Du bon usage de la vodka

La culture de la vodka est très différente de celle du vin. La vodka ne se différenciant pas par des terroirs et n'ayant aucune saveur particulière, on ne la boit pas pour son goût, mais pour ses effets. Un rituel presque immuable permet de partager et de maintenir une agréable griserie collective. La succession codifiée des toasts, appelés par des formules consacrées, renforce la cohésion des convives.Vodka culture is very different from that of wine. Vodka does not differ according to the regions, and it has not any particular flavour: they don’t drink it for the pleasure of its taste, but for its effects. An almost immutable ritual offers partaking and maintaining a pleasant collective inebriation. The codified succession of the toasts, called by accepted formulas, strengthen guest’ cohesion.Культура пития водки резко отличается от культуры пития вина. Так как водка одна и та же во всех уголках страны и не имеет особого вкуса, ее и потребляют не ради вкуса, а ради эффекта. В России существует почти неизменный ритуал для разделения удовольствия коллективного потребления этого напитка и поддержания приятного опьянения. Четко определенное чередование тостов, сопровождаемых соответствующими случаю поговорками, укрепляет сплоченность сотрапезников

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso

Under embargo until: 2022-04-23Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6–8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm).acceptedVersio

Case Rep Oncol

The pretreatment detection of an activating mutation of EGFR is now routinely performed in metastatic nonsquamous non-small cell lung cancer (NSCLC). The therapeutic impact of such a detection is major, as patients with advanced NSCLC exhibiting a mutation of exon 19 or 21 will benefit from EGFR-tyrosine kinase inhibitors (TKI). The presence of an EGFR resistance mutation, such as T790M in EGFR-TKI-naïve patients, is seldom looked for and is related either to a germinal mutation or to somatically mutated subclones. It has a negative predictive impact. We present the case of a patient with a lung papillary adenocarcinoma and miliary intrapulmonary metastases whose tumor displays a somatic complex heterozygous EGFR mutation, combining L858R (exon 21) and a primary resistance mutation T790M (exon 20), both detected by direct sequencing

Irradiation-Induced Deinococcus radiodurans Genome Fragmentation Triggers Transposition of a Single Resident Insertion Sequence

Stress-induced transposition is an attractive notion since it is potentially important in creating diversity to facilitate adaptation of the host to severe environmental conditions. One common major stress is radiation-induced DNA damage. Deinococcus radiodurans has an exceptional ability to withstand the lethal effects of DNA–damaging agents (ionizing radiation, UV light, and desiccation). High radiation levels result in genome fragmentation and reassembly in a process which generates significant amounts of single-stranded DNA. This capacity of D. radiodurans to withstand irradiation raises important questions concerning its response to radiation-induced mutagenic lesions. A recent study analyzed the mutational profile in the thyA gene following irradiation. The majority of thyA mutants resulted from transposition of one particular Insertion Sequence (IS), ISDra2, of the many different ISs in the D. radiodurans genome. ISDra2 is a member of a newly recognised class of ISs, the IS200/IS605 family of insertion sequences

Connexin and pannexin (hemi) channels in the liver

The liver was among the first organs in which connexin proteins have been identified. Hepatocytes harbor connexin32 and connexin26, while non-parenchymal liver cells typically express connexin43. Connexins give rise to hemichannels, which dock with counterparts on adjacent cells to form gap junctions. Both hemichannels and gap junctions provide pathways for communication, via paracrine signaling or direct intercellular coupling, respectively. Over the years, hepatocellular gap junctions have been shown to regulate a number of liver-specific functions and to drive liver cell growth. In the last few years, it has become clear that connexin hemichannels are involved in liver cell death, particularly in hepatocyte apoptosis. This also holds true for hemichannels composed of pannexin1, a connexin-like protein recently identified in the liver. Moreover, pannexin1 hemichannels are key players in the regulation of hepatic inflammatory processes. The current paper provides a concise overview of the features of connexins, pannexins and their channels in the liver.This work was financially supported by the grants of the Agency for Innovation by Science and Technology in Flanders (IWT), the University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-VUB), the Fund for Scientific Research - Flanders (FWO grants G009514N and G010214N), the European Research Council (ERC Starting Grant 335476), the University of Sao Paulo-Brazil (USP) and the Foundation for Research Support of the State of Sao Paulo (FAPESP SPEC grant 2013/50420-6)

A Major Role of the RecFOR Pathway in DNA Double-Strand-Break Repair through ESDSA in Deinococcus radiodurans

In Deinococcus radiodurans, the extreme resistance to DNA–shattering treatments such as ionizing radiation or desiccation is correlated with its ability to reconstruct a functional genome from hundreds of chromosomal fragments. The rapid reconstitution of an intact genome is thought to occur through an extended synthesis-dependent strand annealing process (ESDSA) followed by DNA recombination. Here, we investigated the role of key components of the RecF pathway in ESDSA in this organism naturally devoid of RecB and RecC proteins. We demonstrate that inactivation of RecJ exonuclease results in cell lethality, indicating that this protein plays a key role in genome maintenance. Cells devoid of RecF, RecO, or RecR proteins also display greatly impaired growth and an important lethal sectoring as bacteria devoid of RecA protein. Other aspects of the phenotype of recFOR knock-out mutants paralleled that of a ΔrecA mutant: ΔrecFOR mutants are extremely radiosensitive and show a slow assembly of radiation-induced chromosomal fragments, not accompanied by DNA synthesis, and reduced DNA degradation. Cells devoid of RecQ, the major helicase implicated in repair through the RecF pathway in E. coli, are resistant to γ-irradiation and have a wild-type DNA repair capacity as also shown for cells devoid of the RecD helicase; in contrast, ΔuvrD mutants show a markedly decreased radioresistance, an increased latent period in the kinetics of DNA double-strand-break repair, and a slow rate of fragment assembly correlated with a slow rate of DNA synthesis. Combining RecQ or RecD deficiency with UvrD deficiency did not significantly accentuate the phenotype of ΔuvrD mutants. In conclusion, RecFOR proteins are essential for DNA double-strand-break repair through ESDSA whereas RecJ protein is essential for cell viability and UvrD helicase might be involved in the processing of double stranded DNA ends and/or in the DNA synthesis step of ESDSA

E-cadherin in canine mast cell tumors: Decreased expression and altered subcellular localization in Grade 3 tumors

Mast cell tumors (MCTs) are the most frequent round cell tumors in dogs and comprise approximately 21% of all canine cutaneous tumors. MCTs are highly invasive and metastatic corresponding to the histological grade. E-cadherin is an adhesion molecule expressed in epithelial cells and although it is an epithelial cellular marker, studies have shown expression of E-cadherin in canine round cell tumors. To better characterize the expression pattern of E-cadherin in several different histological grades of MCTs in dogs, the expression and localization of the adhesion molecule was investigated using immunohistochemistry. For this purpose, 18 cutaneous MCTs were classified into three histological grades, 1, 2 or 3. Clinical history and follow-up data were available for all of the dogs. Cytoplasmic and nuclear expressions of E-cadherin in all three types of tumors were verified by immunostaining using two different antibodies. There was decreased E-cadherin expression in the more aggressive MCTs (Grade 3), suggesting an association between E-cadherin and tumor aggressiveness. Additionally, the loss of E-cadherin expression in either the cytoplasm or nucleus in more aggressive and undifferentiated tumor types confirmed the importance of cellular adhesion in tumor behavior. (C) 2012 Published by Elsevier Ltd.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/12827-1]; [2010/08523-4

Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia

BackgroundInfant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother’s viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention.MethodsIndividual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis.ResultsMore barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers’ adherence to their own antiretroviral therapy.ConclusionAccompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries