The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.     

Variation in patient dose due to differences in calibration and dosimetry protocols

For precise and accurate patient dose delivery,the dosimetry system must be calibrated properly according to the recommendations of standard dosimetry protocols such as TG-51 and TRS-398. However, the dosimetry protocol followed by a calibration laboratory is usually different from the protocols that are followed by different clinics, which may result in variations in the patient dose.Our prime objective in this study was to investigate the effect of the two protocols on dosimetry measurements.Dose measurements were performed for a Co-60 teletherapy unit and a high-energy Varian linear accelerator with 6 and 15 MV photon and 6, 9, 12, and 15 MeV electron beams, following the recommendations and procedures of the AAPM TG-51 and IAEA TRS-398 dosimetry protocols. The dosimetry systems used for this study were calibrated in a Co-60 radiation beam at the Secondary Standard Dosimetry Laboratory(SSDL) PINSTECH,Pakistan, following the IAEA TRS-398 protocol. The ratio of the measured absorbed doses to water in clinical setting,D_w(TG-51/TRS-398), was 0.999 and 0.997 for 6 and15 MV photon beams,whereas these ratios were 1.013,1.009, 1.003, and 1.000 for 6, 9, 12, and 15 MeV electron beams, respectively. This difference in the absorbed dosesto-water D_w ratio may be attributed mainly due to beam quality(K_Q) and ion recombination correction factor.     

The Plastome Sequences of Triticum sphaerococcum (ABD) and Triticum turgidum subsp. durum (AB) Exhibit Evolutionary Changes,Structural Characterization,Comparative Analysis,Phylogenomics and Time Divergence

The mechanism and course of Triticum plastome evolution is currently unknown; thus, it remains unclear how Triticum plastomes evolved during recent polyploidization. Here, we report the complete plastomes of two polyploid wheat species, Triticum sphaerococcum (AABBDD) and Triticum turgidum subsp. durum (AABB), and compare them with 19 available and complete Triticum plastomes to create the first map of genomic structural variation. Both T. sphaerococcum and T. turgidum subsp. durum plastomes were found to have a quadripartite structure, with plastome lengths of 134,531 bp and 134,015 bp, respectively. Furthermore, diploid (AA), tetraploid (AB, AG) and hexaploid (ABD, AGA^m) Triticum species plastomes displayed a conserved gene content and commonly harbored an identical set of annotated unique genes. Overall, there was a positive correlation between the number of repeats and plastome size. In all plastomes, the number of tandem repeats was higher than the number of palindromic and forward repeats. We constructed a Triticum phylogeny based on the complete plastomes and 42 shared genes from 71 plastomes. We estimated the divergence of Hordeum vulgare from wheat around 11.04–11.9 million years ago (mya) using a well-resolved plastome tree. Similarly, Sitopsis species diverged 2.8–2.9 mya before Triticum urartu (AA) and Triticum monococcum (AA). Aegilops speltoides was shown to be the maternal donor of polyploid wheat genomes and diverged ~0.2–0.9 mya. The phylogeny and divergence time estimates presented here can act as a reference framework for future studies of Triticum evolution.     

Temperature-Invariant Scaling for Compressible Turbulent Boundary Layers with Wall Heat Transfer

In a recent paper by Zhang et al. in 2012, a Mach number-invariant scaling was proposed to account for the effect of variation of free-stream Mach number in supersonic turbulent boundary layers. The present work focuses on the effect of variation of wall temperature with strong heating and cooling at the wall. Direct numerical simulation is used to study scaling and turbulence structure of a spatially evolving Mach 2 supersonic boundary layer at a friction Reynolds number of 500. A new scaling law is proposed to account for temperature-dependent fluid-property variations. This universal scaling appears superior to the existing models with the novelty that it applies not only for the mean-velocity profile but also extends to the turbulent transport, production, and dissipation terms in the budget of the turbulent kinetic energy.     

Highly-efficient technique for automatic segmentation of X-ray bone images based on fuzzy logic and an edge detection technique

Multidimensional Systems and Signal Processing - Development of medical image segmentation techniques has become one of the most important challenges in many applications that employ...     

Sarcoidosis with nasal obstruction and septal perforation

Although sarcoidosis is predominantly a pulmonary disorder, it often produces disease in the head and neck. For this reason, otolaryngologists should be comfortable in evaluating and treating the disease. The diagnosis of sarcoidosis often can be made with a biopsy of conjunctival or oral mucosa, even when disease manifestations are not apparent in those parts of the body. In a case of sarcoidosis involving the nose, a 54-year-old black man had a proliferation of small lumps on the tip of his nose. For many years, he had had daily epistaxis, anosmia and severe difficulty breathing through this nose. The bridge of his nose was deformed, and he had a large anterior septal perforation. Physical examination revealed palpable bilateral cervical lymphadenopathy. Laboratory test results were, for the most part, normal; however, fine-needle aspiration of one of the cervical lymph nodes showed multiple epithelioid granulomas with interspersed lymphocyte, and an incisional biopsy of the nasal tissue was highly suggestive of sarcoidosis. Unenhanced computed tomography also revealed widespread nasal inflammation and an abnormal soft tissue mass anterior to the maxilla consistent with chronic osteomyelitis. The patient's condition dramatically improved following treatment with oral prednisone; however, he considered undergoing reconstructive surgery for the noticeable nasal septal deformity.     

Specific substitutions at amino acid 256 of the sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase mediate resistance to thapsigargin in thapsigargin-resistant hamster cells

High levels of resistance to thapsigargin (TG), a specific inhibitor of intracellular Ca2+ transport ATPases (SERCAs), can be developed in culture by stepwise exposure of mammalian cells to increasing concentrations of TG. We have identified, in two independently selected TG-resistant hamster cell lines of different lineages, mutant forms of SERCA. In the TG-resistant Chinese hamster lung fibroblast cell line DC-3F/TG, a T --> C change at nucleotide 766 introduces a Phe256 --> Leu alteration within the first cytosolic loop of the SERCA. In contrast, in the TG-resistant Syrian hamster smooth muscle cell line DDT/TG 4 microM, a T --> C change at nucleotide 767 introduces a Phe256 --> Ser mutation at that position. When these specific mutations are introduced into a wild-type full-length avian SERCA1 cDNA, transfection experiments reveal that Ca2+ transport function and ATP hydrolytic activity are not altered by such mutations. However, a 4-5-fold resistance to TG inhibition of Ca2+ transport function occurs upon the introduction of either the Phe256 --> Leu or the Phe256 --> Ser mutation into wild-type SERCA1. These specific mutations also render the hydrolytic activity of the ATPase resistant to inhibition by TG. Our results not only implicate amino acid 256 in TG-SERCA interactions, but also demonstrate that specific mutations within SERCA can mediate resistance to TG.     

Kinetics of catalytic esterification of terephthalic acid with methanol vapour

This paper describes the investigations carried out on the kinetics of the solid-gas reaction between terephthalic acid and methyl alcohol in presence of phosphoric acid as the catalyst. As phosphoric acid itself reacts with the alcohol forming methyl phosphates, the kinetic data obtained have been analysed taking this reaction into account. The rate of formation of monomethyl phosphate has been found to be proportional to the square of the mole fraction of the acid present at any instant. The activation energy involved in this reaction is 11.3 kcal/g mole. The data obtained on terephthalic acid esterification show that; (i) the conversion sharply increases with an increase in the catalyst concentration between 30–35 per cent (w/w), (ii) the ‘shrinking particle’ model, proposed by Levenspiel for solid-gas reactions, can be conveniently adapted to represent the reaction, and (iii) the temperature dependency of the reaction follows the Arrhenius law, with activation energy being 11.5 kcal/g mole.     

Calendering analysis without the lubrication approximation

A general-purpose finite-element program has been used to simulate the flow of Newtonian, power-law, and viscoelastic fluids in calendering. The analysis is fully two-dimensional and does not make use of the lubrication approximation. Isothermal and nonisothermal calendering is studied and the results are compared with predictions from the lubrication approximation. The free surface is determined and circulatory flow patterns are predicted in the melt bank. Detailed calculations have been performed for a rigid poly(vinyl chloride) (PVC) resin that exhibits slip at the wall using rheological data for the melt and machine parameters. The results include determination of the shape and location of the free surface, vortex patterns, temperature and pressure distributions, and predictions of roll-separating force, torque, and power consumption. Comparisons are made with experimental data available in the literature.