BACKGROUND: There is currently no targeted treatment available for neonatal arterial ischemic strokes (NAIS). Epidemiological studies demonstrated that perinatal infection/inflammation, peripartum hypoxia, and occlusion of the internal carotid tree are the main determinants of NAIS. The well-established benefit of therapeutic hypothermia (HT) in neonatal encephalopathy due to diffuse hypoxia-ischemia provides a rationale for the potential use of HT as a neuroprotective strategy in NAIS.
METHODS: We used a rat model to reproduce the most prevalent human physiopathological scenario of NAIS. The neuroprotective effect of HT was measured by morphometric magnetic resonance imaging, [18 F] fluorodeoxyglucose (FDG) metabolic activity by positron emission tomography/computed tomography, and behavioral tests.
RESULTS: HT (a) prevented the occurrence of 44% of NAIS, (b) reduced the volume of strokes by 37%, (c) enhanced [18 F] FDG metabolic activity within the territory of the occluded carotid artery, and (d) improved motor behavior. Both morphometric and metabolic techniques showed consistently that HT provided a neuroprotective effect located in the motor cortex, hippocampus, and caudate-putamen.
CONCLUSIONS: Through combining anatomical, metabolic imaging, and behavioral studies, our study provides evidence of neuroprotective effects of HT in NAIS. These results are potentially translational to human NAIS.

OBJECTIVE: The purpose of this study was to compare the values of integral dose, calculated for treatment plans of dynamic radiotherapy techniques prepared with two different optimization protocols.
BACKGROUND: Delivering radiation by IMRT, VMAT and also HT techniques has an influence on the low dose deposition of large areas of the patient body. Delivery of low dose can induce injury of healthy cells. In this situation, a good solution would be to reduce the area, which receives a low dose, but with appropriate dose level for the target volume.
METHODS: To calculate integral dose values of plans structures, we used 90 external beam radiotherapy plans prepared for three techniques (intensity modulated radiotherapy, volumetric modulated arc therapy and helical tomotherapy). One technique includes three different geometry combinations. 45 plans were prepared with classic optimization protocol and 45 with rings optimization protocol which should reduce the low doses in the normal tissue.
RESULTS: Differences in values of the integral dose depend on the geometry and technique of irradiation, as well as optimization protocol used in preparing treatment plans. The application of the rings optimization caused the value of normal tissue integral dose (NTID) to decrease.
CONCLUSIONS: It is possible to limit the area of low dose irradiation and reduce NTID in dynamic techniques with the same clinical constraints for OAR and PTV volumes by using an optimization protocol other than the classic one.

BACKGROUND: Recent studies have reported that NOS3 plays an important role in cardiovascular pathology, whereas the association of NOS3 and hypertension (HT) has been controversial between African Americans and European whites. Here, we aimed to further investigate the genetic effect of unexplored loci at NOS3 on the susceptibility of HT in the Han Chinese population.
RESULTS: The association of three polymorphisms; rs4496877, rs1808593 and rs3918186 to HT was tested in a case control study that included 2012 HT cases and 2210 controls. Association analysis showed that there was no significant association between rs4496877, rs1808593 and rs3918186 of NOS3 and HT in the whole study population. Stratification analysis indicated that rs3918186 was significantly associated with HT in the ≥55-year-old population (OR = 1.245, 95% CI = 1.010-1.534, P = 0.04). The rs4496877 and rs1808593 were significantly associated with HT in the male population (P = 0.015) and <55-year-old population (P = 0.025), respectively (OR = 3.254, 95% CI = 1.257-8.425 and OR = 1.683, 95% CI = 1.066-2.657, respectively). Quantitative trait analysis showed that there were significant differences in systolic blood pressure (SBP) among the genotypes (AA, AT and TT) of rs3918186 in the non-intervention populations (P = 0.016). GMDR analysis showed that drinking and rs3918186 had significant interaction effects for risk of HT.
CONCLUSIONS: The findings of this study indicated that the rs4496877, rs1808593 and rs3918186 polymorphisms of NOS3 contribute to the genetic susceptibility of HT and that rs3918186 was associated with SBP in the Chinese population. Age and gender might modify the genetic effect of NOS3 on HT, and drinking significantly interacts with rs3918186.

BACKGROUND: Given the association between valvular heart disease and drugs that alter serotonin metabolism, concerns have been raised about the possibility of an association between selective serotonin reuptake inhibitor (SSRI) use and drug-induced valvular disease. In France, SSRI use has been suggested to be an important confounding factor in the development of heart valve lesions in patients exposed to benfluorex in the context of the \'Médiator scandal\'.
OBJECTIVE: To address the relationship between SSRI use and valve regurgitation and morphology in a large cohort of patients exposed to benfluorex.
METHODS: Overall, 832 consecutive patients exposed to benfluorex prospectively referred to 10 centres underwent complete echocardiography examinations according to a standardized protocol. Echocardiograms were independently and blindly read off-line by two experts.
RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more. The proportions of patients with no or trivial, mild, moderate or severe mitral regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies of AR ≥ mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR ≥ mild (14 [15.6%] vs 118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The frequencies of aortic and mitral valve abnormalities suggestive of drug-induced toxicity were also similar in the two patient groups. Multivariable logistic regression analysis confirmed the absence of any identifiable relationship between AR or MR and morphological abnormalities and SSRI use in the present cohort.
CONCLUSIONS: Exposure to SSRIs was not associated with an increased risk of heart valve regurgitation or morphological abnormalities suggestive of drug-induced toxicity in this large cohort of patients exposed to benfluorex.

OBJECTIVE: To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension.
METHODS: Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44-46 years). Cut-point for hypertension was blood pressure ≥140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis.
RESULTS: Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p<0.05), and in the hypertensive MetS group than subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p<0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p<0.05), and in the group with hypertension alone than in controls (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p<0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p<0.05).
CONCLUSIONS: Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.