The Musculoskeletal Tumor Society Scoring system is a valid subjective and objective tool to evaluate outcomes of surgical treatment of patients affected by upper and lower extremity tumors.

PURPOSE: The main purpose of the present study was to evaluate if there is a difference between objective or subjective administration of the MSTS score in a cohort of patients affected by musculoskeletal oncological diseases. MATERIALS AND METHODS: All patients who underwent surgery for bone or soft tissue localization of neoplastic disease in lower or upper limb from June 2015 to June 2020 were considered eligible. In order to administer the score as a PROM, the MSTS was first translated and cross-culturally adapted in Italian. During follow up visits, all patients filled out Italian versions of SF36, TESS and MSTS. Psychometric properties of the Italian version of MSTS were analyzed. Correlation between objective and self-administered MSTS score was assessed through Pearson's coefficient. RESULTS: A finale sample of 110 patients were included: 59 affected by lower extremity involvement and 51 affected by upper extremity involvement. The Italian version of the MSTS score showed good psychometric properties for both lower and upper extremity. The correlation between self-administered and hetero-administered version of the questionnaire was as high as r = 0.97 for lower extremities and r = 0.96 for upper extremities. CONCLUSIONS: The Italian version of the MSTS is a valid tool to evaluate outcomes of surgical treatment of patients affected by extremities tumors and it can be used as a subjective tool for both lower and upper extremity.

Cross-cultural adaptation and validation of the Italian version of the Western Ontario Rotator Cuff (WORC) index.

The aim of the study was to accomplish translation, cross-cultural adaptation and validation of the Western Ontario Rotator Cuff (WORC) Index questionnaire for its use in Italy. The WORC original version was translated and cross-culturally adapted into Italian. Subsequently, it was administered to a population of 60 patients suffering from rotator cuff disease to evaluate the validity and reliability of the Italian version. The content validity evaluated the correlation between questions and total score of each domain through Pearson's correlation coefficient. The construct validity was similarly assessed through Pearson's correlation coefficient by testing the correlation between the Italian WORC and the Italian version of the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Reliability was assessed using two methods: internal consistency by calculating the Cronbach's alpha coefficient for each domain; and test-retest by means of the intraclass correlation coefficient (ICC). The translation and cross-cultural adaptation of the Italian version did not reveal any major problems. No significant floor or ceiling effects were found. All the questions were linearly related to the concept expressed by the domain of belonging. Overall correlation with the DASH score was 0.75. Internal consistency was very high overall (α = 0.93) as well as reliability (overall ICC = 0.87). The Italian version of the WORC questionnaire is a valid and reproducible measuring instrument and can be considered a valid tool for the evaluation of the effectiveness of a treatment in terms of quality of life, in Italian patients affected by rotator cuff diseases.Level of evidence Diagnostic study, level II.

The systemic deletion of interleukin-1α reduces myocardial inflammation and attenuates ventricular remodeling in murine myocardial infarction.

Myocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1ß or the IL-1 receptor. In contrast, the potential role of IL-1α in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1α may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1α deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1α deficiency (IL-1α KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1α therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation.

Metal-insulator transition in single crystalline ZnO nanowires.

In this work, we report on the metal-insulator transition and electronic transport properties of single crystalline ZnO nanowires synthetized by means of Chemical Vapor Deposition. After evaluating the effect of adsorbed species on transport properties, the thermally activated conduction mechanism was investigated by temperature-dependent measurements in the range 81.7-250 K revealing that the electronic transport mechanism in these nanostructures is in good agreement with the presence of two thermally activated conduction channels. More importantly, it was observed that the electrical properties of ZnO NWs can be tuned from semiconducting to metallic-like as a function of temperature with a metal-to-insulator transition (MIT) observed at a critical temperature above room temperature (T c âˆ¼ 365 K). Charge density and mobility were investigated by means of field effect measurements in NW field-effect transistor configuration. Results evidenced that the peculiar electronic transport properties of ZnO NWs are related to the high intrinsic n-type doping of these nanostructures that is responsible, at room temperature, of a charge carrier density that lays just below the critical concentration for the MIT. This work shows that native defects, Coulomb interactions and surface states influenced by adsorbed species can significantly influence charge transport in NWs.

Efficient and realistic simulation of phase coexistence.

We show how an existing concurrent multi-scale method named hybrid particle field-molecular dynamics (hPF-MD) can be adapted to enable the simulation of structure and/or structural dynamics in compressible systems. Implementing such new equations of state (EOS) into hPF-MD, while conserving the efficiency associated with treating intermolecular interactions in a continuum fashion, opens this method up to describe a new class of phenomena in which non-uniform densities play a role, for example, evaporation and crystallization. We carefully consider how compressible hPF-MD compares to its mean-field counterpart for two particular EOS, adopted from the Cell Model for polymers and the Carnahan-Starling expression for hard spheres. Here, we performed a very basic analysis for a single-component system, focusing on the significance of various particle-based parameters and the particle-to-field projection. Our results illustrate the key role of the particle density per field grid cell and show that projection based on a Gaussian kernel is preferred over the standard cloud-in-cell projection. They also suggest that the behavior of hPF-MD close to the critical point is non-classical, i.e., in agreement with a critical exponent for a pure particle description, despite the mean-field origin of the method.

Hydrothermally grown ZnO nanowire array as an oxygen vacancies reservoir for improved resistive switching.

Resistive switching (RS) devices based on self-assembled nanowires (NWs) and nanorods (NRs) represent a fascinating alternative to conventional devices with thin film structure. The high surface-to-volume ratio may indeed provide the possibility of modulating their functionalities through surface effects. However, devices based on NWs usually suffer from low resistive switching performances in terms of operating voltages, endurance and retention capabilities. In this work, we report on the resistive switching behaviour of ZnO NW arrays, grown by hydrothermal synthesis, that exhibit stable, bipolar resistive switching characterized by SET/RESET voltages lower than 3 V, endurance higher than 1100 cycles and resistance state retention of more than 105 s. The physical mechanism underlying these RS performances can be ascribed to nanoionic processes involving the formation/rupture of conductive paths assisted by oxygen-related species in the ZnO active layer. The reported results represent, to the best of our knowledge, the best resistive switching performances observed in ZnO NW arrays in terms of endurance and retention.

Magnetic resonance arthrography accuracy in the detection of labral tears in young patients with chronic unstable shoulder: correlation with arthroscopy.

The aim of this study is to determine the diagnostic performance of Magnetic Resonance Arthrography (MRA) in evaluating lesions of the glenoid labrum, in young active patients with chronic unstable shoulder, compared to shoulder arthroscopy. We retrospectively considered 65 MRA examinations, performed between December 2011 and January 2018. Among them, thirty-five patients (31 men, 4 women; mean age, 27.3 years; range, 16-53 years; 4 patients with a previous arthroscopy of the same shoulder) underwent shoulder arthroscopy after MRA. Arthroscopic reports were collected and analyzed for the correlation with MRA results.

Resistive switching in sub-micrometric ZnO polycrystalline films.

Resistive switching (RS) devices are considered as the most promising alternative to conventional random access memories. They interestingly offer effective properties in terms of device scalability, low power-consumption, fast read/write operations, high endurance and state retention. Moreover, neuromorphic circuits and synapse-like devices are envisaged with RS modeled as memristors, opening the route toward beyond-Von Neumann computing architectures and intelligent systems. This work investigates how the RS properties of zinc oxide thin films are related to both sputtering deposition process and device configuration, i.e. valence change memory and electrochemical metallization memory (ECM). Different devices, with an oxide thickness ranging from 50-250 nm, are fabricated and deeply characterized. The electrical characterization evidences that, differently from typical nanoscale amorphous oxides employed for resistive RAMs (HfO x , WO x , etc), sub-micrometric thicknesses of polycrystalline ZnO layers with ECM configuration are needed to achieve the most reliable devices. The obtained results are deeply discussed, correlating the RS mechanism to material nanostructure.

"No pain, No gain" still true with immunotherapy: When the finger shows the moon, look at the moon!

There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors. In the current context of precision medicine, and along with the constant quest for identifying predictive biomarkers, close monitoring of treatment-related toxicities could therefore be convenient to help predicting therapeutic response, but presents several caveats. The purpose of this review is to briefly describe these relationships across the different treatments, to comment on possible underlying mechanisms and to comment on possible strategies aiming at exploiting this relationship while keeping the maximal safety ensured in patients with cancer. In particular, this review will investigate on how drug exposure along with germinal and somatic genetic issues does impact on the "No Pain, No Gain" aphorism, and why the temptation to use treatment-related toxicities as a cheap and convenient way to predict clinical outcome or to adapt dosing should be resisted. We do advocate instead for developing comprehensive genomic support along with extensive biomathematical modeling to better customize dosing and shift towards a new "No Pain, Maximal Gain" paradigm.

Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer.

INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity. RESULTS: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis. CONCLUSION: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases.

Combining cell-based hydrodynamics with hybrid particle-field simulations: efficient and realistic simulation of structuring dynamics.

We have extended an existing hybrid MD-SCF simulation technique that employs a coarsening step to enhance the computational efficiency of evaluating non-bonded particle interactions. This technique is conceptually equivalent to the single chain in mean-field (SCMF) method in polymer physics, in the sense that non-bonded interactions are derived from the non-ideal chemical potential in self-consistent field (SCF) theory, after a particle-to-field projection. In contrast to SCMF, however, MD-SCF evolves particle coordinates by the usual Newton's equation of motion. Since collisions are seriously affected by the softening of non-bonded interactions that originates from their evaluation at the coarser continuum level, we have devised a way to reinsert the effect of collisions on the structural evolution. Merging MD-SCF with multi-particle collision dynamics (MPCD), we mimic particle collisions at the level of computational cells and at the same time properly account for the momentum transfer that is important for a realistic system evolution. The resulting hybrid MD-SCF/MPCD method was validated for a particular coarse-grained model of phospholipids in aqueous solution, against reference full-particle simulations and the original MD-SCF model. We additionally implemented and tested an alternative and more isotropic finite difference gradient. Our results show that efficiency is improved by merging MD-SCF with MPCD, as properly accounting for hydrodynamic interactions considerably speeds up the phase separation dynamics, with negligible additional computational costs compared to efficient MD-SCF. This new method enables realistic simulations of large-scale systems that are needed to investigate the applications of self-assembled structures of lipids in nanotechnologies.

Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis.

Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039). Meta-analysis yielded nominal significance (at α=0.05) for rs4444903 and rs11543848, but showed no significant results after multiple testing correction; this was unchanged by sensitivity analyses to address subgroups, funnel-plot asymmetries, and study quality. This highlights a tendency for lack of replication in the face of initial positive results, and possibly the unsuitability of relying on tumor response as a surrogate marker in this setting.

Inhibition of ceramide de novo synthesis as a postischemic strategy to reduce myocardial reperfusion injury.

The injury caused by myocardial reperfusion after ischemia can be contained by interventions aimed at reducing the inflammation and the oxidative stress that underlie exacerbation of tissue damage. Sphingolipids are a class of structural and signaling lipid molecules; among them, the inflammation mediator ceramide accumulates in the myocardium upon ischemia/reperfusion. Here, we show that, after transient coronary occlusion in mice, an increased de novo ceramide synthesis takes place at reperfusion in the ischemic area surrounding necrosis (area at risk). This correlates with the enhanced expression of the first and rate-limiting enzyme of the de novo pathway, serine palmitoyltransferase (SPT). The intraventricular administration at reperfusion of myriocin, an inhibitor of SPT, significantly protected the area at risk from damage, reducing the infarcted area by 40.9 % relative to controls not treated with the drug. In the area at risk, myriocin downregulated ceramide, reduced the content in other mediators of inflammation and reactive oxygen species, and activated the Nrf2-HO1 cytoprotective response. We conclude that an enhanced ceramide synthesis takes part in ischemia/reperfusion injury and that myriocin treatment can be proposed as a strategy for myocardial pharmacological postconditioning.