MDMA pharmacokinetics: A population and physiologically based pharmacokinetics model-informed analysis.

Midomafetamine (3,4-methylenedioxymethamphetamine [MDMA]) is under the U.S. Food and Drug Administration review for treatment of post-traumatic stress disorder in adults.

A growth-differentiation factor 15 receptor agonist in randomized placebo-controlled trials in healthy or obese persons.

Background: Growth Differentiation Factor 15 (GDF15), a divergent member of the TGF-β superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer.

The role of major and minor determinants in penicillin allergy testing: Time to revisit an old friend?

Background: Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic.

Forages and pastures symposium: an update on in vitro and in situ experimental techniques for approximation of ruminal fiber degradation.

Static quantification measures of chemical components are commonly used to make certain assumptions about forage or feed nutritive value and quality. In order for modern nutrient requirement models to estimate intake and digestibility more accurately, kinetic measures of ruminal fiber degradation are necessary. Compared to in vivo experiments, in vitro (IV) and in situ (IS) experimental techniques are relatively simple and inexpensive methods to determine the extent and rate of ruminal fiber degradation.

A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis.

Background: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks.

Adverse Reactions Associated with Intravenous Immunoglobulin Administration in the Treatment of Neurological Disorders: A Systematic Review.

Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological disease characteristics associated with adverse reactions, along with strategies to prevent and treat adverse reactions, are uncertain. A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library to summarise studies that report adverse reactions of IVIg therapy in patients with neurological disease.

Effects in air-exposed corn silage of medium chain fatty acids on select spoilage microbes, zoonotic pathogens, and rumen fermentation.

Medium chain fatty acid (MCFA) treatment (0.75% C6, hexanoic; C8, octanoic; C10, decanoic; or equal proportion mixtures of C6:C8:C10:C12 or C8:C10/g; C12 = dodecanoic acid) of aerobically-exposed corn silage on spoilage and pathogenic microbes and rumen fermentation were evaluated . After 24 h aerobic incubation (37 °C), microbial enumeration revealed 3 log colony-forming units (CFU)/g fewer ( = 0.

The Use of Removed Mesquite Brush as a Fiber Replacement in Silage Production.

Mesquite (Prosopis L.) is considered an invasive browse species in most of the American Southwest. Mechanical intervention removes yields an excess of organic debris.

Safety and Pharmacokinetics of Taniborbactam (VNRX-5133) with Cefepime in Subjects with Various Degrees of Renal Impairment.

Taniborbactam, an investigational β-lactamase inhibitor that is active against both serine- and metallo-β-lactamases, is being developed in combination with cefepime to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Anticipating the use of cefepime-taniborbactam in patients with impaired renal function, an open-label, single-dose clinical study was performed to examine the pharmacokinetics of both drugs in subjects with various degrees of renal function. Hemodialysis-dependent subjects were also studied to examine the amounts of cefepime and taniborbactam dialyzed.

Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that may advance to fibrosis and lead to mortality; however, no pharmacotherapy is currently available. We tested the hypothesis that inhibition of both the sodium-glucose cotransporters 1 and 2 with licogliflozin would lead to improvement in NASH. A total of 107 patients with phenotypic or histologic NASH were randomized (1:2:2) to receive oral administration of either placebo (n = 21), licogliflozin 30 mg (n = 43) or 150 mg (n = 43) once daily for 12 weeks.

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

A Systematic Review of Physical Examination Components Adapted for Telemedicine.

The COVID-19 pandemic ushered in a rapid, transformative adoption of telemedicine to maintain patient access to care. As clinicians made the shift from in-person to virtual practice, they faced a paucity of established and reliable clinical examination standards for virtual care settings. In this systematic review, we summarize the accuracy and reliability of virtual assessments compared with traditional in-person examination tools.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

Nutritive Value Variation of Paunch Manure as an Alternative Feed Ingredient.

Ruminants, which have multi-compartmented stomachs, are adapted to digest cellulosic materials, which constitute the primary expense on ranches and dairies. Industrial byproducts can be repurposed for livestock diets to decrease these costs. Therefore, finding alternative feedstuffs may benefit the economics of livestock production.

Nutritive Value Variation and In Vitro Digestibility of Hempseed Meal.

Hempseed meal (HSM) is left after oil extraction of hemp and may act as a protein source in livestock. The first phase of this research evaluated variation in nutritive value and dry matter digestibility (IVDMD) of HSM from various sources in North America; the second phase utilized IVDMD to evaluate the efficacy of hempseed meal as an ingredient in ruminant feed. In phase one, the source had no contribution to variance for neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), or crude protein (CP) ( ≥ 0.

Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist.

Unimolecular triple incretins, combining the activity of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG), have demonstrated reduction in body weight and improved glucose control in rodent models. We developed SAR441255, a synthetic peptide agonist of the GLP-1, GCG, and GIP receptors, structurally based on the exendin-4 sequence. SAR441255 displays high potency with balanced activation of all three target receptors.

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone.

Understanding intake on pastures: how, why, and a way forward.

An assessment of dietary intake is a critical component of animal nutrition. Consumption of feed resources is the basis upon which feeding strategies and grazing management are based. Yet, as far back as 1948, researchers have lauded the trials and tribulations of estimation of the phenomenon, especially when focused on grazing animals and pasture resources.

Impact of Longitudinal Virtual Primary Care on Diabetes Quality of Care.

Background: Lack of healthcare access to due to physician shortages is a significant driver of telemedicine expansion in rural areas. Telemedicine is effective for management of chronic conditions such as diabetes but its effectiveness in primary care settings is unknown.

Objective: To evaluate differences in diabetes care before and after implementation of a longitudinal virtual primary care program.

Pharmacokinetics and tolerability of fedratinib, an oral, selective Janus kinase 2 inhibitor, in subjects with renal or hepatic impairment.

Purpose: Fedratinib is an oral, selective Janus kinase 2 inhibitor that is approved in the United States for the treatment of patients with intermediate-2 or high-risk myelofibrosis. Pharmacokinetics and tolerability of fedratinib in subjects with renal impairment (RI) and hepatic impairment (HI) were evaluated in two separate studies.

Methods: In the renal study, male and female subjects with stable, chronic mild, moderate, and severe RI, as well as those with end-stage renal disease, were included.

Categorization of adverse drug reactions in electronic health records.

The purpose of this study was to evaluate the quality of adverse drug reaction (ADR) documentation in a state-wide electronic health record (EHR), and to assess the impact of the interface design on documentation accuracy and ability to provide decision support. Data were extracted from 43 011 unique records in a state-wide electronic health record in South Australia, Australia. Information obtained included ADR coding as allergy or intolerance, allergen name, reaction, and occupation of those entering data.

Biogeographical variation in specific IgE recognition of temperate and subtropical grass pollen allergens in allergic rhinitis patients.

Objective: Globally, grass pollens (GP) are major aeroallergen triggers of allergic rhinitis (AR) and asthma. However, patterns of allergic sensitisation to pollen of temperate (Pooideae: ) and subtropical (Chloridoideae: and Panicoideae: ) subfamilies in diverse climates remain unclear. This study aims to evaluate the level of allergic sensitisation and IgE specificity for major GP allergens representing the three subfamilies in biogeographically distinct regions.