Quick recovery and no arthrofibrosis in acute anterior cruciate ligament reconstruction. A prospective trial of early versus delayed reconstruction

Background. Anterior cruciate ligaments tears is one of the most frequent orthopae- dics and sports medicine injuries in the athletically active population and timing of reconstruction represents a debated topic. The aim of the study is to compare range of motion (ROM) recovery and clinical outcomes between patients operated for acute reconstruction (maximum 2 weeks injury-surgery interval) and delayed reconstruction (minimum 3 weeks injury-surgery interval). Methods. A total of 52 patients were prospectively involved in the study. 26 patients underwent acute reconstruction and 26 delayed reconstruction. A standard physical examination with Lachman and Pivot shift test and a passive ROM measurement with a goniometer were performed at each follow-up (2, 4, 8, 12 and 24 weeks postoper- atively). Clinical outcomes were measured at final follow-up using Knee Injury and Osteoarthritis outcome score (KOOS), Tegner Lysholm Score and International Knee Documentation Committe (IKDC 2000) and KT-1000 evaluation. Single-leg hop test and thigh circumference measurement were performed at final follow-up. Results. Both groups showed no statistically significant differences regarding the ROM. Full ROM was achieved 12 weeks after surgery in both groups. The mean IKDC was 98.7 and 95.2; the mean Tegner Lysholm was 100 and 93.8 and the mean KOOS was 99 and 95.5 in the acute group and delayed ACLR group respectively. Conclusions. There were no differences between acute and delayed anterior cruci- ate ligament reconstruction regarding the risk of arthrofibrosis and clinical outcomes. Acute reconstruction can be performed safely with no increased risk of arthrofibrosis

Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype

The ICARUS Experiment, A Second-Generation Proton Decay Experiment and Neutrino Observatory at the Gran Sasso Laboratory

The final phase of the ICARUS physics program requires a sensitive mass of liquid Argon of 5000 tons or more. The T600 detector stands today as the first living proof that such large detector can be built and that liquid Argon imaging technology can be implemented on such large scales. After the successful completion of a series of technical tests to be performed at the assembly hall in Pavia, the T600 detector will be ready to be transported into the LNGS tunnel. The operation of the T600 at the LNGS will allow us (1) to develop the local infrastructure needed to operate our large detector (2) to start the handling of the underground liquid argon technology (3) to study the local background (4) to start the data taking with an initial liquid argon mass that will reach in a 5-6 year program the multi-kton goal. The T600 is to be considered as the first milestone on the road towards a total sensitive mass of 5000 tons: it is the first piece of the detector to be complemented by further modules of appropriate size and dimensions, in order to reach in a most efficient and rapid way the final design mass. In this document, we describe the physics program that will be accomplished within the first phase of the program

Observation of long ionizing tracks with the ICARUS T600 first half-module

F. Arneodo, B. Bade"ek, A. Badertscher, B. Baiboussinov, M. Baldo Ceolin, G. Battistoni, B. Bekman, P. Benetti, E. Bernardini, M. Bischofberger, A. Borio di Tigliole, R. Brunetti, A. Bueno, E. Calligarich, M. Campanelli, C. Carpanese, D. Cavalli, F. Cavanna, P. Cennini, S. Centro, A. Cesana, C. Chen, D. Chen, D.B. Chen, Y. Chen, D. Cline, Z. Dai, C. De Vecchi, A. Dabrowska, R. Dolfini*, M. Felcini, A. Ferrari, F. Ferri, Y. Ge, A. Gigli Berzolari, I. Gil-Botella, K. Graczyk, L. Grandi, K. He, J. Holeczek, X. Huang, C. Juszczak, D. Kie"czewska, J. Kisiel, T. Koz"owski, H. Kuna-Ciska", M. Laffranchi, J. Łagoda, Z. Li, F. Lu, J. Ma, M. Markiewicz, A. Martinez de la Ossa, C. Matthey, F. Mauri, D. Mazza, G. Meng, M. Messina, C. Montanari, S. Muraro, S. Navas-Concha, M. Nicoletto, G. Nurzia, S. Otwinowski, Q. Ouyang, O. Palamara, D. Pascoli, L. Periale, G. Piano Mortari, A. Piazzoli, P. Picchi, F. Pietropaolo, W. P ! o"ch"opek, T. Rancati, A. Rappoldi, G.L. Raselli, J. Rico, E. Rondio, M. Rossella, A. Rubbia, C. Rubbia, P. Sala, D. Scannicchio, E. Segreto, F. Sergiampietri, J. Sobczyk, J. Stepaniak, M. Szeptycka, M. Szleper, M. Szarska, M. Terrani, S. Ventura, C. Vignoli, H. Wang, M. W ! ojcik, J. Woo, G. Xu, Z. Xu, A. Zalewska, J. Zalipska, C. Zhang, Q. Zhang, S. Zhen, W. Zipper a INFN Laboratori Nazionali del Gran Sasso, s.s. 17bis Km 18+910, Assergi (L'Aquila), Italy b Institute of Experimental Physics, Warsaw University, Warszawa, Poland c Institute for Particle Physics, ETH H . onggerberg, Z . urich, Switzerland Dipartimento di Fisica e INFN, Universit " a di Padova, via Marzolo 8, Padova, Italy Dipartimento di Fisica e INFN, Universit " a di Milano, via Celoria 16, Milano, Italy f Institute of Physics, University of Silesia, Katowice, Poland Dipartimento di Fisica e INFN, Universit " a di Pavia, via Bassi 6, Pavia, Italy Dpto de F!isica Te ! orica y del Cosmos & C.A.F.P.E., Universidad de Granada, Avda. Severo Ochoa s/n, Granada, Spain Dipartimento di Fisica e INFN, Universit " a dell'Aquila, via Vetoio, L'Aquila, Italy CERN, CH-1211 Geneva 23, Switzerland Politecnico di Milano (CESNEF), Universit " a di Milano, via Ponzio 34/3, Milano, Ital

CD8+T-cell mediated self-reactivity in HLA-B27 context as a consequence of dual peptide conformation

HLA-B*2709 does not predispose for Ankylosing Spondylitis although it differs from B*2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles B*2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B*2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B*2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses