Publications by authors named "Handley T"

Article Synopsis
  • Insulin-like peptide 5 (INSL5) primarily targets the RXFP4 receptor found in the colorectum and has potential for treating gastrointestinal issues like constipation.
  • While INSL5 can bind to the RXFP3 receptor, it does not activate it, highlighting the specificity of the INSL5/RXFP4 pathway for therapeutic applications.
  • The study developed an engineered INSL5 analogue (A13:B7-24-GG) that features a simpler structure, resulting in easier synthesis and improved potency and selectivity compared to native INSL5, making it a strong candidate for constipation treatment.
View Article and Find Full Text PDF

The control of malaria, a disease caused by parasites that kills over half a million people every year, is threatened by the continual emergence and spread of drug resistance. Therefore, new molecules with different mechanisms of action are needed in the antimalarial drug development pipeline. Peptides developed from host defense molecules are gaining traction as anti-infectives due to theood of inducing drug resistance.

View Article and Find Full Text PDF

Human insulin-like peptide 5 (INSL5) is a gut hormone produced by colonic L-cells, and its biological functions are mediated by Relaxin Family Peptide Receptor 4 (RXFP4). Our preliminary data indicated that RXFP4 agonists are potential drug leads for the treatment of constipation. More recently, we designed and developed a novel RXFP4 antagonist, A13-nR that was shown to block agonist-induced activity in cells and animal models.

View Article and Find Full Text PDF
Article Synopsis
  • INSL5 and relaxin-3 are peptides that play key roles in gut and brain functions, targeting class A GPCRs RXFP4 and RXFP3, which may help treat colon and neurological disorders, respectively.
  • The study focuses on developing a tracking system using NanoBiT complementation for better binding assays of RXFP3 and RXFP4, allowing for efficient quantification without complex separation processes.
  • Researchers created a specific agonist (SmBiT-R3/I5) for RXFP3/4, demonstrating its binding affinity in cell lines and optimizing membrane assays for effective high-throughput ligand analysis.
View Article and Find Full Text PDF

A relaxin-like gonad-stimulating peptide (RGP), Aso-RGP, featuring six cysteine residues, was identified in the Crown-of-Thorns Starfish (COTS, Acanthaster cf. solaris) and initially produced through recombinant yeast expression. This method yielded a single-chain peptide with an uncleaved C-peptide (His Tag) and suboptimal purity.

View Article and Find Full Text PDF

Purpose: Malnutrition affects up to 80% of patients with head and neck cancer (HNC) and is associated with higher burden of disease, poorer treatment outcomes, and greater mortality. The Eating As Treatment (EAT) intervention is a behavioral intervention previously demonstrated to be effective in improving nutritional status, depression, and quality of life in patients with HNC. This article examines the effects of the EAT intervention on 5-year mortality among participants.

View Article and Find Full Text PDF

Introduction: Uninsured patients often have poor clinical outcomes associated with lower access to care. Hospital Presumptive Eligibility (HPE) provides up to 60-d emergency Medicaid coverage for uninsured, low-income patients. After obtaining 60-d HPE, patients must file for ongoing Medicaid to sustain coverage; however, navigating HPE approval is complex.

View Article and Find Full Text PDF

Background: Tobacco smoking rates are higher in rural, regional, and remote (RRR) areas in Australia, and strategies to improve access to quit supports are required. This pilot study examined the feasibility of a smoking cessation intervention for people in RRR areas who smoke with the intention of using this data to design a powered effectiveness trial.

Methods: A randomised controlled trial (RCT) of the feasibility of a 12-week 'Outback Quit Pack' intervention consisting of mailout combination nicotine replacement therapy (NRT) and a proactive referral to Quitline, compared with a minimal support control (1-page smoking cessation support information mailout) was conducted between January and October 2021.

View Article and Find Full Text PDF

Unlabelled: Procedural anxiety is a concern for a number of patients undergoing radiation therapy. While procedural anxiety is often treated pharmacologically, there is a clinical need for effective alternative strategies for patients who are contraindicated from medication use, and those who prefer not to take unnecessary medications.

Objectives: The primary objective was to assess the efficacy of nonpharmacological interventions delivered to adults with cancer, in the radiation oncology department, just prior to, or during radiation therapy, in reducing levels of self-reported procedural anxiety.

View Article and Find Full Text PDF

Human relaxin-2 (H2 relaxin) is a peptide hormone with potent vasodilatory and anti-fibrotic effects, which is of interest for the treatment of heart failure and fibrosis. H2 relaxin binds to the Relaxin Family Peptide Receptor 1 (RXFP1). Native H2 relaxin is a two-chain, three-disulfide-bond-containing peptide, which is unstable in human serum and difficult to synthesize efficiently.

