Koagulacija krvi i lipidi u serumu (Studija stanovništva)

Two population groups differing in dietary habits and physical activity were examined on blood lipids and blood coagulability. The results showed a higher lipid concentration and shorter clotting time in the physically less active group, having a higher fat and caloric intake.Dvije populacione grupe, koje se razlikuju po svojoj prehrani, a osobito po povećanoj potrošnji masnoća i smanjenom fizičkom aktivitetu, ispitivane su s obzirom na nivo krvnih lipida i na koagulabilitet krvi. Rezultati pokazuju, da prehrana, osobito povećana potrošnja animalnih masnoća, te smanjena psihička aktivnost utječu na povećanje nivoa krvnih lipida i bržeg koagulabiliteta krvi mjerenog kao vrijeme zgrušavanja i protrombinsko vrijeme. Ti rezultati potvrđuju već ranija zapažanja autora o povećanom koagulabilitetu krvi u populacionim grupama, koje se istovremeno razlikuju i u koncentraciji krvnih lipida i u učestalosti koronarnih bolesti

A high-resolution aeromagnetic survey over the Cape Roberts Rift Basin: Correlations with seismic reflection and magnetic susceptibility log data

A high-resolution aeromagnetic survey (altitude 125 m asl, spacing 500 m , area 800 km2) was carried out in 1994 offshore of Cape Roberts by the GITARA (German ITalian Aeromagnetic Research in Antarctica) Group. The availability from drilling of whole-core physical properties logs for magnetic susceptibility, P-wave velocity and density/porosity data allows new insights to be inferred from reprocessed and reviewed HRAM aeromagnetic data. Aeromagnetic data have been reprocessed to image with greater detail the structural framework along the western flank of the Victoria Land Basin. New processing includes 2D Werner and 3D Euler deconvolution, the production of maps of the maximum horizontal gradient of pseudo-gravity, and 2D, 3D modelling. Magnetic trends and anomalies are discussed in conjunction with now available drilling results from the CRP, existing bathymetric data and recently published interpretations of a multichannel seismic reflection survey

M.Somma-Vesuvio: attività sismica

In the tex

SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Endovascular Abdominal Aortic Aneurysm Repair With Ovation Alto Stent Graft: Protocol for the ALTAIR (ALTo endogrAft Italian Registry) Study

Background: Since 2010, the Ovation Abdominal Stent Graft System has offered an innovative sealing option for abdominal aortic aneurysm (AAA) by including a sealing ring filled with polymer 13 mm from the renal arteries. In August 2020, the redesigned Ovation Alto, with a sealing ring 6 mm closer to the top of the fabric, received CE Mark approval. Objective: This registry study aims to evaluate intraoperative, perioperative, and postoperative results in patients treated by the Alto stent graft (Endologix Inc.) for elective AAA repair in a multicentric consecutive experience. Methods: All consecutive eligible patients submitted to endovascular aneurysm repair (EVAR) by Alto Endovascular AAA implantation will be included in this analysis. Patients will be submitted to EVAR procedures based on their own preferences, anatomical features, and operators experience. An estimated number of 300 patients submitted to EVAR with Alto stent graft should be enrolled. It is estimated that the inclusion period will be 24 months. The follow-up period is set to be 5 years. Full data sets and cross-sectional images of contrast-enhanced computed tomography scan performed before EVAR, at the first postoperative month, at 24 or 36 months, and at 5-year follow-up interval will be reported in the central database for a centralized core laboratory review of morphological changes. The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with the Alto stent graft in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will be also addressed: operative time; intraoperative radiation exposure; contrast medium usage; AAA sac shrinkage at 12-month and 5-year follow-up; any potential role of patients' baseline characteristics, valuated on preoperative computed tomography angiographic study, and of device configuration (number of component) in the primary endpoint. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of 2023 and then followed up for 5 years. A total of 300 patients will be recruited. Analyses will focus on primary and secondary endpoints. Updated results will be shared at 1- and 3-5-year follow-ups. Conclusions: The results from this registry study could validate the safety and effectiveness of the new design of the Ovation Alto Stent Graft. The technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on-label

A Record of Antarctic Climate and Ice Sheet History Recovered

Antarctica’s late Cenozoic (the past ~15 million years) climate history is poorly known from direct evidence, owing to its remoteness, an extensive sea ice apron, and an ice sheet cover over the region for the past 34 million years. Consequently, knowledge about the role of Antarctica’s ice sheets in global sea level and climate has relied heavily upon interpretations of oxygen isotope records from deep-sea cores. Whereas these isotopic records have revolutionized our understanding of climate-ice-ocean interactions, questions still remain about the specific role of Antarctic ice sheets in global climate. Such questions can be addressed from geological records at the marine margin of the ice sheets, recovered by drilling from floating ice platforms [e.g., Davey et al., 2001; Harwood et al., 2006; Barrett, 2007]. During the austral summer of 2006–2007, a new Antarctic geological drilling program (ANDRILL) successfully recovered a 1285- meter-long record of climate and ice sheet variability spanning the past 13 million years from beneath the McMurdo Ice Shelf (Figure 1). The cores contain sedimentary rocks deposited by the ice sheets grounded in the sea, and they provide the best direct evidence to date of past Antarctic ice sheet and climate fluctuations for this period of Earth’s history. The new geological evidence is being used to provide direct physical calibrationfor deep-sea isotope records, low-latitude continental margin sea level records, and numerical climate and ice sheet models, especially for times of past global warmth. Such analogs are becoming increasingly important because of the difficulties in predicting the dynamic response of ice sheets to global warming [Vaughan and Athern, 2007]. In this article we summarize the initial results of the ANDRILL program’s first drilling project from the McMurdo Ice Shelf (MIS) site [Naish et al., 2007a, 2007b], with an emphasis on the potential of the record for improving our knowledge of Antarctica’s influence on, and response to, global climate change

Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma

Background: The anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019. Methods: We conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs. Results: A total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol. Conclusions: Our findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion