6 research outputs found

    The Israeli Experience with the “Green Pass” Policy Highlights Issues to Be Considered by Policymakers in Other Countries

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    In the first half of 2021, Israel had been ahead of other countries concerning the speed of its rollout and coverage of COVID-19 vaccinations. During that time, Israel had implemented a vaccine certificate policy, the “Green Pass Policy” (GPP), to reduce virus spread and to allow the safe relaxation of COVID-19 restrictions in a time of great uncertainty. Based on an analysis of GPP regulations and public statements compiled from the Israeli Ministry of Health website, we describe the design and implementation of the GPP. We also look back and discuss lessons learned for countries that are considering a GPP policy, given the current upsurge of the Delta variant as of summer 2021. To reduce equity concerns when introducing a GPP, all population groups should be eligible for the vaccine (contingent on approval from the manufacturer) and have access to it. Alternatively, health authorities can grant temporary certificates based on a negative test. We also highlight the fact that in practice, there will be gaps between the GPP regulations and implementation. While some places might require a GPP without legal need, others will not implement it despite a legal obligation. The GPP regulations should have standardised epidemiological criteria, be implemented gradually, remain flexible, and change according to the epidemiological risks.DFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische UniversitĂ€t Berli

    Mechanical forces drive ordered patterning of hair cells in the mammalian inner ear

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    The periodic organization of cells is typically associated with mechanisms based on intercellular signaling such as lateral inhibition and Turing patterning. Here the authors show that hair cells in the inner ear rearrange gradually into a checkerboard-like pattern through a tissue-wide shear motion that coordinates intercalation and delamination events

    Monogenic Causes of Apparently Idiopathic Perinatal Intracranial Hemorrhage

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    Objective: Perinatal intracranial hemorrhage (pICH) is a rare event that occurs during the fetal/neonatal period with potentially devastating neurological outcome. However, the etiology of pICH is frequently hard to depict. We investigated the role of rare genetic variations in unexplained cases of pICH. Methods: We performed whole-exome sequencing (WES) in fetuses and term neonates with otherwise unexplained pICH and their parents. Variant causality was determined according to the American College of Medical Genetics and Genomics (ACMG) criteria, consistency between suggested genes and phenotypes, and mode of inheritance. Results: Twenty-six probands (25 families) were included in the study (9 with a prenatal diagnosis and 17 with a postnatal diagnosis). Intraventricular hemorrhage (IVH) was the most common type of hemorrhage (n = 16, 62%), followed by subpial (n = 4, 15%), subdural (n = 4, 15%), and parenchymal (n = 2, 8%) hemorrhage. Causative/likely causative variants were found in 4 subjects from 3 of the 25 families (12%) involving genes related to the brain microenvironment (COL4A1, COL4A2, and TREX-1). Additionally, potentially causative variants were detected in genes related to coagulation (GP1BA, F11, Von Willebrand factor [VWF], FGA, and F7; n = 4, 16%). A potential candidate gene for phenotypic expansion related to microtubular function (DNAH5) was identified in 1 case (4%). Fifty-five percent of the variants were inherited from an asymptomatic parent. Overall, these findings showed a monogenic cause for pICH in 12% to 32% of the families. Interpretation: Our findings reveal a clinically significant diagnostic yield of WES in apparently idiopathic pICH and support the use of WES in the evaluation of these cases. ANN NEUROL 2021;89:813–822

    Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma-Targeted Dendritic Polyglycerol Nanopolyplexes

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    The presence of dormant, microscopic cancerous lesions poses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized pairs of dormant and fast-growing human osteosarcoma models. Using these pairs of mouse tumor models, we identified three novel regulators of osteosarcoma dormancy: miR-34a, miR-93, and miR-200c. This report shows that loss of these microRNAs occurs during the switch from dormant avascular into fast-growing angiogenic phenotype. We validated their downregulation in patients’ tumor samples compared to normal bone, making them attractive candidates for osteosarcoma therapy. Successful delivery of miRNAs is a challenge; hence, we synthesized an aminated polyglycerol dendritic nanocarrier, dPG-NH<sub>2</sub>, and designed dPG-NH<sub>2</sub>-microRNA polyplexes to target cancer. Reconstitution of these microRNAs using dPG-NH<sub>2</sub> polyplexes into Saos-2 and MG-63 cells, which generate fast-growing osteosarcomas, reduced the levels of their target genes, MET proto-oncogene, hypoxia-inducible factor 1α, and moesin, critical to cancer angiogenesis and cancer cells’ migration. We further demonstrate that these microRNAs attenuate the angiogenic capabilities of fast-growing osteosarcomas <i>in vitro</i> and <i>in vivo</i>. Treatment with each of these microRNAs using dPG-NH<sub>2</sub> significantly prolonged the dormancy period of fast-growing osteosarcomas <i>in vivo</i>. Taken together, these findings suggest that nanocarrier-mediated delivery of microRNAs involved in osteosarcoma tumor–host interactions can induce a dormant-like state