ASL mRNA-LNP Therapeutic for the Treatment of Argininosuccinic Aciduria Enables Survival Benefit in a Mouse Model.

Argininosuccinic aciduria (ASA) is a metabolic disorder caused by a deficiency in argininosuccinate lyase (ASL), which cleaves argininosuccinic acid to arginine and fumarate in the urea cycle. ASL deficiency (ASLD) leads to hepatocyte dysfunction, hyperammonemia, encephalopathy, and respiratory alkalosis. Here we describe a novel therapeutic approach for treating ASA, based on nucleoside-modified messenger RNA (modRNA) formulated in lipid nanoparticles (LNP).

Evaluation and acceptability of patient-reported outcome measures in women following pelvic organ prolapse procedures.

Background: The Australasian Pelvic Floor Procedure Registry (APFPR) captures clinical and surgical data in women undergoing pelvic floor procedures. The inclusion of patient reported outcome measures (PROMs) in the APFPR is a critical activity providing the additional patient perspective of their condition prior to surgery as well as monitoring beyond the usual post-surgical follow-up time. This study aimed to evaluate the acceptability of seven PROMs for women with pelvic organ prolapse (POP) and to determine the most suitable instrument for the APFPR.

Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications.

Lipid nanoparticles (LNPs) have proven a successful platform for the delivery of nucleic acid (NA)-based therapeutics and vaccines, with the ionizable lipid component playing a key role in modulating potency and tolerability. Here, a library of 16 novel ionizable lipids is screened hypothesizing that short, branched trialkyl hydrophobic domains can improve LNP fusogenicity or endosomal escape, and potency. LNPs formulated with the top-performing trialkyl lipid (Lipid 10) encapsulating transthyretin siRNA elicit significantly greater gene silencing and are better tolerated than those with the benchmark Onpattro lipid DLin-MC3-DMA.

An International Continence Society (ICS)/ International Urogynecological Association (IUGA) joint report on the terminology for the assessment and management of obstetric pelvic floor disorders.

Aims: The terminology of obstetric pelvic floor disorders should be defined and reported as part of a wider clinically oriented consensus.

Methods: This Report combines the input of members of two International Organizations, the International Continence Society (ICS) and the International Urogynecological Association (IUGA). The process was supported by external referees.

The identification of highly efficacious functionalised tetrahydrocyclopenta[]pyrroles as inhibitors of HBV viral replication through modulation of HBV capsid assembly.

Disruption of the HBV viral life cycle with small molecules that prevent the encapsidation of pregenomic RNA and viral polymerase through binding to HBV core protein is a clinically validated approach to inhibiting HBV viral replication. Herein we report the further optimisation of clinical candidate AB-506 through core modification with a focus on increasing oral exposure and oral half-life. Maintenance of high levels of anti-HBV cellular potency in conjunction with improvements in pharmacokinetic properties led to multi-log reductions in serum HBV DNA following low, once-daily oral dosing for key analogues in a preclinical animal model of HBV replication.

Evaluation of the acceptability of patient-reported outcome measures in women following pelvic floor procedures.

Purpose: Patient-reported outcome measures (PROMs) are valuable tools in evaluating the outcomes of surgical treatment health-related quality of life (HRQoL) of women with stress urinary incontinence (SUI) and may be incorporated into related clinical quality registries. The aim of this study was to assess the feasibility and acceptability of incorporating PROMs into the Australian Pelvic Floor Procedure Registry (APFPR).

Methods: Semi-structured qualitative interviews were conducted with women with SUI (N = 12) and their managing clinicians (N = 11) in Victoria, Australia.

Effects of rotational thromboelastometry-guided transfusion management in patients undergoing surgical intervention for postpartum hemorrhage: An observational study.

Background: Postpartum hemorrhage (PPH) can be associated with coagulopathy, which may be difficult to rapidly assess and may exacerbate blood loss. Rotational thromboelastometry (ROTEM) at the point of care can guide clinician choice of blood products and has been shown in some settings to reduce transfusions and improve outcomes. This hospital-based observational study aims to measure effects of a ROTEM-guided transfusion protocol on transfusion practice and clinical outcomes in patients with PPH managed in the operating theater.

Evidence of egg-laying grounds for critically endangered flapper skate (Dipturus intermedius) off Orkney, UK.

Essential fish habitats (EFHs) are critical for fish life-history events, including spawning, breeding, feeding or growth. This study provides evidence of EFHs for the critically endangered flapper skate (Dipturus intermedius) in the waters around the Orkney Isles, Scotland, based on citizen-science observation data. The habitats of potential egg-laying sites were parametrised as >20 m depth, with boulders or exposed bedrock, in moderate current flow (0.

A Longitudinal Person-Centered Examination of Affinity for Aloneness Among Children and Adolescents.

Affinity for aloneness among youth often is viewed negatively. However, some youth may enjoy solitude for positive reasons, rather than because of social anxiety. The prevalence and adjustment over time of youth with high affinity for aloneness is unclear.

Increasing competence in wound care: A cross-sectional study to evaluate use of a virtual patient by undergraduate student nurses.

Concerns have arisen internationally over the competency of student nurses to perform wound care. A global shortage of nursing faculty and clinical practice opportunities is regarded as a contributing factor. Virtual simulation offers a possible solution.

Using reusable learning objects (RLOs) in wound care education: Undergraduate student nurse's evaluation of their learning gain.

Background: Both nationally and internationally concerns have been expressed over the adequacy of preparation of undergraduate nurses for the clinical skill of wound care. This project describes the educational evaluation of a series of Reusable Learning Objects (RLOs) as a blended learning approach to facilitate undergraduate nursing students learning of wound care for competence development. Constructivism Learning Theory and Cognitive Theory of Multimedia Learning informed the design of the RLOs, promoting active learner approaches.

Physical illness in those with mental illness: psychiatric services need to change focus.

Those with mental illness die prematurely. One reason may be that psychiatrists are overly concerned with risk, focusing too much on this aspect of practice and neglecting the physical health needs of our patients. We need to reconsider how we approach our patients and their needs.

CEP164-null cells generated by genome editing show a ciliation defect with intact DNA repair capacity.

Primary cilia are microtubule structures that extend from the distal end of the mature, mother centriole. CEP164 is a component of the distal appendages carried by the mother centriole that is required for primary cilium formation. Recent data have implicated CEP164 as a ciliopathy gene and suggest that CEP164 plays some roles in the DNA damage response (DDR).

Orthopaedic triage at a physiotherapist-led 'Musculoskeletal Assessment Clinic': a seven-month service evaluation of outcomes.

Background: A number of clinical specialist physiotherapist (CSP)-led musculoskeletal triage clinics have been established in the Republic of Ireland as a means of managing patients referred for an outpatient orthopaedic consultation.

Aims: The purpose of this study was to evaluate the outcomes of a recently established 'Musculoskeletal Assessment Clinic' (MAC) in St Vincent's University Hospital (SVUH) Dublin. We identified the (a) number of patients independently managed by the CSPs and (b) conversion rate to orthopaedic intervention as a useful measure of this.

Loss of centrioles causes chromosomal instability in vertebrate somatic cells.

Most animal cells contain a centrosome, which comprises a pair of centrioles surrounded by an ordered pericentriolar matrix (PCM). Although the role of this organelle in organizing the mitotic spindle poles is well established, its precise contribution to cell division and cell survival remains a subject of debate. By genetically ablating key components of centriole biogenesis in chicken DT40 B cells, we generated multiple cell lines that lack centrioles.

Meeting report - building a centrosome.

Located in the 16th century Wiston House in West Sussex, UK, the 'Building a Centrosome' Workshop was organised by The Company of Biologists and chaired by Fanni Gergely and David Glover (University of Cambridge). Held in March 2013, the Workshop gathered together many of the leaders in the field of centrosome biology, as well as postdocs and students who were given the opportunity to meet and interact with many of the scientists who inspired their early careers. The diverse range of speakers provided a multi-disciplinary forum for the exchange of ideas, and gave fresh impetus to tackling outstanding questions related to centrosome biology.

Calcium-binding capacity of centrin2 is required for linear POC5 assembly but not for nucleotide excision repair.

Centrosomes, the principal microtubule-organising centres in animal cells, contain centrins, small, conserved calcium-binding proteins unique to eukaryotes. Centrin2 binds to xeroderma pigmentosum group C protein (XPC), stabilising it, and its presence slightly increases nucleotide excision repair (NER) activity in vitro. In previous work, we deleted all three centrin isoforms present in chicken DT40 cells and observed delayed repair of UV-induced DNA lesions, but no centrosome abnormalities.

Can levator avulsion be repaired surgically? A prospective surgical pilot study.

Introduction And Hypothesis: Avulsion of the puborectalis muscle from its bony insertion is common in women presenting with prolapse. We present a simple vaginal technique for levator reconstruction.

Methods: This is a prospective surgical pilot study comprising 17 patients enrolled to undergo levator repair in the context of prolapse surgery.