Biomechanical analysis of peri-prosthetic bone response to hybrid threaded zirconia dental implants: An in silico model.

The biomechanical response of mandibular bone determines primary stability and concomitant osseointegration of dental implants. This study explores the impact of nature of loading and bone conditions on biomechanical response of hybrid threaded single-piece zirconia dental implants. To develop such understanding, three implants (SQ_V, V_BUT, and V_V), with different combinations of threads, square (SQ), buttress (BUT), and triangular (V), have been investigated. Finite Element Analysis (FEA) was carried out to simulate implantation at the molar position of mandible of varying densities under axial (≤500 N) and oblique (118.2 N) loadings. Patient-specific bone conditions (for a wider population) were considered by scaling the density and the elastic modulus of mandible to represent, 'weak', 'healthy', and 'strong' bone conditions. FEA results revealed that SQ_V and V_BUT implants exhibited a better biomechanical response without significant variation (<0.5%) in von Mises stress, regardless of bone density and axial loadings. These implants are predicted to perform with clinically acceptable factor of safety under investigated implantation scenarios, whereas V_BUT implant showed a larger variation (∼±12%). FEA simulation with oblique loading further validated such results. The 'weak' bone conditions resulted in maximum peri-implant microstrain, whereas 'strong and healthy' bone exhibited values close to the permissible range of physiological remodeling. The maximum micromotion (∼12.3 ± 6.2 µm for 'weak' bone) at bone-implant interface suggested that implant loosening and impaired osseointegration will not occur in any of selected virtual implantation cases. Both SQ_V and V_BUT implants will be considered further in implant development, involving manufacturing and product prototype validation. Taken together, the critical analysis of FEA results indicates a significant impact of bone density and distinct combinations of external threads on the biomechanical responses, in both the implant and the surrounding bone.

Prescriptive analytics applications in sustainable operations research: conceptual framework and future research challenges.

In the broad sphere of Analytics, prescriptive analytics is one of the emerging areas of interest for both academicians and practitioners. As prescriptive analytics has transitioned from its inception to an emerging topic, there is a need to review existing literature in order to ascertain development in this area. There are a very few reviews in the related field but not specifically on the applications of prescriptive analytics in sustainable operations research using content analysis. To address this gap, we performed a review of 147 articles published in peer-reviewed academic journals from 2010 to August 2021. Using content analysis, we have identified the five emerging research themes. Through this study, we aim to contribute to the literature on prescriptive analytics by identifying and proposing emerging research themes and future research directions. Based on our literature review, we propose a conceptual framework for studying the impacts of the adoption of prescriptive analytics and its impact on sustainable supply chain resilience, sustainable supply chain performance and competitive advantage. Finally, the paper acknowledges the managerial implications, theoretical contribution and the limitations of this study.

Myricetin: a potential plant-derived anticancer bioactive compound-an updated overview.

The globe is currently confronting a global fight against the deadliest cancer sickness. Chemotherapy, hormonal therapy, surgery, and radiation therapy are among cancer treatment options. Still, these treatments can induce patient side effects, including recurrence, multidrug resistance, fever, and weakness. As a result, the scientific community is always working on natural phytochemical substances. Numerous phytochemical compounds, including taxol analogues, vinca alkaloids such as vincristine and vinblastine, and podophyllotoxin analogues, are currently undergoing testing and have shown promising results against a number of the deadliest diseases, as well as considerable advantages due to their safety and low cost. According to research, secondary plant metabolites such as myricetin, a flavonoid in berries, herbs, and walnuts, have emerged as valuable bio-agents for cancer prevention. Myricetin and its derivatives have antiinflammatory, anticancer, apoptosis-inducing, and anticarcinogenic properties and can prevent cancer cell proliferation. Multiple studies have found that myricetin has anticancer characteristics in various malignancies, including colon, breast, prostate, bladder, and pancreatic cancers. Current knowledge of the anticancer effects of myricetin reveals its promise as a potentially bioactive chemical produced from plants for the prevention and treatment of cancer. This review aimed to study the numerous bioactivities, mode of action, and modification of several cellular processes that myricetin possesses to impede the spread of cancer cells. This review also addresses the challenges and future prospects of using myricetin as a anticancer drug.

Agility in humanitarian supply chain: an organizational information processing perspective and relational view.

Humanitarian organizations are increasingly facing challenges in terms of improving the efficiency and the effectiveness of their disaster relief efforts. These challenges often arise due to a lack of trust, poor collaboration and an inability to respond to disaster affected areas in a timely manner. Our study attempts to understand how these challenges are overcome by seeking answers to questions related to the topics of swift-trust, collaboration and agility in humanitarian supply chains. For instance, in our study we have attempted to examine how information sharing and supply chain visibility in humanitarian supply chains improve the swift-trust among the humanitarian actors engaged in disaster relief operations. Further, we attempt to understand how-swift trust, commitment and collaboration among the humanitarian actors improve the agility in humanitarian supply chains. In our study we provide both theoretical and data-driven answers to our stated research gaps. Our theoretical model is firmly grounded in organizational information process theory and relational view. We tested our research hypotheses using variance based structural equation modelling with survey data collected using a web based pre-tested instrument from 147 NGOs respondents drawn from the National Disaster Management Authority database. Our results help to advance the theoretical debates surrounding "swift-trust", "collaboration" and "agility" in humanitarian settings. We further provide direction to managers engaged in disaster relief operations. The humanitarian actors engaged in disaster relief often fail to understand how to build swift-trust. Moreover, how swift-trust further affects commitment and collaboration which in turn further affect agility in humanitarian supply chains. Thus humanitarian organizations must understand how information sharing and supply chain visibility is key to swift-trust among humanitarian actors and agility in humanitarian supply chains. Finally, we outline the limitations of our study and offer some future research directions for investigation.

