Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid.

Osteoarthritis (OA), also called degenerative joint disease, is the most frequently occurring chronic musculoskeletal disease, particularly affecting the aging population. The use of viscosupplementation, i.e. intra-articular (IA) hyaluronic acid (HA) drug therapy, to treat OA, is growing worldwide, due to important results obtained from several clinical trials, which reported IA HA-related improvements in functional activity and pain management. This review is an update of the IA use of this compound in the treatment of OA, with clinical evidence from the last few years being discussed and used to delineate new trends for the future

High accuracy CO2_2 line intensities determined from theory and experiment

Atmospheric CO$_2$ concentrations are being closely monitored by remote sensing experiments which rely on knowing line intensities with an uncertainty of 0.5\%\ or better. Most available laboratory measurements have uncertainties much larger than this. We report a joint experimental and theoretical study providing rotation-vibration line intensities with the required accuracy. The {\it ab initio} calculations are extendible to all atmospherically important bands of CO$_2$ and to its isotologues. As such they will form the basis for detailed CO$_2$ spectroscopic line lists for future studies.Comment: 5 pages, 2 figures, 1 tabl

A variable neurodegenerative phenotype with polymerase gamma mutation

mtDNA replication and repair, causes mitochondrial diseases including autosomal dominant progressive external ophthalmoplegia (PEO),1 childhood hepato-encephalopathy (Alpers– Huttenlocher syndrome), adult-onset spinocerebellar ataxia, and sensory nerve degeneration with dysarthria and ophthalmoparesis (SANDO)

Extreme-Point-based Heuristics for the Three-Dimensional Bin Packing problem

One of the main issues in addressing three-dimensional packing problems is finding an efficient and accurate definition of the points at which to place the items inside the bins, because the performance of exact and heuristic solution methods is actually strongly influenced by the choice of a placement rule. We introduce the extreme point concept and present a new extreme point-based rule for packing items inside a three-dimensional container. The extreme point rule is independent from the particular packing problem addressed and can handle additional constraints, such as fixing the position of the items. The new extreme point rule is also used to derive new constructive heuristics for the three-dimensional bin-packing problem. Extensive computational results show the effectiveness of the new heuristics compared to state-of-the-art results. Moreover, the same heuristics, when applied to the two-dimensional bin-packing problem, outperform those specifically designed for the proble

An in-line coaxial-to-waveguide transition for q-band single-feed-per-beam antenna systems

An in-line transition between a coaxial cable and rectangular waveguide operating in Q-band (33–50 GHz) is presented. The aim of the work is to minimize the modifications in the waveguide to the strictly necessary to overcome the manufacturing issues due to the high frequencies involved. In addition, the transition is compact and it does not increase the space occupation on the transverse section, this suggests its application in horn antennas clusters arrangement. The operating principle consists of both a modal conversion and an impedance matching between the devices. The modal conversion is realized in an intermediate region, where the coaxial penetrates in the waveguide: the device geometry is designed so that the electric field in the transition is a trade-off between the TEM mode of the coaxial and the TE10 of the guide. A shaped waveguide backshort and a reactive air gap in the coaxial cable co-participate to achieve the matching. An optimized Chebyshev stepped transformer completes the transition to fulfil the impedance mismatch with the full waveguide. The design issues and technological aspects are considered. The influences of the feeding pin misalignment, the presence of groove is included in the analysis and these practical aspects are discussed and numerically validated via the scattering parameters analysis of the proposed design. The return loss is higher than 25 dB over the whole Q-band

A yeast-based repurposing approach for the treatment of mitochondrial DNA depletion syndromes led to the identification of molecules able to modulate the dNTP pool

Mitochondrial DNA depletion syndromes (MDS) are clinically heterogenous and often severe diseases, characterized by a reduction of the number of copies of mitochondrial DNA (mtDNA) in affected tissues. In the context of MDS, yeast has proved to be both an excellent model for the study of the mechanisms underlying mitochondrial pathologies and for the discovery of new therapies via high-throughput assays. Among the several genes involved in MDS, it has been shown that recessive mutations in MPV17 cause a hepatocerebral form of MDS and Navajo neurohepatopathy. MPV17 encodes a non selective channel in the inner mitochondrial membrane, but its physiological role and the nature of its cargo remains elusive. In this study we identify ten drugs active against MPV17 disorder, modelled in yeast using the homologous gene SYM1. All ten of the identified molecules cause a concomitant increase of both the mitochondrial deoxyribonucleoside triphosphate (mtdNTP) pool and mtDNA stability, which suggests that the reduced availability of DNA synthesis precursors is the cause for the mtDNA deletion and depletion associated with Sym1 deficiency. We finally evaluated the effect of these molecules on mtDNA stability in two other MDS yeast models, extending the potential use of these drugs to a wider range of MDS patients

Mechanistic insights on the mode of action of an antiproliferative thiosemicarbazone-nickel complex revealed by an integrated chemogenomic profiling study

Thiosemicarbazones (TSC) and their metal complexes display diverse biological activities and are active against multiple pathological conditions ranging from microbial infections to abnormal cell proliferation. Ribonucleotide reductase (RNR) is considered one of the main targets of TSCs, yet, the existence of additional targets, differently responsible for the multifaceted activities of TSCs and their metal complexes has been proposed. To set the basis for a more comprehensive delineation of their mode of action, we chemogenomically profiled the cellular effects of bis(citronellalthiosemicarbazonato)nickel(II) [Ni(S-tcitr)2] using the unicellular eukaryote Saccharomyces cerevisiae as a model organism. Two complementary genomic phenotyping screens led to the identification of 269 sensitive and 56 tolerant deletion mutant strains and of 14 genes that when overexpressed make yeast cells resistant to an otherwise lethal concentration of Ni(S-tcitr)2. Chromatin remodeling, cytoskeleton organization, mitochondrial function and iron metabolism were identified as lead cellular processes responsible for Ni(S-tcitr)2 toxicity. The latter process, and particularly glutaredoxin-mediated iron loading of RNR, was found to be affected by Ni(S-tcitr)2. Given the multiple pathways regulated by glutaredoxins, targeting of these proteins by Ni(S-tcitr)2 can negatively affect various core cellular processes that may critically contribute to Ni(S-tcitr)2 cytotoxicity