View Article and Find Full Text PDF

Introduction: Tobacco smoking rates in high-income countries are greater in rural, regional, and remote (RRR) areas compared to cities. Yet, there is limited knowledge about interventions targeted to RRR smokers. This review describes the effectiveness of smoking cessation interventions for RRR smokers in supporting smoking abstinence.

View Article and Find Full Text PDF

H2 relaxin is a peptide hormone that exerts its biological actions through the G protein-coupled receptor, RXFP1. The numerous important biological functions of H2 relaxin, including potent renal, vasodilatory, cardioprotective, and anti-fibrotic actions, have resulted in considerable interest in its use as a therapeutic for various cardiovascular diseases and other fibrotic indications. Interestingly though, H2 relaxin and RXFP1 have been shown to be overexpressed in prostate cancer, allowing for the downregulation or blocking of relaxin/RXFP1 to decrease prostate tumor growth.

View Article and Find Full Text PDF

Introduction: Trauma patients are twice as likely to be uninsured as the general population, which can lead to limited access to postinjury resources and higher mortality. The Hospital Presumptive Eligibility (HPE) program offers emergency Medicaid for eligible patients at presentation. The HPE program underwent several changes during the COVID-19 pandemic; we quantify the program's success during this time and seek to understand features associated with HPE approval.

View Article and Find Full Text PDF

Human relaxin-2 (H2 relaxin) is therapeutically very important due to its strong anti-fibrotic, vasodilatory, and cardioprotective effects. Therefore, relaxin's receptor, relaxin family peptide receptor 1 (RXFP1), is a potential target for the treatment of fibrosis and related disorders, including heart failure. H2 relaxin has a complex two-chain structure (A and B) and three disulfide bridges.

View Article and Find Full Text PDF

Introduction: Adverse childhood experiences (ACEs) are associated with health and social problems in later life, with an early intervention highly desirable for better outcomes.

Description: The Family-Referral-Services-In-Schools (FRSIS) is an early-intervention case management program for children and families with complex unmet needs, providing access to family support, housing, mental health care, and/or drug and alcohol services. The in-school trial setting was aimed at improving service uptake which was low in its community counterpart.

View Article and Find Full Text PDF

Introduction: Liver transplantation is a highly successful treatment for liver failure and disease. However, demand continues to outstrip our ability to provide transplantation as a treatment. Many livers initially considered for transplantation are not used because of concerns about their viability or logistical issues.

View Article and Find Full Text PDF

Objective: To evaluate the acceptability and effectiveness of a small community-based hospice on the end-of-life experiences of patients and families.

Methods: Mixed-methods study.

Design: Patient admission data were used to assess utilisation of the hospice.

View Article and Find Full Text PDF

Introduction: Understanding the prevalence of cannabis use among tobacco smokers has important implications for research in terms of intervention effectiveness and measurement in smoking cessation trials. The co-use of these substances also has important implications for health service planning, specifically ensuring appropriate and adequate clinical treatment. To date, there have been no synthesis of the literature on the prevalence of tobacco and cannabis co-use in adult clinical populations.

View Article and Find Full Text PDF

The day is rapidly approaching where current antibiotic therapies will no longer be effective due to the development of multi-drug resistant bacteria. Antimicrobial peptides (AMPs) are a promising class of therapeutic agents which have the potential to help address this burgeoning problem. Proline-rich AMPs (PrAMPs) are a sub-class of AMPs, that have multiple modes of action including modulation of the bacterial protein folding chaperone, DnaK.

View Article and Find Full Text PDF

Background: Clinicians need to be able to assess the quality of the available information to aid clinical decision-making. The internet has become an important source of health information for consumers and their families.

Objective: This study aimed to rate the quality of websites with psychosis-related information (to provide clinicians with a basis for recommending material to guide clinical decision-making with consumers and their families), using a validated instrument as well as a purpose-developed checklist, and consider improvement in quality over a 4-year period.

View Article and Find Full Text PDF

Background: In the USA, chronic kidney disease (CKD) affects 1 in 7 adults and costs $100 billion annually. The DAPA-CKD trial found dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, to be effective in reducing CKD progression and mortality in patients with diabetic and non-diabetic CKD. Currently, SGLT2 inhibitors are not considered standard of care for patients with non-diabetic CKD.

View Article and Find Full Text PDF