Dynamic changes of mmp-9 plasma levels correlate with jvc reactivation and immune activation in natalizumab-treated multiple sclerosis patients

The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples. T-lymphocyte phenotype was assessed with flow cytometry. MMP-9 plasma levels resulted increased from 12 to 24 natalizumab infusions. Stratifying plasma samples according to JCV-DNA detection, MMP-9 plasma levels were significantly increased in JCV-DNA positive than JCV-DNA negative samples. MMP-9 plasma levels resulted positively correlated with JCV viral load. CD4 immune senescence, CD8 immune activation and CD8 effector percentages were positively correlated to MMP-9 plasma levels, whereas a negative correlation between CD8 naïve percentages and MMP-9 plasma levels was found. Our data indicate an increase of MMP-9 plasma levels between 12 and 24 natalizumab infusions and a correlation with JCV-DNA detection in plasma, T-lymphocyte immune activation and senescence. These findings could contribute to understand PML pathogenesis under natalizumab treatment, suggesting a potential role of MMP-9 as a predictive marker of PML in RRMS patients

Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells

Background: ERBB2 is overexpressed in up to 20\u201330% of human breast cancers (BCs), and it is associated with aggressive disease. Trastuzumab (Tz), a humanized monoclonal antibody, improves the prognosis associated with ERBB2-amplified BCs. However, the development of resistance remains a significant challenge. Carnosic acid (CA) is a diterpene found in rosemary and sage, endowed with anticancer properties. In this in vitro study, we have investigated whether Tz and CA have cooperative effects on cell survival of ERBB2 overexpressing (ERBB2+) cells and whether CA might restore Tz sensitivity in Tz-resistant cells. Methods: We have studied BC cell migration and survival upon CA and Tz treatment. In particular, migration ability was assessed by transwell assay while cell survival was assessed by MTT assay. In addition, we have performed cell cycle and apoptosis analysis by high-resolution DNA flow cytometry and annexin-V, resazurin and sytox blue staining by flow cytometry, respectively. The expression of proteins involved in cell cycle progression, ERBB2 signaling pathway, and autophagy was evaluated by immunoblot and immunofluorescence analysis. Cellular structures relevant to the endosome/lysosome and autophagy pathways have been studied by immunofluorescence and transmission electron microscopy. Results: We report that, in ERBB2+ BC cells, CA reversibly enhances Tz inhibition of cell survival, cooperatively inhibits cell migration and induces cell cycle arrest in G0/G1. These events are accompanied by ERBB2 downregulation, deregulation of the PI3K/AKT/mTOR signaling pathway and up-regulation of both CDKN1A/p21WAF1 and CDKN1B/p27KIP1. Furthermore, we have demonstrated that CA impairs late autophagy and causes derangement of the lysosomal compartment as shown by up-regulation of SQSTM1/p62 and ultrastructural analysis. Accordingly, we have found that CA restores, at least in part, sensitivity to Tz in SKBR-3 Tz-resistant cell line. Conclusions: Our data demonstrate the cooperation between CA and Tz in inhibiting cell migration and survival of ERBB2+ BC cells that warrant further studies to establish if CA or CA derivatives may be useful in vivo in the treatment of ERBB2+ cancers

Pyogenic Granuloma of the Sigmoid Colon causing Intussusception in an Infant

Pyogenic granuloma is a benign vascular tumor that may affect the gastrointestinal tract. This report describes a rare case of sigmoid-colon pyogenic granuloma in a 4-month-old boy causing intussusception. Resection and anastomosis were curative. The mother had history of high dose of progesterone exposure during initial weeks of conception for vaginal bleeding. This may point towards etiology of the lesion

It is time to define an organizational model for the prevention and management of infections along the surgical pathway : a worldwide cross-sectional survey

Background The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. Methods A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. Results Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. Conclusion Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened.Peer reviewe

It is time to define an organizational model for the prevention and management of infections along the surgical pathway: a worldwide cross-sectional survey

Background The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. Methods A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. Results Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. Conclusion Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe