Search

This article presents the development of the Equity, Diversity, Inclusivity, and Accessibility (EDIA) Cross-Cutting Theme Project within the Team Primary Care (TPC) initiative, aimed at addressing systemic inequities through innovative educational strategies. Grounded in the social accountability of health professions framework, this project aims to equip primary care teams with the knowledge, skills, and attitudes necessary to promote health equity. The EDIA Integrated Educational Experience (IEE) model includes a self-assessment tool, digital learning space, and national mentorship network, providing a comprehensive approach for primary care teams to promote health equity. The IEE model utilizes a layered micro, meso, and macro approach to support cultural transformation within highly complex healthcare environments. Key lessons learned involve trust- and relationship-building processes to help dismantle historical silos and encourage open dialogue. Future efforts focus on implementation, ensuring adaptability, scalability, and sustainability, positioning the model as a catalyst for equitable primary care delivery.

The benefit of personalized medicine is that it allows the customization of drug therapy – maximizing efficacy while avoiding side effects. Genetic polymorphisms are one of the major contributors to interindividual variability. Currently, the only gold standard for applying personalized medicine is dose titration. Because of technological advancements, converting genotypic data into an optimum dose has become easier than in earlier years. However, for many medications, determining a personalized dose may be difficult, leading to a trial-and-error method. On the other hand, the technologically oriented pharmaceutical industry has a plethora of smart drug delivery methods that are underutilized in customized medicine. This article elaborates the genetic polymorphisms of tacrolimus as case study, and extensively covers the diagnostic and therapeutic technologies which aid in the delivery of personalized tacrolimus treatment for better clinical outcomes, thereby providing a new strategy for implementing personalized medicine.

The Hedgehog (Hh) signaling pathway coordinates cell–cell communication in development and regeneration. Defects in this pathway underlie diseases ranging from birth defects to cancer. Hh signals are transmitted across the plasma membrane by two proteins, Patched 1 (PTCH1) and Smoothened (SMO). PTCH1, a transporter-like tumor-suppressor protein, binds to Hh ligands, but SMO, a G-protein-coupled-receptor family oncoprotein, transmits the Hh signal across the membrane. Recent structural, biochemical and cell-biological studies have converged at the surprising model that a specific pool of plasma membrane cholesterol, termed accessible cholesterol, functions as a second messenger that conveys the signal between PTCH1 and SMO. Beyond solving a central puzzle in Hh signaling, these studies are revealing new principles in membrane biology: how proteins respond to and remodel cholesterol accessibility in membranes and how the cholesterol composition of organelle membranes is used to regulate protein function.

Personalized medicine has been a booming area in clinical research for the past decade, in which the detailed information about the patient genotype and clinical conditions were collected and considered to optimize the therapy to prevent adverse reactions. However, the utility of commercially available personalized medicine has not yet been maximized due to the lack of a structured protocol for implementation. In this narrative review, we explain the role of pharmacogenetics in personalized medicine, next-generation personalized medicine, i.e., patient-centric personalized medicine, in which the patient’s comfort is considered along with pharmacogenomics to be a primary factor. We extensively discuss the classifications, strategies, tools, and drug delivery systems that can support the implementation of patient-centric personalized medicine from an industrial perspective.

The developments in the field of artificial intelligence (AI) and decision making systems are identified as virtuous models for banking and finance sector (BFS) applications. Even though AI provides great advantage in application changes it is essential to remodel the system using explainable artificial intelligence (XAI) design system. Also the standard sensing models provides appropriate monitoring values but huge size of sensors is considered as a major drawback. Thus two diverse problems are addressed in this research work where XAI has been integrated with micro electro-mechanical systems (MEMS) for solving the problems related to BFS applications. Further the data security has been enhanced as XAI is implemented with conviction managements and real time experiments are carried out by developing a unique application by integrating new mathematical designs. To validate the effectiveness of BFS application the developed model is tested with five scenarios which includes multiple parametric arrangements with interpretability process. The tested and compared outcomes with existing models indicates that XAI and MEMS provides inordinate improvements in terms of data impairments thus increasing the transparency of the projected system to an average 96%.

Pharmaceutical spraying technology is an amplified method of delivering aseptic medication. The improved version of spray bandage contains either liquid or solid particle in a container that can be delivered via fine spray nozzle once activated by actuator. In other words, a bandage film formed in situ on a skin surface by actuating a hydrophilic polymer and a low volatile plasticizer with the solvent system. They are commonly used to guard and prevent infection of topical abrasion and cut which exist in minor level. By changing the spray drug concentration it can also be considered as a drug delivery film on the skin to the systemic circulation. This review deals with the preparation and evaluation methods of spray-on bandages, their existing problem and strategies to overcome the issue, there by summarizing as a future novel drug delivery system with huge market potential and also details current schemes (market and research) in spray on bandages.

The gravity of the impact of renal failure on human health is well known and as there is no specific pharmacotherapy for renal failure, the current study was undertaken to evaluate the effect of root extract of Azima tetracantha, an ancient medicinal plant used in Siddha and Ayurvedhic systems of medicine.

