Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Crossing the Phantom Divide Line in a DGP-Inspired F(R,ϕ)F(R,\phi)-Gravity

We study possible crossing of the phantom divide line in a DGP-inspired $F(R,\phi)$ braneworld scenario where scalar field and curvature quintessence are treated in a unified framework. With some specific form of $F(R,\phi)$ and by adopting a suitable ansatz, we show that there are appropriate regions of the parameters space which account for late-time acceleration and admit crossing of the phantom divide line.Comment: 23 Pages, 10 figs, Submitted to JCA

Effect of increasing age on percutaneous coronary intervention vs coronary artery bypass grafting in older adults with unprotected left main coronary artery disease: A meta-analysis and meta-regression

Background: Older adults (≥70-year-old) are under-represented in the published data pertaining to unprotected left main coronary artery disease (ULMCAD).Hypothesis: Percutaneous coronary intervention (PCI) might be comparable to coronary artery bypass grafting (CABG) for revascularization of ULMCAD.Methods: We compared PCI versus CABG in older adults with ULMCAD with an aggregate data meta-analyses (4880 patients) of clinical outcomes [all-cause mortality, myocardial infarction (MI), repeat revascularization, stroke and major adverse cardiac and cerebrovascular events(MACCE)] at 30 days, 12-24 months & ≥36 months in patients with mean age ≥70 years and ULMCAD. A meta-regression analysis evaluated the effect of age on mortality after PCI. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using random-effects model.Results: All-cause mortality between PCI and CABG was comparable at 30-days (OR0.77, 95% CI 0.42- 1.41) and 12-24-months (OR 1.22, 95% CI 0.78-1.93). PCI was associated with a markedly lower rate of stroke at 30-day follow-up in octogenarians (OR 0.14, 95% CI 0.02-0.76) but an overall higher rate of repeat revascularization. At ≥36-months, MACCE (OR 1.26,95% CI 0.99-1.60) and all-cause mortality (OR 1.39, 95% CI 1.00-1.93) showed a trend favoring CABG but did not reach statistical significance. On meta-regression, PCI was associated with a higher mortality with advancing age (coefficient=0.1033, p=0.042).Conclusions: PCI was associated with a markedly lower rate of early stroke in octogenarians as compared to CABG. All-cause mortality was comparable between the two arms with a trend favoring CABG at ≥36-months.PCI was however associated with increasing mortality with advancing age as compared to CABG

Spatio-temporal patterns of pre-eclampsia and eclampsia in relation to drinking water salinity at the district level in Bangladesh from 2016 to 2018

This analysis examines whether salinity in drinking water is associated with pre-eclampsia and eclampsia (PE/E), a leading cause of maternal morbidity and mortality. Bangladesh’s national health information system data were extracted at the district level (n = 64) to assess PE/E rates, and these were overlaid with three environmental measures approximating drinking water salinity, remotely sensed low-elevation coastal zone (LECZ), monthly rainfall data, and electrical conductivity of groundwater (i.e., water salinity). Results from a negative binomial fixed effects model suggest PE/E rates are higher with less rainfall (dry season), lower population density, and that district level rates of PE/E increase with higher groundwater salinity and in the high risk LECZ category closest to the coast. Results suggest that drinking water salinity may be associated with PE/E and that using national health surveillance data can improve understanding of this association. This approach can potentially be leveraged in the future to inform targeted interventions to high risk regions and times

Synthesize of pluronic-based nanovesicular formulation loaded with Pistacia atlantica extract for improved antimicrobial efficiency

One of the current concerns to human health is antibiotic resistance, which promotes the use of antibiotics that are more harmful, expensive, and ineffective. In this condition, researchers are turning to innovative options to combat this alarming situation. Combining herbal medicine with nanotechnology has created a new strategy to increase the effectiveness of phytochemical compounds in overcoming antimicrobial resistance. Pistacia atlantica is one of the promising herbs with medicinal benefits, but its poor solubility in biological fluids is challenging. In this regard, we seek to evaluate the antibacterial efficacy of Pistacia atlantica extract-loaded nanovesicle. Cholesterol, Span 40, and Pluronic F127 modified nanoformulation was developed using an environmentally friendly improved heating technique, and it was evaluated for size distribution, zeta potential, morphology, entrapment efficiency (EE%), release behavior, stability, and antimicrobial performance. By using DLS, spherical nanovesicles were identified with a size distribution of 50–150 nm and a zeta potential of −43 mV. The extract's encapsulation efficiency was 72.03%. The developed loaded nanovesicles demonstrated controlled extract release in the tested 96 h and storage stability of at least 12 months at 25 °C. Also, Comparing the two samples, the encapsulated extract had greater antibacterial activity against Candida albicans, Staphylococcus aureus, and Pseudomonas plecoglossicida with MIC of 1320, 570, and 1100 µg/mL, respectively. Besides reducing the misuse of antibiotics by allowing for the controlled release of drugs made from natural sources, we expect the findings described here to help provide alternative plant-based formulations with greater stability and antibacterial activity

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology