Transcriptional control of the B3GALT5 gene by a retroviral promoter and methylation of distant regulatory elements

We focused on transcription factors and epigenetic marks that regulate the B3GALT5 gene through its retroviral long terminal repeat (LTR) promoter. We compared the expression levels of the B3GALT5 LTR transcript, quantitated by competitive RT-PCR, with those of the candidate transcription factors HNF1\u3b1/\u3b2 and Cdx1/2, determined by Western blot analysis, in colon cancer biopsies, various cell lines, and cell models serving as controls. We found that HNF1\u3b1/\u3b2 were easily detected, irrespective of the amount of LTR transcript expressed by the source, whereas Cdx1/2 were undetectable, and no sample lacking HNF1\u3b1/\u3b2 expressed the LTR transcript. On transfection in proper host cells, both HNF1\u3b1 and HNF1\u3b2 provided detectable LTR transcript, whereas shRNA-mediated silencing of HNF1\u3b2 impaired transcription. Treating cells with 5\u2032-aza-2\u2032-deoxycytidine (5AZA) strongly reduced expression, without affecting HNF1\u3b1/\u3b2, despite the lack of CpG islands in the LTR and proximal sequences. By electrophoresis mobility shift and luciferase reporter assays, the LTR promoter binding and activity did not correlate with the amounts of LTR transcript expressed in the cells and depended on the levels of the transcription factors. We conclude that HNF1\u3b1/\u3b2 are necessary but insufficient to activate and regulate B3GALT5 LTR transcription, which depends on unknown regulatory elements that are active when methylated and located outside of and far from the LTR promoter

Acoustic Nature of the Boson Peak in Vitreous Silica

New temperature dependent inelastic x-ray (IXS) and Raman (RS) scattering data are compared to each other and with existing inelastic neutron scattering data in vitreous silica (v-SiO_2), in the 300 - 1775 K region. The IXS data show collective propagating excitations up to Q=3.5 nm^-1. The temperature behaviour of the excitations at Q=1.6 nm^-1 matches that of the boson peak found in INS and RS. This supports the acoustic origin of the excess of vibrational states giving rise to the boson peak in this glass.Comment: 10 pages and 4 figure

Commissioning of the MEG II tracker system

The MEG experiment at the Paul Scherrer Institut (PSI) represents the state of the art in the search for the charged Lepton Flavour Violating (cLFV) $\mu^+ \rightarrow e^+ \gamma$ decay. With the phase 1, MEG set the new world best upper limit on the \mbox{BR}(\mu^+ \rightarrow e^+ \gamma) < 4.2 \times 10^{-13} (90% C.L.). With the phase 2, MEG II, the experiment aims at reaching a sensitivity enhancement of about one order of magnitude compared to the previous MEG result. The new Cylindrical Drift CHamber (CDCH) is a key detector for MEG II. CDCH is a low-mass single volume detector with high granularity: 9 layers of 192 drift cells, few mm wide, defined by $\sim 12000$ wires in a stereo configuration for longitudinal hit localization. The filling gas mixture is Helium:Isobutane (90:10). The total radiation length is $1.5 \times 10^{-3}$ \mbox{X}_0, thus minimizing the Multiple Coulomb Scattering (MCS) contribution and allowing for a single-hit resolution $< 120$ $\mu$m and an angular and momentum resolutions of 6 mrad and 90 keV/c respectively. This article presents the CDCH commissioning activities at PSI after the wiring phase at INFN Lecce and the assembly phase at INFN Pisa. The endcaps preparation, HV tests and conditioning of the chamber are described, aiming at reaching the final stable working point. The integration into the MEG II experimental apparatus is described, in view of the first data taking with cosmic rays and $\mu^+$ beam during the 2018 and 2019 engineering runs. The first gas gain results are also shown. A full engineering run with all the upgraded detectors and the complete DAQ electronics is expected to start in 2020, followed by three years of physics data taking.Comment: 10 pages, 12 figures, 1 table, proceeding at INSTR'20 conference, accepted for publication in JINS

Single-hit resolution measurement with MEG II drift chamber prototypes

Drift chambers operated with helium-based gas mixtures represent a common solution for tracking charged particles keeping the material budget in the sensitive volume to a minimum. The drawback of this solution is the worsening of the spatial resolution due to primary ionisation fluctuations, which is a limiting factor for high granularity drift chambers like the MEG II tracker. We report on the measurements performed on three different prototypes of the MEG II drift chamber aimed at determining the achievable single-hit resolution. The prototypes were operated with helium/isobutane gas mixtures and exposed to cosmic rays, electron beams and radioactive sources. Direct measurements of the single hit resolution performed with an external tracker returned a value of 110 $\mu$m, consistent with the values obtained with indirect measurements performed with the other prototypes.Comment: 18 pages, 18 figure

Post-graduate medical education in public health: The case of Italy and a call for action

Public health technical expertise is of crucial importance to inform decision makers\u2019 action in the field of health and its broader determinants. Improving education and training of public health professionals for both practice and research is the starting point to strengthen the role of public health so that current health challenges can be efficiently tackled. At the Association of Schools of Public Health in the European Region (ASPHER) Deans\u2019 & Directors\u2019 2017 Annual Retreat, we presented the structure and management of public health training system in Italy, and we reported recent data on Italian public health specialists\u2019 educational experience, employment opportunities and job satisfaction. Public health training in Italy is implemented in the context of the post-graduate medical education residency programme in Hygiene and Preventive Medicine, delivered by 34 University-based Schools of Public Health. We report relatively high employment rates across the county and wide spectrum of career opportunities for young public health specialists. However, job security is low and training expectations only partially met. We call upon other Schools of Public Health to scale up the survey within the broad ASPHER community in a shared and coordinated action of systematically collecting useful data that can inform the development of public health education and training models, their implementation and fruitful interaction with population health, health systems and services

MEG Upgrade Proposal

We propose the continuation of the MEG experiment to search for the charged lepton flavour violating decay (cLFV) \mu \to e \gamma, based on an upgrade of the experiment, which aims for a sensitivity enhancement of one order of magnitude compared to the final MEG result, down to the $6 \times 10^{-14}$ level. The key features of this new MEG upgrade are an increased rate capability of all detectors to enable running at the intensity frontier and improved energy, angular and timing resolutions, for both the positron and photon arms of the detector. On the positron-side a new low-mass, single volume, high granularity tracker is envisaged, in combination with a new highly segmented, fast timing counter array, to track positron from a thinner stopping target. The photon-arm, with the largest liquid xenon (LXe) detector in the world, totalling 900 l, will also be improved by increasing the granularity at the incident face, by replacing the current photomultiplier tubes (PMTs) with a larger number of smaller photosensors and optimizing the photosensor layout also on the lateral faces. A new DAQ scheme involving the implementation of a new combined readout board capable of integrating the diverse functions of digitization, trigger capability and splitter functionality into one condensed unit, is also under development. We describe here the status of the MEG experiment, the scientific merits of the upgrade and the experimental methods we plan to use.Comment: A. M. Baldini and T. Mori Spokespersons. Research proposal submitted to the Paul Scherrer Institute Research Committee for Particle Physics at the Ring Cyclotron. 131 Page

Microvascular Decompression for Trigeminal Neuralgia Secondary to Vertebrobasilar Dolichoectasia: Review of the Literature and Illustrative Case

Classical trigeminal neuralgia (TN) is a chronic pain disorder characterized by severe, unilateral facial pain, often resulting from vasculonervous conflict. A less common cause of TN is vertebrobasilar dolichoectasia (VBD). Microvascular decompression (MVD) is the preferred surgical intervention for TN, but in case of VBD, the surgical procedure is more complex due to the aberrant vascular anatomy. This study aims to review the evidence on MVD for VBD-induced TN, and analyze operative challenges, efficacy, and postoperative outcomes. An illustrative case is also presented. We report on the case of a 62-year-old male with a 7-year history of right-sided TN affecting the maxillary (V2) and mandibular (V3) territories. The patient underwent MVD using the interposition technique, where Teflon sponges were placed between the basilar artery and the nerve. Postoperatively, the patient experienced complete pain relief without neurological deficits. At 12 months follow-up, the patient remained pain-free and off medications. We performed an extensive literature review using PubMed, Scopus, and Web of Sciences, highlighting the most relevant studies and findings on the topic. The literature review showed that, while MVD is effective in providing long-term pain relief in VBD-induced TN, the choice between interposition and transposition techniques remains debated. Interposition is easier to perform but may inadvertently increase nerve compression in some cases, whereas transposition offers more definitive decompression but carries higher technical risks. Our case and the available literature highlight the importance of individualized treatment planning in achieving optimal outcomes for patients with VBD-induced TN. Further research is needed to refine surgical techniques and minimize complications in this subset of TN patients

