Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates

ABSTRACT — Knee pathologies including focal cartilage injuries, osteoarthritis (OA), and ligament injuries are common. The poor regeneration and healing potential of cartilage has led to the search for other treatment modalities with improved healing capacity. Furthermore, with an increasing elderly population that desires to remain active, the burden of knee pathologies is expected to increase. Increased sports participation and the desire to return to activities faster is also demanding more effective and minimally invasive treatment options. Thus, the use of biologic agents in the treatment of knee pathologies has emerged as a potential option. Despite the increasing use of biologic agents for knee pathology, there are conflicting results on the efficacy of these products. Furthermore, strong data supporting the optimal preparation methods and composition for widely used biologic agents, such as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), largely remain absent from the literature. This review presents the literature on the most commonly employed biologic agents for the different knee pathologies

Role of poly [adp-ribose] polymerase 1 in activating the kirsten ras (Kras) gene in response to oxidative stress

In pancreatic Panc-1 cancer cells, an increase of oxidative stress enhances the level of 7,8-dihydro-8-oxoguanine (8OG) more in the KRAS promoter region containing G4 motifs than in non-G4 motif G-rich genomic regions. We found that H2O2 stimulates the recruitment to the KRAS promoter of poly [ADP-ribose] polymerase 1 (PARP-1), which efficiently binds to local G4 structures. Upon binding to G4 DNA, PARP-1 undergoes auto PARylation and thus becomes negatively charged. In our view this should favor the recruitment to the KRAS promoter of MAZ and hnRNP A1, as these two nuclear factors, because of their isoelectric points >7, are cationic in nature under physiological conditions. This is indeed supported by pulldown assays which showed that PARP-1, MAZ, and hnRNP A1 form a multiprotein complex with an oligonucleotide mimicking the KRAS G4 structure. Our data suggest that an increase of oxidative stress in Panc-1 cells activates a ROS-G4-PARP-1 axis that stimulates the transcription of KRAS. This mechanism is confirmed by the finding that when PARP-1 is silenced by siRNA or auto PARylation is inhibited by Veliparib, the expression of KRAS is downregulated. When Panc-1 cells are treated with H2O2 instead, a strong up-regulation of KRAS transcription is observed

The Plio-Quaternary uplift of the Apennine Chain: new data from the analysis of topography and river valleys in Central Italy

This study aimed at the reconstruction of magnitude and timing of uplift of a wide sector of the Central Apennines (Italy) by means of morphometric and morphostructural analyses. In the internal portion of the chain (where stratigraphic and geomorphological markers of past sea-level positions are lacking) the study was based on analysis of erosional landforms and river valleys. A large-scale topographic analysis was performed, processing 90-m and 230-m DEMs. The spatial distribution of several morphometric parameters, together with characteristic wavelengths of relief, allowed the distinction of three main regions affected by different cumulative surface uplift and tectonic/erosional fragmentation: a Peri-Tyrrhenian Belt; an Axial Belt; a Peri-Adriatic Belt. Particular attention was devoted to fluvial landforms, with analysis of longitudinal profiles and geometric pattern of the main stream-trunks and their relations with major structures. Major differences occur between the Tyrrhenian and Adriatic valley systems, the former being generally longitudinal and showing overall concave-upward longitudinal profiles, whereas the latter are generally transverse and possess less regular longitudinal profiles. Topographic features and river valleys architecture seem related to different styles and amounts of uplift in the three Belts. Within the study area, a narrower coast to coast transect (Gaeta-Vasto Transect, GVT) was investigated in detail, devoting particular attention to its axial sector, lying around the Apennines main divide (main divide area: MDA), and a possible scheme of the Quaternary surface uplift inside this transect was proposed. In the MDA, the main stages of landscape evolution and river network organization were reconstructed by analysis of paleosurfaces coupled with analysis of relic and present-day hydrographic network. This allowed recognition of a major phase of surface uplift (exceeding 1500 m in the Meta-Mainarde massif) occurred in response to thrusting during the Pliocene, whereas for the Quaternary uplift a minimum value around 400 m was estimated. Our study suggests that, during the Quaternary and in the GVT, the Peri-Tyrrhenian Belt suffered a subdued uplift operating over small wavelengths (10-15 km), while Axial and Peri- Adriatic Belts were subject to a stronger and long-wavelength (90 km) surface uplift, with maximum values (about 700 m) shifted NE of the Axial Belt and tapering to zero towards the Adriatic coast. The reconstructed pattern of uplift is coherent with the topographic properties of the three Belts and with the observed drainage features

Seminario di Linguistica e Didattica delle Lingue. Scritti in onore degli ottant’anni di Giovanni Freddi

Include, di Balboni: “La glottodidattica veneziana: una ‘scuola’?”, pp. 19-54

MV-MS-FETE: Multi-view multi-scale feature extractor and transformer encoder for stenosis recognition in echocardiograms

Background: aortic stenosis is a common heart valve disease that mainly affects older people in developed countries. Its early detection is crucial to prevent the irreversible disease progression and, eventually, death. A typical screening technique to detect stenosis uses echocardiograms; however, variations introduced by other tissues, camera movements, and uneven lighting can hamper the visual inspection, leading to misdiagnosis. To address these issues, effective solutions involve employing deep learning algorithms to assist clinicians in detecting and classifying stenosis by developing models that can predict this pathology from single heart views. Although promising, the visual information conveyed by a single image may not be sufficient for an accurate diagnosis, especially when using an automatic system; thus, this indicates that different solutions should be explored. Methodology: following this rationale, this paper proposes a novel deep learning architecture, composed of a multi-view, multi-scale feature extractor, and a transformer encoder (MV-MS-FETE) to predict stenosis from parasternal long and short-axis views. In particular, starting from the latter, the designed model extracts relevant features at multiple scales along its feature extractor component and takes advantage of a transformer encoder to perform the final classification. Results: experiments were performed on the recently released Tufts medical echocardiogram public dataset, which comprises 27,788 images split into training, validation, and test sets. Due to the recent release of this collection, tests were also conducted on several state-of-the-art models to create multi-view and single-view benchmarks. For all models, standard classification metrics were computed (e.g., precision, F1-score). The obtained results show that the proposed approach outperforms other multi-view methods in terms of accuracy and F1-score and has more stable performance throughout the training procedure. Furthermore, the experiments also highlight that multi-view methods generally perform better than their single-view counterparts. Conclusion: this paper introduces a novel multi-view and multi-scale model for aortic stenosis recognition, as well as three benchmarks to evaluate it, effectively providing multi-view and single-view comparisons that fully highlight the model's effectiveness in aiding clinicians in performing diagnoses while also producing several baselines for the aortic stenosis recognition task

A novel mutation in calcium-sensing receptor gene associated to hypercalcemia and hypercalciuria.

Background: Familial Hyperparathyroidism (HPT) and Familial benign Hypocalciuric Hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. FHH has been demonstrated to be caused by inactivating mutations of calcium-sensing receptor (CaSR) gene, involved in PTH regulation as well as in renal calcium excretion.Case presentation: In two individuals, father and son, we found a novel heterozygous mutation in CaSR gene. The hypercalcemia was present only in father, which, by contrast to the classic form of FHH showed hypercalciuria (from 300 to 600 mg/24 h in different evaluations) and a Calcium/Creatinine ratio of 0.031, instead of low or normal calciuria (<0.01 typical finding in FHH). His son showed the same mutation in CaSR gene, but no clinical signs or hypercalcemia although serum ionized calcium levels were close to the upper limit of normal values (1.30 mmol/L: normal range: 1.12-1.31 mmol/L). Sequence analysis revealed a point mutation at codon 972 of CaSR gene (chromosome 3q), located within cytoplasmic domain of the CaSR, that changes Threonine with Methionine. The father was treated with Cinacalcet 90 mg/day, with a decrease of total serum calcemia from an average value of 12.2 mg/dl to 10.9 mg/dl.Conclusion: This is a case of a novel inactivating point mutation of CaSR gene that determines an atypical clinical presentation of FHH, characterized by hypercalcemia, hypercalciuria and inadequate normal PTH levels. Functional assay demonstrated that the 972 M variant influenced the maturation of the protein, in terms of the post-translational glycosylation. The impairment of the receptor activity is in keeping with the specific localization of the 972 residue in the C-terminal tail, assigned to the intracellular signalling, that on the basis of the our findings appears to be differently modulated in parathyroid gland and in kidne

Evolutive follow-up of the photocatalytic degradation of real textile effluents in TiO2 and TiO2/H2O2 systems and their toxic effects on Lactuca sativa seedlings

Textile industry wastes raise a great concern due to their strong coloration and toxicity. The objective of the present work was to characterize the degradation and mineralization of textile effluents by advanced oxidative processes using either TiO2 or TiO2/H2O2 association and to monitor the toxicity of the products formed during 6 h irradiation in relation to that of the in natura effluent. The results obtained demonstrated that the TiO2/H2O2 association was more efficient in the mineralization of textile effluents than TiO2 alone, with high mineralized ion concentrations (NH4+, NO3-, and SO4(2-)) and significant organic matter reduction rates (represented by the COD and TOC). The toxicity of the degradation products to lettuce seeds (Lactuca sativa) was not significant, since percent germination was not significantly affected and neither was root and sprout percent growth. However, while the TiO2/H2O2 association was more toxic in the first hours of irradiation and less so in the end of the 6 h irradiation, the toxicity of TiO2 increased only slightly in the end of the experiments. Comparatively, the photogenerated products of both the TiO2 and the TiO2/H2O2 association were less toxic than the in natura effluent

Synchrotron nano-FTIR spectroscopy for probing anticancer drugs at subcellular scale

The cellular response to cisplatin was assessed in human osteosarcoma cells, using synchrotron-based (SR) Fourier Transform InfraRed nanospectroscopy (nano-FTIR) at the MIRIAM beamline B22 of Diamond Light Source (UK). This label-free mapping method delivered simultaneous morphological and biochemical information on a subcellular level (i.e. 100 s nanometer or better). Based on specific spectral biomarkers, the main biochemical constituents affected by the drug were identified at distinct locations within the cell´s inner body. Cisplatin was shown to have a noteworthy effect on proteins, mostly within the cytoplasm. A clear drug impact on cellular lipids was also observed. Within current literature on s-SNOM, this nanospectroscopy work represents a first successful application in life sciences providing full fingerprint nano-FTIR spectra across intact human cancer cells