TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

AAGGG repeat expansions trigger -independent synaptic dysregulation in human CANVAS neurons.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative disorder caused by intronic biallelic, nonreference CCCTT/AAGGG repeat expansions within . To investigate how these repeats cause disease, we generated patient induced pluripotent stem cell-derived neurons (iNeurons). CCCTT/AAGGG repeat expansions do not alter neuronal splicing, expression, or DNA repair pathway function.

TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, highly prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT PREDICT Study.

Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit.

The effects of lifestyle and behavioural interventions on cancer recurrence, overall survival and quality of life in breast cancer survivors: A systematic review and network meta-analysis.

Lifestyle/behavioural interventions may improve breast cancer outcomes and quality of life (QoL); however, uncertainty remains about the most effective interventions due to limited evidence. This study aimed to assess and compare the effects of lifestyle/behavioural interventions on cancer recurrence, survival and QoL in breast cancer survivors. Electronic databases including Medline, EMBASE, PsycINFO, CINAHL and EBM Reviews were searched for relevant literature.

How midwives facilitate informed decisions in the third stage of labour - an exploration through portraiture.

Problem: Midwifery philosophy promotes informed decision-making. Despite this, midwives report a lack of informed decision-making in standard maternity care systems.

Background: Previous research has shown a woman's ability to make informed decisions within her maternity care significantly impacts her childbearing experience.

Perinatal mental health screening for women of refugee background: Addressing a major gap in pregnancy care.

Background: Perinatal mental health disorders affect up to 20% of all women. Women of refugee background are likely to be at increased risk, yet little research has explored this. This study aimed to assess if women of refugee background are more likely to screen risk positive for depression and anxiety than non-refugee women, using the Edinburgh Postnatal Depression Scale (EPDS); and if screening in pregnancy using the EPDS enables better detection of depression and anxiety symptoms in women of refugee background than routine care.

Midwifery professional placement: Undergraduate students' experiences with novice and expert preceptors.

Background: In recent decades, increased midwifery university places have been offered to address midwifery workforce shortages. As a result, more graduate midwives entered the workforce, in turn leading to more midwifery students precepted by novice midwives when on professional placement. It is not known whether this more junior midwifery workforce impacts student experience.

Pregnancy Curriculum: Advocating for a Healthier Pregnancy in General Surgery Residency.

Introduction: With an increasing number of women entering surgical careers, pregnancy amongst surgical residents is anecdotally rising. There is no single resource to inform expectant surgical residents of potential occupational risks, or to help them optimize workplace safety during and after pregnancy. The aim of this initiative is to provide surgical residents with an overview of residency occupational risks applicable to maternal-fetal health, propose systemic and situational modifications, and to empower pregnant residents to better plan and advocate for a healthy pregnancy.

Intracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA.

The most widely used method for intracellular RNA fluorescence labeling is MS2 labeling, which generally relies on the use of multiple protein labels targeted to multiple RNA (MS2) hairpin structures installed on the RNA of interest (ROI). While effective and conveniently applied in cell biology labs, the protein labels add significant mass to the bound RNA, which potentially impacts steric accessibility and native RNA biology. We have previously demonstrated that internal, genetically encoded, uridine-rich internal loops (URILs) comprised of four contiguous UU pairs (8 nt) in RNA may be targeted with minimal structural perturbation by triplex hybridization with 1 kD bifacial peptide nucleic acids (bPNAs).

Impact of the physical therapy-managed spinal orthoses program on cost of care in the hospital setting: a retrospective interrupted time-series study.

Background: The physical therapy (PT) department at a level 1 trauma center identified vendor delivery delays of off-the-shelf (OTS) spinal orthoses that delayed patient mobilization.

Objective: This study aimed to identify improvements in mobilization times, discharge times and reduction in the cost of care after centralizing the management of orthoses within the therapy department.

Method: The centralized management of OTS spinal orthoses included stocking three adjustable lumbosacral and thoraco-lumbosacral orthosis sizes and ensuring that all personnel received training to appropriately fit the orthoses to patients.

Evaluation of online interprofessional simulation workshops for obstetric and neonatal emergencies.

Objectives: To explore student perceptions of learning and interprofessional aspects of obstetric and neonatal emergencies through online simulation-based workshops.

Methods: This qualitative study was conducted at Monash University, Australia. Data were obtained from six separate online Obstetric Neonatal Emergency Simulation workshops held between May 2020 and August 2021.

Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator.

Background: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known.

Methods: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system.

Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study.

Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). Pre-processed data revealed 2494 ions in total.

Introducing and integrating perinatal mental health screening: Development of an equity-informed evidence-based approach.

Background: Pregnancy is a time of increased risk for developing or re-experiencing mental illness. Perinatal mental health screening for all women is recommended in many national guidelines, but a number of systems-level and individual barriers often hinder policy implementation. These barriers result in missed opportunities for detection and early intervention and are likely to be experienced disproportionately by women from culturally and linguistically diverse backgrounds, including women of refugee backgrounds.

Identifying and dismantling racism in Australian perinatal settings: Reframing the narrative from a risk lens to intentionally prioritise connectedness and strengths in providing care to First Nations families.

Introduction: The perinatal period is a time when provision of responsive care offers a life course opportunity for positive change to improve health outcomes for mothers, infants and families. Australian perinatal systems carry the legacy of settler-colonialism, manifesting in racist events and interactions that First Nations parents encounter daily.

Objective: The dominance of a western risk lens, and conscious and unconscious bias in the child protection workforce, sustains disproportionately high numbers of First Nations infants being removed from their parents' care.

Blended (online and in-person) Women's Health Interprofessional Learning by Simulation (WHIPLS) for medical and midwifery students.

Background: Blended teaching combines traditional in-person components (simulation-based training and clinical-based placement) with online resources. Due to the COVID-19 pandemic, we modified our Women's Health Interprofessional Learning through Simulation (WHIPLS) program - to develop core obstetric and gynaecological skills - into a blended teaching program. There is limited literature reporting the observations of blended teaching on learning.

Midwives' experiences of facilitating informed decision-making - a narrative literature review.

Background: Informed decision-making is a vital component of midwifery philosophy and a core recommendation of the global respectful maternity care charter; however, women and midwives report a lack of informed decision-making in actual practice. Research reveals informed decision-making improves physical and mental health outcomes for women, regardless of childbearing experience, and is a protective factor for midwives' job satisfaction. There is currently little known about midwives' experiences of facilitating informed decision-making, and associated barriers.

Psychosocial impact of proactive rapid genetic counseling following breast cancer diagnosis.

Objective: As germline genetic referral becomes increasingly routine as part of the care of newly diagnosed breast cancer patients, it is important to understand the psychosocial impact of genetic counseling at the time of diagnosis. We examined the psychosocial and quality of life (QOL) impact of providing proactive rapid genetic counseling and testing (RGCT) in the immediate aftermath of a breast cancer diagnosis.

Methods: We randomized 330 patients in a 2:1 ratio to proactive rapid genetic counseling (RGCT; N = 222) versus usual care (UC; N = 108).

The extravascular implantable cardioverter-defibrillator: The pivotal study plan.

Background: Transvenous implantable cardioverter defibrillators (TV ICD) provide life-saving therapy for millions of patients worldwide. However, they are susceptible to several potential short- and long- term complications including cardiac perforation and pneumothorax, lead dislodgement, venous obstruction, and infection. The extravascular ICD system's novel design and substernal implant approach avoids the risks associated with TV ICDs while still providing pacing features and similar generator size to TV ICDs.

Racism, healthcare access and health equity for people seeking asylum.

People seeking asylum are at risk of receiving poorer quality healthcare due, in part, to racist and discriminatory attitudes, behaviours and policies in the health system. Despite fleeing war and conflict; exposure to torture and traumatic events and living with uncertainty; people seeking asylum are at high-risk of experiencing long-term poor physical and mental health outcomes in their host country. This article aims to raise awareness and bring attention to some common issues people seeking asylum face when seeking healthcare in high-income countries where the health system is dominated by a Western biomedical view of health.

The Clinical Utility of DCISionRT on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery.

Background: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT) that evaluates recurrence risk has been developed and validated.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

Background: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment.