Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers.

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson's disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with a neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO modulated pathways to slow symptom onset and limit pathology in PD patients.

Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Healthcare Costs Before and After Diagnosis of Cancer of Unknown Primary Versus Ovarian Cancer in Australia.

BACKGROUND: Little is known about the healthcare resource usage and costs for patients with cancer of unknown primary (CUP). OBJECTIVE: The aim of this study was to describe and quantify healthcare resource use and costs in Australia, 6 months prior to and after a diagnosis of CUP, and compare to those of women with ovarian cancer. METHODS: Individual-level data combining baseline surveys, clinical records and Medicare Benefits Schedule (MBS) claim records were analysed for 149 patients with CUP and 480 patients with ovarian cancer from two prospective cohort studies. MBS data were aggregated for the period 6 months prior to diagnosis date and 6 months after diagnosis. Data included doctor consultations, pathology, diagnostics, therapeutic procedures, imaging, allied health and medicines. Generalised linear models were used to evaluate the cost differences between CUP and ovarian cancer using gamma family and log link functions. Models were adjusted for age, employment, marital status, surgery, chemotherapy and number of comorbidities. RESULTS: The mean healthcare costs in the 6 months prior to diagnosis of CUP were Australian (AU) $3903 versus AU$1327 for ovarian cancer (adjusted cost ratio 2.94, 95% confidence interval [CI] 2.08-4.15). Mean healthcare costs 6 months post-diagnosis were higher for patients with CUP versus ovarian cancer (AU$20,339 vs AU$13,819, adjusted cost ratio 1.47, 95% CI 1.13-1.92). Higher costs for patients with CUP were driven by imaging (AU$1937 vs AU$1387), procedures (AU$5403 vs AU$2702) and prescribed medicines for all conditions (AU$10,111 vs AU$6717). CONCLUSIONS: Pre-diagnosis costs for patients with CUP are nearly triple those for ovarian cancer. Six months after diagnosis, healthcare costs for CUP remained higher than for ovarian cancer due to imaging, procedures and medicines.

A Comprehensive Method of Assessing Body Composition Using Kinanthropometry in Human Performance Training.

Nutrition is an essential component of Human Performance Optimization in Special Operations Forces (SOF) to enhance physical and mental performance, unit readiness, and mission success. Body composition is frequently used to monitor individual nutrition progress; however, using body fat percentage is limited both by the accuracy of the assessment method and its association with SOF relevant performance outcomes. Lower body fat and/or body mass index have generally, but not universally, been correlated with higher levels of physical performance, yet they poorly predict performance in military relevant tasks. As a complement to body fat, many performance dietitians in the SOF Human Performance Programs utilize the International Society for Advanced Kinanthropometry (ISAK) profile to assess body composition, proportionality, ratio of muscle to bone, and somatotype in combat Operators. Kinanthropometry is the study of human size, shape, proportion, composition, maturation, and gross function, and it is a helpful tool for monitoring nutrition and training progress in athletes and active individuals. The ISAK profile has been well established as an international method for talent identification, distinguishing characteristics between athletes across and within elite sports, and identifying predictors of sport performance that can be applied in the military setting. While some SOF dietitians are utilizing the ISAK profile, the challenge lies in translating sport data to military relevant outcomes. We present a series of four case studies demonstrating the utility of this method as a portable comprehensive assessment for cross-sectional and longitudinal body composition tracking in a military setting.

P-FLUX: A phosphorus budget dataset spanning diverse agricultural production systems in the United States and Canada.

Quantifying spatial and temporal fluxes of phosphorus (P) within and among agricultural production systems is critical for sustaining agricultural production while minimizing environmental impacts. To better understand P fluxes in agricultural landscapes, P-FLUX, a detailed and harmonized dataset of P inputs, outputs, and budgets, as well as estimated uncertainties for each P flux and budget, was developed. Data were collected from 24 research sites and 61 production systems through the Long-term Agroecosystem Research (LTAR) network and partner organizations spanning 22 U.S. states and 2 Canadian provinces. The objectives of this paper are to (a) present and provide a description of the P-FLUX dataset, (b) provide summary analyses of the agricultural production systems included in the dataset and the variability in P inputs and outputs across systems, and (c) provide details for accessing the dataset, dataset limitations, and an example of future use. P-FLUX includes information on select site characteristics (area, soil series), crop rotation, P inputs (P application rate, source, timing, placement, P in irrigation water, atmospheric deposition), P outputs (crop removal, hydrologic losses), P budgets (agronomic budget, overall budget), uncertainties associated with each flux and budget, and data sources. Phosphorus fluxes and budgets vary across agricultural production systems and are useful resources to improve P use efficiency and develop management strategies to mitigate environmental impacts of agricultural systems. P-FLUX is available for download through the USDA Ag Data Commons (https://doi.org/10.15482/USDA.ADC/1523365).

COVID-19: using chest CT of major trauma patients to monitor and evaluate the second wave in London and the development of routine monitoring in practice.

