Oxytocin Analogues for the Oral Treatment of Abdominal Pain.

Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon-innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery. However, the low gastrointestinal stability of OTR's endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development.

Improving Cardiovascular Disease Prediction With Machine Learning Using Mental Health Data: A Prospective UK Biobank Study.

Background: Robust and accurate prediction of cardiovascular disease (CVD) risk facilitates early intervention to benefit patients. The intricate relationship between mental health disorders and CVD is widely recognized. However, existing models often overlook psychological factors, relying on a limited set of clinical and lifestyle parameters, or being developed on restricted population subsets.

CRISPR-mediated megabase-scale transgene de-duplication to generate a functional single-copy full-length humanized DMD mouse model.

Background: The development of sequence-specific precision treatments like CRISPR gene editing therapies for Duchenne muscular dystrophy (DMD) requires sequence humanized animal models to enable the direct clinical translation of tested strategies. The current available integrated transgenic mouse model containing the full-length human DMD gene, Tg(DMD)72Thoen/J (hDMDTg), has been found to have two copies of the transgene per locus in a tail-to-tail orientation, which does not accurately simulate the true (single) copy number of the DMD gene. This duplication also complicates analysis when testing CRISPR therapy editing outcomes, as large genetic alterations and rearrangements can occur between the cut sites on the two transgenes.

What lurks beneath the symptom? Why more basic scientists are needed in cancer supportive care and survivorship research.

With a growing population of people living with and beyond cancer, a larger portion of cancer research has shifted to ensuring that these people not only survive but survive well, and so supportive oncology has emerged as a critical component of modern cancer care. However, research and advancements in supportive care strategies have largely centered around symptom management, without an appreciation for the physiological mechanisms underlying the symptom. By placing a greater emphasis on understanding the pathophysiological mechanisms that lurk beneath the symptom in supportive care and survivorship research, superior symptom control and greater improvements to quality of life, through the development of targeted interventions, can be achieved.

Star Ratings in Long-Term Care Facilities in Australia: Facility Characteristics Associated with High Ratings and Changes in Ratings Over Time.

Objectives: A Star Rating system (1 to 5 stars) of long-term care facilities in Australia is based on 4 sub-categories: compliance, quality measures, residents' experience, and staffing. The objectives were to examine associations between facility characteristics and the odds of receiving a 4- or 5-star rating, and changes in ratings between the earliest reporting period (October-December 2022) to the most recent (April-June 2023).

Design: Cross-sectional, ecological study, with an additional longitudinal component.

CBL mutations in chronic myelomonocytic leukemia often occur in the RING domain with multiple subclones per patient: Implications for targeting.

Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations in the ubiquitin ligase Cbl occur frequently in CMML and share biological and molecular features with a clonal disease occurring in children, juvenile myelomonocytic leukemia (JMML). Here we analyzed the clinical presentations, molecular features and immunophenotype of CMML patients with CBL mutations enrolled in a prospective Phase II clinical trial stratified according to molecular markers.

Concurrent use of hormonal long-acting reversible contraception by women of reproductive age dispensed teratogenic medications, Australia, 2013-2021: a retrospective cohort study.

Objectives: To examine patterns in the dispensing of category X medications (Therapeutic Goods Administration categorisation system for prescribing medicines in pregnancy) to women aged 15-49 years in Australia during 2008-2021, and patterns of concurrent use of hormonal long-acting reversible contraception (LARC) and other hormonal contraception.

Study Design: Retrospective cohort study; analysis of 10% random sample of national Pharmaceutical Benefits Scheme dispensing data.

Participants, Setting: Women aged 15-49 years dispensed category X medications, Australia, 1 January 2013 - 31 December 2021.

Stemless anatomic and reverse shoulder arthroplasty in patients under 55 years of age with primary glenohumeral osteoarthritis: an analysis of the Australian Orthopedic Association National Joint Replacement Registry at 5 years.

Background: Primary glenohumeral osteoarthritis in young patients poses challenging treatment decisions. Arthroplasty options have different failure profiles and implant survivorship patterns. This registry study aims to analyze the cumulative per cent revision (CPR) rate of different types of arthroplasties conducted for primary osteoarthritis in patients below 55 years of age.

Towards Understanding Tumour Colonisation by Probiotic Bacterium Nissle 1917.

The last decade has seen a rapid increase in studies utilising a genetically modified probiotic, Nissle 1917 (EcN), as a chassis for cancer treatment and detection. This approach relies on the ability of EcN to home to and selectively colonise tumours over normal tissue, a characteristic common to some bacteria that is thought to result from the low-oxygen, nutrient-rich and immune-privileged niche the tumour provides. Pre-clinical studies have used genetically modified EcN to deliver therapeutic payloads that show efficacy in reducing tumour burden as a result of high-tumour and low off-target colonisation.

Adjunctive use of hypnosis for clinical pain: a systematic review and meta-analysis.

Systematic reviews suggest that stand-alone hypnotic suggestions may improve pain outcomes compared with no treatment, waitlist, or usual care. However, in clinical practice, hypnosis is often provided adjunctively with other interventions, which might have different effects than those reported in previous reviews. This systematic review aimed to summarize the analgesic effects of adjunctive hypnosis in adults with clinical pain.

Human milk lactoferrin and lysozyme concentrations vary in response to a dietary intervention.

It is known that human milk (HM) antimicrobial protein composition varies during lactation. However, the impact of maternal diet on these antimicrobial proteins, particularly lactoferrin and lysozyme remains unknown. In addition, it is unclear whether daily, circadian, and between breast variations exist for lactoferrin and lysozyme concentrations.

Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial.

Background And Aims: In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥ 100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C.

The impact of breaking up sitting during simulated nightshifts on musculoskeletal pain: A randomised controlled trial.

Objectives: Prolonged sitting is associated with an increased risk of musculoskeletal pain, especially in nightshift workers. However, research investigating effects of breaking up sitting on musculoskeletal pain during nightshifts is lacking. This study evaluated effects of prolonged sitting or breaking up sitting with short bouts of light-intensity physical activity on pain in healthy adults during simulated nightshifts.

Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression.

Our work demonstrates that the bidirectional interplay between sympathetic nerves and NGF-expressing CAFs drives colorectal tumorigenesis. This study also offers novel mechanistic insights into catecholamine action in colorectal cancer. Inhibiting the neuro-mesenchymal interaction by TRK blockade could be a potential strategy for treating colorectal cancer.

Evaluation of neuroretina following i.v. or intra-CSF AAV9 gene replacement in mice with MPS IIIA, a childhood dementia.

Background: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra-cerebrospinal fluid (CSF) injection of AAV9-gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness.

The effects of fasting compared to eating a meal or snack during simulated night shift on changes in metabolism associated with circadian misalignment: a protocol and methods paper.

Study Objectives: This protocol paper outlines the methods that will be used to examine the impact of altering meal timing on metabolism, cognitive performance, and mood during the simulated night shift.

Methods: Participants (male and female) will be recruited according to an a priori selected sample size to complete a 7-day within and between participant's laboratory protocol. Participants will be randomly assigned to one of the three conditions: meal at night or snack at night or no meal at night.

The impact of ageing-in-place reforms on the provision of home care packages for older Australians, 2008-21: a repeated cross-sectional study.

Objectives: To assess changes following the 2013-21 Home Care Package (HCP) reforms in the rate of HCPs provided to Australians aged 65 years or older, the characteristics of people who have received HCPs, and the capacity of the program to meet demand for its services during 2018-21.

Study Design: Repeated cross-sectional population-based study; analysis of Australian Institute of Health and Welfare GEN Aged Care and Australian Department of Health Home Care Packages program data.

Setting, Participants: HCPs provided to non-Indigenous Australians aged 65 years or older, 2008-09 to 2020-21.

The role of the gut microbiota in regulating responses to vaccination: current knowledge and future directions.

Antigen-specific B and T cell responses play a critical role in vaccine-mediated protection against infectious diseases, but these responses are highly variable between individuals and vaccine immunogenicity is frequently sub-optimal in infants, the elderly and in people living in low- and middle-income countries. Although many factors such as nutrition, age, sex, genetics, environmental exposures, and infections may all contribute to variable vaccine immunogenicity, mounting evidence indicates that the gut microbiota is an important and targetable factor shaping optimal immune responses to vaccination. In this review, we discuss evidence from human, preclinical and experimental studies supporting a role for a healthy gut microbiota in mediating optimal vaccine immunogenicity, including the immunogenicity of COVID-19 vaccines.

Modulation of energetic and lipid pathways by curcumin as a potential chemopreventive strategy in human prostate cancer cells.

In Western industrialized countries, prostate cancer (PCa) is the second most common malignant disease and prevalent cause of death for men. Epidemiological studies have shown that curcumin (CUR) either prevents PCa initiation or delays its progression to a more aggressive and treatment-refractory form, thus reducing related mortality. Our previous studies have proven the anticancer, antioxidant, and anti-inflammatory properties of CUR on PCa cells.

A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements.

A covalent adduct of DFOB and DOTA separated by a l-lysine residue (DFOB-l-Lys- -DOTA) exhibited remarkable regioselective metal binding, with {H}-C NMR spectral shifts supporting Zr(iv) coordinating to the DFOB unit, and Lu(iii) coordinating to the DOTA unit. This first-in-class, dual-chelator theranostic design could enable the use of imaging-therapy radiometal pairs of different elements, such as Zr for positron emission tomography (PET) imaging and Lu for low-energy β-particle radiation therapy. DFOB-l-Lys- -DOTA was elaborated with an amine-terminated polyethylene glycol extender unit (PEG4) to give DFOB- -(PEG4)-l-Lys- -DOTA (compound D2) to enable installation of a phenyl-isothiocyanate group (Ph-NCS) for subsequent monoclonal antibody (mAb) conjugation (mAb = HuJ591).