Biology subjects

Balshaw, R.

Publications and source records attributed to Balshaw, R..

3 recordsLinked to original sources

bioRxiv2026

Prenatal diet buffers infant epigenetic changes linked to pollution and transient wheeze

Prenatal air pollution exposure is associated with childhood asthma, particularly among biological males. The mechanisms remain unclear, but may involve lasting epigenetic changes, such DNA methylation (DNAm), that occur during gestation in response to oxidative stress and inflammation. Higher maternal intake of "protective" micronutrients, like antioxidants, could buffer pollution-induced oxidative stress and inflammation to mitigate potentially adverse DNAm differences contributing to asthma. Using data from 515 CANDLE participants, we examined associations between prenatal NO2, PM2.5, and PM10 and cord blood DNAm, evaluated DNAm mediation of pollution associations with childhood wheeze phenotypes (transient, persistent, and late-onset), and assessed buffering of DNAm by maternal polyunsaturated fatty acid, vitamin C, or folate intake, and overall diet quality measured by the Alternative Healthy Eating Index-Pregnancy (AHEI-P). We identified 19, seven, and five regional DNAm differences associated NO2, PM2.5, and PM10. Mediation analyses suggested a role for HLA-DPA1/DPB1 DNAm in NO2 and PM2.5 associations with transient wheeze. To assess buffering, we fit pollutant-by-diet interaction models, defining buffering as an interaction opposite in sign to the main pollutant effect. One or more micronutrients or AHEI-P attenuated pollutant effects at 16 of 19 NO2-associated DMRs, including HLA-DPA1/DPB1, and all PM2.5- and PM10-associated DMRs. However, attenuation of HLA-DPA1/DPB1 DNAm did not significantly reduce the indirect effect of NO2 on transient wheeze. In sex-stratified analyses, biological males exhibited lower PM2.5-associated DNAm in SERPINB9, a gene linked to lung function. These findings suggest prenatal air pollution alters DNAm, which may contribute to transient wheeze, with some differences partially buffered by maternal diet. Significance StatementPrenatal air pollution exposure contributes to child wheeze and asthma, potentially through the oxidative stress response and subsequent changes to infant DNA methylomes. Here, we used data from the CANDLE cohort to identify cord blood DNAm differences associated with NO2, PM2.5, or PM10. We examined if any alterations mediated the relationship between prenatal air pollution exposures and transient, persistent, or late-onset wheeze at age 4 to 6 years. Some of these DNAm differences appeared to be at least partially buffered by maternal micronutrients and/or overall diet quality.

genomics↗

bioRxiv2021

Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

neuroscience↗

bioRxiv2016

Development of a multivariate clinical prediction model for the diagnosis of mild stroke/TIA in physician first-contact patient settings

OBJECTIVETo develop a clinical prediction model for diagnosing mild stroke/transient ischemic attack (TIA) in first-contact patient settings. DESIGN: Retrospective study design utilizing logistic regression modeling of patient clinical symptoms collected from patient chart histories and referral data. SETTING: Regional fast-track TIA clinic on Vancouver Island, Canada, accepting referrals from emergency departments (ED) and general practice (GP). PARTICIPANTS: Model development: 4187 ED and GP referred patients from 2008-2011 who were assessed at the TIA clinic. Temporal hold-out validation: 1953 ED and GP referred patients from 2012-2013 assessed at the same clinic. OUTCOMES: Diagnosis of mild stroke/TIA by clinic neurologists. RESULTS: 123 candidate predictors were assessed using univariate feature selection for inclusion in the model, and culminated in the selection of 50 clinical features. Post-hoc investigation of the selected predictors revealed 12 clinically relevant interaction terms. Model performance on the temporal hold-out validation set achieved a sensitivity/specificity of 71.8% / 72.8% using the ROC01 cutpoint ([≥] 0.662), and an AUC of 79.9% (95% CI, 77.9%-81.9%). In comparison, the ABCD2 score ([≥] 4) achieved a sensitivity/specificity of 70.4% / 54.5% and an AUC of 67.5% (95% CI, 65.2%-69.9%). The logistic regression model demonstrated good calibration on the hold-out set ({beta}0 = -0.257); {beta}linear = 1.047).\n\nCONCLUSIONSThe developed diagnostic model performs better than the ABCD2 score at diagnosing mild stroke/TIA on the basis of clinical symptoms. The model has the potential to replace the use of the prognostic ABCD2 score in diagnostic medical contexts in which the ABCD2 score is currently used, such as patient triage.

bioinformatics↗