BACKGROUND ; There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations ...are associated with smoking. METHODS ; Observational studies published 1959-2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS ; Significant positive associations with maternal smoking were found for: cardiovascular/heart defects OR 1.09, 95% confidence interval (CI) 1.02-1.17; musculoskeletal defects (OR 1.16, 95% CI 1.05-1.27); limb reduction defects (OR 1.26, 95% CI 1.15-1.39); missing/extra digits (OR 1.18, 95% CI 0.99-1.41); clubfoot (OR 1.28, 95% CI 1.10-1.47); craniosynostosis (OR 1.33, 95% CI 1.03-1.73); facial defects (OR 1.19, 95% CI 1.06-1.35); eye defects (OR 1.25, 95% CI 1.11-1.40); orofacial clefts (OR 1.28, 95% CI 1.20-1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18-1.36); gastroschisis (OR 1.50, 95% CI 1.28-1.76); anal atresia (OR 1.20, 95% CI 1.06-1.36); hernia (OR 1.40, 95% CI 1.23-1.59); and undescended testes (OR 1.13, 95% CI 1.02-1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85-0.95) and skin defects (OR 0.82, 0.75-0.89). For all defects combined the OR was 1.01 (0.96-1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS ; Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.
Combinations of BRAF inhibitors and MEK inhibitors (BRAFi + MEKi) are FDA-approved to treat
-mutant melanoma. Efficacy of BRAFi + MEKi associates with cancer cell death and alterations in the tumor ...immune microenvironment; however, the links are poorly understood. We show that BRAFi + MEKi caused durable melanoma regression in an immune-mediated manner. BRAFi + MEKi treatment promoted cleavage of gasdermin E (GSDME) and release of HMGB1, markers of pyroptotic cell death. GSDME-deficient melanoma showed defective HMGB1 release, reduced tumor-associated T cell and activated dendritic cell infiltrates in response to BRAFi + MEKi, and more frequent tumor regrowth after drug removal. Importantly, BRAFi + MEKi-resistant disease lacked pyroptosis markers and showed decreased intratumoral T-cell infiltration but was sensitive to pyroptosis-inducing chemotherapy. These data implicate BRAFi + MEKi-induced pyroptosis in antitumor immune responses and highlight new therapeutic strategies for resistant melanoma. SIGNIFICANCE: Targeted inhibitors and immune checkpoint agents have advanced the care of patients with melanoma; however, detailed knowledge of the intersection between these two research areas is lacking. We describe a molecular mechanism of targeted inhibitor regulation of an immune-stimulatory form of cell death and provide a proof-of-principle salvage therapy concept for inhibitor-resistant melanoma.
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In a world conceptualised as Anthropocene, in which human activities are transforming every part of the biosphere, funerals have become political and ethical activities in new and unforeseen ways. ...The use of formaldehyde in embalming practices and the release of air pollutants during cremation are only two of many points of criticism which have led to the rise of alternative ‘greener’ burial methods. The ‘infinity burial project’ is one such alternative, but it exceeds discourses on sustainable funerals by highlighting the toxicity of human bodies and challenging cultural taboos surrounding corporeal decomposition. Infinity burial employs ‘mycoremediation’, the usage of fungi for decomposing and cleaning up contaminated bodies and landscapes. Departing from Donna Haraway’s call for embracing situated technical projects in order to make ‘oddkin’, this article explores how the infinity burial project engenders queer communities which dismiss taxonomical lines between species as well as ontological claims about life and death. Drawing on new materialisms’ work on the radical openness of bodies, I explore how the infinity burial project sheds light on the material reality of decaying and the implications of dying in a polluted world.
In vivo studies represent an essential step in drug development and currently rely largely on mice, yet limitations of mammalian models motivated the search for complementary vertebrate model ...systems. This review focuses on zebrafish, Danio rerio, as a facile model system to study human disease and drug responses. Zebrafish are particularly suited for this purpose because they represent a vertebrate species, their genome is sequenced, and a large number of synchronously developing, transparent embryos can be produced. Zebrafish embryos are permeable to drugs and can easily be manipulated using well‐established genetic and molecular approaches. Here, we summarize recent work on drug discovery and toxicity in zebrafish embryos. In addition, we provide a synopsis of current efforts to establish disease models in zebrafish focusing on neoplasia. The results of these studies highlight the potential of zebrafish as a viable addition to established animal models by offering medium and, potentially, high throughput capabilities.
Clinical Pharmacology & Therapeutics (2007) 82, 70–80. doi:10.1038/sj.clpt.6100223; published online 9 May 2007
Body ideals conveyed by the media and by body comparisons often result in body dissatisfaction, which can cause risky health behaviours and eating disorders, especially in adolescents. We conducted a ...meta-analytic review of existing school-based interventions designed to enhance media literacy in order to reduce body dissatisfaction and to promote a positive body image. We included controlled trials examining children and adolescents from grade five to nine (age 10–15 years) after a manual search and a comprehensive literature search using PsycINFO, Medline, Web of Science, and CENTRAL. We computed average weighted effect sizes (Hedges’ g) with the help of a random effects model and identified seventeen different programme evaluations with 7392 participants. We found a significantly larger effect on positive body image and media literacy in the intervention compared to control groups. However, heterogeneity was substantial for both outcomes. Results suggest that media literacy interventions have the potential to improve media literacy and reduce body dissatisfaction. Interventions that worked with the principle of induction of cognitive dissonance were the most effective.
In a world conceptualised as Anthropocene, in which human activities are transforming every part of the biosphere, funerals have become political and ethical activities in new and unforeseen ways. ...The use of formaldehyde in embalming practices and the release of air pollutants during cremation are only two of many points of criticism which have led to the rise of alternative ‘greener’ burial methods. The ‘infinity burial project’ is one such alternative, but it exceeds discourses on sustainable funerals by highlighting the toxicity of human bodies and challenging cultural taboos surrounding corporeal decomposition. Infinity burial employs ‘mycoremediation’, the usage of fungi for decomposing and cleaning up contaminated bodies and landscapes. Departing from Donna Haraway’s call for embracing situated technical projects in order to make ‘oddkin’, this article explores how the infinity burial project engenders queer communities which dismiss taxonomical lines between species as well as ontological claims about life and death. Drawing on new materialisms’ work on the radical openness of bodies, I explore how the infinity burial project sheds light on the material reality of decaying and the implications of dying in a polluted world.
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