Coronavirus (Sars-cov-2) pandemic: Future challenges for dental practitioners

In the context of the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) pandemic, the medical system has been subjected to many changes. Face-to-face treatments have been suspended for a period of time. After the lockdown, dentists have to be aware of the modalities to protect themselves and their patients in order not to get infected. Dental practitioners are potentially exposed to a high degree of contamination with SARS-CoV-2 while performing dental procedures that produce aerosols. It should also be noted that the airways, namely the oral cavity and nostrils, are the access pathways for SARS-CoV-2. In order to protect themselves and their patients, they have to use full personal protective equipment. Relevant data regarding this pandemic are under evaluation and are still under test. In this article, we made a synthesis about the way in which SARS-CoV-2 spreads, how to diagnose a novel corona virus infection, what the possible treatments are, and which protective personal equipment we can use to stop its spreading

Visitor expectations of contact with staff at a protected site

The importance of managing visitor expectations has been highlighted in natural and protected areas. However, minimal research has been completed on visitor expectations of contact with staff in national parks and protected areas. Staff can play an important role in delivering information and in interpreting significant natural and heritage attributes. This research aims to address this gap by examining visitors' expectations regarding staff contact at one protected site, Cape Byron State Conservation Area (CBSCA) in New South Wales, Australia. A mixed method approach including interviews with staff and a survey of park visitors was implemented to achieve the research aim. Results indicate that visitors have a diverse range of expectations of park staff regarding when, where, and how staff are expected to provide services and information. Peak-season visitors were more likely to want information about European heritage and the lighthouse than were off-season visitors. Visitors over 25 years of age were significantly more likely to expect information about wildlife, native plants and vegetation, the marine environment, whales and whale watching, Indigenous heritage, European heritage, and recreation opportunities within CBSCA than visitors under 25. Visitors between 36 and 45 years of age were the most likely to participate in activities involving staff. Overall, visitors were no more likely to participate in activities involving staff than in self-directed activities. Finally, some implications for the management of CBSCA and avenues for future research are proposed.No Full Tex

HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS

The Importance of the Protected Area for the Life of the Local Community—A Case Study of the Deliblato Sands Special Nature Reserve

The Deliblato Sands Special Nature Reserve encompasses five municipalities and several settlements. This significantly protected region has a strong relationship between its ecosystem and the people who live there. The local population benefits from various advantages provided by this reserve. The residents’ quality of life greatly depends on the reserve’s resources. When used responsibly, they can guarantee a sustainable system with assets that are renewable. Additionally, both locals and tourists benefit from the utilization of forest space for recreation. Above all, endangered plant and animal species are protected in the Deliblato Sands woodlands. Therefore, the role of the local population in protecting this reserve is crucial for the survival of these species. Visitors from both domestic and foreign countries visit this reserve each year in considerable numbers. The study included a quantitative methodology, in which data were collected using questionnaires. The study’s goal is to find out whether the nature reserve has an impact on residents’ lives, activities, and habits, i.e., whether characteristics have an impact on respondents’ contentment. This research aims to examine how the protected area (PA) affects the life of the local community. A total of 1450 residents were surveyed regarding the impact of the Deliblato Sands ecosystem on their habits and activities. Analysis of the data indicates that the inhabitants are significantly impacted by the PA. The strongest impacts are grouped into the ecological and socio-cultural dimensions, while the economic dimension is the one with the weakest impact. The study’s value is evident in the crucial information that was supplied for the creation of national and local planning documents pertaining to the development of rural areas and tourism. The active participation of communities must be the foundation of any planning for tourism growth

Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site

Antigenic variants resistant to eight neutralizing monoclonal antibodies were selected from wild (Mahoney) and attenuated (Sabin) type 1 infectious poliovirions. Cross-immunoprecipitation revealed interrelationships between epitopes which were not detected by cross-neutralization. Operational analysis of antigenic variants showed that seven of eight neutralization epitopes studied were interrelated. Only one neutralization epitope, named Kc, varied independently from all the others. This latter, recognized by C3 neutralizing monoclonal antibody, was present not only on infectious virions but also on heat-denatured (C-antigenic) particles and on isolated capsid protein VP1. Loss of the neutralization function of an epitope did not necessary result from the loss of its antibody-binding capacity. Such potential, but not functional, neutralization epitopes exist naturally on Mahoney and Sabin 1 viruses. Their antibody-binding property could be disrupted by isolating antigenic variants in the presence of the nonneutralizing monoclonal antibody and anti-mouse immunoglobulin antibodies. Single-point mutations responsible for the acquisition of resistance to neutralization in the antigenic variants were located by sequence analyses of their genomes. Mutants selected in the presence of C3 neutralizing monoclonal antibody always had the mutation located inside the antibody-binding site (residues 93 through 103 of VP1) at the amino acid position 100 of VP1. On the contrary, antigenic variants selected in the presence of neutralizing monoclonal antibodies reacting only with D-antigenic particles had mutations situated in VP3, outside the antibody-binding site (residues 93 through 103 of VP1). The complete conversion of the Mahoney to the Sabin 1 epitope map resulted from a threonine-to-lysine substitution at position 60 of VP3.</jats:p

Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma

Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R. Nutlin-3 treatment increased IGF-1R/Mdm2 association with enhanced IGF-1R ubiquitination and a dual functional outcome: Receptor downregulation and selective downstream signaling activation confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. This Nutlin-3 functional selectivity translated into IGF-1-mediated bioactivities with biphasic effects on the proliferative and metastatic phenotype: An early increase and late decrease in the number of proliferative and migratory cells, while the invasiveness was completely inhibited following Nutlin-3 treatment through an impaired IGF-1-mediated matrix metalloproteinases type 2 activation mechanism. Taken together, these experiments reveal the biased agonistic properties of Nutlin-3 for the mitogen-activated protein kinase pathway, mediated by Mdm2 through IGF-1R ubiquitination and provide fundamental insights into destabilizing p53/Mdm2/IGF-1R circuitry that could be developed for therapeutic gain

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

As our understanding of the driver mutations necessary for initiation and progression of cancers improves, we gain critical information on how specific molecular profiles of a tumor may predict responsiveness to therapeutic agents or provide knowledge about prognosis. At our institution a tumor genotyping program was established as part of routine clinical care, screening both hematologic and solid tumors for a wide spectrum of mutations using two next-generation sequencing (NGS) panels: a custom, 33 gene hematological malignancies panel for use with peripheral blood and bone marrow, and a commercially produced solid tumor panel for use with formalin-fixed paraffin-embedded tissue that targets 47 genes commonly mutated in cancer. Our workflow includes a pathologist review of the biopsy to ensure there is adequate amount of tumor for the assay followed by customized DNA extraction is performed on the specimen. Quality control of the specimen includes steps for quantity, quality and integrity and only after the extracted DNA passes these metrics an amplicon library is generated and sequenced. The resulting data is analyzed through an in-house bioinformatics pipeline and the variants are reviewed and interpreted for pathogenicity. Here we provide a snapshot of the utility of each panel using two clinical cases to provide insight into how a well-designed NGS workflow can contribute to optimizing clinical outcomes