Interposition versus transposition technique in microvascular decompression for trigeminal neuralgia secondary to vertebrobasilar dolichoectasia: a systematic review and pooled meta-analysis

Introduction: Limited data are available comparing the interposition and transposition techniques for microvascular decompression (MVD) in patients with trigeminal neuralgia (TN) secondary to vertebrobasilar dolichoectasia (VBD); this study aims to review current findings on TN associated with VBD and compare the interposition and transposition techniques in terms of surgical morbidity and patient outcomes. Methods: Following the PRISMA guidelines, PubMed/Medline, Web of Science, and SCOPUS databases were searched to identify studies reporting patients undergoing MVD for TN secondary to VBD. The studies were divided into two groups, interposition and transposition, based on the microvascular decompression technique used. Studies not reporting the diagnostic criteria, included less than five cases, or were not available in English were excluded. Results: Fourteen eligible papers were retrieved, of which five studies reported cases undergoing the interposition technique, eight studies for the transposition technique, and one study reported cases from both groups. Data including preoperative and postoperative BNI class, comorbidities, and postoperative complications were retrieved to analyze and compare the two techniques in terms of efficacy and long-term outcomes in treating TN secondary to VBD. Conclusion: Both interposition and transposition techniques for MVD yield high rates of pain relief in patients with TN secondary to VBD. While both approaches demonstrate similar efficacy, the interposition method is associated with a lower rate of long-term complications. Further research, preferably through randomized prospective studies, is needed to refine surgical strategies and improve patient outcomes

Anterior Petrosectomy vs. Retrosigmoid Approach—Surgical Anatomy and Navigation-Augmented Morphometric Analysis: A Comparative Study in Cadaveric Laboratory Setting

Background: Different lateral and postero-lateral cranial approaches to the petroclival region and to the mid-upper brain stem have been described so far, some of which require extensive osseous demolition and possible damage of neurovascular structures. Neuronavigational systems are now extensively available for preoperative planning and intraoperative navigation to assist the surgeons in choosing the optimally invasive approach for each pathology. Herein, we describe a detailed navigation-augmented morphometric analysis to bring insight into the usefulness of an anterior petrosectomy (AP) to handle lesions in the petroclival region. Methods: Eight cadaveric, silicone injected heads were used. A total of 14 approaches (AP, n = 8; retrosigmoid, RS, n = 6) using a standard microsurgical dissection technique were performed. All specimens had preoperative CT and MRI scans, as well as a post-dissection CT. The neuronavigational system was used for distance measurements, craniotomy sizes and surgical corridor volumes, for each approach. Results: The distance from the skull surface to the petrous apex was significantly shorter in the AP approach when compared with the RS (46.0 ± 1.9 mm versus 71.3 ± 1.8 mm, respectively, p &lt; 0.001). Although the craniotomy size was not different, the volume of the surgical corridor was significantly larger with the AP approach (21.31 ± 1.91 cm3 vs. 13.39 ± 1.8 cm3). The AP approach increased the length of the basilar artery exposure from 6.9 ± 1.5 mm (obtained with a standard subtemporal approach) to 22.1 ± 1.7 mm (p &lt; 0.0001). Conclusions: The surgical corridor to the petroclival region achieved by virtue of an AP was significantly larger and featured shorter working distances, resulting in a higher degree of surgical freedom. Although significant individual anatomical variations of fundamental neurovascular and bony structures were found, these difficulties were overcome by careful pre- and intraoperative use of neuronavigation