Mixed-Valve Disease: Management of Patients with Aortic Stenosis and Mitral Regurgitation: Thresholds for Surgery Versus Percutaneous Therapies

Significant mitral regurgitation (MR), frequently seen in the presence of severe aortic stenosis (AS), results in an association that negatively affects prognosis and imposes particular challenges for both the assessment of the severity of valvular lesions and decisions regarding treatment allocation. This article reviews the available literature with regards to the assessment of MR and AS in the presence of both; surgical management and results in patients with concomitant AS and MR; the effect of MR on outcomes in patients undergoing transcatheter aortic valve replacement; the effect of transcatheter aortic valve replacement on MR severity; and percutaneous treatment for MR after transcatheter aortic valve implantation. The authors aim to provide assistance in the decision-making process to treat patients with either a higher-risk double-valve procedure or a simpler, but perhaps incomplete, single-valve option

CUIDADOS PALIATIVOS E A INTERVENÇÃO DO ASSISTENTE SOCIAL JUNTO ÀS EQUIPES MULTIPROFISSIONAIS

The Palliative Care concept was re-signified from the holistic perspective of health that sees the being in its multidimensions, valuing care with physical, psychological, social, emotional and spiritual well-being, through promotion actions aimed at citizenship. Interdisciplinary action is a prerequisite of Palliative Care and the social worker is one of the professionals who make up the teams. The objective of this work is to understand Palliative Care and the role of social workers in multidisciplinary teams. The investigation was anchored in qualitative research, with a bibliographical approach and sought in the literature subsidies for critical-theoretical reflection. It is concluded that there is a need for recognition of the multidisciplinary work in Palliative Care and appropriation of the social worker to the area, so that he has mastery of the dimensions that make up his work.                                        O conceito Cuidados Paliativos foi ressignificado a partir da perspectiva holística de saúde que enxerga o ser em suas multidimensões, prezando cuidados com o bem-estar físico, psicológico, social, emocional e espiritual, através de ações de promoção que visam à cidadania. A atuação interdisciplinar é pressuposto dos Cuidados Paliativos e o assistente social é um dos profissionais que compõem as equipes. O objetivo deste trabalho é compreender os Cuidados Paliativos e a atuação dos assistentes sociais nas equipes multiprofissionais. A investigação ancorou-se na pesquisa qualitativa, de abordagem bibliográfica e buscou na literatura subsídios para a reflexão crítico-teórica. Conclui-se que há necessidade de reconhecimento do trabalho multiprofissional nos Cuidados Paliativos e apropriação do assistente social à área, para que possua domínio das dimensões que compõem sua atuação

Palaeoproteomic analyses of dog palaeofaeces reveal a preserved dietary and host digestive proteome.

The domestic dog has inhabited the anthropogenic niche for at least 15 000 years, but despite their impact on human strategies, the lives of dogs and their interactions with humans have only recently become a subject of interest to archaeologists. In the Arctic, dogs rely exclusively on humans for food during the winter, and while stable isotope analyses have revealed dietary similarities at some sites, deciphering the details of provisioning strategies have been challenging. In this study, we apply zooarchaeology by mass spectrometry (ZooMS) and liquid chromatography tandem mass spectrometry to dog palaeofaeces to investigate protein preservation in this highly degradable material and obtain information about the diet of domestic dogs at the Nunalleq site, Alaska. We identify a suite of digestive and metabolic proteins from the host species, demonstrating the utility of this material as a novel and viable substrate for the recovery of gastrointestinal proteomes. The recovered proteins revealed that the Nunalleq dogs consumed a range of Pacific salmon species (coho, chum, chinook and sockeye) and that the consumed tissues derived from muscle and bone tissues as well as roe and guts. Overall, the study demonstrated the viability of permafrost-preserved palaeofaeces as a unique source of host and dietary proteomes.DNRF, E

Predicting leakage of the VERCORS mock-up and concrete containment buildings - a digital twin approach

EDF operates a nuclear power generation fleet made up of 56 reactors. This fleet contains 24 reactors designed as double-walled concrete containment building. The inner concrete containment vessel has no metallic liner and is a prestressed reinforced concrete building. The inner concrete containment vessel is designed to withstand a severe accident, in terms of mechanical and sealing behaviour. The tightness of the containment is tested every 10 years, by carrying out a pressurization test and by measuring the leak rate. The leak rate is required to be below a regulatory threshold to continue operation of the concrete containment building for the next ten years. Ageing of concrete due to drying, creep and shrinkage leads to increase prestress loss and then leak rate with time. For some containment buildings, the leak rate gets closer to the regulatory threshold with time, so important coating programs are planned to mitigate and limit the leak rate under the regulatory threshold. Therefore, it is very important for EDF to have a concrete containment building leak rate prediction tool. To address this issue, an important research program around a 1/3 scale concrete containment building mock-up called "VERCORS" have been launched at EDF. The mock-up is heavily instrumented, and its materials (concrete, prestressing cables) have been widely characterized and studied. An important numerical effort has also been made to implement structural computations of the mock-up and to capitalize these computations as well as their post-processing (so as to compare automatically with the monitoring data) in what can be called a digital twin of the mock-up. This digital twin is now used to predict the leakage of VERCORS mock-up before yearly pressure test, and also to optimize the repair programs on the real containments

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells

RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families

BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5′ UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001). Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene

Innate antibacterial activity in female genital tract secretions is associated with increased risk of HIV acquisition.

CAPRISA, 2015.Abstract available in pdf

Bmcc1s, a Novel Brain-Isoform of Bmcc1, Affects Cell Morphology by Regulating MAP6/STOP Functions

The BCH (BNIP2 and Cdc42GAP Homology) domain-containing protein Bmcc1/Prune2 is highly enriched in the brain and is involved in the regulation of cytoskeleton dynamics and cell survival. However, the molecular mechanisms accounting for these functions are poorly defined. Here, we have identified Bmcc1s, a novel isoform of Bmcc1 predominantly expressed in the mouse brain. In primary cultures of astrocytes and neurons, Bmcc1s localized on intermediate filaments and microtubules and interacted directly with MAP6/STOP, a microtubule-binding protein responsible for microtubule cold stability. Bmcc1s overexpression inhibited MAP6-induced microtubule cold stability by displacing MAP6 away from microtubules. It also resulted in the formation of membrane protrusions for which MAP6 was a necessary cofactor of Bmcc1s. This study identifies Bmcc1s as a new MAP6 interacting protein able to modulate MAP6-induced microtubule cold stability. Moreover, it illustrates a novel mechanism by which Bmcc1 regulates cell morphology