Zebrafish model of amyloid light chain cardiotoxicity: regeneration versus degeneration.

Cardiac dysfunction is the most frequent cause of morbidity and mortality in amyloid light chain (AL) amyloidosis caused by a clonal immunoglobulin light chain (LC). Previously published transgenic animal models of AL amyloidosis have not recapitulated the key phenotype of cardiac dysfunction seen in AL amyloidosis, which has limited our understanding of the disease mechanisms in vivo, as well as the development of targeted AL therapeutics. We have developed a transgenic zebrafish model in which a λ LC derived from a patient with AL amyloidosis is conditionally expressed in the liver under the control of the Gal4 upstream activation sequence enhancer system. Circulating LC levels of 125 µg/ml in these transgenic zebrafish are comparable to median pathological serum LC levels. Functional analysis links abnormal contractile function with evidence of cellular and molecular proteotoxicity in the heart, including increased cell death and autophagy. However, despite pathological and functional phenotypes analogous to human AL, the lifespan of the transgenic fish is comparable to control fish without the expressed AL-LC transgene. Nuclear labeling experiments suggest increased cardiac proliferation in the transgenic fish, which can be counteracted by treatment with a small molecule proliferation inhibitor leading to increased zebrafish mortality because of cardiac apoptosis and functional deterioration. This transgenic zebrafish model provides a platform to study underlying AL disease mechanisms in vivo further. NEW & NOTEWORTHY Heart failure is a major cause of mortality in amyloid light (AL) amyloidosis, yet it has been difficult to model in animals. We report the generation of a transgenic zebrafish model for AL amyloidosis with pathological concentration of circulating human light chain protein that results in cardiac dysfunction. The light chain toxicity triggers regeneration in the zebrafish heart resulting in functional compensation early in life, but with age develops into cardiac dysfunction.

Dexamethasone-loaded reconstitutable charged polymeric (PLGA)n -b-bPEI micelles for enhanced nuclear delivery of gene therapeutics.

This study investigates the potential of dexamethasone (Dex) to enhance the nuclear accumulation and subsequent gene expression of plasmid DNA (pDNA) delivered using a charged polymeric micelle-based gene delivery system. (PLGA)n -b-bPEI25kDa block copolymers are synthesized and used to prepare Dex-loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI1.8kDa is coated on the complexes using a Layer-by-Layer (LbL) technique to construct DexCM/pDNA/bPEI1.8kDa complexes (i.e., LbL-DexCM polyplexes) that are 100-180 nm in diameter and have a zeta potential of 30-40 mV. In MCF7 cells, LbL-DexCM polyplexes cause 3-13-fold higher transfection efficiencies compared to LbL-CM polyplexes and show negligible cytotoxicity. LbL-DexCM3 polyplexes induce much higher nuclear delivery of pDNA compared to LbL-CM3 polyplexes. These results suggest that Dex-loaded polyplexes could be used in gene and drug delivery applications to increase nuclear accumulation of therapeutic payloads, further leading to a decrease in the dose of the drug and gene necessary to achieve equivalent therapeutic effects.

Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy.

Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.

Poly(ethylene glycol) cross-linked hemoglobin with antioxidant enzymes protects pancreatic islets from hypoxic and free radical stress and extends islet functionality.

The objective of this study was to investigate the efficiency of multifunctional poly(ethylene glycol)-based hemoglobin conjugates crosslinked with antioxidant enzymes for their ability to protect an oxygen carrier (hemoglobin) and insulin secreting islets from the combination of hypoxic and free radical stress under simulated transplantation conditions. In this study, RINm5F cells and isolated pancreatic islets were challenged with oxidants (H(2)O(2) or xanthine and xanthine oxidase) and incubated with conjugates (hemoglobin-hemoglobin or superoxide dismutase-catalase-hemoglobin) in normoxia (21% oxygen) or hypoxia (6% or 1% oxygen). Hemoglobin protection, intracellular free radical activity and cell viability in RINm5F cells measured by methemoglobin, dichlorofluorescein-diacetate, and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, respectively, showed that cells were better protected by conjugates containing antioxidant enzymes. Insulin secretion from islets and qualitative confocal evaluation of viability showed beta cells were protected by conjugates containing antioxidant enzymes when exposed to induced stress. Our study suggested that antioxidant enzymes play a significant role in hemoglobin protection and thus extended cell protection.

Reconstitutable charged polymeric (PLGA)(2)-b-PEI micelles for gene therapeutics delivery.

This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA(36kDa))(2)-b-bPEI(25kDa) (PLGA MW 36 kDa, bPEI M(w) 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for "reconstituted" micelle/pDNA/bPEI(1.8kDa) (WR 1) complexes was 16-fold higher than its "fresh" counterpart. Although transfection levels achieved using "reconstituted" micelle/pDNA/bPEI(1.8kDa) complexes were 3.6-fold lower than control "fresh" bPEI(25kDa)/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than "reconstituted" bPEI(25kDa)/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI(1.8kDa) system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 µg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.