Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial.

Context: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia in childhood with considerable risk of lifelong neurological sequelae. Available pharmacological therapies are limited. Dasiglucagon is a glucagon analog for the treatment of hypoglycemia.

Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review.

In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development.

A bioengineering investigation of cervical collar design and fit: Implications on skin health.

Background: Cervical collars restrict cervical spine movement to minimise the risk of spinal cord injury. Collars apply mechanical loading to the skin putting it at risk of skin damage. Indeed, cervical collar-related pressure ulcers are unacceptably prevalent, especially at the occiput, mandibles, and chin.

Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children.

Context: Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI.

Objective: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC).

Novel peptide calcitonin gene-related peptide antagonists for migraine therapy.

Objectives: It has previously been shown that the peptide (34Pro,35Phe)CGRP27-37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides.

Methods: Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies.

Key Findings: A 10 amino acid-containing peptide VPTDVGPFAF-NH2 (P006) was identified as a key candidate to take forward for in vivo evaluation, where it was shown to be an effective antagonist after intraperitoneal injection into mice.

The development and optimisation of an HPLC-based in vitro serum stability assay for a calcitonin gene-related peptide receptor antagonist peptide.

Evaluation of the stability of peptide drug candidates in biological fluids, such as blood serum, is of high importance during the lead optimisation phase. Here, we describe the optimisation and validation of a method for the evaluation of the stability of a lead calcitonin gene-related peptide antagonist peptide (P006) in blood serum. After initially determining appropriate peptide and human serum concentrations and selection of the quenching reagent, the HPLC method optimisation used two experimental designs, Plackett-Burman design and Taguchi design.

Guidance for the use and reporting of anaesthetic agents in BJP manuscripts involving work with animals.

Scientists who plan to publish in the British Journal of Pharmacology (BJP) should read this article before undertaking studies utilising anaesthetics in mammalian animals. This editorial identifies certain gaps in the reporting of details on the use of anaesthetics in animal research studies published in the BJP. The editorial also provides guidance, based upon current best practices, for performing in vivo experiments that require anaesthesia.

Development of a novel cell-based, In-Cell Western/ERK assay system for the high-throughput screening of agonists acting on the delta-opioid receptor.

Extracellular signal-regulated kinases (ERKs) are important signaling mediators in mammalian cells and, as a result, one of the major areas of research focus. The detection and quantification of ERK phosphorylation as an index of activation is normally conducted using immunoblotting, which does not allow high-throughput drug screening. Plate-based immunocytochemical assays provide a cheaper and relatively high-throughput alternative method for quantifying ERK phosphorylation.

Planning experiments: Updated guidance on experimental design and analysis and their reporting III.

Scientists who plan to publish in British Journal of Pharmacology (BJP) must read this article before undertaking a study. This editorial provides guidance for the design of experiments. We have published previously two guidance documents on experimental design and analysis (Curtis et al.

Response to the Letter to the Editor From Page (2022) Regarding Ellis and Kendall (2021), "Time to Act: Confronting Systemic Racism in Communication Sciences and Disorders Academic Training Programs".

The purpose of this letter is to respond to Page's (2022) letter to the editor, "Time to RE-Act: Ellis and Kendall's Discussion of Systemic Racism," published by the

Dasiglucagon demonstrates reduced costs in the treatment of severe hypoglycemia in a budget impact model.

Approximately 7.3 million people with type 1 or type 2 diabetes (T1D/T2D) are treated with insulin, placing them at higher risk of severe hypoglycemia (SH). SH requires assistance of another individual and often necessitates the prompt administration of intravenous glucose, injectable glucagon, or both.

The Challenge of Achieving Greater Generalization in Phonological Treatment of Aphasia.

Background: Stimulus selection is important to anomia treatment because similarity between trained and untrained words in the mental lexicon may influence treatment generalization. We focused on phonological similarity between trained and untrained words from a clinical trial of Phonomotor Treatment (PMT) that showed gains in confrontation naming accuracy of untrained words post-treatment. One way to capture the amount of similarity between the trained and untrained words is to consider the phonological network path distance between words.

Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families.

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients' lives.

Structure-Activity Relationship in the Leucettine Family of Kinase Inhibitors.

The protein kinase DYRK1A is involved in Alzheimer's disease, Down syndrome, diabetes, viral infections, and leukemia. Leucettines, a family of 2-aminoimidazolin-4-ones derived from the marine sponge alkaloid Leucettamine B, have been developed as pharmacological inhibitors of DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases). We report here on the synthesis and structure-activity relationship (SAR) of 68 Leucettines.

A Comparative Study of Dasiglucagon Ready-to-Use Autoinjector and Glucagon Emergency Kit During Rescue from Simulated Severe Hypoglycemia.

Severe hypoglycemic episodes are life-threatening events demanding rapid administration of glucagon by a caregiver or bystander. The glucagon analog dasiglucagon is stable in aqueous formulation and therefore suitable for delivery in a ready-to-use autoinjector, potentially increasing speed and ease of use compared with standard glucagon emergency kits (GEKs). In an open label, randomized, crossover, comparative device handling study, trained caregivers and untrained bystanders administered the dasiglucagon autoinjector or Eli Lilly GEK to manikins in a simulated emergency hypoglycemia situation.

The Cannabinoid Receptor Type 1 Positive Allosteric Modulator ZCZ011 Attenuates Naloxone-Precipitated Diarrhea and Weight Loss in Oxycodone-Dependent Mice.

Opioid use disorder reflects a major public health crisis of morbidity and mortality in which opioid withdrawal often contributes to continued use. However, current medications that treat opioid withdrawal symptoms are limited by their abuse liability or lack of efficacy. Although cannabinoid 1 (CB) receptor agonists, including Δ-tetrahydrocannabinol, ameliorate opioid withdrawal in both clinical and preclinical studies of opioid dependence, this strategy elicits cannabimimetic side effects as well as tolerance and dependence after repeated administration.

Time to Act: Confronting Systemic Racism in Communication Sciences and Disorders Academic Training Programs.

Purpose The intent of this tutorial is to radically shift engagement around the "types of questions" we ask around racism in communication sciences and disorders (CSD). We propose to move conversations away from diversity and inclusion and go deeper to look at the racist systems of oppression in higher education that have produced our predominantly White discipline. This low number of representations of racial minorities in CSD is extremely problematic and has deep, harmful, and far-reaching implications.

Building and Sustaining Effective Partnerships for Training the Next Generation of Global Health Leaders.

Introduction: Partnerships are essential to creating effective global health leadership training programs. Global pandemics, including the HIV/AIDS pandemic, and more recently the COVID-19 pandemic, have tested the impact and stability of healthcare systems. Partnerships must be fostered to prepare the next generation of leaders to collaborate effectively and improve health globally.

Effects of a CB Subtype Selective Agonist ABK5-1 on Cytokine Production in Microglia.

Background And Objectives: Neuroinflammation is closely associated with various diseases including neuropathic pain. Microglia are immune cells in the central nervous system which are the main players of immunity and inflammation. Since microglia are activated by nerve injury, and they produce proinflammatory mediators to cause neuropathic pain, targeting activated microglia is considered to be a strategy for treating neuropathic pain.