Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

The nature of the exposure-response relationship has a profound influence on risk analyses. Several arguments have been proffered as to why all exposure-response relationships for both cancer and noncarcinogenic end-points should be assumed to be linear at low doses. We focused on three arguments that have been put forth for noncarcinogens. First, the general “additivity-to-background” argument proposes that if an agent enhances an already existing disease-causing process, then even small exposures increase disease incidence in a linear manner. This only holds if it is related to a specific mode of action that has nonuniversal properties—properties that would not be expected for most noncancer effects. Second, the “heterogeneity in the population” argument states that variations in sensitivity among members ofthe target population tend to “flatten out and linearize” the exposure-response curve, but this actually only tends to broaden, not linearize, the dose-response relationship. Third, it has been argued that a review of epidemiological evidence shows linear or no-threshold effects at low exposures in humans, despite nonlinear exposure-response in the experimental dose range in animal testing for similar endpoints. It is more likely that this is attributable to exposure measurement error rather than a true non-threshold association. Assuming that every chemical is toxic at high exposures and linear at low exposures does not comport to modern-day scientific knowledge of biology. There is no compelling evidence-based justification for a general low-exposure linearity; rather, case-specific mechanistic arguments are needed

A Pilot Study Examining Vitamin C Levels in Periodontal Patients

BACKGROUND: Periodontal disease is the leading cause of tooth loss worldwide. Current periodontal treatment is limited by its dependency on patients learning and maintaining good dental habits, and repeated visits to oral health physicians. Vitamin C's role in collagen synthesis and immune function makes it important in wound healing and possibly periodontal healing. Therefore, if some patients are deficient, this may worsen patient outcomes. METHODS: Patients were invited to participate following assessment and treatment at the Westmead Centre of Oral Health Periodontic Clinic, regardless of current disease stage or treatment. Adults were eligible if they gave informed consent and had current periodontal disease. Study involvement consisted of periodontal assessment and care followed by an interview and measurement of serum vitamin C and C-reactive protein (CRP). RESULTS: A total of 6 out of 20 patients had vitamin C levels less than the institutional normal range, of whom 2 had levels <11.4 μmol/L and one <28 μmol/L. Low vitamin C was associated with higher periodontal disease stage (p = 0.03). Elevated CRP was found in 2/3 of people with low vitamin C and CRP was negatively correlated with vitamin C (p < 0.01). Vitamin C did not correlate with patient-reported fruit or vegetable consumption, but high processed meat intake was associated with lower vitamin C. CONCLUSION: Although a small study, this rate of vitamin C deficiency in the periodontal clinic is clinically important and correlations with disease severity and CRP suggests biological importance. This warrants further studies to assess vitamin C and whether supplementation improves periodontal outcomes, particularly in deficient subjects

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients.

PURPOSE: While fever may be a presenting symptom of COVID-19, fever at hospital admission has not been identified as a predictor of mortality. However, hyperthermia during critical illness among ventilated COVID-19 patients in the ICU has not yet been studied. We sought to determine mortality predictors among ventilated COVID-19 ICU patients and we hypothesized that fever in the ICU is predictive of mortality. MATERIALS AND METHODS: We conducted a retrospective cohort study of 103 ventilated COVID-19 patients admitted to the ICU between March 14 and May 27, 2020. Final follow-up was June 5, 2020. Patients discharged from the ICU or who died were included. Patients still admitted to the ICU at final follow-up were excluded. RESULTS: 103 patients were included, 40 survived and 63(61.1%) died. Deceased patients were older {66 years[IQR18] vs 62.5[IQR10], ( CONCLUSIONS: This is one of the first studies to identify ICU hyperthermia as predictive of mortality in ventilated COVID-19 patients. Additional predictors included male sex, age, and acidosis. With COVID-19 cases increasing, identification of ICU mortality predictors is crucial to improve risk stratification, resource management, and patient outcomes

Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose- response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.JRC.H.5-Rural, water and ecosystem resource

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines