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Purpose Management of renal cell carcinoma (RCC) with inferior vena cava (IVC) extension is one of the greatest challenges in urology. The gold standard treatment includes extracorporeal circulation and deep hypothermic circulatory arrest (DHCA). However, this surgical treatment has an impact on survival and prognosis. We aim to present a less invasive surgical approach for the treatment of level III and IV IVC thrombi in RCC. Methods We identified all patients undergoing radical nephrectomy and thrombectomy at our Institution between 2016 and 2020. Patients with level IV thrombi were treated with a combined thoracic and abdominal procedure: beating heart surgery with normothermic cardiopulmonary bypass (CPB) was used for thrombus retrieval. Level III thrombi were approached exclusively through an abdominal access. Results We identified 12 patients treated with radical nephrectomy and thrombectomy among 243 patients undergoing radical nephrectomy for RCC. Mean age was 69.3 years, most patients were in T3c clinical stage, without lymph-node involvement (75%) and no metastases (66.7%); 58.3% of patients had Mayo III thrombus classification. Median intensive care unit stay was 2 days and total in-hospital stay 10.5 days. In-hospital mortality was 0%, with a 66.6% survival rate at 2 years. Conclusions Beating heart surgery with normothermic CPB can be considered a less invasive method for radical resection of Mayo level IV IVC thrombi. This surgical approach is safe and feasible, with good in-hospital and short-term outcomes.

High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane. Accordingly, AMPAR current amplitudes and, more importantly, their potentiation underlying synaptic plasticity were inhibited, as well as hippocampal-dependent memory. Hippocampus-specific silencing of Zdhhc3 and, interestingly enough, intranasal injection of the palmitoyltransferase inhibitor, 2-bromopalmitate, counteract GluA1 hyper-palmitoylation and restore synaptic plasticity and memory in HFD mice. Our data reveal a key role of FoxO3a/Zdhhc3/GluA1 axis in the HFD-dependent impairment of cognitive function and identify a novel mechanism underlying the cross talk between metabolic and cognitive disorders. Metabolic diseases have been associated with cognitive impairment. Here, the authors show that brain insulin resistance induced by high-fat diet leads to increased palmitoylation of AMPA receptors and thus changes in hippocampal plasticity, learning and memory.

The Land Surface, Snow and Soil Moisture Model Intercomparison Project (LS3MIP) is designed to provide a comprehensive assessment of land surface, snow and soil moisture feedbacks on climate variability and climate change, and to diagnose systematic biases in the land modules of current Earth system models (ESMs). The solid and liquid water stored at the land surface has a large influence on the regional climate, its variability and predictability, including effects on the energy, water and carbon cycles. Notably, snow and soil moisture affect surface radiation and flux partitioning properties, moisture storage and land surface memory. They both strongly affect atmospheric conditions, in particular surface air temperature and precipitation, but also large-scale circulation patterns. However, models show divergent responses and representations of these feedbacks as well as systematic biases in the underlying processes. LS3MIP will provide the means to quantify the associated uncertainties and better constrain climate change projections, which is of particular interest for highly vulnerable regions (densely populated areas, agricultural regions, the Arctic, semi-arid and other sensitive terrestrial ecosystems). The experiments are subdivided in two components, the first addressing systematic land biases in offline mode (\"LMIP\", building upon the 3rd phase of Global Soil Wetness Project; GSWP3) and the second addressing land feedbacks attributed to soil moisture and snow in an integrated framework (\"LFMIP\", building upon the GLACE-CMIP blueprint).

The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario suggests an important role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.