Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

Velocity-Based Training With Weightlifting Derivatives: Barbell and System Velocity Comparisons.

Suchomel, TJ, Kissick, CR, Techmanski, BS, Mann, JB, and Comfort, P. Velocity-based training with weightlifting derivatives: Barbell and system velocity comparisons. J Strength Cond Res XX(X): 000-000, 2024-The aim of this study was to examine the differences in barbell and system (i.

Bipolar Ablation From the Anterior Interventricular Vein to the Left Ventricle.

Ventricular tachycardia from the left ventricular summit can be challenging for catheter ablation due to difficult accessibility and proximity to coronary arteries. This paper presents a case of premature ventricular contraction-induced ventricular tachycardia from the left ventricular summit that was ablated using bipolar radiofrequency ablation from the anterior interventricular vein and adjacent left ventricular endocardium.

Flexible modelling of the dissolution performance of directly compressed tablets.

In this study, a compartmental disintegration and dissolution model is proposed for the prediction and evaluation of the dissolution performance of directly compressed tablets. This dissolution model uses three compartments (Bound, Disintegrated, and Dissolved) to describe the state of each particle of active pharmaceutical ingredient. The disintegration of the tablet is captured by three fitting parameters.

Developing a robust in vitro release method for a polymeric nanoparticle: Challenges and learnings.

Nanomedicines have emerged as a promising approach for targeted therapeutic delivery and specifically as a beneficial alternative to conventional cancer therapies as they can deliver higher concentrations of chemotherapeutic agents at the tumour site compared to healthy tissue, thus providing improved drug efficacy and lower systemic toxicity. Long acting injectables are increasingly becoming the focus of pharmaceutical research, as they can reduce dosing frequency and improve the life quality of patients. Development of an in vitro release (IVR) method for modified release nanomedicines is challenging because of the uniqueness and range of different formulation design approaches, as well as the complex nature of drug release mechanisms which may result in inherent variability.

Acalabrutinib Maleate Tablets: The Physiologically Based Biopharmaceutics Model behind the Drug Product Dissolution Specification.

Acalabrutinib maleate tablets correspond to an improved formulation compared to acalabrutinib capsules as they can be dosed with and without acid reducing agents and therefore benefit more cancer patients. The dissolution specification for the drug product was determined using all the information available on the drug safety, efficacy, and in vitro performance. In addition, a physiologically based biopharmaceutics model was developed for acalabrutinib maleate tablets on the back of a previously published model for acalabrutinib capsules to establish that the proposed drug product dissolution specification would ensure safe and effective products for all patients including those under acid reducing agent treatment.

Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity.

Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown.

PrimedSherlock: a tool for rapid design of highly specific CRISPR-Cas12 crRNAs.

Background: CRISPR-Cas based diagnostic assays provide a portable solution which bridges the benefits of qRT-PCR and serological assays in terms of portability, specificity and ease of use. CRISPR-Cas assays are rapidly fieldable, specific and have been rigorously validated against a number of targets, including HIV and vector-borne pathogens. Recently, CRISPR-Cas12 and CRISPR-Cas13 diagnostic assays have been granted FDA approval for the detection of SARS-CoV-2.

Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.

Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or previously treated mantle cell lymphoma. As the bioavailability of the acalabrutinib capsule (AC) depends on gastric pH for solubility and is impaired by acid-suppressing therapies, coadministration with proton-pump inhibitors (PPIs) is not recommended. Three studies in healthy subjects (N = 30, N = 66, N = 20) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of acalabrutinib maleate tablet (AT) formulated with pH-independent release.

Aedes japonicus japonicus in Nebraska and Texas.

Aedes japonicus japonicus continues to spread westward and in this study, its presence is documented in 8 counties in Nebraska and in Bowie County, TX. In 1998, Ae. japonicus was collected in Connecticut, New Jersey, and New York for the 1st records of this species in North America.

Tablet disintegration performance: Effect of compression pressure and storage conditions on surface liquid absorption and swelling kinetics.

The disintegration process of pharmaceutical tablets is a crucial step in the oral delivery of a drug. Tablet disintegration does not only refer to the break up of the interparticle bonds, but also relates to the liquid absorption and swelling behaviour of the tablet. This study demonstrates the use of the sessile drop method coupled with image processing and models to analyse the surface liquid absorption and swelling kinetics of four filler combinations (microcrystalline cellulose (MCC)/mannitol, MCC/lactose, MCC/dibasic calcium phosphate anhydrous (DCPA) and DCPA/lactose) with croscarmellose sodium as a disintegrant.