Publications by authors named "MCCARTHY H"

Magnesium (Mg) alloys have gained significant attention as a desirable choice of biodegradable implant for use in bone repair applications, largely owing to their unique material properties. More recently, Mg and Mg-based alloys have been used as load-bearing metallic scaffolds for bone tissue engineering applications, offering promising opportunities in the field. The mechanical properties and relative density of Mg-based alloys closely approximate those of natural human bone tissue, thereby mitigating the risk of stress-shielding effects.

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  • New multipurpose prevention technologies for women prioritize reducing HIV risks and preventing unwanted pregnancies, promoting greater sexual health choices.
  • A novel long-acting injectable platform combines the HIV drug MIV-150 and the contraceptive etonogestrel using a specially designed D-peptide that forms a drug-releasing hydrogel after injection.
  • The technology shows promising biostability, low toxicity, and sustained delivery of both drugs in animal models for nearly 50 days, indicating its potential for effective long-term use.
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Cell-penetrating peptides (CPP) have gained rapid attention over the last 25 years; this is attributed to their versatility, customisation, and 'Trojan horse' delivery that evades the immune system. However, the current CPP rational design process is limited, as it requires several rounds of peptide synthesis, prediction and wet-lab validation, which is expensive, time-consuming and requires extensive knowledge in peptide chemistry. Artificial intelligence (AI) has emerged as a promising alternative which can augment the design process, for example by determining physiochemical characteristics, secondary structure, solvent accessibility, disorder and flexibility, as well as predicting in vivo behaviour such as toxicity and peptidase degradation.

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Background: Financial incentives delivered via apps appear to be effective in encouraging physical activity. However, the literature on different incentive strategies is limited, and the question remains whether financial incentives offer a cost-effective intervention that could be funded at the population level.

Objective: This study aimed to explore patterns of tracked physical activity by users of an incentive-based app before and after a change in incentive strategy.

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  • - The study investigates how tendon maturation into strong tissue is regulated, noting significant mechanical property changes in chick embryos between days E16 and E18, but lacking clarity on the underlying cellular and molecular factors.
  • - Researchers analyzed late tendon development by examining collagen fiber alignment, cell organization, and Yap pathway activity, assessing the impact of both constant loading and no loading on tendon maturation.
  • - Findings revealed that YAP signaling is influenced by movement, with collagen alignment improving under static loading; however, immobilization disrupted the organized structure of tendon cells, highlighting the importance of dynamic stimulation for proper tendon development.
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Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays.

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Introduction: Inequitable access to health care based on demographic factors such as ethnicity, socioeconomic status and geographical location has been consistently found in children with chronic kidney disease (CKD). However, little is known about the perspectives of caregivers on accessing health care. We described caregivers' perspectives on accessing health care for children with CKD from socioeconomically disadvantaged backgrounds and/or rural or remote areas.

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Objective: To determine if mesenchymal stromal cells (MSCs) derived from human umbilical cords (hUC) could reduce degeneration developing when injected into the knee of a large animal model of osteoarthritis (OA).

Design: Ten million culture-expanded UC-MSCs (pooled from 3 human donors) were injected in 50 μL of tissue culture medium into the left stifle joints of 7 sheep whose medial meniscus was transected 4 weeks previously. Seven other sheep had only 50 μL of medium injected as the no treatment "control" group.

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Objective: Traditional autologous chondrocyte implantation (ACI) involves arthroscopically harvesting a cartilage biopsy (stage 1), followed by arthrotomy 3 to 4 weeks later to apply a periosteal patch and implant culture-expanded chondrocytes underneath (stage 2). This study aimed to determine if patch application during stage 1 rather than stage 2 improved clinical outcome.

Design: A randomized controlled trial was conducted from 1998 to 2001.

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  • There is a significant increase in the mechanical properties and load-bearing capabilities of tendons during embryonic development, but the exact structural elements contributing to this growth are not fully understood.
  • Researchers used various methods, including shear lag modeling and mechanical testing, to analyze the changes in tendon structure and function in embryonic chick development, revealing that increases in fibril length and crosslinking are key to enhanced mechanics.
  • Inhibiting collagen crosslinking and inducing muscle paralysis demonstrated that both crosslink formation and fibril elongation are essential for developing strong load-bearing tendons and are sensitive to mechanical stimulation.
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  • - CRISPR gene editing provides precise control over cell function, but delivering CRISPR components safely to cells is challenging due to issues with traditional delivery methods like viral vectors and some non-viral systems.
  • - The RALA cell-penetrating peptide forms nanoparticles and has shown promise for delivering various CRISPR formats with low toxicity, outperforming other non-viral delivery systems in terms of cell viability and transfection rates.
  • - RALA successfully delivered CRISPR components for gene editing tasks, including knock-ins and knock-outs in primary mesenchymal stem cells, positioning it as a valuable tool for safer and effective CRISPR delivery across different applications.
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The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia.

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  • The study investigated how perioperative management affects early kidney graft function in pediatric patients who received living donor kidney transplants.
  • Data was collected from two pediatric centers in New South Wales, Australia, analyzing early graft function through estimated glomerular filtration rate (eGFR) at 7 days and 1 month post-transplant.
  • Despite managing fluid levels and blood pressure during and after surgery, the findings revealed that these factors did not significantly influence early graft function in the analyzed patients.
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Hyperlipidemia and its associated cardiovascular complications are the major causes of mortality and disability worldwide. Simvastatin (SIM) is one of the most commonly prescribed lipid-lowering drugs for the treatment of hyperlipidemia by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. However, the extensive first-pass metabolism leading to low oral bioavailability and frequent daily doses may lead to poor patient compliance and adverse effects caused by plasma fluctuations.

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Nutritional intake during pregnancy can affect gestational length, fetal development, and impact postnatal growth and health in offspring. Perturbations in maternal nutrition with either an excess or deficiency in nutrients during pregnancy may have harmful effects on the offspring's development and increase the risk of developing chronic diseases later in life. In pregnancy, nutrients transfer from the mother to the fetus via the placenta.

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Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies.

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In women, breast cancer (BC) is the most common cancer, and despite advancements in diagnosis and treatment, 20-30% of early stage BC patients develop metastatic disease. Metastatic BC is deemed an incurable disease, which accounts for 90% of BC related deaths, with only 26% of metastatic patients reaching a 5 year survival rate. Therefore, there is an unmet need for the prevention or treatment of metastasis in early stage breast cancer patients.

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The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi.

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  • Diagnostic genomic sequencing is becoming essential in nephrology, with efforts to enhance its national implementation to benefit patient outcomes.
  • A national study established 20 kidney genetics clinics across Australia from 2013 to 2022, offering genomic testing for patients with suspected monogenic kidney diseases and facilitating the collection of data on diagnostic experiences.
  • The initiative successfully integrated a multidisciplinary approach to kidney genetics, optimizing care for patients while adapting to ongoing technological advancements and preparing for broader healthcare funding for genomic testing.
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The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients.

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The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faces challenges due to poor solubility and low bioavailability. This study explores the development of dissolving microneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention, aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soya lecithin, water, and polysorbate 80 micelles.

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Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors.

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  • Hydrogel-forming microneedle array patches (HFMAPs) can deliver drugs like risperidone (RIS) transdermally while avoiding sharps waste by creating microconduits in the skin.
  • The study enhanced the solubility of RIS by using cyclodextrin derivatives, specifically hydroxypropyl-beta-cyclodextrin (HP-β-CD), which increased RIS solubility by 4.75 times.
  • In vivo experiments demonstrated that HFMAPs provided prolonged release of RIS and its metabolite, significantly maintaining higher blood levels over several days compared to traditional intramuscular delivery.
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  • Patient navigators help adult patients navigate complex health systems, aiming to improve access and health outcomes; this study focused on the effects of such a program for children with chronic kidney disease (CKD).
  • In a multi-center trial, children with CKD from low socioeconomic backgrounds were randomly assigned to receive immediate patient navigation or waitlisted for six months.
  • Results showed no significant difference in self-rated health between the two groups after six months, but caregivers reported gaining skills for better care coordination and support despite some challenges in the process.
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