The aim of this observational study was to assess safety and clinical outcomes of percutaneous image-guided cryoablation (CA) to treat osteoblastomas (OBs) at various osseous sites.
A retrospective ...search was performed to identify patients presenting with painful OBs who underwent CA at the University Hospitals of Strasbourg between March 2007 and December 2018. Ten patients (seven men, three women; median age, 21 years old) were identified and included. Medical records were reviewed to assess complications and clinical outcomes.
Median OB diameter was 16.5 mm (range, 16-28 mm). OBs were located in the spine (
= 7), calcaneus (
= 1), fibula (
= 1), and third metacarpal bone (
= 1). In 90% of cases (
= 9), one or more critical structures were within 1 cm of the OB (median distance, 5 mm; range, 2-8 mm), thus requiring extensive protective measures. Technical success was achieved in all cases. Two (20%) immediate neural complications were noted. One major complication was consistent with a permanent sensory deficit of the arm. One minor complication was consistent with a transient right Horner syndrome, which completely resolved after 48 hours with high-dose steroids. Median clinical follow-up was 12 months. Primary clinical success was 100% and 78% at 1 and 12 months of follow-up, respectively, with two patients presenting with recurring pain.
Percutaneous image-guided CA represents an effective therapeutic option for patients affected by painful OBs; the safety profile of the procedure is acceptable as long as comprehensive protective measures are deployed in light of the frequent close proximity of critical structures.
In root canal therapy, irrigating solutions are employed to eliminate the bacterial load and also prepare dentin for sealer interaction. The aim of this research was to assess how irrigating ...solutions employed on their own or in sequence affected the tooth structure. The best way to prepare the tooth for obturation using hydraulic calcium silicate cement (HCSC) sealers and gutta-percha, thus guiding clinicians on a matched irrigation-obturation strategy for optimized root canal treatment was investigated. The effect of irrigating solutions on dentine was investigated by assessing changes in dentin microhardness, ultrastructure and mineral content, organic/inorganic matter, surface roughness and Young's modulus. The interaction of four root canal sealers with the dentin was analysed by assessing the changes in microhardness of the dentin after sealer placement and also the sealer to dentin interface by scanning electron and confocal laser microscopy. The irrigating solutions damaged the dentin irreversibly both when used on their own and in combination. The best sequence involved sodium hypochlorite followed by chelator and a final rinse with sodium hypochlorite and obturation using HCSC sealers that enabled the restoration of dentin properties. The HCSC sealers did not rely on chelator irrigating solutions for a good material adaptation to dentin.
G-quadruplexes (G4) are alternative nucleic acid structures involved in transcription, translation and replication. Aberrant G4 formation and stabilisation is linked to genome instability and cancer. ...G4 ligand treatment disrupts key biological processes leading to cell death. To discover genes and pathways involved with G4s and gain mechanistic insights into G4 biology, we present the first unbiased genome-wide study to systematically identify human genes that promote cell death when silenced by shRNA in the presence of G4-stabilising small molecules. Many novel genetic vulnerabilities were revealed opening up new therapeutic possibilities in cancer, which we exemplified by an orthogonal pharmacological inhibition approach that phenocopies gene silencing. We find that targeting the WEE1 cell cycle kinase or USP1 deubiquitinase in combination with G4 ligand treatment enhances cell killing. We also identify new genes and pathways regulating or interacting with G4s and demonstrate that the DDX42 DEAD-box helicase is a newly discovered G4-binding protein.
It all clicks into place: A potent telomere‐targeting small molecule has been identified by using the copper‐free 1,3‐dipolar cycloaddition of a series of alkyne and azide building blocks catalyzed ...by a non‐Watson–Crick DNA secondary structure (see picture). This method rapidly identifies, otherwise unanticipated, potent small‐molecule probes to selectively target a given RNA or DNA.
G-quadruplexes are nucleic acids secondary structures that can be formed in guanine-rich sequences. More than 30 years ago, their formation was first observed in telomeric DNA. Since then, a number ...of other sequences capable of forming G-quadruplex structures have been described and increasing evidence supporting their formation in the context of living cells has been accumulated. To fully underpin the biological significance of G-quadruplexes and their potential as therapeutic targets, several chemical-biology tools and methods have been developed to map and visualise these nucleic acids secondary structures in human cells. In this review, we critically present the most relevant methods developed to investigate G-quadruplex prevalence in human cells and to study their biological functions, presenting the next key chemical-biology challenges that need to be addressed to fully unravel G-quadruplex mediated biology and their therapeutic potential.
G‐quadruplexes (G4s) are nucleic acid secondary structures that have been linked to the functional regulation of eukaryotic organisms. G4s have been extensively characterised in humans and emerging ...evidence suggests that they might also be biologically relevant for human pathogens. This indicates that G4s might represent a novel class of therapeutic targets for tackling infectious diseases. Bioinformatic studies revealed a high prevalence of putative quadruplex‐forming sequences (PQSs) in the genome of protozoans, which highlights their potential roles in regulating vital processes of these parasites, including DNA transcription and replication. In this work, we focus on the neglected trypanosomatid parasites, Trypanosoma and Leishmania spp., which cause debilitating and deadly diseases across the poorest populations worldwide. We review three examples where G4‐formation might be key to modulate transcriptional activity in trypanosomatids, providing an overview of experimental approaches that can be used to exploit the regulatory roles and relevance of these structures to fight parasitic infections.
In this concept article, we discuss the potential roles of DNA G‐quadruplexes (G4s) secondart structures, in modulating the transcriptional control of neglected trypanosomatid parasites, which cause deadly diseases in the poorest populations worldwide. We provide an overview of experimental approaches that can be used to exploit the regulatory roles and relevance of G4s to fight parasitic infections.
Water management has an important role to play in the circular economy transition, through the water treatment and reuse. Its optimal and coherent regulation is also of vital common interest, since ...water knows no borders or lines artificially set out by the States and the dramatic overconsumption and pollution of freshwater are threatening irreparable damage to the world's ecosystems. However, States are reluctant to common regulations, which would have important economic impacts. International and regional organizations face with the fundamental principle of permanent sovereignty of States over natural resources. By analysing the European environmental competence, this study examines the role of Union water law in green economic transition. By investigating the interdependent relationships between the several elements of the water management, the essay suggests that territory use and economic town and country planning would be drawn into the scope of Treaties because of the integrated nature of water services. The case of water reuse illustrates limits and perspectives of the European objective to promote rational utilization of natural resources and combat climate change, introducing the idea according to which freshwater is a European res communis on which the sovereign right of European Union Member States over their own natural resources could be lawfully limited.
Abstract
A heatwave (HW) is a large-scale meteorological event characterised by persistent and extremely high-temperature condition. At the local scale, the urban heat island (UHI) is another ...thermal-related phenomenon defined as an urban area warmer than its surrounding regions due to different surfaces’ capabilities to absorb and store heat. However, the assessment about the effect produced on UHI by HW events is not homogeneous. Indeed, regarding the capability of HWs to influence the urban-rural temperature difference, several studies report different conclusions describing both an exacerbation and a reduction of UHI during HW events. In this context, the present study analyses
in situ
long records of temperature measurements (20 years) to provide observational shreds of evidence of UHI modification under HW conditions. We examine data from the European Climate Assessment & Dataset and World Meteorological Organization computing the UHI index (UHII) to quantify the UHI effect intensity in 37 European cities during the last 20 summers. The results show an UHII intensification for 28 of the 32 cities affected by positive UHI during extremely high temperatures at night, while substantial variations are not observed during the daytime. The time evolution of UHI during a HW highlights that a more significant and persistent urban-rural temperature gradient explains the UHI intensification. Finally, the relationship between the large and local-scale temperature phenomena reveals that continental high-temperature periods are often associated with prominent temperature differences between small-scale urban and rural environments, assessing the impact of large-scale features on thermal stress at the local scale.
Abstract
This study argues that the Minimum Wages Directive reveals a shift in the Union’s political-economic approach to the social competition in the Single Market, which introduces a creeping ...extension of the Treaty’s scope and a potential enlargement of the Union’s competences on social matters. While representing a timid starting point for the right to a minimum wage protection, it recognises that the dumping wages phenomena are partly triggered by an (unresolved) structural legal vacuum. By analysing the instrumental function of the fair remuneration towards human dignity, the idea of the right to fair and just working conditions as an open scoped right is advanced; the thesis of a general Union competence on working conditions is finally proposed. The aim is to illustrate what limits and perspectives the European upward social convergence is currently facing, and to what extent the Union is not necessarily a mere reflection of market completion interests.
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