %HRR vs. %VO_2R regression for both IE and DE did not differ from the identity line %VO_2R IE = 0.99 × HRR IE(%) + 0.01(r^2= 0.91, SEE = 11%); %VO_2R DE = 0.94 × HRR DE(%) + 0.01(r^2= 0.94, SEE = 8%). Similar mean values for %HRmax, %VO_2R, and %HRR at equal Pext were observed on IE and DE. Predicted VO_2 obtained according to rpm on IE is represented by: VO_2(L/min) = 0.000542 × rpm2-0.026 × rpm + 0.739(r = 0.91, SEE = 0.319 L/min).Conclusion: The %HRR–%VO_2R relationship appears to be the most accurate for exercise training prescription on IE. This study offers new tools to better prescribe, control, and individualize exercise intensity on IE.

Practical diastology

Left ventricular(LV) diastolic dysfunction is being recognized as an important part in the pre-operative evaluation. Pre-operative LV diastolic dysfunction has been associated with increased risk of post-operative complications. Furthermore guidelines have been published on the assessment of LV diastolic function. However LV diastolic function is significantly influenced by loading conditions which are typically altered during cardiac and non-cardiac surgery. In addition, waveform analysis from the pulmonary artery catheter tend to correlate with diastolic function and loading conditions. The advantage of hemodynamic monitoring being that they are continuously displayed as opposed to intermittent diastolic parameters. Finally if the importance of diastolic function assessment is to estimate filling pressure, the presence of B lines with the use of lung ultrasound is a simpler method in detecting pulmonary edema. Another indirect evidence of either LV systolic or diastolic dysfunction is an abnormal near-infrared spectroscopy value. Finally it might be more important to evaluate right ventricular(RV) diastolic dysfunction as RV dysfunction is significantly associated with pulmonary hypertension and consequently mortality. Such assessment of RV diastolic dysfunction can be obtained continuously with the use of RV pressure waveform monitoring.

血管紧张素转换酶抑制剂降低高血压患者心房纤颤的发生

Objective The objective of this study was to determine the effects of a ngioten sin-converting enzyme inhibition (ACEI)-versus long-acting calcium-channel b lockade(CCB) on atrial fibrillation(AF) in patients with hypertension. Backgroun d Atrial fibrillation is the most common significant cardiac arrhythmia, and ang iotensin II has been implicated in its pathophysiology. Methods This was a retro spective, longitudinal cohort study from a database of 8 million people in the U .S. Patients age ≥18 years with hypertension were eligible if they filled a pre scription for either an ACEI or a CCB between January 1995 and June 1999. The us e of all other antihypertensive medications was permitted. Patient chronic disea se burden was assessed using a modified Charlson index. Patients were matched on a propensity score generated from a logistic regression model. A survival analy sis approach was used to compare the incidence of AF between groups. The final c ohorts were evaluated until June 2002, and the average follow-up was 4.5 years. Results After cohort matching, 10,926 patients were included in the analysis an d divided equally into the ACEI and CCB groups. Mean patient age was 65 years. T he adjusted hazards ratio (95%confidence interval <<CI>>) in the ACEI versus CCB groups for the entire follow-up period was 0.85(95%CI: 0.74 to 0.97) for new- onset AF, and the adjusted incidence ratio for AF-related hospitalizations was 0.74(95%CI: 0.62 to 0.89). Conclusions Angiotensin-converting enzyme inhibitio n was associated with a reduced incidence of AF for patients with hypertension i n a usual care setting. These results need to be confirmed in a large-scale ran domized clinical trial.

动脉粥样硬化消退对血管内超声测定的冠状动脉腔内总面积的影响

We assessed vascular changes during atherosclerosis regression. Compensatory enlargement of coronary arteries accommodates plaque burden during atherosclerosis development. Lipid-lowering therapy has altered the natural history of coronary atherosclerosis, but the arterial changes that occur during disease regression need to be clarified. Intravascular ultrasound was performed at baseline and after ～18 months in 432 patients with coronary disease. Mean plaque, lumen, and total vessel area were computed in a 30-mm coronary segment of interest. Mean low-density lipoprotein cholesterol level was 2.4 mmol/L, and 88%of patients received statins. Overall, changes in plaque and total vessel areas were highly correlated(r=0.82, p< 0.0001). Among the 227 patients with plaque regression, the plaque area decrease was-0.58±0.54 mm2, and changes in total vessel and lumen areas were-1.02±1.10 and-0.44±0.86 mm2, respectively. The decrease in plaque area correlated better with the change in total vessel area(r=0.64, p< 0.0001) than with the change in lumen area(r=0.20, p=0.003). The relation between plaque regression and decrease in total vessel area was significantly better(p=0.019) for patients with a >40%atheroma area(r=0.72; p< 0.0001) than for those with ≤40%(r=0.48; p=0.0004). In conclusion, regression of atherosclerotic plaque is generally accompanied by a decrease in total vessel size, without an increase in luminal dimensions. This reverse vascular remodeling may be responsible for the “regression paradox,”whereby secondary prevention is associated with clinical benefits despite minimal improvement in coronary lumen dimensions.

患有稳定性冠状动脉疾病且有运动诱发心肌灌注缺损证据的男性与女性患者的心绞痛症状

Background: To examine sex differences in pain and associated symptoms in patients with exercise-related ischemia, as well as the independence of these findings from other clinical factors. Methods: Prospective study of 482 women and 425 men(mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging(MPI). Analyses were performed on 38 women and 94 men with both angina and MPI evidence of ischemia during exercise. Measures: Chest pain localization, extension, intensity, quality, and presence of various non-pain-related symptoms. Results: Women rated their pain as more intense, used different words to describe it, and reported more non-pain-related symptoms than men(P< .05). They experienced pain and other sensations in the neck area more frequently(P< .05). Most of these differences remained after controlling for clinical or psychological variables, with the exception of pain intensity measures. Conclusions: Sex differences in the experience of symptoms associated with MPI evidence of myocardial ischemia may complicate timely and accurate diagnosis of ischemia in women.

充血性心脏病女性患者的妊娠结局

Background -Pregnant women with congenital heart disease are at increased risk for cardiac and neonatal complications, yet risk factors for adverse outcomes are not fully defined. Methods and Results -Between January 1998 and September 2004, 90 pregnancies at age 27.7±6.1 years were followed in 53 women with congenital heart disease. Spontaneous abortions occurred in 11 pregnancies at 10.8±3.7 weeks, and 7 underwent elective pregnancy termination. There were no maternal deaths. Primary maternal cardiac events complicated 19.4%of ongoing pregnancies, with pulmonary edema in 16.7%and sustained arrhythmias in 2.8%. Univariate risk factors included prior history of heart failure(odds ratio[OR], 15.5), NYHA functional class ≥2(OR, 5.4), and decreased subpulmonary ventricular ejection fraction(OR, 7.7). Independent predictors were decreased subpulmonary ventricular ejection fraction and/or severe pulmonary regurgitation(OR, 9.0) and smoking history(OR, 27.2). Adverse neonatal outcomes occurred in 27.8%of ongoing pregnancies and included preterm delivery(20.8%), small for gestational age(8.3%), respiratory distress syndrome(8.3%), intraventricular hemorrhage(1.4%), intrauterine fetal demise(2.8%), and neonatal death(1.4%). A subaortic ventricular outflow tract gradient >30 mm Hg independently predicted an adverse neonatal outcome(OR, 7.5). Cardiac risk assessment was improved by including decreased subpulmonary ventricular systolic function and/or severe pulmonary regurgitation(OR, 10.3) in a previously proposed risk index developed in pregnant women with acquired and congenital heart disease. Conclusions -Maternal cardiac and neonatal complication rates are considerable in pregnant women with congenital heart disease. Patients with impaired subpulmonary ventricular systolic function and/or severe pulmonary regurgitation are at increased risk for adverse cardiac outcomes.

Adipocytes modulate vascular smooth muscle cells migration potential through their secretions

Impairment of vascular smooth muscle cells (VSMC) is recognized as a predisposition factor for atherosclerosis development. We hypothesize that the metabolic syndrome has a direct impact on VSMC migration and phenotypic switching, which may increase the incidence of atherosclerotic events. Aortic VSMC were extracted from 10 weeks old C57BL6 mice and incubated for 24 hr in adipocytes conditioned cell culture medium. Adipocytes were extracted from diabetic C57BL6 male mice fed with either a vegetal or an animal High-Fat-Diet (HFD) for 20 weeks. Migration of VSMC in response to conditioned media stimulations was significantly modulated compared to control. The most extended effects on VSMC were triggered by adipocytes from mice fed with animal HFD. These effects were concurrent with increased leptin concentrations and decreased adiponectin levels in conditioned media. A significant up-regulation of CD36 mRNA level was found in VSMC treated with adipocytes from HFD-fed mice. In conclusion, we have shown that the development of adipocyte-induced VSMC alterations is linked to diet fatty acid composition and the degree of metabolic alterations. The modulation of adipokine secretions in the adipose tissue that is linked to metabolic alterations may alter the physiology of VSMC and thus accelerate the development of metabolic-related vascular diseases.

A Cognitive Behavioural Intervention for the Treatment of Vasovagal and Unexplained Syncope

Vasovagal syncope and unexplained syncope are the most commonly observed types of syncope in outpatient and hospital settings. Medical interventions usually target at the physiological mechanisms responsible for loss of consciousness in an attempt to limit the frequency of recurrences. However, this type of intervention does not take into account the psychological and functional impact of syncope, nor the importance of psychological variables in triggering and maintaining syncope. In the present pilot study, four participants presenting significant psychological distress and recurrent syncope were treated using a multimodal intervention targeting at both the medical and psychological aspects of the problem. Results showed a significant reduction in the frequency of syncope/presyncope, in the level of emotional distress experienced, as well as improved functional status in three of the four participants. Several recommendations are made to medical practitioners and psychologists, in view of identifying patients likely to benefit from this type of intervention or components thereof.