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Vincenzo Di Stefano,1 Antonella Fava,2 Luca Gentile,3 Pietro Guaraldi,4 Luca Leonardi,5 Loris Poli,6 Matteo Tagliapietra,7 Michele Vastola,8,9 Salvatore Fanara,1 Bruno Ferrero,10 Mauro Giorgi,2 Federico Perfetto,8 Massimo Russo,3 Domitilla Russo11 1Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, Italy; 2Division of Cardiology, Heart Vascular and Thoracic Department, Città della Salute e della Scienza (Molinette Hospital- University of Turin), Turin, Italy; 3Unit of Neurology and Neuromuscular Disease, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 4IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 5Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome Sant’Andrea Hospital, Rome, Italy; 6Department of Neurology, ASST Spedali Civili, Brescia, Italy; 7Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; 8Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy; 9Neurosciences Department, Florence University, Rome, Italy; 10SC Neurology 2U, Department of Neuroscience “Rita Levi Montalcini”, Città della Salute e della Scienza (Molinette Hospital -University of Turin), Turin, Italy; 11Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, ItalyCorrespondence: Vincenzo Di Stefano, Department of Biomedicine, Neuroscience and advanced Diagnostic (BIND), University of Palermo Palermo, Italy, Via del Vespro 143, Palermo, 90127, Italy, Tel +39 3285781786, Fax +390916552974, Email vincenzo19689@gmail.comAbstract: Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensorimotor nerves, heart, autonomic function and other organs. The actual scenario of pharmaceutical approaches for ATTRv amyloidosis includes five main groups: TTR stabilizers, TTR mRNA silencers, TTR fibril disruptors, inhibitor of TTR fibril seeding and gene therapy. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, able to penetrate into hepatocytes, where it selectively targets TTR mRNA, reducing TTR production. We report and discuss 9 cases of different patients with ATTRv amyloidosis successfully managed with patisiran in the real clinical practice. Literature data, as well as the above presented case reports, show that this drug is effective and safe in improving both neurological and cardiovascular symptoms of ATTRv amyloidosis, and to maintain a good QoL, independently form the stage of the disease and the involved mutation. Recent studies correlated improved functional and biochemical outcomes with a regression of amyloid burden, especially at the cardiac level. Today, patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis and polyneuropathy and cardiovascular symptoms.Keywords: hereditary transthyretin amyloidosis, patisiran, real-life, case reports

Massimo Mammucari,1 Teresa Paolucci,2 Domenico Russo,3 Enrica Maggiori,1 Raffaele Di Marzo,4 Alberto Migliore,5 Umberto Massafra,5 Gianpaolo Ronconi,6 Paola Emilia Ferrara,6 Fabio Gori,7 Barbara Bifarini,7 Stefano Brauneis,8 Renato Vellucci,9 Rocco Domenico Mediati,9 Bartolomeo Violo,10 Silvia Natoli,11 Carmen Pediliggieri,12 Cristiana Di Campli,12 Maria Chiara Collina12 1Primary Care Unit, ASL RM 1, Rome, Italy; 2Unit of Physical Medicine and Rehabilitation, G. D’ Annunzio University of Chieti-Pescara, Department of Oral Medical Science and Biotechnology (DSMOB), Chieti, Italy; 3“San Marco” Hospice and Palliative Care, Latina, Italy; 4Member of the Italian Society of Mesotherapy, Rome, Italy; 5Unit of Rheumatology, San Pietro Fatebenefratelli Hospital, Rome, Italy; 6Physical Medicine and Rehabilitation Unit, IRCCS, Catholic University of Sacred Heart, Rome, Italy; 7Section of Anaesthesia, Intensive Care, and Pain Medicine, University Hospital Santa Maria Della Misericordia, Perugia, Italy; 8Pain Centre “Enzo BorzomatI”, University Hospital of Rome “Policlinico Umberto I”, Rome, Italy; 9Anaesthesiology Department, University Hospital Careggi, Florence, Italy; 10Pain Therapy Unit, S. Spirito Nuovo Regina Margherita Hospital, Rome, Italy; 11Department of Clinical Science and Translational Medicine, Tor Vergata University, Rome, Italy; 12Department of Vascular Surgery, Limb Salvage and Diabetic Foot, IDI-IRCCS, Rome, ItalyCorrespondence: Massimo MammucariPrimary Care Unit, Local Health, ASL RM 1, Rome, 00165, ItalyTel +39-06-61560695 Email massimo.mammucari@libero.itAbstract: Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths.Keywords: mesotherapy, intradermal therapy, research plan

