Pre‐natal brain development as a target for urban air pollution

Air pollution is the main urban‐related environmental hazard and one of the major contributors to the global burden of disease based on its cardiovascular‐respiratory impacts. In children, exposure to urban air pollution is associated, among others, with decelerated neurodevelopment early in life and increased risk of neurodevelopmental problems such as attention‐deficit hyperactivity disorder, autism spectrum disorders, academic failure and the start of Alzheimer's pathogenesis. However, the evidence of the effects of air pollution on brain development is still inadequate, mainly due to the limitations in (a) characterizing brain development (most studies were based on subjective tools such as questionnaires or neuropsychological tests) and (b) air pollution exposure (most studies only used residential levels based on geographical modelling and also overlooking the variation in the mixture of air pollutants as well as the composition and hence toxicity of particulate pollutants in different settings), (c) the lack of studies during the most vulnerable stages of brain development (foetal and early life (first two years post‐natally)) and (d) the lack of structural and functional imaging data underlying these effects. In mice, in utero exposure to fine particles was linked to structural brain changes and there is a need to establish the generalizability of these findings in human beings. Though scarce, current evidence in children supports the importance of the pre‐natal period as a susceptible window of exposure. Two studies in schoolchildren found that pre‐natal air pollution exposure might damage brain structure while exposure during childhood was not linked to any structural alteration. Another study showed that children with higher traffic‐related air pollution at school had lower functional integration in key brain networks, but no changes in brain structure, possibly partly because of the time window of air pollution exposure (in utero versus childhood exposure). A key development is to discover the windows of greatest sensitivity of structural brain changes to air pollution exposure by incorporating the recent advances in non‐invasive imaging to characterize natal and post‐natal brain development and exploring whether and to what extend placental dysfunction could mediate such an association. Studying pre‐natal life is important because effects at this time are of a potentially irreversible nature and because the largest preventive opportunities occur during these periods.     

High Mortality in Late Octogenarians Undergoing Isolated Aortic Valve Replacement for Aortic Valve Stenosis: EuroSCORE Underestimates Mortality in this Cohort

Objectives Considering the expanding technology of catheter-based aortic valve implantation, high-risk patients who would not be suitable for conventional aortic valve replacement (AVR) should be identified.Methods From 1997 to April 2007, 190 patients aged from 80 and 89 years old received isolated AVR. Patients between 80 and 84 years old were categorized as the early octogenarians (n = 148) and patients between 85 and 89 years old were categorized as the late octogenarians (n = 42).Results Thirty days mortality in the early and late octogenarians were 6 and 21%, respectively (p = 0.003). The additive and logistic EuroSCORE were 8.0 ± 2.4 and 8.8 ± 1.8 in the early octogenarians and 13.2 ± 11.8 and 14.6 ± 8.7 in the late octogenarians. Multivariate analysis revealed the late octogenarians (OR 6.7, 95%CL 1.8-24.4, p = 0.004) and poor left ventricular function (OR 8.0, 95%CL 1.2-53.5, p = 0.032) as significant risk factors for 30 days mortality. Early octogenarians showed 1-year, 3-year, 5-year, and 8-year survival of 82.4, 67.6, 54.7, and 33%, respectively. Late octogenarians showed 1-year, 3-year, 5-year, and 8-year survivals of 69.0, 66.2, 41.6, 22.3%, respectively.Conclusions Mortality after AVR in the late octogenarians was very high, and was underestimated by EuroSCORE in this patients group. In late octogenarians, catheter-based aortic valve implantation despite relative low EuroSCORE level could be considered as a reasonable alternative.     

In utero repair of myelomeningocele with autologous amniotic membrane in the fetal lamb model

Background

Despite advances in prenatal repair, myelomeningocele (MMC) still produces devastating neurologic deficits. The amniotic membranes (AM) are a biologically active tissue that has been used anecdotally for human fetal MMC repair. This study evaluated the use of autologous AM compared to skin closure in an established fetal MMC model.

Methods

Seven fetal lambs underwent surgical creation of MMC at gestational age of 75 days followed by in utero repair at gestational age of 100 days. Lambs were repaired with an autologous AM patch followed by skin closure (n = 4) or skin closure alone (n = 3). Gross necropsy and histopathology of the spinal cords were performed at term to assess neuronal preservation at the lesion.