AIM: To follow-up previous work evaluating incidental findings of COVID-19 signs on computed tomography (CT) images of major trauma patients to include the second wave prior to any major effects from vaccines. MATERIALS AND METHODS: The study population included all patients admitted following major trauma between 1 January 2020 and 28 February 2021 with CT including the lungs (n=1776). Major trauma patients admitted pre-COVID-19 from alternate months from January 2019 to November 2019 comprised a control group (n=837). The assessing radiologists were blinded to the time period and used double reading in consensus to determine if the patient had signs of COVID-19. Lung appearances were classified as no evidence of COVID-19, minor signs, or major signs. RESULTS: The method successfully tracked the second wave of the COVID-19 pandemic in London. The estimated population affected by the disease based on those with major signs was similar to estimates of the proportion of the population in London with antibodies (around 30% by end February 2021) and the total of major and minor signs produced a much higher figure of 68%, which may include all those with both antibody and just T-cell responses. CONCLUSIONS: Incidental findings on CT from major trauma patients may provide a novel and sensitive way of tracking the virus. It is recommended that all major trauma units include a simple question on signs of COVID-19 to provide an early warning system for further waves.

Impact of air, water and dock microbial communities on boat microbial community composition.

AIMS: This study explores the microbial diversity of sources which may influence boat microbial communities. We investigated the impact of dock, air and water microbial communities on the hull, transom and bilge microbial communities over the span of 11 days. METHODS AND RESULTS: Using source tracking software, we investigated the extent to which each of our potential sources (air, water and dock) influenced the overall microbial community. This study concluded that the dock impacted 14-64% of the hull and transom microbial community. Micro-organisms from the water were shown to impact 5·6% the bilge microbial community but had minimal impact on hull and transom microbial communities. Micro-organisms from the air had minimal impact in all areas of the boat. CONCLUSIONS: Our results demonstrate that micro-organisms from sources other than water can influence the microbial community of a boat, suggesting that terrestrial micro-organisms can impact the boat microbial community. SIGNIFICANCE AND IMPACT OF THE STUDY: Outside of ballast tanks, microbial diversity on boats is largely unexplored. While ballast water is widely recognized as a route for dispersal of allochthonous micro-organisms, comparatively little is known about the microbial diversity on other areas of the boat. If the organisms on a boat originate from sources other than water, there is potential that terrestrial micro-organisms could be dispersed by shipping activity.

Evaluating the impact of dose reductions and delays on progression-free survival in women with ovarian cancer treated with either three-weekly or dose-dense carboplatin and paclitaxel regimens in the national prospective OPAL cohort study.

OBJECTIVES: To determine the impact of chemotherapy dose reductions and dose delays on progression-free survival (PFS) in women with ovarian cancer receiving first line chemotherapy in a real world prospective cohort study. METHODS: Patients with newly diagnosed epithelial ovarian (or peritoneal, fallopian tube) cancer enrolled in a national Australian prospective study, OPAL, who commenced three-weekly carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m2 (CP) or carboplatin (AUC 5 or 6) and dose-dense weekly paclitaxel 80 mg/m2 (DD-CP) were eligible. Primary endpoint was PFS. RESULTS: 634 evaluable patients, 309 commenced CP and 325 DD-CP. Patient's age was similar in the two groups (median 62 years, range 21-79). All planned chemotherapy doses were completed by 66% vs 40% (p < 0.001) in the CP and DD-CP groups respectively. There was at least one treatment delay in 28% vs 58% (p < 0.001) in the CP and DD-CP groups, respectively, and 29% vs 49% (p < 0.001), respectively, required at least a 15% dose reduction for either carboplatin or paclitaxel. Median PFS was 29.2 [22.9, 43.8] and 21.5 [19.4, 23.1] months in the CP and DD-CP groups respectively. Adjusting for age, histology and FIGO stage PFS did not differ between treatment groups. Median PFS was similar in patients irrespective of dose reduction or dose delay. CONCLUSION: Patients receiving DD-CP required more dose reductions and delays due to haematological toxicities and lower completion rates than CP without significant difference in median PFS between CP and DD-CP. Median PFS was similar in patients irrespective of dose reduction or dose delay.

Dietary inflammatory index, risk and survival among women with endometrial cancer.

PURPOSE: Chronic inflammation has been implicated in endometrial carcinogenesis yet the impact of potentially modifiable exposures that might affect inflammation, like diet, has been understudied. This study examined the association between the dietary inflammatory index (DII®), a literature-derived tool to assess the inflammatory potential of diet, and risk of developing, and survival after a diagnosis of endometrial cancer (EC). METHODS: This study included data from 1,287 women with EC and 1,435 population controls who participated in the Australian National Endometrial Cancer Study. Energy-adjusted DII (E-DII) scores were calculated from pre-diagnostic dietary intake obtained using a semi-quantitative food frequency questionnaire. Logistic regression was used to assess the association between E-DII scores and risk of EC and proportional-hazards models were used for survival analyses. RESULTS: Higher E-DII scores, reflecting a more pro-inflammatory diet, were not associated with risk of EC [adjusted odds ratio (OR) 0.98, 95% CI 0.77-1.24, p-trend = 0.7]. However, in stratified analyses, higher E-DII scores were associated with increased risk of EC among very obese (BMI 35 + kg/m2) women (OR 1.60, 95% CI 0.80-3.21, p-trend = 0.049, p-interaction = 0.045). After a median follow-up of 7.2 years there were 160 deaths, of which 110 (69%) were from EC. We found no association between E-DII score and survival. CONCLUSION: Greater inflammatory potential of pre-diagnostic diet was not associated with EC risk or survival. Secondary stratified analysis suggested greater inflammatory potential may be associated with EC risk in very obese women.