Alcohol consumption trajectories over the life course and all-cause and disease-specific mortality: the Melbourne Collaborative Cohort Study.

Background: Published studies rarely assess associations between trajectories of drinking and mortality.

Methods: We aimed to assess associations between long-term sex-specific drinking trajectories and all-cause and disease-specific mortality for 39 588 participants (23 527 women; 16 061 men) enrolled in the Melbourne Collaborative Cohort Study in 1990-94 aged 40-69 years. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular disease- and cancer-specific mortality in relation to group-based alcohol intake trajectories.

Epidemiologic Studies of Biomarkers and Their Role in Carcinogenesis: The Need for a Formal Causal Inference Approach.

In this issue of Cancer Epidemiology, Biomarkers & Prevention, Brantley and colleagues investigated the relationships between estrogen metabolites and postmenopausal breast cancer, using data from a nested case-control study within the Nurses' Health Study. One study aim was to investigate the extent to which estrogen metabolism patterns provided further insights into mechanisms in breast cancer development beyond the role of estradiol. In this editorial, we describe the challenges in interpreting results from observational studies of biomarkers and their role in carcinogenesis due to: (i) a general lack of clarity in the research question, (ii) the limits of current knowledge about the complex underlying causal structure involving interrelated biomarkers, and (iii) the limitations in existing data sources (e.

Estimating cancer incidence attributable to physical inactivity in the United States.

Background: Previous estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose-response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites.

Waist circumference, a body shape index, and molecular subtypes of colorectal cancer: A pooled analysis of four cohort studies.

Background Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer (CRC); however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods Data from 2,772 CRC cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analysed individually and in combination (Jass-types).

Rescue of in vitro models of CSF1R-related adult-onset leukodystrophy by iluzanebart: mechanisms and therapeutic implications of TREM2 agonism.

Microglia dysfunction is implicated in several neurodegenerative disorders, including a rare microgliopathy; CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP). CSF1R-ALSP is caused by heterozygous loss-of-function mutations in the colony stimulating factor 1 receptor (CSF1R) gene, which encodes a receptor required for the differentiation of myeloid cells, as well as for microglial survival and proliferation. Similar functions have also been ascribed to triggering receptor expressed on myeloid cells 2 (TREM2), which shares an analogous microglia enrichment profile and converging intracellular signaling pathway mediated by spleen associated tyrosine kinase (SYK) and phosphoinositide-3-kinase (PI3K).

Identifying metabolomic mediators of the physical activity and colorectal cancer relationship.

Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear.

Methods: Targeted metabolomics data from 6,055 participants in the EPIC cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels.

Insulin and insulin-like growth factor and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Background: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Further, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer.

Methods: This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study.

Aberrant neural event segmentation during a continuous social narrative in trauma-exposed older adolescents and young adults.

Post-traumatic stress and major depressive disorders are associated with "overgeneral" autobiographical memory, or impaired recall of specific life events. Interpersonal trauma exposure, a risk factor for both conditions, may influence how symptomatic trauma-exposed (TE) individuals segment everyday events. The ability to parse experience into units (event segmentation) supports memory.

A 4-year outbreak of MRSA ST72-MRSA-IV type t1597 in a surgical high dependency unit in Ireland linked to repeated healthcare worker recolonisation.

Background: Patients undergoing cardiac surgery are identified as high risk for infection, including MRSA. An outbreak of MRSA was identified when two patients experienced MRSA infection concurrently in a cardiothoracic high dependency unit with uncommon detection of MRSA previously and an established screening programme.

Methods: An outbreak control team was convened and interventions applied including refresher training in hand and environmental hygiene, review of practice with regard to aseptic access of medical devices and consideration of antibiotic use in the unit.

Case series report: Equine coronavirus in Australia.

Background: Equine Coronavirus (ECoV) can cause gastrointestinal disease and was first described in 2000 in the USA followed by several international outbreak case reports. Disease manifestation is characterised by vague clinical signs, including mild pyrexia, lethargy and anorexia. Morbidity ranges greatly from 10% to 83%.

Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.

Background: Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.

Methods: Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls).

Lack of genotoxicity and subchronic toxicity in safety assessment studies of formulation.

A powder formulation of viable bacteria (AMUC) was evaluated in a 90-day repeated-dose toxicity study in rats and a battery of genotoxicity studies to evaluate AMUC as a food ingredient. All studies followed Organisation for Economic Co-operation and Development protocols (OECD TG 408, 471 473, 474). AMUC was administered to rats gavage at 0, 500, 1000, and 2000 mg/kg body weight/day (equivalent to 0, 4.

A 2-year Review of the Diagnostic Performance of Serum and Bronchoalveolar Lavage Galactomannan Testing in Lung Transplant Recipients in a National Heart and Lung Transplant Centre.

Background: The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly.

Methods: A single-center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA.

Physical activity and DNA methylation-based markers of ageing in 6208 middle-aged and older Australians: cross-sectional and longitudinal analyses.

Epigenetic age quantifies biological age using DNA methylation information and is a potential pathway by which physical activity benefits general health. We aimed to assess the cross-sectional and longitudinal associations between physical activity and epigenetic age in middle-aged and older Australians. Blood DNA methylation data for 6208 participants (40% female) in the Melbourne Collaborative Cohort Study (MCCS) were available at baseline (1990-1994, mean age, 59 years) and, of those, for 1009 at follow-up (2003-2007, mean age, 69 years).

Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial.

Background: Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT.

Methods: Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (activity; n=30) or usual care (UC; n=32).

Impact of Family Structure on Adolescent Depression Outcomes in a Collaborative Care Program.

Introduction/objectives: We aimed to investigate the effect of family structure on depression program outcomes for adolescents enrolled in a depression-focused, primary care-based collaborative care program.

Methods: This was a retrospective study of primary care patients ages 12 to 18 years seen at a Midwestern academic center with data obtained by medical record review. We used logistic regression models to assess the effect of family structure on program graduation and achievement of a single Patient Health Questionnaire 9-Modified for Adolescents (PHQ-9M) score <5 at any time while enrolled.

Are the Relationships of Physical Activity and Television Viewing Time With Mortality Robust to Confounding? A Study, Utilizing E-Values, From the Melbourne Collaborative Cohort Study.

Background: Physical activity and sedentary behavior are associated with health outcomes. However, evidence may be affected by confounding bias. This study aimed to examine the relationships of physical activity and television (TV) viewing time with all-cause, cardiovascular, and cancer mortality in a cohort of Australian adults, and determine the robustness of these relationships to residual and unmeasured confounding.

The Need for Near-Earth Multi-Spacecraft Heliospheric Measurements and an Explorer Mission to Investigate Interplanetary Structures and Transients in the Near-Earth Heliosphere.

Based on decades of single-spacecraft measurements near 1 au as well as data from heliospheric and planetary missions, multi-spacecraft simultaneous measurements in the inner heliosphere on separations of 0.05-0.2 au are required to close existing gaps in our knowledge of solar wind structures, transients, and energetic particles, especially coronal mass ejections (CMEs), stream interaction regions (SIRs), high speed solar wind streams (HSS), and energetic storm particle (ESP) events.

Epidermal renewal during the treatment of atopic dermatitis lesions: A study coupling line-field confocal optical coherence tomography with artificial intelligence quantifications: LC-OCT reveals new biological markers of AD.

Objective: This study explores the application of Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging coupled with artificial intelligence (AI)-based algorithms to investigate atopic dermatitis (AD), a common inflammatory dermatosis.

Materials And Methods: AD acute and chronic lesions (ADL) were compared to clinically healthy-looking skin (ADNL). LC-OCT was used noninvasively and in real-time to image the skin of AD patients during flare-ups and monitor remissions under topical steroid treatment for 2 weeks.

Bifidobacterium longum subsp. infantis YLGB-1496-Toxicological evaluation.

Bifidobacterium infantis YLGB-1496, originally isolated from breast milk from a Taiwanese mother, is under study for use as a probiotic. As part of safety assessment, an Ames, in vivo mouse micronucleus, and in vivo mouse spermatocyte chromosome aberration assay were conducted along with a 13-week oral rat toxicity study. B.