Bordetella petrii Clinical Isolate

We describe the first clinical isolate of Bordetella petrii from a patient with mandibular osteomyelitis. The only previously documented isolation of B. petrii occurred after the initial culture of a single strain from an environmental source

Memórias das experiências com o brincar: narrativas e mônadas de professoras de educação infantil

The purpose of this work was to reflect on the memories of the experiences with the teachers’ playing that work in early childhood education, reconstructing, in the form of narratives and monads, the ludic universe lived by them. According to the perspective of oral history, three teachers from an early childhood education centre of a public university in São Paulo were interviewed. Reflecting on shared memories, we found that, as historical subjects immersed in a social reality, teachers have experiences with playing that are significant and constitute their singularity, reverberating in the way they see and mediate playing  in their teaching practice.El trabajo tuvo como objetivo reflexionar sobre las memorias de las experiencias con el jugar de profesoras que actúan en la educación infantil, reconstruyendo, en forma de narrativas y mónadas, el universo lúdico vivido por ellas. Tomando como referencia la perspectiva de la historia oral, fueron entrevistadas tres profesoras de un centro de educación infantil de una universidad pública paulista. A partir de las memorias compartidas, constatamos que, como sujetos históricos inmersos en una realidad social, las profesoras poseen experiencias con el jugar que son significativas y constituyen su singularidad, reverberando en la forma como las mismas ven y hacen la mediación del juego en su práctica docente.O trabalho teve como objetivo refletir sobre as memórias das experiências com o brincar de professoras que atuam na educação infantil, reconstruindo, em forma de narrativas e mônadas, o universo lúdico vivido por elas. Tomando como referência a perspectiva da história oral, foram entrevistadas três professoras de um centro de educação infantil de uma universidade pública paulista. Com base nas memórias compartilhadas, constatamos que, como sujeitos históricos imersos numa realidade social, as professoras possuem experiências com o brincar que são significativas e constituem sua singularidade, reverberando na forma como as mesmas veem e fazem a mediação das brincadeiras na sua prática docente

Enhanced TP53 Reactivation Disrupts MYC Transcriptional Program and Overcomes Venetoclax Resistance in Acute Myeloid Leukemias

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Enhanced TP53 reactivation disrupts MYC transcriptional program and overcomes venetoclax resistance in acute myeloid leukemias

The tumor suppressor TP53 is frequently inactivated in a mutation-independent manner in cancers and is reactivated by inhibiting its negative regulators. We here cotarget MDM2 and the nuclear exporter XPO1 to maximize transcriptional activity of p53. MDM2/XPO1 inhibition accumulated nuclear p53 and elicited a 25- to 60-fold increase of its transcriptional targets. TP53 regulates MYC, and MDM2/XPO1 inhibition disrupted the c-MYC-regulated transcriptome, resulting in the synergistic induction of apoptosis in acute myeloid leukemia (AML). Unexpectedly, venetoclax-resistant AMLs express high levels of c-MYC and are vulnerable to MDM2/XPO1 inhibition in vivo. However, AML cells persisting after MDM2/XPO1 inhibition exhibit a quiescence- and stress response-associated phenotype. Venetoclax overcomes that resistance, as shown by single-cell mass cytometry. The triple inhibition of MDM2, XPO1, and BCL2 was highly effective against venetoclax-resistant AML in vivo. Our results propose a novel, highly translatable therapeutic approach leveraging p53 reactivation to overcome nongenetic, stress-adapted venetoclax resistance

Plasticity of fruit and oil traits in olive among diferent environments

Olive is a long-living perennial species with a wide geographical distribution, showing a large genetic and phenotypic variation in its growing area. There is an urgent need to uncover how olive phenotypic traits and plasticity can change regardless of the genetic background. A two-year study was conducted, based on the analysis of fruit and oil traits of 113 cultivars from fve germplasm collections established in Mediterranean Basin countries and Argentina. Fruit and oil traits plasticity, broad‐sense heritability and genotype by environment interaction were estimated. From variance and heritability analyses, it was shown that fruit fresh weight was mainly under genetic control, whereas oleic/(palmitic+linoleic) acids ratio was regulated by the environment and genotype by environment interaction had the major efect on oil content. Among the studied cultivars, diferent level of stability was observed, which allowed ranking the cultivars based on their plasticity for oil traits. High thermal amplitude, the diference of low and high year values of temperature, negatively afected the oil content and the oleic acid percentage. Information derived from this work will help to direct the selection of cultivars with the highest global ftness averaged over the environments rather than the highest ftness in each environment separately.EEA San JuanFil: Mousavi, Soraya. Consiglio Nazionale delle Ricerche. Institute of Biosciences and Bioresources; ItaliaFil: Mousavi, Soraya. Consiglio Nazionale delle Ricerche. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: De la Rosa, Raúl. Instituto Andaluz de Investigación y Formación Agraria, Pesquera, Alimentaria y de la Producción Ecológica (IFAPA). - Centro Alameda del Obispo; EspañaFil: Moukhli, Abdelmajid. Institut National de la Recherche Agronomique (INRA). Centre Régional de la Recherche Agronomique( CRRA); MarruecosFil: El Riachy, Milad. Lebanese Agricultural Research Institute (LARI); LíbanoFil: Mariotti, Roberto. Consiglio Nazionale delle Ricerche. Institute of Biosciences and Bioresources; ItaliaFil: Torres, Myriam Mariela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina.Fil: Torres, Myriam Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pierantozzi, Pierluigi. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina.Fil: Pierantozzi, Pierluigi. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stanzione, Vitale. Consiglio Nazionale delle Ricerche. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: Mastio, Valerio. Consiglio Nazionale delle Ricerche. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: Zaher, Hayat. Institut National de la Recherche Agronomique (INRA). Centre Régional de la Recherche Agronomique; MarruecosFil: El Antari, Abderraouf. Institut National de la Recherche Agronomique (INRA). Centre Régional de la Recherche Agronomique; MarruecosFil: Ayoub, Salam. National Agricultural Research Center (NARC); JordaniaFil: Dandachi, Faten. Lebanese Agricultural Research Institute (LARI); LíbanoFil: Youssef, Hiyam. Lebanese Agricultural Research Institute (LARI); LíbanoFil: Aggelou, Nikolas. Mediterranean Agronomic Institute of Chania (MAICh). Department of Horticultural Genetics and Biotechnology; GreciaFil: Contreras Valetín, Ana Cibeles. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina.Fil: Contreras Valetín, Ana Cibeles. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maestri, Damián. Universidad Nacional de Córdoba. Instituto Multidisciplinario de Biología Vegetal (IMBV); ArgentinaFil: Maestri, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belaj, Angjelina. Instituto Andaluz de Investigación y Formación Agraria, Pesquera, Alimentaria y de la Producción Ecológica (IFAPA). - Centro Alameda del Obispo; EspañaFil: Bufacchi, Marina. Consiglio Nazionale delle Ricerche. Institute for Agricultural and Forest Systems of the Mediterranean; ItaliaFil: Baldoni, Luciana. Consiglio Nazionale delle Ricerche. Institute of Biosciences and Bioresources; ItaliaFil: León, Lorenzo. Instituto Andaluz de Investigación y Formación Agraria, Pesquera, Alimentaria y de la Producción Ecológica (IFAPA). - Centro Alameda del Obispo; Españ

The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters

Combinations of direct-acting antivirals are needed to minimize drug resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and testing of a number of drug regimens has led to conflicting results. Here, we show that cobicistat, which is an FDA-approved drug booster that blocks the activity of the drug-metabolizing proteins cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Two independent cell-to-cell membrane fusion assays showed that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low-micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. This was consistent with the effects of cobicistat on two of its known targets, CYP3A4 and P-gp, the silencing of which boosted the in vitro antiviral activity of remdesivir in a cobicistat-like manner. When administered in vivo to Syrian hamsters at a high dose, cobicistat decreased viral load and mitigated clinical progression. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19

Meeting of the Ecosystem Approach Correspondence Group on on Pollution Monitoring (CorMon Pollution)

In accordance with the UNEP/MAP Programme of Work adopted by COP 21 for the biennium 2020-2021, the United Nations Environment Programme/Mediterranean Action Plan-Barcelona Convention Secretariat (UNEP/MAP) and its Programme for the Assessment and Control of Marine Pollution in the Mediterranean (MED POL) organized the Meeting of the Ecosystem Approach Correspondence Group on Pollution Monitoring (CorMon on Pollution Monitoring). The Meeting was held via videoconference on 26-27 April 2021. 2. The main objectives of the Meeting were to: a) Review the Monitoring Guidelines/Protocols for IMAP Common Indicator 18, as well as the Monitoring Guidelines/Protocols for Analytical Quality Assurance and Reporting of Monitoring Data for IMAP Common Indicators 13, 14, 17, 18 and 20; b) Take stock of the state of play of inter-laboratory testing and good laboratory practice related to IMAP Ecological Objectives 5 and 9; c) Analyze the proposal for the integration and aggregation rules for IMAP Ecological Objectives 5, 9 and 10 and assessment criteria for contaminants and nutrients; d) Recommend the ways and means to strengthen implementation of IMAP Pollution Cluster towards preparation of the 2023 MED Quality Status Report

Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion