Granzyme B in inflammatory diseases: apoptosis, inflammation, extracellular matrix remodeling, epithelial-to-mesenchymal transition and fibrosis

Inflammation is strictly interconnected to anti-inflammatory mechanisms to maintain tissue homeostasis. The disruption of immune homeostasis can lead to acute and chronic inflammatory diseases, as cardiovascular, pulmonary, metabolic diseases and cancer. The knowledge of the mechanisms involved in the development and progression of these pathological conditions is important to find effective therapies. Granzyme B (GrB) is a serine protease produced by a variety of immune, non-immune and tumor cells. Apoptotic intracellular and multiple extracellular functions of GrB have been recently identified. Its capability of cleaving extracellular matrix (ECM) components, cytokines, cell receptors and clotting proteins, revealed GrB as a potential multifunctional pro-inflammatory molecule with the capability of contributing to the pathogenesis of different inflammatory conditions, including inflammaging, acute and chronic inflammatory diseases and cancer. Here we give an overview of recent data concerning GrB activity on multiple targets, potentially allowing this enzyme to regulate a wide range of crucial biological processes that play a role in the development, progression and/or severity of inflammatory diseases. We focus our attention on the promotion by GrB of perforin-dependent and perforin-independent (anoikis) apoptosis, inflammation derived by the activation of some cytokines belonging to the IL-1 cytokine family, ECM remodeling, epithelial-to-mesenchymal transition (EMT) and fibrosis. A greater comprehension of the pathophysiological consequences of GrB-mediated multiple activities may favor the design of new therapies aim to inhibit different inflammatory pathological conditions such as inflammaging and age-related diseases, EMT and organ fibrosis

The Virtues of Balm in Late Medieval Literature

This article argues that balm, or balsam, was, by the late medieval period, believed to be a panacea, capable of healing wounds and illnesses, and also preventing putrefaction. Natural history and pharmacological texts on balm from the ancient and late antique periods emphasized specific qualities of balm, especially its heat; these were condensed and repeated in medieval encyclopedias. The rarity and cost of balsam, from antiquity through the medieval period, and the high rate of counterfeiting also demonstrate its high demand and significance in medicine and religious ritual. Travel writing and itineraria from the early and central medieval periods added a new layer to ideas about the capabilities of balsam: that it originated from a Christian miracle and was a particularly Christian plant

Early versus delayed endoscopic treatment of acute pilonidal abscess: a propensity score-matched analysis

Background: According to the Italian Society of Colorectal Surgery guidelines, the most effective approach to the pilonidal abscess is adequate surgical drainage, concerning incision and drainage of the pilonidal cavity. Few recent studies have demonstrated that endoscopic approach could be a valid treatment option even in the case of acute pilonidal abscess. The aim of our study is to assess if video-assisted ablation of pilonidal sinus (VAAPS) could be an alternative to treat an acute pilonidal abscess and to evaluate if an immediate endoscopic approach to the pilonidal abscess is preferable to a delayed procedure after incision and drainage. Methods: All consecutive patients with an acute pilonidal abscess since 1 January 2014 to 31 December 2018 were enrolled in our propensity score-matched analysis and divided into two groups: the early VAAPS group and the delayed VAAPS group. Primary outcomes were recurrence rate at 1-year, 3-year, and 5-year follow-up. Secondary outcomes were time off, time to wound healing, incomplete wound healing, perioperative infection, patients’ satisfaction 1 month after the complete wound healing, and their health status before surgery and 6 months after complete wound healing. Results: After the propensity score matching, 82 patients were included in the final analysis (41 in each group). No differences were found in terms of recurrence in the two groups. Early endoscopic approach was associated with a better patients’ satisfaction (8.17 ± 1.2 vs 6.06 ± 1.48, p = 0.001) and a better postoperative health status (86.27 ± 6.54 vs 77.32 ± 5.85, p = 0.001). Conclusions: Our results encouraged to perform an immediate endoscopic approach to an acute pilonidal abscess

Granzyme B expression in visceral adipose tissue associates with local inflammation and glyco-metabolic alterations in obesity

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with “sick” fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases

Upgrades Of the SPS, Transfer Line and LHC Injection Protection Devices For the HL-LHC Era

The challenging High Luminosity LHC (HL-LHC) beam requirements will lead in the future to unprecedented beam parameters along the LHC injector chain. In the SPS accelerator these requests translate into about a factor two higher intensity and brightness than the present design performance. In addition to the challenge of producing and accelerating such beams, these parameters affect the resistance of the existing equipment against beam impact. Most of the protection devices in the SPS ring, its transfer lines and the LHC injection areas will be put under operational constraints which are beyond their design specification. The equipment concerned has been reviewed and their resistance to the HL-LHC beams checked. Theoretical and simulation studies have been performed for the SPS beam scraping system, the protection devices and the dump absorbers of the SPS-to-LHC transfer lines, as well as for the LHC injection protection devices. The first results of these studies are reported, together with the future prospects.Comment: 3 p. Presented at 4th International Particle Accelerator Conference (IPAC 2013

Comparison between LigaSure™ and Harmonic® in Laparoscopic Sleeve Gastrectomy: A Single-Center Experience on 422 Patients

Background. New laparoscopic devices, such as electrothermal bipolar-activated devices (LigaSure™ (LS)) or ultrasonic systems (Harmonic® scalpel (HS)), have been applied recently to bariatric surgery allowing to reduce blood loss and surgical risks. The aim of this study was to retrospectively compare intraoperative performance of HS and LS, postoperative results, and clinical outcomes in a large cohort of patients undergoing LSG. Methods. Data from 422 morbidly obese patients undergoing LSG in our Bariatric Unit at the Advanced Biomedical Sciences Department of the “Federico II” University of Naples (Italy) between January 2009 and December 2017 were retrospectively analyzed. Subjects were divided into two groups (HS and LS), and operative time, intraoperative complications, and postoperative (within 30 days from surgery) complications were compared. Bleeding from the omentum or from the staple line, use of hemostatic clips, and absorbable hemostat were recorded as intraoperative complications; hemorrhages, abscess formation, gastric leaks, fever, and mortality were considered as postoperative complications. Results. Statistical analysis showed no difference in terms of baseline demographics between the two cohorts. Operative time (48 ± 9 vs 49 ± 6 min, p=0.646) and the rates of intraoperative and postoperative complications did not significantly differ between groups. Conclusion. Harmonic® and LigaSure™ are both useful tools in bariatric surgery, and these two advanced power devices are user-friendly and can facilitate surgeon work; from this point of view, the choice of the energy device should be based on the preference of the surgeon and on the hospital costs policy and availability

The ENUBET Beamline

The ENUBET ERC project (2016-2021) is studying a narrow band neutrino beam where lepton production can be monitored at single particle level in an instrumented decay tunnel. This would allow to measure $\nu_{\mu}$ and $\nu_{e}$ cross sections with a precision improved by about one order of magnitude compared to present results. In this proceeding we describe a first realistic design of the hadron beamline based on a dipole coupled to a pair of quadrupole triplets along with the optimisation guidelines and the results of a simulation based on G4beamline. A static focusing design, though less efficient than a horn-based solution, results several times more efficient than originally expected. It works with slow proton extractions reducing drastically pile-up effects in the decay tunnel and it paves the way towards a time-tagged neutrino beam. On the other hand a horn-based transferline would ensure higher yields at the tunnel entrance. The first studies conducted at CERN to implement the synchronization between a few ms proton extraction and a horn pulse of 2-10 ms are also described.Comment: Poster presented at NuPhys2018 (London 19-21 December 2018). 4 pages, 3 figure

Progress with the Upgrade of the SPS for the HL-LHC Era

The demanding beam performance requirements of the High Luminosity (HL-) LHC project translate into a set of requirements and upgrade paths for the LHC injector complex. In this paper the performance requirements for the SPS and the known limitations are reviewed in the light of the 2012 operational experience. The various SPS upgrades in progress and still under consideration are described, in addition to the machine studies and simulations performed in 2012. The expected machine performance reach is estimated on the basis of the present knowledge, and the remaining decisions that still need to be made concerning upgrade options are detailed.Comment: 3 p. Presented at 4th International Particle Accelerator Conference (IPAC 2013