A gis spatial analysis model for landslide hazard mapping application in alpine area

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Multiple pancreaticoduodenal penetrating gunshot trauma evolving into acute necrotizing pancreatitis. A combined surgical and minimally invasive approach

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DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

Hereditary haemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome) is an autosomal dominant disorder characterized by localized angiodysplasia due to mutations in endoglin, ALK-1 gene, and a still unidentified locus. The lack of highly recurrent mutations, locus heterogeneity, and the presence of mutations in almost all coding exons of the two genes makes the screening for mutations time-consuming and costly. In the present study, we developed a DHPLC-based protocol for mutation detection in ALK1 and ENG genes through retrospective analysis of known sequence variants, 20 causative mutations and 11 polymorphisms, and a prospective analysis on 47 probands with unknown mutation. Overall DHPLC analysis identified the causative mutation in 61 out 66 DNA samples (92.4%). We found 31 different mutations in the ALK1 gene, of which 15 are novel, and 20, of which 12 are novel, in the ENG gene, thus providing for the first time the mutational spectrum in a cohort of Italian HHT patients. In addition, we characterized the splicing pattern of ALK1 gene in lymphoblastoid cells, both in normal controls and in two individuals carrying a mutation in the non-invariant -3 position of the acceptor splice site upstream exon 6 (c.626-3C>G). Functional essay demonstrated the existence, also in normal individuals, of a small proportion of ALK1 alternative splicing, due to exon 5 skipping, and the presence of further aberrant splicing isoforms in the individuals carrying the c.626-3C>G mutation

New cost-effective technologies applied to the study of the glacier melting influence on physical and biological processes in Kongsfjorden area (Svalbard)

The Arctic region is greatly affected by climate change, with evident alterations in both physical and biological processes: temperatures are changing at a rate that is twice the global average and phytoplankton productivity is directly affected by ice melting. Continuous monitoring of this ecosystem is fundamental to gain greater understanding of the impact of changes on the natural environment, but the Global Ocean Observing System only provides partial coverage in these extreme areas, which are particularly difficult to reach. Technological progress in oceanographic measurement capabilities is indispensable for the implementation of marine observatories, especially in these remote regions. In recent years, autonomous systems and cost-effective technologies have proved to be valuable for increasing spatial and temporal coverage of data. This is the case with the innovative ArLoC (Arctic Low-Cost) probe, which was designed and developed for easy integration into various types of platforms, enabling continuous measurement of temperature, pressure and fluorescence of chlorophyll a. This work reports on the results of two scientific campaigns carried out in Kongsfjorden (Svalbard Islands) in 2018 in the framework of the UVASS (Unmanned Vehicles for Autonomous Sensing and Sampling) research project. The ArLoC probe was integrated onboard the PROTEUS (Portable RObotic TEchnology for Unmanned Surveys) unmanned semi-submersible vehicle and this allowed us to collect important data in the stretches of sea near tidewater glacier fronts. The acquired data showed several significant effects of glacier melting such as: high temperature and salinity gradients, which cause considerable variations in water mass stratification, and an increase in turbidity and the chlorophyll a concentration, which directly affects primary productivity and the trophic chain. During the surveys, ArLoC proved to be an easy-to-integrate, very reliable instrument, which permitted high spatial resolution investigation of ecological processes during glacier melting as never studied before

Prognostic and therapeutic role of angiogenic microenvironment in thyroid cancer

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target

COVID-19 affects serum brain-derived neurotrophic factor and neurofilament light chain in aged men. Implications for morbidity and mortality

Background and Methods: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. Results: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. Conclusions: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men

Evaluation of BAFF, APRIL and CD40L in ocrelizumab-treated pwMS and infectious risk

Simple Summary Since B cells have been linked to multiple sclerosis (MS) and its progression as well as T cells, the second-generation anti-CD20 recombinant humanized monoclonal antibody ocrelizumab has been approved for MS treatment. Although ocrelizumab efficiently depletes B cells in peripheral blood, some B cells and CD20 negative plasma cells persist in lymphatic organs, and their survival is regulated by the B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system. Moreover, ocrelizumab may result in higher infectious risk. Herein, we investigated plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated people with (pw) MS at baseline, at 6 months and at 12 months after starting the treatment, comparing the above-mentioned findings with a control group. At baseline, plasma levels of all three cytokines were higher compared to the control group. In pwMS, the longitudinal assessment showed a significant increase in plasma BAFF levels and a significant reduction in plasma APRIL and CD40L. Moreover, when stratifying pwMS according to the onset of an infectious event during the 12-month follow-up period, significantly higher plasma BAFF levels were found at all time-points in the group with an infectious event than in the group without an infectious event. Hence, BAFF may have a role as a marker of immune dysfunction and infectious risk. Background: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. Methods: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. Results: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p < 0.0001), APRIL (p = 0.0223) and CD40L (p < 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p < 0.0001 and p < 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p < 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p < 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk

Increased sCD163 and sCD14 plasmatic levels and depletion of peripheral blood pro-inflammatory monocytes, myeloid and plasmacytoid dendritic cells in patients with severe COVID-19 pneumonia

Background: Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects). Methods: On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups. Results: Compared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1–68.4] specificity 73.8% [CI: 58.9–84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492). Conclusions: The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia

Sex-related mortality differences in young adult septic shock patients

Septic shock survival rate and host immune response are intimately interlaced. In the last years, biological and pre-clinical studies demonstrated sex-specific differences in the immune response to infection. In the hypothesis that survival rate is related to the hormonal framework, the aim of the present study was to observe sex-specific differences in 28-day mortality rate between women of childbearing potential and same-age men. This multicenter study was conducted in six Italian intensive care units (ICUs). We enrolled consecutive patients ≤ 55 years old admitted to the Intensive Care Unit from January 2011 to January 2020, who were diagnosed with septic shock at the time of ICU admission or during the ICU stay. We gathered baseline characteristics and outcomes. The primary outcome was 28-day mortality; secondary outcomes included ICU mortality, in-hospital mortality and length of stay in the ICU and in the hospital. Moreover, data from >55 years old patients were collected and analyzed. We enrolled 361 young patients with septic shock: 215 were males (60%) and 146 females (40%). While baseline and ICU characteristics were similar between the two groups, males had a higher 28-day mortality rate (39.5% vs. 29%, p = 0.035), ICU mortality rate (49% vs. 38%, p = 0.040) and hospital mortality rate (61% vs. 50%, p = 0.040) as compared to females. Findings were confirmed in patients with septic shock at ICU admission. Young adult females developed septic shock less frequently than young males, displaying a reduced mortality rate as compared to that of their same-age male counterpart. These findings may stimulate future research and therapies