REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness.

Background: Animal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if the in vivo activity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep.

A pilot study of a ketogenic diet in bipolar disorder: clinical, metabolic and magnetic resonance spectroscopy findings.

Background: Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

Aims: To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Method: Euthymic individuals with bipolar disorder ( = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet.

A connection between motility and inter-animal transmission.

Outbreaks of cholera are caused by the highly transmissive pathogen . Here, a transposon screen revealed that inactivation of the motility-linked gene increases infant mouse intestinal colonization. Compared to wild-type , a Δ mutant, which exhibits heightened motility in the form of constitutive straight swimming, localizes to the crypts earlier in infection and over a larger area of the small intestine.

Quantification of serovar Typhimurium population dynamics in murine infection using a highly diverse barcoded library.

Murine models are often used to study the pathogenicity and dissemination of the enteric pathogen serovar Typhimurium. Here, we quantified . Typhimurium population dynamics in mice using the STAMPR analytic pipeline and a highly diverse .

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls.

Incidence trends of ductal carcinoma in situ in New Zealand women between 1999 and 2022.

Background: In New Zealand, BreastScreen Aotearoa (BSA), a biennial national breast screening programme, was implemented in 1998. This study examines the incidence trends of ductal carcinoma in situ (DCIS) in New Zealand women from 1999 to 2022.

Methods: All women with a primary diagnosis of DCIS over the 24-year study period were identified from the New Zealand Cancer Registry and BSA records.

Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing.

High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-function variants. For validation, we undertook case-control analyses using genomic data from disease-free controls.

Reduced Breast and Ovarian Cancer Through Targeted Genetic Testing: Estimates Using the NEEMO Microsimulation Model.

The effectiveness and cost-effectiveness of genetic testing for hereditary breast and ovarian cancer largely rely on the identification and clinical management of individuals with a pathogenic variant prior to developing cancer. Simulation modelling is commonly utilised to evaluate genetic testing strategies due to its ability to synthesise collections of data and extrapolate over long time periods and large populations. Existing genetic testing simulation models use simplifying assumptions for predictive genetic testing and risk management uptake, which could impact the reliability of their estimates.

Exploring the relationship between proactive inhibition and restrictive eating behaviours in severe and enduring anorexia nervosa (SE-AN).

Background: There is a need for improved understanding of why 20-30% of individuals with anorexia nervosa (AN) develop a severe and enduring form of illness (SE-AN). Previously, we reported differences in proactive inhibition (a pre-emptive slowing of responses) in individuals with AN compared to healthy controls (after controlling for intolerance of uncertainty). The present study is a preliminary exploration of proactive inhibition in which we compared women with SE-AN with healthy comparison (HC) women and explored its association with restrictive/avoidant eating behaviours.

Collecting resilience points for a smooth transition to adult healthcare services: Co-creating a playful resource for Spina Bifida.

Background: The transition of young people with a disability or a chronic health condition, from paediatric to adult-focused health and social care services, in Scotland, is known to be difficult. There is a significant body of evidence to suggest that a transition should start early, be holistic and inclusive, as well as structured to build essential capabilities and promote resilience. The nurse-led project, reported here, created a playful mechanism for meaningful interaction between young people, families and healthcare professionals.

Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial.

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis).

Development of a straightforward direct injection UHPLC-MS/MS method for quantification of plastic additive chemicals in roadside retention ponds.

There is growing interest in road pollution that enters surface waters. Additive chemicals used in the manufacture of plastics, including tyre rubber, are mobile pollutants that pose a threat to aquatic life. Therefore, an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to measure 25 plastic additive chemicals in road runoff and water of retention ponds used to manage road runoff.

Outcomes after hospital discharge in children requiring post-cardiotomy extracorporeal membrane oxygenation: A binational retrospective cohort study.

Objectives: To describe longer-term survival and morbidity outcomes after hospital discharge in a binational cohort of children who required extracorporeal membrane oxygenation after cardiac surgery.

Methods: This was a retrospective cohort study from the Australia and New Zealand Congenital Outcomes Registry for Surgery database. All patients younger than 18 years of age (n = 12,290) undergoing pediatric cardiac surgical procedures between January 1, 2013, and December 31, 2021, who required post-cardiotomy extracorporeal membrane oxygenation in the same admission were included.

Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders.

Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease.

Bone Fracture History in Women With First Episode or With Persistent Anorexia Nervosa.

Objective: To investigate fractures history in women with first episode anorexia nervosa (AN) (FE-AN: ≤ 3 years duration) and those with persistent AN (P-AN: ≥ 7 years), compared to healthy controls (HC).

Method: One hundred nineteen women (FE-AN = 49, P-AN = 46 and HC = 24) completed online questionnaires on eating disorders symptoms, their menstrual and their fracture history.

Results: Average illness duration was 1.

Cognitive Intra-individual Variability in Cognitively Healthy APOE ε4 Carriers, Mild Cognitive Impairment, and Alzheimer's Disease: a Meta-analysis.

Intra-individual variability (IIV) quantifies an individual's scatter in performances across a test battery (dispersion) or across reaction times within a single task (consistency). No studies have meta-analyzed the cross-sectional IIV literature in those with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). An additional aim of this meta-analysis was to examine IIV in APOE ε4 + healthy control (HC) samples.

Regional response to light illuminance across the human hypothalamus.

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.

Sleep restriction and age effects on distinct aspects of cognition in adolescents.

Insufficient sleep negatively impacts scholastic performance in children and adolescents. Here we use a dose-response time in bed (TIB) restriction study to evaluate associations between sleep loss and multiple aspects of cognition. We evaluated changes in cognitive measures across ages 10 to 23 years and determined whether the effects of sleep loss changed across this age range.

Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling.

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown.

Outcomes from low-risk ductal carcinoma in situ: a systematic review and meta-analysis.

Purpose: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches.