Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice

Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E₂) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis remain unknown. E₂ regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young and old, after either oophorectomy (OVX) or oophorectomy plus E₂ (OVX + E₂) replacement. We found that absence of E₂ was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old mice responded better to E₂ replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our findings represent a new understanding of the role of E₂ in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition, this evidence suggests that old individuals may show a better response to E₂ administration in terms of reverting the high levels of marrow fat seen in age-related bone loss.     

Genetic susceptibility and ischaemic stroke

In the past year the search for genetic susceptibility factors involved in ischaemic stroke has motivated a number of important studies in humans and animals. These have been focused on genetic susceptibility as a risk factor for ischaemic stroke, or as a determinant of ischaemic stroke outcome. Because there is increasing evidence that genetic factors play a role, it seems that epidemiological studies assessing both environmental and genetic risk factors may help to understand the cause of ischaemic stroke better. This may have therapeutic and preventive implications.     

Spontaneous breakage of intracorneal ring segments (ICRS) 8 years after implantation

We present a case of spontaneous in situ breakage of intracorneal ring segments (ICRSs) 8?years after their implantation in a patient with keratoconus. The patient presented to our clinic with a red and painful right eye that had not improved despite topical steroids and antibiotics. The decision was made to explant the broken ICRSs from the cornea and send them for laboratory analyses, by which manufacturer defects were excluded. It is noteworthy that corneal curvature re-steepening was observed 4?months after ICRS removal despite the performance of crosslinking (CXL) 1?year prior to ICRS implantation.     

Successful percutaneous transcatheter patent foramen ovale closure through the right internal jugular vein using a steerable catheter

Percutaneous transcatheter closure of a patent foramen ovale (PFO) remains challenging when femoral venous approach is not available. We describe the successful closure of a PFO using the right internal jugular venous approach and a deflectable catheter delivery system in a patient with a PFO, recurrent stroke, and an inferior vena cava filter. © 2013 Wiley Periodicals, Inc.     

20-Year prevalence projections for dementia and impact of preventive policy about risk factors

Incidence of dementia increases sharply with age and, because of the increase in life expectancy, the number of dementia cases is expected to rise dramatically over time. Some studies suggest that controlling some modifiable risk factors for dementia like diabetes or hypertension could lower its incidence. However, as treating these vascular factors would also reduce mortality risk, the actual impact of such public-health intervention on dementia prevalence is not known. Accounting for the impact of dementia and risk factors on mortality, the aim of this work was (1) to compute projections of age- and-sex specific prevalence of dementia in France from 2010 to 2030, (2) to evaluate how public-health interventions targeting risk factors for dementia could change these projections. Age-and-sex specific incidence of dementia and mortality of demented subjects were estimated from the Paquid population-based cohort using a semi-parametric illness-death model. Future global mortality rates and population sizes were obtained from national demographic projections. Under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75 % from 2010 to 2030 with a 200 % increase after 90 years of age. Therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality and would have a modest impact on the number of dementia cases. On the other hand, a preventive dementia treatment targeting ApoE4 carriers would probably not improve survival and hence would decrease dementia prevalence by 15–25 %.     

Electromechanical mapping of myocardial ischemia in coronary occlusion in the pig

The NOGA-Biosense catheter-based mapping technique has been well studied experimentally in infarction model. However, chronic myocardial ischemia with this new device has not been well explored. Thus, the aim of our study was to assess electromechanical changes in a pig aneroid constricor model. To achieved this aim, ten pigs were studied 21 days after the implantation of an aneroid constrictor around the circumflex artery. Coronary reserve assess by intracoronary Doppler flow wire was reduced in the ischemic lateral area (ILA) compared with the nonischemic zone (NIZ) (1.3 +/- 0.1 in the ILA vs. 2.3 +/- 0.2 in the NSZ; p < 0.01). TM echocardiography was used to evaluate myocardial regional contractility under basal condition and after stress induced by rapid atrial pacing. In stress state, the ischemic zone showed an impaired contractility compared with basal state (wall thickening, 32.7 +/- 7.4% vs. 59.7 +/- 8.6%; p < 0.05) whereas the non ischemic zone did not (53.8 +/- 7.6% vs. 60.8 +/- 10.1%; p = ns). Constrast echography showed a decrease in contrast intensity in subendocardium of the ila compared with the niz (46.2 +/- 16.6 vs. 99.2 +/- 35.6; p = 0.03) in pacing. Ventricular mapping quantified unipolar (UV). bipolar (BV) voltage potentials and endocardial local shortening (LLS) in 9 left ventricular regions. In basal state, electrical potentials were preserved in both zones (UV: 9.1 +/- 1.8 mV in the ischemic vs 11.3 +/- 3.6 mV in the non ischemic zone; p = ns; BV: 4.2 +/- 1.1 mV in the ILA vs. 3.9 +/- 1.5 mV; p = ns). In contrast, LLS was significantly lower in the ischemic compared with non ischemic zone (6.4 +/- 5.4% vs. 17.9 +/- 3.0%, p < 0.001). In conclusion, ventricular mapping with the NOGA-Biosense system can identify the ischemic myocardium. In this pig model, the association of a preserved electrical activity and an impaired mechanical activity characterizes the ischemic myocardium. These findings could be interesting in this model in regard of the new developments of the system in particular in the field of angiogenesis.     

Assessment of atrial septal defect size with 3D-transesophageal echocardiography: comparison with balloon method

BACKGROUND: Transcatheter closure of atrial septal defect (ASD) is an alternative approach to surgery in selected patients. Balloon stretched diameter (BSD) is considered as the standard way of measuring ASD size. Three-dimensional transesophageal echocardiography (3D-TEE) provides views of the ASD allowing its measurement and identifying its spatial relation with neighboring structures. Our aim was to compare the BSD and 3D-TEE methods to measure the ASD size before transcatheter closure. METHODS AND RESULTS: Seventy-six consecutive patients were enrolled for ASD device closure. Three-dimensional transesophageal echocardiography and balloon sizing were adequately performed in 70 patients before the defect closure. The mean maximal diameter measured by 3D-TEE was 20 +/- 15 mm (range 10-28) while the mean BSD was 22 +/- 4.8 mm (range 9-31). When comparing the 3D-TEE and transcatheter measurements, there was a good correlation between the two methods (y = 3.15 + 0.77x; r = 0.8). The defect as viewed by 3D-TEE was unique in 54 patients and multiple in 16 patients. In patients with a single defect, the correlation between the two methods was high (y = 1.74 + 0.84x; r = 0.85) while patients with multiple ASDs, the correlation was poor (y = 12.4 + 0.4x; r = 0.45). Transcatheter closure was performed successfully in 86%. The mean size of the Amplatzer device was 23 +/- 4.8 mm (range 4-32). The reference to choose the size of the device was the BSD in single defects and the 3D-TEE maximal diameter in multiple defects. CONCLUSION: Three-dimensional transesophageal echocardiography and transcatheter methods are two complementary techniques for the success of transcatheter ASDs closure.     

Inadequate management of dyslipidaemic patients in France. Results of the Odyssée study

The objective of this study was to compare the results of the management of dyslipidaemic patients in the community with the objectives fixed by the AFSSAPS recommendations. An observational epidemiological study was set up among 4 000 general practitioners and 527 cardiologists. This study included 22 323 patients (average age 60.6 years) affected by a documented primary dyslipidaemia. The average number of associated risk factors, according to the AFSSAPS criteria, was 1.8. The prevalence of secondary prevention in patients was 17.5%. More than 80% of patients were being treated by a lipid lowering agent (fibrate or statin) combined or not with lifestyle guidelines. In primary prevention, although the target levels of LDL-C fixed by the AFSSAPS were attained in 94.4% and 82.6% respectively for patients with no other risk factor or with one associated risk factor, the objectives were reached in only 55.4% of patients with two other risk factors and in 29.6% of patients with more than two other risk factors. In secondary prevention, the AFSSAPS objectives were attained in only 45.2% of patients. Following this lipid result, 34.8% of patients underwent therapeutic adjustment, principally the use of medication in the patients receiving lifestyle advice or reinforcement of pharmacological treatment. This study underlines the inadequate management in France of dyslipidaemic patients in the community.