Abstract
One of the biggest challenges of the COVID-19 pandemic is the heterogeneity in disease severity exhibited amongst patients. Among multiple factors, latest studies suggest vitamin D ...deficiency and pre-existing health conditions to be major contributors to death from COVID-19. It is known that certain urban form attributes can impact sun exposure and vitamin D synthesis. Also, long-term exposure to air pollution can play an independent role in vitamin D deficiency. We conducted a correlational analysis of urban form and air quality in relation to the demographics and COVID-19 incidence and mortality across 32 London boroughs between March 2020 and January 2021. We found total population, number of residents of Asian ethnicity, 4-year average PM
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levels and road length to be positively correlated with COVID-19 cases and deaths. We also found percentage of households with access to total open space to be negatively correlated with COVID-19 deaths. Our findings link COVID-19 incidence and mortality across London with environmental variables linked to vitamin D status. Our study is entirely based on publicly available data and provides a reference framework for further research as more data are gathered and the syndemic dimension of COVID-19 becomes increasingly relevant in connection to health inequalities within large urban areas.
Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess ...adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status.
We carried out a cross-sectional study with 132 participants, aged 10-18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2'-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay.
As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability.
Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.
Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity leads ...to a physiological imbalance in the regulation of adipose tissue and its normal functioning, resulting in hyperglycaemia, dyslipidaemia and inflammation. These states promote the generation of oxidative stress, which is exacerbated in obesity by a decline in anti-oxidant defence systems. Oxidative stress can have a marked impact on DNA, producing mutagenic lesions that could prove carcinogenic. Here we review the current evidence for genomic instability, sustained DNA damage and accelerated genome ageing in obesity. We explore the notion of genotoxicity, ensuing from systemic oxidative stress, as a key oncogenic factor in obesity. Finally, we advocate for early, pre-malignant assessment of genome integrity and stability to inform surveillance strategies and interventions.
Obesity in children is one of the most serious, global, public health challenges of the 21st century. The accumulation of adipose tissue is associated with a range of metabolic complications ...including diabetes, cardiovascular disease and dyslipidaemia. Epidemiological evidence links obesity in childhood with developing certain types of cancer later in life. It is postulated that excess adipose tissue and consequent inflammation derived oxidative stress may inflict an accumulation of deleterious DNA mutations and promote genome instability and drive carcinogenesis. Furthermore, a deficiency in micronutrients that are essential for DNA repair may exacerbate this pathological state. This research combined the assessment of anthropometric, inflammatory, micro-nutritional and DNA damage biomarkers via non-invasive techniques. In total, 112 children were recruited from schools and NHS obesity clinics. Anthropometric markers assessed were waist to hip ratio, body fat percentage via bioelectrical impedance, and body mass index standard deviation scores (BMI-SDS). These markers were used to classify participants as obese or nonobese and used for correlational analysis. Inflammation and micronutrient status were determined via C-reactive protein and vitamin D Enzyme Immune Assay (EIA) in saliva. DNA damage assessments include a microscopic assessment of nuclear anomalies via the buccal cytome assay, salivary telomere length via quantitative Polymerase Chain Reaction (qPCR) and urinary 8- hydroxyguanosine (8-OHdG) via EIA. The results from this study indicate obesity to be concurrent with increased inflammation and vitamin D deficiency in this cohort of participants. In addition, obesity was associated with increased oxidative DNA damage (8-OHdG) in urine and DNA damage events in the buccal mucosa. Salivary telomere length was positively correlated with obesity and the total frequency of nuclear anomalies found in buccal epithelial cells. Furthermore, there was a negative correlation between vitamin D and the frequency of nuclear anomalies in the oral cavity. Importantly, odds ratio analysis indicates a high BMI Z-score, waist circumference, body fat percentage, salivary CRP and low salivary vitamin D to be independent risk factors for increased nuclear anomalies in the buccal mucosa. This research is the first to accrue evidence for acquired DNA damage in multiple tissues obtained non-invasively from children with obesity. Our findings instigate that biomonitoring of ‘genome health’ for pre-cancerous molecular and morphological markers in obese patients may inform prioritization and severity of clinical intervention measures to prevent malignancy.
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