Range of the perfluorooctanoate (PFOA) safe dose for human health: An international collaboration.

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different. This sort of discrepancy invites scrutiny and explanation. Otherwise what is the lay public to make of this disparity? The Steering Committee of the Alliance for Risk Assessment (2022) called for scientists interested in attempting to understand and narrow these disparities. An advisory committee of nine scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three technical teams (for a total of 24 scientists from 8 countries). The teams reviewed relevant information and independently developed ranges for estimated PFOA safe doses. All three teams determined that the available epidemiologic information could not form a reliable basis for a PFOA safe dose-assessment in the absence of mechanistic data that are relevant for humans at serum concentrations seen in the general population. Based instead on dose-response data from five studies of PFOA-exposed laboratory animals, we estimated that PFOA dose-rates 10-70 ng/kg-day are protective of human health.

Identifying trends over time in food affordability: The Illawarra Healthy Food Basket survey, 2011-2019.

OBJECTIVE: To determine the affordability of a healthy food basket (HFB) for welfare recipients and average income earners in 2019 and to compare trends from 2011. METHODS: Fifty-seven food items' prices were collected from fifteen stores across five suburbs representing low, medium and high socio-economic status. Costs were compared with average weekly income and welfare payments to assess the baskets' affordability for a family of four and five. RESULTS: In 2019, a HFB was affordable (below 30% of household income) for a five-person reference family with a pensioner, representing 24.8% of weekly welfare payments, but not for a four-person reference family (33.0%). The cost of the HFB increased slightly over time from AU$288.91 in 2011 to AU$291.79 in 2019. The food affordability improved for a family of five including a pensioner over this period due to an increase of average weekly earnings and welfare payments. CONCLUSION: In 2019, the HFB was affordable for a five-person family; however, a four-person family receiving welfare benefits would have experienced significant "food stress," with the food basket costing above 30% of household income. IMPLICATIONS FOR HEALTH PROMOTION: Inequity in the affordability of healthy food is a major public health concern and one that demands recognition and national action. The impact of policies affecting welfare support and wages needs to be considered, as well as food pricing strategies and possible food subsidies for those at greatest risk of food insecurity.

Adopting Urinary Tract Infection Guidelines to Promote Antibiotic Stewardship in the Time of Telehealth Medicine.

Background: The most modifiable risk factor contributing to antibiotic resistance is the inappropriate prescription of antibiotics. Urinary tract infections (UTIs) are a common outpatient infection in the United States, with increasing antimicrobial resistance to uropathogens. As empiric UTI treatment is often appropriate, telemedicine offers an opportunity to enhance practice by adopting current clinical practice guidelines. Objective: The project aims to improve appropriate first-line antibiotic choice and decrease urinalysis and urine culture orders in the telehealth management of uncomplicated UTIs. Methods: Chart reviews of women aged 18-65 years diagnosed with an uncomplicated UTI and/or symptoms during a telehealth primary care visit were conducted for a period of 30 days prior to and following a provider educational intervention. Results: Improvement (37.5%-62.1%, p = .133), though not significant, of appropriate first-line antibiotics prescribing postintervention was achieved. There was a minimal (3%) improvement in the appropriate urine labs ordered. Conclusion: Following the intervention, there was not a statistically significant practice change, albeit somewhat of an improvement in the ordering of first-line antibiotics. Adopting evidence-based practice in telehealth could provide an opportunity to improve antibiotic stewardship. Providers are potentially better engaged through the presence of champions, in-person education sessions, and the availability of streamlined algorithms.

Non-antibiotic treatment sore throat.

Sore throats are common presentations in emergency and primary care settings and, although only between 5 and 10 per cent of adults with this condition are found to have bacterial infections, the use of antibiotics is still widespread. This article refers to a case study to describe the causes and complications of acute sore throats, and reviews the literature on the use of antibiotics. It also recommends the McIsaac scoring system as a reliable method of diagnosis and treatment decision making.

Circadian profiling in two mouse models of lysosomal storage disorders; Niemann Pick type-C and Sandhoff disease.

Sleep and circadian rhythm disruption is frequently associated with neurodegenerative disease, yet it is unclear how the specific pathology in these disorders leads to abnormal rest/activity profiles. To investigate whether the pathological features of lysosomal storage disorders (LSDs) influence the core molecular clock or the circadian behavioural abnormalities reported in some patients, we examined mouse models of Niemann-Pick Type-C (Npc1 mutant, Npc1(nih)) and Sandhoff (Hexb knockout, Hexb(-/-)) disease using wheel-running activity measurement, neuropathology and clock gene expression analysis. Both mutants exhibited regular, entrained rest/activity patterns under light:dark (LD) conditions despite the onset of their respective neurodegenerative phenotypes. A slightly shortened free-running period and changes in Per1 gene expression were observed in Hexb(-/-) mice under constant dark conditions (DD); however, no overt neuropathology was detected in the suprachiasmatic nucleus (SCN). Conversely, despite extensive cholesterol accumulation in the SCN of Npc1(nih) mutants, no circadian disruption was observed under constant conditions. Our results indicate the accumulation of specific metabolites in LSDs may differentially contribute to circadian deregulation at the molecular and behavioural level.

The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress and influence of mutation-type.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. Substantial evidence implicates oxidative stress and mitochondrial dysfunction as early events in disease progression. Our aim was to ascertain whether mutation of the SOD1 protein increases metabolic functional susceptibility to oxidative stress. Here we used a motor neuron-like cell line (NSC34) stably transfected with various human mutant SOD1 transgenes (G93A, G37R, H48Q) to investigate the impact of oxidative stress on cell viability and metabolic function within intact cells. NSC34 cells expressing mutant SOD1 showed a dose dependent reduction in cell viability when exposed to oxidative stress induced by hydrogen peroxide, with variation between mutations. The G93A transfectants showed greater cell death and LDH release compared to cells transfected with the other SOD1 mutations, and H48Q showed an accelerated decline at later time points. Differences in mitochondrial bioenergetics, including mitochondrial respiration, coupling efficiency and proton leak, were identified between the mutations, consistent with the differences observed in viability. NSC34 cells expressing G93A SOD1 displayed reduced coupled respiration and mitochondrial membrane potential compared to controls. Furthermore, the G93A mutation had significantly increased metabolic susceptibility to oxidative stress, with hydrogen peroxide increasing ROS production, reducing both cellular oxygen consumption and glycolytic flux in the cell. This study highlights bioenergetic defects within a cellular model of ALS and suggests that oxidative stress is not only detrimental to oxygen consumption but also glycolytic flux, which could lead to an energy deficit in the cell.