AN ASSESSMENT OF POTENTIAL DRUG-DRUG INTERACTIONS IN HYPERTENSIVE PATIENTS IN A TERTIARY CARE HOSPITAL

Objective: To an assessment of potential drug-drug interactions in hypertensive patients in a tertiary care hospital. Methods: A prospective, observational study was conducted at a tertiary care hospital, Erode for a period of 8 mo. A sample of 480 patients was assessed for PDDIs using drug checker in Micromedex®-2.7. Results: A total of 430 patients were analyzed and it was found to be 396 (82.50%) hypertensive patients had PDDIs, and a sum total of 1160 PDDIs were observed. Potential drug-drug interactions (PDDIs) higher in female hypertensive patients [255 (64.39%)] compared to males. Incidences of PDDIs were found to be higher in the age group of 60-70 y were [177 (44.69%)] and incidences of interactions based on the duration of (4-6 d) hospital stays were 272 (68.68%). Moreover, 49.24% of patients were found to be prescribed with more than 7 drugs, with higher incidences of PDDIs. Some of the most common drug interacting pair was between aspirin and clopidogrel combination observed in 325 PDDIs in the major, with pharmacodynamics in nature. Conclusion: Clinical pharmacist ought to have the role of regular monitoring of drug therapy in identifying and preventing the medications that have the potential to cause drug-drug interactions, thereby minimizing the undesirable outcomes in drug medical care and improving the quality of care

High Performance Pre-computation based Self-Controlled Precharge-Free Content-Addressable Memory

Content-addressable memory (CAM) is a special type of memory used in networking applications for very-high-speed searching operation. It compares input search data with the table of stored data, and returns the address of matching data in a parallel search method. Also the use of parallel comparison results in reduced search time, it also significantly increases power consumption when compared to precharge based CAM. The low-power NAND-type and high-speed NOR-type CAM methods require the precharge prior to the search. This PF phase leads to increase the settling time of the output and also reduce the speed of the search operation. In this paper, a High performance Pre-computation Based Self-Controlled Precharge-Free CAM (PB-SCPF CAM) structure is proposed for high-speed applications which reduce the settling time as well as improve the speed of the search. Where search time is very important for designing larger word lengths, SCPF architecture is efficacious in applications. The experimental results show that PB-SCPF approach can attain on average 32% in power reduction and 80% in delay reduction. The most important contribution of this project is that it offers theoretical and practical proofs to verify that our suggested PB-SCPF CAM system can achieve greater power reduction without the requirement of special CAM cell design. This shows that the approach which we have used is more flexible and adaptive for general designs and high speed applications

Surface and grain boundary scattering in nanometric Cu thin films: A quantitative analysis including twin boundaries

The relative contributions of various defects to the measured resistivity in nanocrystalline Cu were investigated, including a quantitative account of twin-boundary scattering. It has been difficult to quantitatively assess the impact twin boundary scattering has on the classical size effect of electrical resistivity, due to limitations in characterizing twin boundaries in nanocrystalline Cu. In this study, crystal orientation maps of nanocrystalline Cu films were obtained via precession-assisted electron diffraction in the transmission electron microscope. These orientation images were used to characterize grain boundaries and to measure the average grain size of a microstructure, with and without considering twin boundaries. The results of these studies indicate that the contribution from grain-boundary scattering is the dominant factor (as compared to surface scattering) leading to enhanced resistivity. The resistivity data can be well-described by the combined Fuchs-Sondheimer surface scattering model and Mayadas-Shatzkes grain-boundary scattering model using Matthiessen\u27s rule with a surface specularity coefficient of p = 0.48 and a grain-boundary reflection coefficient of R = 0.26

Numerical study of chemical reaction effects in magnetohydrodynamic Oldroyd B oblique stagnation flow with a non-Fourier heat flux model

Reactive magnetohydrodynamic (MHD) flows arise in many areas of nuclear reactor transport. Working fluids in such systems may be either Newtonian or non-Newtonian. Motivated by these applications, in the current study, a mathematical model is developed for electrically-conducting viscoelastic oblique flow impinging on stretching wall under transverse magnetic field. A non-Fourier Cattaneo-Christov model is employed to simulate thermal relaxation effects which cannot be simulated with the classical Fourier heat conduction approach. The Oldroyd-B non-Newtonian model is employed which allows relaxation and retardation effects to be included. A convective boundary condition is imposed at the wall invoking Biot number effects. The fluid is assumed to be chemically reactive and both homogeneous-heterogeneous reactions are studied. The conservation equations for mass, momentum, energy and species (concentration) are altered with applicable similarity variables and the emerging strongly coupled, nonlinear non-dimensional boundary value problem is solved with robust well-tested Runge-Kutta-Fehlberg numerical quadrature and a shooting technique with tolerance level of 10−4. Validation with the Adomian decomposition method (ADM) is included. The influence of selected thermal (Biot number, Prandtl number), viscoelastic hydrodynamic (Deborah relaxation number), Schmidt number, magnetic parameter and chemical reaction parameters, on velocity, temperature and concentration distributions are plotted for fixed values of geometric (stretching rate, obliqueness) and thermal relaxation parameter. Wall heat transfer rate (local heat flux) and wall species transfer rate (local mass flux) are also computed and it is observed that local mass flux increases with strength of heterogeneous reactions whereas it decreases with strength of homogeneous reactions. The results provide interesting insights into certain nuclear reactor transport phenomena and furthermore a benchmark for more general CFD simulations

Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease

Actin-associated nonmuscle myosin II (NM2) motor proteins play critical roles in a myriad of cellular functions, including endocytosis and organelle transport pathways. Cell type–specific expression and unique subcellular localization of the NM2 proteins, encoded by the Myh9 and Myh10 genes, in the mouse kidney tubules led us to hypothesize that these proteins have specialized functional roles within the renal epithelium. Inducible conditional knockout (cKO) of Myh9 and Myh10 in the renal tubules of adult mice resulted in progressive kidney disease. Prior to overt renal tubular injury, we observed intracellular accumulation of the glycosylphosphatidylinositol-anchored protein uromodulin (UMOD) and gradual loss of Na+ K+ 2Cl– cotransporter from the apical membrane of the thick ascending limb epithelia. The UMOD accumulation coincided with expansion of endoplasmic reticulum (ER) tubules and activation of ER stress and unfolded protein response pathways in Myh9&10-cKO kidneys. We conclude that NM2 proteins are required for localization and transport of UMOD and loss of function results in accumulation of UMOD and ER stress–mediated progressive renal tubulointerstitial disease. These observations establish cell type–specific role(s) for NM2 proteins in regulation of specialized renal epithelial transport pathways and reveal the possibility that human kidney disease associated with MYH9 mutations could be of renal epithelial origin

Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events

BACKGROUND AND OBJECTIVE: The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process. METHODS: A systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types. RESULTS: A total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4–6.6%) of ETFO, 28.6% (26.6–30.6%) of ESD, and 0.53% (0.2–1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1–1.3%), 11% (9.2–13.0%), and 3.2% (2.5–3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed. CONCLUSION: Considering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications

Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma

Clustered miRNAs can affect functioning of downstream pathways due to possible coordinated function. We observed 78-88% of the miR-379/miR-656 cluster (C14MC) miRNAs were downregulated in three sub-types of diffuse gliomas, which was also corroborated with analysis from The Cancer Genome Atlas (TCGA) datasets. The miRNA expression levels decreased with increasing tumor grade, indicating this downregulation as an early event in gliomagenesis. Higher expression of the C14MC miRNAs significantly improved glioblastioma prognosis (Pearson’s r=0.62; p<3.08e-22). ENCODE meta-data analysis, followed by reporter assays validated existence of two novel internal regulators within C14MC. CRISPR activation of the most efficient internal regulator specifically induced members of the downstream miRNA sub-cluster and apoptosis in glioblastoma cells. Luciferase assays validated novel targets for miR-134 and miR-485-5p, two miRNAs from C14MC with the most number of target genes relevant for glioma. Overexpression of miR-134 and miR-485-5p in human glioblastoma cells suppressed invasion and proliferation, respectively. Furthermore, apoptosis was induced by both miRs, individually and in combination. The results emphasize the tumor suppressive role of C14MC in diffuse gliomas, and identifies two specific miRNAs with potential therapeutic value and towards better disease management and therapy

Synthesis of a Dual Functional Anti-MDR Tumor Agent PH II-7 with Elucidations of Anti-Tumor Effects and Mechanisms

Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major issue that cripples the efficacy of chemotherapy agents. Aimed for improved efficacy against resistant cancer cells, we designed and synthesized 25 oxindole derivatives based on indirubin by structure-activity relationship analysis. The most potent one was named PH II-7, which was effective against 18 cancer cell lines and 5 resistant cell lines in MTT assay. It also significantly inhibited the resistant xenograft tumor growth in mouse model. In cell cycle assay and apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle arrest and apoptosis even in resistant cells. Consistently revealed by real-time PCR, it modulates the expression of genes related to the cell cycle and apoptosis in these cells, which may contributes to its efficacy against them. By side-chain modification and FITC-labeling of PH II-7, we were able to show with confocal microscopy that not only it was not pumped by P-glycoprotein, it also attenuated the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken together, PH II-7 is a dual-functional compound that features both the cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug efflux

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo

Efficient Nonlinear Programming Algorithms for Chemical Process Control and Operations

Nonlinear programming (NLP) has been a key enabling tool for model-based decision-making in the chemical industry for over 50 years. Opti-mization is frequently applied in numerous ar-eas of chemical engineering including the de-velopment of process models from experimen-tal data, design of process flowsheets and equip-ment, planning and scheduling of chemical pro-cess operations, and the analysis of chemical pro-cesses under uncertainty and adverse conditions. These off-line tasks frequently require the solu-tion of NLPs formulated with detailed, lareg-scale process models. More recently, these tasks are complemented by time-critical, on-line optimization problem