Many cellular processes are sensitive to levels of cholesterol in specific membranes and show a strongly sigmoidal dependence on membrane composition. The sigmoidal responses of the cholesterol sensors involved in these processes could arise from several mechanisms, including positive cooperativity (protein effects) and limited cholesterol accessibility (membrane effects). Here, we describe a sigmoidal response that arises primarily from membrane effects due to sharp changes in the chemical activity of cholesterol. Our models for eukaryotic membrane-bound cholesterol sensors are soluble bacterial toxins that show an identical switch-like specificity for endoplasmic reticulum membrane cholesterol. We show that truncated versions of these toxins fail to form oligomers but still show sigmoidal binding to cholesterol-containing membranes. The nonlinear response emerges because interactions between bilayer lipids control cholesterol accessibility to toxins in a threshold-like fashion. Around these thresholds, the affinity of toxins for membrane cholesterol varies by >100-fold, generating highly cooperative lipid-dependent responses independently of protein-protein interactions. Such lipid-driven cooperativity may control the sensitivity of many cholesterol-dependent processes.

Polymeric nanoparticles were found to be an effective drug delivery system to improve the bioavailability of drugs by increasing their solubility and circulation half-life in comparison with pure cefixime. In the current investigation, cefixime was used as a model drug and orally administered polymeric nanoparticles were developed using chitosan and Azadirachta indicafruit mucilage as natural polymers to achieve enhanced permeation, solubility and sustained release of therapeutically active agent. As a result, improved half-life, bioavailability and better therapeutic index of cefixime can be achieved when compared to pure cefixime. Polymeric cefixime nanoparticles were formulated using modified coacervation technique and then evaluated for various physico-chemical parameters such as average particle size, percentage entrapment efficiency and in-vitrodrug release behavior, in-vitroantimicrobial efficiency and in-vivoanimal studies (i.e., pharmacokinetics, acute toxicity and the efficacy studies) in comparison to the pure cefixime. The formulations were found to have a mean particle size range of 85.6 ± 4.5 to 250.6 ± 9.3 nm, and percentage entrapment efficiency was found to be in the range of 76.2 ± 1.3% to 90.4 ± 1.5%. The in-vitrodrug release data showed an initial burst release of drug followed by a sustained up to 28 h. The in-vitroantimicrobial efficiency studies for the selected formulation revealed that the formulations found to have an improved zone of inhibition with lower minimum inhibitory concentration compared to the pure cefixime. The in-vivopharmacokinetic study of formulation revealed sustained release of cefixime into the blood stream with a 14.59-fold increase in oral bioavailability and one fold increase in half-life compared to the pure cefixime when administered orally in rats (20 mg/kg weight). The acute toxicity study revealed that the formulation was found to be safe up to 2000 mg/kg with improved efficacy. Therefore, the developed formulation might be a novel carrier that improves the oral bioavailability of cefixime and thereby improved therapeutic activity can be achieved when compared to pure cefixime.

We report that the monolayer phase diagram for binary mixtures of dimyristoylphosphatidylethanolamine (DMPE) and dihydrocholesterol (DChol) is largely unchanged when each phospholipid molecule is replaced by two myristic acid (MA) molecules or various mixtures of the lysophospholipid and myristic acid. The corresponding phase diagrams all show the formation of "condensed complexes" of DChol and lipid. The condensed complex stoichiometry is thus largely determined by the C14 fatty acid acyl chains, in this case about 4-4.6 per DChol molecule.

Some binary mixtures of cholesterol and phospholipids in monolayers have thermodynamic phase diagrams with two upper miscibility critical points. This feature has been interpreted in terms of ‘condensed complexes’ between the phospholipid and cholesterol. The present work gives evidence for the formation of complexes with a common simple integral stoichiometry in binary mixtures of cholesterol and a series of five sphingomyelins where the amide-linked acyl chain length is varied. This indicates that these complexes have a distinct geometry even though they form a liquid phase.

Mixtures of dihydrocholesterol and phospholipids form immiscible liquids in monolayer membranes at the air-water interface under specified conditions of temperature and 2-dimensional pressure. In recent work it has been discovered that a number of these mixtures exhibit two upper miscibility critical points. Pairs of upper critical points can be accounted for by a theoretical model that implies the cooperative formation of molecular complexes of dihydrocholesterol and phospholipid molecules. These complexes are calculated to be present in the membranes both above and below the critical points. Below the critical points the complexes form a separate phase, whereas above the critical points the complexes are completely miscible with the other lipid components. The cooperativity of complex formation prompts the use of the terminology condensed complex.

A pair of recent studies has reopened debate on the subject of phase separations in model bilayer mixtures of cholesterol (Chol) and dipalmitoyl-phosphatidylcholine (DPPC). Fluorescence microscopy methods have not been able to detect phase separations in binary DPPC-Chol mixtures that have been inferred from NMR studies. However, micron-scale phase-separated liquid domains are observed by fluorescence in ternary mixtures of DPPC, Chol, and diphytanoyl-phosphatidylcholine (DiPhyPC). Here, a model of condensed complexes of Chol and DPPC is used to account for these results. In particular, it is shown that the orientation of tie-lines in ternary mixtures of DiPhyPC/DPPC/Chol is compatible with phase separation in binary DPPC/Chol mixtures.

It is shown that the calculated temperature dependence of the deuterium nuclear magnetic resonance (NMR) of labeled cholesterol-phospholipid bilayers is changed by magic-angle spinning. This makes it possible to distinguish different molecular motions at temperatures near a miscibility critical point, for motions with distinct temperature-dependent correlation times. In this way one finds that NMR line broadening due to critical point composition fluctuations can be distinguished from broadening due to the formation and dissociation of complexes.