Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

Two-step sinter-crystallization of K2O–CaO–P2O5–SiO2 (45S5-K) bioactive glass

Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K₂O-26.9CaO-46.1SiO₂-2.6P₂O₅ mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration.     

Unsupervised Segmentation of Stereoscopic Video Objects: Constrained Segmentation Fusion Versus Greedy Active Contours

In this paper, we present a novel memory access reduction scheme (MARS) for two-dimension fast cosine transform (2-D FCT). It targets programmable DSPs with high memory-access latency. It reduces the number of memory accesses by: 1) reducing the number of weighting factors and 2) combining butterflies in vector-radix 2-D FCT pruning diagram from two stages to one stage with an efficient structure. Hardware platform based on general purpose processor is used to verify the effectiveness of the proposed method for vector-radix 2-D FCT pruning implementation. Experimental results validate the benefits of the proposed method with reduced memory access, less clock cycle and fewer memory space compared with the conventional implementation.     

Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Tough salami-inspired Cf/ZrB2 UHTCMCs produced by electrophoretic deposition

One of the biggest challenges of the materials science is the mutual exclusion of strength and toughness. This issue was minimized by mimicking the natural structural materials. To date, few efforts were done regarding materials that should be used in harsh environments. In this work we present novel continuous carbon fiber reinforced ultra-high-temperature ceramic matrix composites (UHTCMCs) for aerospace featuring optimized fiber/matrix interfaces and fibers distribution. The microstructures – produced by electrophoretic deposition of ZrB₂ on unidirectional carbon fibers followed by ZrB₂ infiltration and hot pressing – show a maximum flexural strength and fracture toughness of 330 MPa and 14 MPa m^1/2, respectively. Fracture surfaces are investigated to understand the mechanisms that affect strength and toughness. The EPD technique allows the achievement of a peculiar salami-inspired architecture alternating strong and weak interfaces.     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.