Optimizing medication therapy in elderly patients: The impact of medication review using STOPP and START criteria version 2.

Higher prevalence of inappropriate medication use among cancer patients increases risk of drug-related problems(DRP) like drug-drug interactions, ADR, and non-adherence. Potentially inappropriate medication (PIM) and Potential Prescription Omission (PPO) were identified using Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to the Right Treatment (START) criteria. The study objective was to optimize prescriptions for the elderly by analyzing the impact of medication review.

Machine Learning Guided Rational Design of a Non-Heme Iron-Based Lysine Dioxygenase Improves its Total Turnover Number.

Highly selective C-H functionalization remains an ongoing challenge in organic synthetic methodologies. Biocatalysts are robust tools for achieving these difficult chemical transformations. Biocatalyst engineering has often required directed evolution or structure-based rational design campaigns to improve their activities.

Equilibrium dialysis with HPLC detection to measure substrate binding affinity of a non-heme iron halogenase.

Determination of substrate binding affinity (K) is critical to understanding enzyme function. An extensive number of methods have been developed and employed to study ligand/substrate binding, but the best approach depends greatly on the substrate and the enzyme in question. Below we describe how to measure the K of BesD, a non-heme iron halogenase, for its native substrate lysine using equilibrium dialysis coupled with High Performance Liquid Chromatography (HPLC) for subsequent detection.

Diabetes and Functional Impairment in Osteoarthritis: Investigating Correlations, Associations, and Progression.

Introduction Diabetes and osteoarthritis (OA) are prevalent chronic conditions, often occurring concurrently and complicating patient management. While the individual impact of each condition on functional impairment is well documented, their combined effect remains poorly understood. This study aims to elucidate the relationship between diabetes and OA-related functional impairment.

Genome-scale exon perturbation screens uncover exons critical for cell fitness.

CRISPR-Cas technology has transformed functional genomics, yet understanding of how individual exons differentially shape cellular phenotypes remains limited. Here, we optimized and conducted massively parallel exon deletion and splice-site mutation screens in human cell lines to identify exons that regulate cellular fitness. Fitness-promoting exons are prevalent in essential and highly expressed genes and commonly overlap with protein domains and interaction interfaces.

Machine learning guided rational design of a non-heme iron-based lysine dioxygenase improves its total turnover number.

Highly selective C-H functionalization remains an ongoing challenge in organic synthetic methodologies. Biocatalysts are robust tools for achieving these difficult chemical transformations. Biocatalyst engineering has often required directed evolution or structure-based rational design campaigns to improve their activities.

Exosomes isolated from citrus lemon: a promising candidate for the treatment of Alzheimer's disease.

To investigate the efficacy of exosome-like nanovesicles from citrus lemon (EXO-CLs) in combating oxidative stress associated with Alzheimer's disease. EXO-CLs were isolated through differential ultracentrifugation, characterized for particle size and evaluated for antioxidant activity. EXO-CLs exhibited a mean size of 93.

Controllable multi-halogenation of a non-native substrate by SyrB2 iron halogenase.

Geminal, multi-halogenated functional groups are widespread in natural products and pharmaceuticals, yet no synthetic methodologies exist that enable selective multi-halogenation of unactivated C-H bonds. Biocatalysts are powerful tools for late-stage C-H functionalization, as they operate with high degrees of regio-, chemo-, and stereoselectivity. 2-oxoglutarate (2OG)-dependent non-heme iron halogenases chlorinate and brominate aliphatic C-H bonds offering a solution for achieving these challenging transformations.

Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in Mycobacterium tuberculosis.

DosT and DosS are heme-based kinases involved in sensing and signaling O tension in the microenvironment of Mycobacterium tuberculosis (Mtb). Under conditions of low O, they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.

The First Nations experience of accessing rheumatology services in a metropolitan hospital: A qualitative study.

Objective: First Nations Australians experience a higher burden and severity of Rheumatic Disease with poorer outcomes than the general population. Despite a widely acknowledged need to improve health outcomes, there has been minimal research assessing existing models of care from a First Nations perspective in Australia. The objective of this study was to describe First Nations experiences and barriers and enablers to accessing a hospital-based adult Rheumatology service in Sydney.

Equilibrium dialysis with HPLC detection to measure substrate binding affinity of a non-heme iron halogenase.

Determination of substrate binding affinity () is critical to understanding enzyme function. An extensive number of methods have been developed and employed to study ligand/substrate binding, but the best approach depends greatly on the substrate and the enzyme in question. Below we describe how to measure the of BesD, a non-heme iron halogenase, for its native substrate lysine using equilibrium dialysis with subsequent detection with High Performance Liquid Chromatography (HPLC).

Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in .

DosT and DosS are heme-based kinases involved in sensing and signaling O tension in the microenvironment of (). Under conditions of low O, they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.

Novel therapeutic approaches for the management of hepatitis infections.

Hepatitis B virus (HBV) & hepatitis C virus (HCV) infection is a substantial reason for morbidity and mortality around the world. Chronic hepatitis B (CHB) infection is connected with an enhanced risk of liver cirrhosis, liver decompensation and hepatocellular carcinoma (HCC). Conventional therapy do face certain challenges, for example, poor tolerability and the growth of active resistance.

Grazing preferences of three species of amoebae on cyanobacteria and green algae.

Twenty species/isolates of cyanobacteria and green algae were isolated from cyanobacterial bloom samples in lakes associated with the upper Qu'Appelle River drainage system in southern Saskatchewan, Canada. Three amoebae species (Cochliopodium sp., Vannella sp.

Gas tunnel engineering of prolyl hydroxylase reprograms hypoxia signaling in cells.

Cells have evolved intricate mechanisms for recognizing and responding to changes in oxygen (O) concentrations. Here, we have reprogrammed cellular hypoxia (low O) signaling via gas tunnel engineering of prolyl hydroxylase 2 (PHD2), a non-heme iron dependent O sensor. Using computational modeling and protein engineering techniques, we identify a gas tunnel and critical residues therein that limit the flow of O to PHD2's catalytic core.

Vitreoretinal disease: a critical review on current technological perspectives and innovative drug-delivery strategies.

To review the state of the art aspects and contemporary innovative drug delivery strategies, for the treatment of vitreoretinal diseases, their mechanism of action through ocular routes and their future perspectives. Scientific databases such as PubMed, Science Direct, Google scholar were used to obtain 156 papers for review. The keywords searched were vitreoretinal diseases; ocular barriers; intravitreal injections; nanotechnology; biopharmaceuticals.

Understanding ATP binding to DosS catalytic domain with a short ATP-lid.

DosS is a heme-sensor histidine kinase that responds to redox-active stimuli in mycobacterial environments by triggering dormancy transformation. Sequence comparison of the catalytic ATP-binding (CA) domain of DosS to other well-studied histidine kinases suggests that it possesses a rather short ATP-lid. This feature has been thought to inhibit DosS kinase activity by blocking ATP binding in the absence of interdomain interactions with the dimerization and histidine phospho-transfer (DHp) domain of full-length DosS.

Electrostatically regulated active site assembly governs reactivity in non-heme iron halogenases.

Non-heme iron halogenases (NHFe-Hals) catalyze the direct insertion of a chloride/bromide ion at an unactivated carbon position using a high-valent haloferryl intermediate. Despite more than a decade of structural and mechanistic characterization, how NHFe-Hals preferentially bind specific anions and substrates for C-H functionalization remains unknown. Herein, using lysine halogenating BesD and HalB enzymes as model systems, we demonstrate strong positive cooperativity between anion and substrate binding to the catalytic pocket.

Integrating UV-Vis Spectroscopy and Oxygen Optode for Accurate Determination of Oxygen Affinity of Proteins.

Protein-based oxygen sensors exhibit a wide range of affinity values ranging from low nanomolar to high micromolar. How proteins utilize different metals, cofactors, and macromolecular structure to regulate their oxygen affinity (K) to a value that is appropriate for their biological function is an important question in biochemistry and microbiology. In this chapter, we describe a simple setup that integrates a UV-Vis spectrometer with an oxygen optode for direct determination of K of heme-containing oxygen sensors.

Deducing the Interplay Between Gut Flora and Respiratory Diseases: A New Therapeutic Strategy?

The gastrointestinal system, also referred to as the gut, is a universe that colonizes trillions of microbes. In addition to its digestive functions, the gut represents a biosystem that determines all the health vectors. It is now recognized as one of the body's defense systems, and good gut health regulates the body's immune responses.

VEXAS syndrome: lessons learnt from an early Australian case series.

VEXAS is a newly recognised adult-onset autoinflammatory syndrome resulting from a somatic mutation in the UBA1 gene. Herein, we present three cases of VEXAS syndrome in Sydney, Australia, that capture key clinical features and the refractory nature of the condition. They highlight the importance of multidisciplinary collaboration for early diagnosis and the need for new therapeutic options.

Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide.

Objectives: To demonstrate the synergistic effect of 4-hexylresorcinol (4-HR) with niacinamide in boosting anti-melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial.

Methods: Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4-HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double-blind, split-face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12-week study period.