Range verification for eye proton therapy based on proton-induced x-ray emissions from implanted metal markers.

Metal fiducial markers are often implanted on the back of the eye before proton therapy to improve target localization and reduce patient setup errors. We aim to detect characteristic x-ray emissions from metal targets during proton therapy to verify the treatment range accuracy. Initially gold was chosen for its biocompatibility properties. Proton-induced x-ray emissions (PIXE) from a 15 mm diameter gold marker were detected at different penetration depths of a 59 MeV proton beam at the CATANA proton facility at INFN-LNS (Italy). The Monte Carlo code Geant4 was used to reproduce the experiment and to investigate the effect of different size markers, materials, and the response to both mono-energetic and fully modulated beams. The intensity of the emitted x-rays decreases with decreasing proton energy and thus decreases with depth. If we assume the range to be the depth at which the dose is reduced to 10% of its maximum value and we define the residual range as the distance between the marker and the range of the beam, then the minimum residual range which can be detected with 95% confidence level is the depth at which the PIXE peak is equal to 1.96 σbkg, which is the standard variation of the background noise. With our system and experimental setup this value is 3 mm, when 20 GyE are delivered to a gold marker of 15 mm diameter. Results from silver are more promising. Even when a 5 mm diameter silver marker is placed at a depth equal to the range, the PIXE peak is 2.1 σbkg. Although these quantitative results are dependent on the experimental setup used in this research study, they demonstrate that the real-time analysis of the PIXE emitted by fiducial metal markers can be used to derive beam range. Further analysis are needed to demonstrate the feasibility of the technique in a clinical setup

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease

Purpose: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. Methods: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Results: Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. Conclusion: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future

Water aerobics II: maternal body composition and perinatal outcomes after a program for low risk pregnant women

<p>Abstract</p> <p>Background</p> <p>To evaluate the effectiveness and safety of water aerobics during pregnancy.</p> <p>Methods</p> <p>A randomized controlled trial carried out in 71 low-risk sedentary pregnant women, randomly allocated to water aerobics or no physical exercise. Maternal body composition and perinatal outcomes were evaluated. For statistical analysis Chi-square, Fisher's or Student's t-tests were applied. Risk ratios and their 95% CI were estimated for main outcomes. Body composition was evaluated across time using MANOVA or Friedman multiple analysis.</p> <p>Results</p> <p>There were no significant differences between the groups regarding maternal weight gain, BMI or percentage of body fat during pregnancy. Incidence of preterm births (RR = 0.84; 95%CI:0.28–2.53), vaginal births (RR = 1.24; 95%CI:0.73–2.09), low birthweight (RR = 1.30; 95%CI:0.61–2.79) and adequate weight for gestational age (RR = 1.50; 95%CI:0.65–3.48) were also not significantly different between groups. There were no significant differences in systolic and diastolic blood pressure and heart rate between before and immediately after the water aerobics session.</p> <p>Conclusion</p> <p>Water aerobics for sedentary pregnant women proved to be safe and was not associated with any alteration in maternal body composition, type of delivery, preterm birth rate, neonatal well-being or weight.</p

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Fetal cardiotocography before and after water aerobics during pregnancy

<p>Abstract</p> <p>Objective</p> <p>To evaluate the effect of moderate aerobic physical activity in water on fetal cardiotocography patterns in sedentary pregnant women.</p> <p>Method</p> <p>In a non-randomized controlled trial, 133 previously sedentary pregnant women participated in multiple regular sessions of water aerobics in a heated swimming pool. Cardiotocography was performed for 20 minutes before and just after the oriented exercise. Cardiotocography patterns were analyzed pre- and post-exercise according to gestational age groups (24-27, 28-31, 32-35 and 36-40 weeks). Student's t and Wilcoxon, and McNemar tests were used, respectively, to analyze numerical and categorical variables.</p> <p>Results</p> <p>No significant variations were found between pre- and post-exercise values of fetal heart rate (FHR), number of fetal body movements (FM) or accelerations (A), FM/A ratio or the presence of decelerations. Variability in FHR was significantly higher following exercise only in pregnancies of 24-27 weeks.</p> <p>Conclusions</p> <p>Moderate physical activity in water was not associated with any significant alterations in fetal cardiotocography patterns, which suggests no adverse effect on the fetus.</p

APOEε4 associates with microglial activation independently of Aβ plaques and tau tangles

Animal studies suggest that the apolipoprotein E ε4 (APOEε4) allele is a culprit of early microglial activation in Alzheimer's disease (AD). Here, we tested the association between APOEε4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomography for amyloid-β (Aβ; [18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28). We found that APOEε4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of APOEε4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of APOE mRNA expression predicted the patterns of APOEε4-related microglial activation in our population, suggesting that APOE gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the APOEε4 genotype exerts Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset