The future burden of oesophageal and stomach cancers attributable to modifiable behaviours in Australia: a pooled cohort study.

BACKGROUND: We quantified the individual and joint contribution of contemporaneous causal behavioural exposures on the future burden of oesophageal and stomach cancers and their subtypes and assessed whether these burdens differ between population groups in Australia, as such estimates are currently lacking. METHODS: We combined hazard ratios from seven pooled Australian cohorts (N = 367,058) linked to national cancer and death registries with exposure prevalence from the 2017-2018 National Health Survey to estimate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death. RESULTS: Current and past smoking explain 35.2% (95% CI = 11.7-52.4%), current alcohol consumption exceeding three drinks/day 15.7% (95% CI = 0.9-28.4%), and these exposures jointly 41.4% (95% CI = 19.8-57.3%) of oesophageal squamous cell carcinomas in Australia. Current and past smoking contribute 38.2% (95% CI = 9.4-57.9%), obesity 27.0% (95% CI = 0.6-46.4%), and these exposures jointly 54.4% (95% CI = 25.3-72.1%) of oesophageal adenocarcinomas. Overweight and obesity explain 36.1% (95% CI = 9.1-55.1%), current and past smoking 24.2% (95% CI = 4.2-40.0%), and these exposures jointly 51.2% (95% CI = 26.3-67.8%) of stomach cardia cancers. Several population groups had a significantly higher smoking-attributable oesophageal cancer burden, including men and those consuming excessive alcohol. CONCLUSIONS: Smoking is the leading preventable behavioural cause of oesophageal cancers and overweight/obesity of stomach cancers.

Hospital admissions for alcohol use disorders before, during, and after pregnancy: a study based on linked population data in new South Wales, Australia.

BACKGROUND: Alcohol use disorders (AUD) during pregnancy can have profound lifelong effects on the baby, including fetal alcohol spectrum disorders (FASD). Hospital admission for AUD during pregnancy provides an opportunity for intervention. Characterization of women along the AUD spectrum during pregnancy aids the development of prevention strategies, policy, and clinical management guidelines aimed at this population. This study describes the hospital admission levels for AUD between the sixth month before pregnancy and the first year after birth and explores risk factors associated with the hospital admissions. METHODS: This study was based on linked population data between 2002 and 2005 using the New South Wales (NSW) Midwives Data Collection (MDC) and the NSW Admitted Patients Data Collection (APDC), Australia. The study subjects included primiparous mothers who were admitted to hospital in the period from the sixth month before pregnancy to 1 year after birth with at least 1 of the following diagnoses (ICD-10-AM): mental and behavioral disorders due to the use of alcohol (MBDA) (F10.0-10.9); toxic effects of alcohol (T51.0-51.9); maternal care for suspected damage to fetus from alcohol (O35.4); or alcohol rehabilitation (Z50.2). RESULTS: A total of 175 new mothers had 287 hospital admissions with the principal or stay AUD diagnoses during the study period in NSW. Of the 287 admissions, 181 admissions (63.07%) were reported for an alcohol-related disorder as the principal diagnosis. The hospital admission rate for AUD was 1.76/1,000 person-years (PY) (95% CI: 1.45 to 2.07) during the 6 months prepregnancy. The rate decreased to 0.49/1,000 PY (95% CI: 0.36 to 0.63) during pregnancy and to 0.82/1,000 PY (95% CI: 0.67 to 0.97) in the first year after birth. Women who smoked during pregnancy, lived in a remote area and were younger than 25 years, were more likely to be admitted to hospital with AUD diagnoses. Women in the middle disadvantaged quintile and born in other countries were less likely to be admitted to hospital with AUD diagnoses. CONCLUSIONS: Hospital admission for AUD decreased significantly in pregnancy and the first year postpartum compared to the prepregnancy period.

Mental and behavioral disorders due to substance abuse and perinatal outcomes: a study based on linked population data in New South Wales, Australia.

BACKGROUND: The effects of mental and behavioral disorders (MBD) due to substance use during peri-conception and pregnancy on perinatal outcomes are unclear. The adverse perinatal outcomes of primiparous mothers admitted to hospital with MBD due to substance use before and/or during pregnancy were investigated. METHOD: This study linked birth and hospital records in NSW, Australia. Subjects included primiparous mothers admitted to hospital for MBD due to use of alcohol, opioids or cannabinoids during peri-conception and pregnancy. RESULTS: There were 304 primiparous mothers admitted to hospital for MBD due to alcohol use (MBDA), 306 for MBD due to opioids use (MBDO) and 497 for MBD due to cannabinoids (MBDC) between the 12 months peri-conception and the end of pregnancy. Primiparous mothers admitted to hospital for MBDA during pregnancy or during both peri-conception and pregnancy were significantly more likely to give birth to a baby of low birthweight (AOR = 4.03, 95%CI: 1.97-8.24 for pregnancy; AOR = 9.21, 95%CI: 3.76-22.57 both periods); preterm birth (AOR = 3.26, 95% CI: 1.52-6.97 for pregnancy; AOR = 4.06, 95%CI: 1.50-11.01 both periods) and admission to SCN or NICU (AOR = 2.42, 95%CI: 1.31-4.49 for pregnancy; AOR = 4.03, 95%CI: 1.72-9.44 both periods). Primiparous mothers admitted to hospital for MBDO, MBDC or a combined diagnosis were almost three times as likely to give birth to preterm babies compared to mothers without hospital admissions for psychiatric or substance use disorders. Babies whose mothers were admitted to hospital with MBDO before and/or during pregnancy were six times more likely to be admitted to SCN or NICU (AOR = 6.29, 95%CI: 4.62-8.57). CONCLUSION: Consumption of alcohol, opioids or cannabinoids during peri-conception or pregnancy significantly increased the risk of adverse perinatal outcomes.

Does infant feeding method impact on maternal mental health?

BACKGROUND: Breastfeeding has been reported to reduce the risk of postpartum anxiety and depression. However, little is known of the effects of breastfeeding on hospital admissions for postpartum mental disorders. MATERIALS AND METHODS: This is a population-based longitudinal cohort study using linked data. All mothers who gave birth to a live infant between 2007 and 2008 in New South Wales, Australia were followed up for 1 year for hospital admissions with diagnoses of psychiatric and/or substance use disorders. RESULTS: There were 186,452 women who were reported as giving birth in New South Wales between 2007 and 2008. The "any breastfeeding" rate at the time of discharge was 87.1%. In total, 2,940 mothers were admitted to the hospital with psychiatric diagnoses within 12 months of birth. The first hospital admission for the diagnoses of overall mental illness was 32 days earlier for non-breastfeeding mothers compared with those with full breastfeeding. Mothers who did not breastfeed were more likely to be admitted to the hospital in the first year postpartum for schizophrenia (adjusted relative risk [ARR]=2.0; 95% confidence interval [CI] 1.3, 3.1), bipolar affective disorders (ARR=1.9; 95% CI 1.1, 3.5), and mental illness due to substance use (ARR=1.8; 95% CI 1.3, 2.5) compared with full breastfeeding mothers. CONCLUSIONS: Breastfeeding is associated with a decrease in the risk of subsequent maternal hospital admissions for schizophrenia, bipolar affective disorders, and mental illness due to substance use, in the first postpartum year.

Peroxide-inducible Ets-1 mediates platelet-derived growth factor receptor-alpha gene transcription in vascular smooth muscle cells.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of vascular occlusive disorders such as atherosclerosis and restenosis in part due to its regulation of smooth muscle cell phenotype. The molecular mechanisms regulating the expression of PDGF-Ralpha, which binds all known dimeric forms of PDGF except PDGF-DD, are poorly understood. Here we demonstrate that the winged helix-turn-helix proto-oncogene Ets-1 controls PDGF-Ralpha transcription and mRNA expression in smooth muscle cells. Mutational analysis, electrophoretic mobility shift assay, and chromatin immunoprecipitation revealed the existence of a reverse Ets binding motif (-45TTCC-42) in the proximal region of the PDGF-Ralpha promoter, which bound both recombinant and endogenous Ets-1. Ets-1-inducible PDGF-Ralpha expression depended on the integrity of both the -45TTCC-42 motif and the -61G10(-52) element, which resides upstream of -45TTCC-42 and mediates Sp1 induction. Hydrogen peroxide (H2O2) at nanomolar concentrations stimulated levels of Ets-1 and increased PDGF-Ralpha transcription and mRNA expression without affecting Sp1 expression. H2O2 activation of the PDGF-Ralpha promoter was abolished by disrupting -45TTCC-42 or -61G10(-52). These studies identify a functional Ets motif in the PDGF-Ralpha promoter that plays a pivotal role in agonist-inducible PDGF-Ralpha transcription.

Fibroblast growth factor-2 represses platelet-derived growth factor receptor-alpha (PDGFR-alpha) transcription via ERK1/2-dependent Sp1 phosphorylation and an atypical cis-acting element in the proximal PDGFR-alpha promoter.

Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs) whose biological activity is mediated via its high affinity interaction with specific cell surface receptors. The molecular mechanisms governing the expression of PDGF receptor-alpha (PDGFR-alpha) are poorly understood. Here we demonstrate that PDGFR-alpha protein and transcriptional regulation in SMCs is under the positive regulatory influence of the zinc finger nuclear protein, Sp1. Electrophoretic mobility shift, competition, and supershift analysis revealed the existence of an atypical G-rich Sp1-binding element located in the PDGFR-alpha promoter -61 to -52 bp upstream of the transcriptional start site. Mutation of this sequence ablated endogenous Sp1 binding and activation of the PDGFR-alpha promoter. PDGFR-alpha transcription, mRNA, and protein expression were repressed in SMCs exposed to fibroblast growth factor-2 (FGF-2). This inhibition was rescued by the blockade of extracellular signal-regulated kinase-1/2 (ERK1/2). FGF-2 repression of PDGFR-alpha transcription was abrogated upon mutation of this Sp1-response element. FGF-2 stimulated Sp1 phosphorylation in an ERK1/2- but not p38-dependent manner, the growth factor enhancing Sp1 interaction with the PDGFR-alpha promoter. Mutation of residues Thr(453) and Thr(739) in Sp1 (amino acids phosphorylated by ERK) blocked FGF-2 repression of PDGFR-alpha transcription. These findings, taken together, demonstrate that FGF-2 stimulates ERK1/2-dependent Sp1 phosphorylation, thereby repressing PDGFR-alpha transcription via the -61/-52 element in the PDGFR-alpha promoter. Phosphorylation triggered by FGF-2 switches Sp1 from an activator to a repressor of PDGFR-alpha transcription, a finding previously unreported in any Sp1-dependent gene.