Alberto Migliore,1 Gianfranco Gigliucci,1 Raffaele Di Marzo,2 Domenico Russo,3 Massimo Mammucari4 1Department of Internal Medicine, Unit of Rheumatology, San Pietro Fatebenefratelli Hospital, Rome, Italy; 2Italian Society of Mesotherapy, Rome, Italy; 3“San Marco” Hospice and Palliative Care, Latina, Italy; 4Primary Care Unit ASL RM 1, Rome, ItalyCorrespondence: Alberto Migliore Email migliore.alberto60@gmail.comAbstract: This narrative review is the final output of an initiative of the SIM (Italian Society of Mesotherapy). A narrative review of scientific literature on the efficacy of fractional intradermal vaccination in comparison with full doses has been conducted for the following pathogens: influenza virus, rabies virus, poliovirus (PV), hepatitis B virus (HBV), hepatitis A virus (HAV), diphtheria-tetanus-pertussis bacterias (DTP), human papillomavirus (HPV), Japanese encephalitis virus (JE), meningococcus, varicella zoster virus (VZV) and yellow fever virus. The findings suggest that the use of the intradermal route represents a valid strategy in terms of efficacy and efficiency for influenza, rabies and HBV vaccines. Some systematic reviews on influenza vaccines suggest the absence of a substantial difference between immunogenicity induced by a fractional ID dose of up to 20% and the IM dose in healthy adults, elderly, immunocompromised patients and children. Clinical studies of remaining vaccines against other pathogens (HAV, DTP bacterias, JE, meningococcal disease, VZV, and yellow fever virus) are scarce, but promising. In the context of a COVID-19 vaccine shortage, countries should investigate if a fractional dosing scheme may help to save doses and achieve herd immunity quickly. SIM urges the scientific community and health authorities to investigate the potentiality of fractionate intradermal administration in anti-COVID-19 vaccination.Keywords: vaccination, intradermal, COVID-19, dose sparing

Lucia Musacchio,1 Giuseppe Caruso,1 Carmela Pisano,2 Sabrina Chiara Cecere,2 Marilena Di Napoli,2 Laura Attademo,2 Rosa Tambaro,2 Daniela Russo,3 Daniela Califano,3 Innocenza Palaia,1 Ludovico Muzii,1 Pierluigi Benedetti Panici,1 Sandro Pignata2 1Department of Maternal and Child Health and Urological Sciences, University “Sapienza”, Policlinico Umberto I, Rome, Italy; 2Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy; 3Functional Genomic Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, ItalyCorrespondence: Sandro PignataDepartment of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Via Semmola, Naples 80131, ItalyTel +39 0815903409Fax +39 0815903861Email s.pignata@istitutotumori.na.itAbstract: Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endometrial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.Keywords: endometrial cancer, PARP inhibitors, PTEN mutation, P53 mutation, homologous recombination deficiency, immune checkpoint inhibitors

Loris Butti,1 Olga Bierti,1 Raffaela Lanfrit,1 Romina Bertolini,1 Sara Chittaro,1 Stefania Delli Compagni,1 Davide Del Russo,1 Rossella Letizia Mancusi,2 Franco Pertoldi1 1S.O.C. Emergency Medicine, AAS3 Ospedale Sant’Antonio di San Daniele del Friuli, 2C.R.E.A. Sanità, University of Tor Vergata, Rome, Italy Introduction: Pain is a common symptom presented in the emergency department (ED) although it is often underestimated, poorly evaluated and treated. The application of a protocol for timely pain management ensured by the nurse can avoid the delays in the analgesic treatment and improve the patient’s quality of waiting.Aims: To check the effectiveness and efficiency of the protocol aimed at early pain management in triage, active in our ED. In particular, the response to analgesic treatment was evaluated 60 minutes after the administration and at discharge. Patient satisfaction was also evaluated using two anonymous questionnaires both at discharge and 48 hours later via telephone.Methods: A single-center, observational study was conducted on a prospective cohort of patients (aged ≥4 years) with a pain symptom at admission in ED with no surgical picture.Results: In the observation period (June 2015–May 2016), 382 patients were enrolled, and of these, 312 (84.8%) accepted pain therapy during triage stage in the ED. In 97.4% of the cases, orosoluble paracetamol 1000 mg was administered. In the re-evaluation done 60 minutes later, 65.9% of the patients showed a reduction of at least 2 points on Numeric Rating Scale (NRS), equal to a mean reduction of 2.24 points (95% CI: 2.03–2.45). The mean time of analgesia intake was equal to 5.9 minutes (95% CI: 3.8–8.1). In the re-evaluation done at discharge, 33.2% of the patients showed a reduction of NRS score >50%, leading to a mean reduction of 39% (95% CI: 35.3%−41.9%). The level of patient satisfaction was high with a mean value >9 points (maximum satisfaction =10).Conclusion: This protocol shows that optimal pain management was achieved by patients rapidly receiving an effective painkiller therapy at triage, leading to substantial patient satisfaction. In moderate pain, orosoluble paracetamol 1000 mg provided a reduction of NRS score by 2 points in 67.6% of the patients, confirming to be the analgesic of choice in ED. Keywords: pain management, protocol, triage, analgesic, orosoluble paracetamol

Research and development efforts are currently underway worldwide to examine the potential use of a wide range of non-destructive technologies (NDT) for evaluating wood and wood-based materials, from the assessment of standing trees to in-place structures. For this purpose, acoustic velocity by the Fakopp time of flight (TOF) tool was used to estimate the influence of four thinning treatments performed in Southern Italy. The objective of the study was to determine if the effects of silvicultural practices on wood quality can be identified using acoustic measurement to assess the MOEd of standing trees with non-destructive method in Calabrian pine (Pinus nigra Arnold subsp. calabrica). Four hundred and fifty standing trees from four sites were non-destructively tested using a time-of-flight acoustic wave technique. The thinning trials were conducted on 60-year-old plantations of Calabrian pine in four plots under different treatments: Control (T), light thinning (A), intermediate thinning (B) and heavy thinning (C). Statistical analysis demonstrated significant stress wave time differences between the stands with moderate thinning (A and B) and those with heavy thinning (C). The results showed that tree diameter has significant influence on acoustic wave measurements and a valid relationship exists between diameter at breast height and tree velocity. The results of these studies proved that the stress wave technique can be successfully applied on standing trees.

Background. Mesotherapy is a technique through which active ingredients are administered into the thickness of the skin in order to increase the local analgesic effect. Methods. 141 patients with spinal pain not responding to systemic therapy with NSAIDs were randomized to receive one or more intracutaneous drugs on a weekly basis. Results. All patients achieved a pain reduction of at least 50% compared to baseline, and all tolerated the therapy without having to resort to systemic drug dose increases. Conclusions. The data from our study show that the active ingredients infiltrated into the skin induce a mesodermal modulation between the infiltrated liquid and the cutaneous nervous and cellular structures from which the typical drug-saving effect of mesotherapy arises. Although further studies are needed to establish how to integrate mesotherapy in various clinical settings, it appears to be a useful technique available to the practicing physician. This research is also useful in guiding future clinical research. [ABSTRACT FROM AUTHOR]

The University of Waterloo, Waterloo, ON, Canada, is home to North America's first undergraduate program in nanotechnology. As part of the Nanotechnology Engineering degree program, a scanning probe microscopy (SPM)-based laboratory has been developed for students in their fourth year. The one-term laboratory course "Nanoprobing and Lithography" is accompanied by a preceding one-term lecture course, "Nanoprobing and Lithography." The lecture course lays the theoretical foundation for the concepts covered in the laboratory course. The students work in groups of two and obtain hands-on experience in biweekly 3-h laboratory sessions. The labs use a dedicated undergraduate SPM teaching facility consisting of five atomic force microscope stations. The laboratory course covers all common standard modes of operation, as well as force spectroscopy, electrostatic force microscopy, magnetic force microscopy, and scanning probe lithography by electrochemical oxidation and scratching/ploughing of resist. In light of the breadth of the nanotechnology engineering educational program in terms of synthesis and characterization of nanomaterials, the authors designed a dedicated SPM lab with a capacity of up to 130 students per term. (Contains 3 footnotes and 11 figures.)