Advances in non-invasive biosensing measures to monitor wound healing progression

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed

NF-κB signaling and its relevance to the treatment of mantle cell lymphoma

Abstract Mantle cell lymphoma is an aggressive subtype of non-Hodgkin B cell lymphoma that is characterized by a poor prognosis determined by Ki67 and Mantle Cell International Prognostic Index scores, but it is becoming increasingly treatable. The majority of patients, especially if young, achieve a progression-free survival of at least 5 years. Mantle cell lymphoma can initially be treated with an anti-CD20 antibody in combination with a chemotherapy backbone, such as VR-CAP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, and prednisone) or R-CHOP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, vincristine, and prednisone). While initial treatment can facilitate recovery and complete remission in a few patients, many patients experience relapsed or refractory mantle cell lymphoma within 2 to 3 years after initial treatment. Targeted agents such as ibrutinib, an inhibitor of Bruton’s tyrosine kinase, which has been approved only in the relapsed setting, can be used to treat patients with relapsed or refractory mantle cell lymphoma. However, mantle cell lymphoma cells often acquire resistance to such targeted agents and continue to survive by activating alternate signaling pathways such as the PI3K-Akt pathway or the NF-κB pathways. NF-κB is a transcription factor family that regulates the growth and survival of B cells; mantle cell lymphoma cells depend on NF-κB signaling for continued growth and proliferation. The NF-κB signaling pathways are categorized into canonical and non-canonical types, wherein the canonical pathway prompts inflammatory responses, immune regulation, and cell proliferation, while the non-canonical leads to B cell maturation and lymphoid organogenesis. Since these pathways upregulate survival genes and tumor-promoting cytokines, they can be activated to overcome the inhibitory effects of targeted agents, thereby having profound effects on tumorigenesis. The NF-κB pathways are also highly targetable in that they are interconnected with numerous other pathways, including B cell receptor signaling, PI3K/Akt/mTOR signaling, and toll-like receptor signaling pathways. Additionally, elements of the non-canonical NF- κB pathway, such as NF-κB-inducing kinase, can be targeted to overcome resistance to targeting of the canonical NF- κB pathway. Targeting the molecular mechanisms of the NF-κB pathways can facilitate the development of novel agents to treat malignancies and overcome drug resistance in patients with relapsed or refractory mantle cell lymphoma

Knowledge and application of CBCT imaging amongst the dental interns - A pan India web-based, cross-sectional survey

Objective: Evaluating the level of knowledge and applicative knowledge regarding Cone Beam Computer Tomography (CBCT) among interns from various dental institutes in the country. Materials and Methods: A Questionnaire with 15 close-ended questions was circulated to 2000 interns from various dental institutes across India. 1154 interns participated in the study. The response rate was 94.8%. Results: The majority of the interns (48.6%) gained knowledge regarding CBCT from lectures and faculty seminars while 15.3% through conferences. The maximum knowledge mean score was noted from the central zone (7.66 ± 3.8). Demographic variables did not show any signs of the impact of technical knowledge on the applicative knowledge of the study population. Conclusion: This study suggests CBCT be a definitive 3D imaging technology in the maxilla-facial region and awareness regarding the same needs to be increased. There is a need to include CBCT-based information in the undergraduate curriculum to improve knowledge levels

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis.

Significance: Fibrosis is the endpoint of chronic disease in multiple organs, including the skin, heart, lungs, intestine, liver, and kidneys. Pathologic accumulation of fibrotic tissue results in a loss of structural integrity and function, with resultant increases in morbidity and mortality. Understanding the pathways governing fibrosis and identifying therapeutic targets within those pathways is necessary to develop novel antifibrotic therapies for fibrotic disease. Recent Advances: Given the connection between inflammation and fibrogenesis, Interleukin-10 (IL-10) has been a focus of potential antifibrotic therapies because of its well-known role as an anti-inflammatory mediator. Despite the apparent dissimilarity of diseases associated with fibrotic progression, pathways involving IL-10 appear to be a conserved molecular theme. More recently, many groups have worked to develop novel delivery tools for recombinant IL-10, such as hydrogels, and cell-based therapies, such as ex vivo activated macrophages, to directly or indirectly modulate IL-10 signaling. Critical Issues: Some efforts in this area, however, have been stymied by IL-10's pleiotropic and sometimes conflicting effects. A deeper, contextual understanding of IL-10 signaling and its interaction with effector cells, particularly immune cells, will be critical to future studies in the field. Future Directions: IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling. The development of novel therapeutics and cell-based therapies that capitalize on targets within the IL-10 signaling pathway could have far-reaching implications for patients suffering from the consequences of organ fibrosis

Fault classification of three phase induction motors using Bi-LSTM networks

Abstract The induction motors are back bone of the modern industry and play very important role in manufacturing and transportation sectors. The induction motor faults are mainly classified into internal faults such as inter turn short circuits , broken rotors and external faults such as over load, over voltage faults and asymmetry in supply voltage. The identification of type of fault is very important for safe operation and for preventing risk of machine failures. In this work, a Bidirectional Long Short Term memory networks (Bi-LSTM)-based machine learning methodology is proposed for classification of external faults of Induction Motors. The line voltages of the three phases and the three line currents are considered as the inputs to the Bi-LSTM network for identifying types of fault. Line voltage and line current data sets are considered for six different types of fault conditions. The six different conditions of the three phase induction motor are normal output (NO), overload (OL), over voltage (OV), under voltage (UV), Voltage unbalance (VUB) and single phasing (SP). The BI-LSTM network is trained using Adam optimization algorithm. The classification results are obtained with Bi-LSTM network are compared with LSTM networks to show the advantage of the proposed approach

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis.

Significance: Fibrosis is the endpoint of chronic disease in multiple organs, including the skin, heart, lungs, intestine, liver, and kidneys. Pathologic accumulation of fibrotic tissue results in a loss of structural integrity and function, with resultant increases in morbidity and mortality. Understanding the pathways governing fibrosis and identifying therapeutic targets within those pathways is necessary to develop novel antifibrotic therapies for fibrotic disease. Recent Advances: Given the connection between inflammation and fibrogenesis, Interleukin-10 (IL-10) has been a focus of potential antifibrotic therapies because of its well-known role as an anti-inflammatory mediator. Despite the apparent dissimilarity of diseases associated with fibrotic progression, pathways involving IL-10 appear to be a conserved molecular theme. More recently, many groups have worked to develop novel delivery tools for recombinant IL-10, such as hydrogels, and cell-based therapies, such as ex vivo activated macrophages, to directly or indirectly modulate IL-10 signaling. Critical Issues: Some efforts in this area, however, have been stymied by IL-10's pleiotropic and sometimes conflicting effects. A deeper, contextual understanding of IL-10 signaling and its interaction with effector cells, particularly immune cells, will be critical to future studies in the field. Future Directions: IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling. The development of novel therapeutics and cell-based therapies that capitalize on targets within the IL-10 signaling pathway could have far-reaching implications for patients suffering from the consequences of organ fibrosis

Attenuating Fibrotic Markers of Patient-Derived Dermal Fibroblasts by Thiolated Lignin Composites

Engineering composite biomaterials requires the successful integration of multiple feed- stocks to formulate a final product for functional improvement. Here we engineered biomaterial scaffolds to attenuate the fibrotic phenotype exhibited by high scarring (HS) patient-derived der- mal fibroblasts (hdFBs) by valorizing lignosulfonate from waste feedstocks of lignin. We utilized phenolic functional groups of lignosulfonate to impart antioxidant properties and the cell binding domains of gelatin to enhance cell adhesion for poly(ethylene glycol)-based scaffolds. Highly ef- ficient chemoselective thiol-ene chemistry was utilized for the formation of composites with thio- lated lignosulfonate (TLS) and methacrylated fish gelatin (fGelMA) in the PEG(poly (ethylene gly- col))-diacrylate matrix. Antioxidant properties of lignosulfonate was not altered after thiolation and the levels of antioxidation were comparable to a well-known antioxidant, L-ascorbic acid, as evi- denced by DPPH (2,2-diphenyl-1-picrylhydrazyl) and TAC (Total Antioxidant Capacity) assays. Unlike porcine gelatin, fGelMA remained liquid at room temperature and exhibited low viscosities, resulting in no issues of miscibility when mixed with PEG. PEG-fGelMA-TLS composites signifi- cantly reduced the differential of five different fibrotic markers (COL1A1, ACTA2, TGFB1 and HIF1A) between HS and low scarring (LS) hdFBs, providing the potential utility of TLS in a bio- material scaffold to attenuate fibrotic responses. </div