Results

An increase in preserved motor neurons and a larger area of spinal cord tissue were seen in AM-repaired lambs, as was decreased wound healing of the overlying skin. Loss of nearly all spinal cord tissue with limited motor neuron preservation was seen in skin only-repaired lambs.

Conclusions

AM-repaired lambs showed increased protection of spinal cord tissue compared to skin only-repaired lambs, but the overlying skin failed to close in AM-repaired lambs. These results suggest a potential role for AM in fetal MMC repair that warrants further study.     

Risks and Benefits of Green Spaces for Children: A Cross-Sectional Study of Associations with Sedentary Behavior,Obesity, Asthma,and Allergy

Background: Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce.Objectives: We aimed to simultaneously evaluate health benefits and risks associated with different types of greenness in children, in terms of sedentary behavior (represented by excessive screen time), obesity, current asthma, and allergic rhinoconjunctivitis.Methods: We conducted a cross-sectional study of a population-based sample of 3,178 schoolchildren (9–12 years old) in Sabadell, Spain, in 2006. Information on outcomes and covariates was obtained by questionnaire. We measured residential surrounding greenness as the average of satellite-derived Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, 500 m, and 1,000 m around each home address. Residential proximity to green spaces was defined as living within 300 m of a forest or a park, as separate variables. We used logistic regression models to estimate associations separately for each exposure–outcome pair, adjusted for relevant covariates.Results: An interquartile range increase in residential surrounding greenness was associated with 11–19% lower relative prevalence of overweight/obesity and excessive screen time, but was not associated with current asthma and allergic rhinoconjunctivitis. Similarly, residential proximity to forests was associated with 39% and 25% lower relative prevalence of excessive screen time and overweight/obesity, respectively, but was not associated with current asthma. In contrast, living close to parks was associated with a 60% higher relative prevalence of current asthma, but had only weak negative associations with obesity/overweight or excessive screen time.Conclusion: We observed two separable patterns of estimated health benefits and risks associated with different types of greenness.Citation: Dadvand P, Villanueva CM, Font-Ribera L, Martinez D, Basagaña X, Belmonte J, Vrijheid M, Gražulevičienė R, Kogevinas M, Nieuwenhuijsen MJ. 2014. Risks and benefits of green spaces for children: a cross-sectional study of associations with sedentary behavior, obesity, asthma, and allergy. Environ Health Perspect 122:1329–1335; http://dx.doi.org/10.1289/ehp.1308038     

A novel customizable modular bioreactor system for whole-heart cultivation under controlled 3D biomechanical stimulation

In the last decade, cardiovascular tissue engineering has made great progress developing new strategies for regenerative medicine applications. However, while tissue engineered heart valves are already entering the clinical routine, tissue engineered myocardial substitutes are still restrained to experimental approaches. In contrast to the heart valves, tissue engineered myocardium cannot be repopulated in vivo because of its biological complexity, requiring elaborate cultivation conditions ex vivo. Although new promising approaches—like the whole-heart decellularization concept—have entered the myocardial tissue engineering field, bioreactor technology needed for the generation of functional myocardial tissue still lags behind in the sense of user-friendly, flexible and low cost systems. Here, we present a novel customizable modular bioreactor system that can be used for whole-heart cultivation. Out of a commercially obtainable original equipment manufacturer platform we constructed a modular bioreactor system specifically aimed at the cultivation of decellularized whole-hearts through perfusion and controlled 3D biomechanical stimulation with a simple but highly flexible operation platform based on LabVIEW^®. The modular setup not only allows a wide range of variance regarding medium conditioning under controlled 3D myocardial stretching but can also easily be upgraded for e.g. electrophysiological monitoring or stimulation, allowing for a tailor-made low-cost myocardial bioreactor system.     

Case report and literature review: primary cutaneous carcinosarcoma

Carcinosarcomas are rare but aggressive neoplasms commonly described in organs such as the breast, urinary bladder, uterus, liver, and lungs. Histopathologically, they are characterized by the presence of malignant epithelial and mesenchymal components. The exact histogenesis of carcinosarcomas remains unknown and is debated in the literature. Primary carcinosarcomas of the skin are uncommon. To our knowledge, 20 cases of primary cutaneous carcinosarcoma have been described in the world literature. Most of these tumors were seen on the head and neck region of older individuals, both male and female. Microscopically, the more common carcinoma component is a squamous cell carcinoma followed by basal cell carcinoma, whereas the most common sarcoma component is an osteosarcoma. We report an example of this rare entity and speculate on its histogenesis in the skin.