Search

Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy. Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Seagrasses and lucinid bivalves inhabit highly reduced sediments with elevated sulphide concentrations. Lucinids house symbiotic bacteria (Ca. Thiodiazotropha) capable of oxidising sediment sulphide, and their presence in sediments has been proposed to promote seagrass growth by decreasing otherwise phytotoxic sulphide levels. However, vast and productive seagrass meadows are present in ecosystems where lucinids do not occur. Hence, we hypothesised that seagrasses themselves host these sulphur-oxidising Ca. Thiodiazotropha that could aid their survival when lucinids are absent. We analysed newly generated and publicly available 16S rRNA gene sequences from seagrass roots and sediments across 14 seagrass species and 10 countries and found that persistent and colonising seagrasses across the world harbour sulphur-oxidising Ca. Thiodiazotropha, regardless of the presence of lucinids. We used fluorescence in situ hybridisation to visually confirm the presence of Ca. Thiodiazotropha on roots of Halophila ovalis, a colonising seagrass species with wide geographical, water depth range, and sedimentary sulphide concentrations. We provide the first evidence that Ca. Thiodiazotropha are commonly present on seagrass roots, providing another mechanism for seagrasses to alleviate sulphide stress globally.

The development of early warning indicators that identify ecosystem stress is a priority for improving ecosystem management. As microbial communities respond rapidly to environmental disturbance, monitoring their composition could prove one such early indicator of environmental stress. We combined 16S rRNA gene sequencing of the seagrass root microbiome of Halophila ovalis with seagrass health metrics (biomass, productivity and Fsulphide) to develop microbial indicators for seagrass condition across the Swan-Canning Estuary and the Leschenault Estuary (south-west Western Australia); the former had experienced an unseasonal rainfall event leading to declines in seagrass health. Microbial indicators detected sites of potential stress that other seagrass health metrics failed to detect. Genera that were more abundant in 'healthy' seagrasses included putative methylotrophic bacteria (e.g. Methylotenera and Methylophaga), iron cycling bacteria (e.g. Deferrisoma and Geothermobacter) and N2 fixing bacteria (e.g. Rhizobium). Conversely, genera that were more abundant in 'stressed' seagrasses were dominated by putative sulphur-cycling bacteria, both sulphide-oxidising (e.g. Candidatus Thiodiazotropha and Candidatus Electrothrix) and sulphate-reducing (e.g. SEEP-SRB1, Desulfomonile and Desulfonema). The sensitivity of the microbial indicators developed here highlights their potential to be further developed for use in adaptive seagrass management, and emphasises their capacity to be effective early warning indicators of stress., (© FEMS 2019.)

Seagrasses thrive in anoxic sediments where sulphide can accumulate to phytotoxic levels. So how do seagrasses persist in this environment? Here, we propose that radial oxygen loss (ROL) from actively growing root tips protects seagrasses from sulphide intrusion not only by abiotically oxidising sulphides in the rhizosphere of young roots, but also by influencing the abundance and spatial distribution of sulphate-reducing and sulphide-oxidising bacteria. We used a novel multifaceted approach combining imaging techniques (confocal fluorescence in situ hybridisation, oxygen planar optodes, and sulphide diffusive gradients in thin films) with microbial community profiling to build a complete picture of the microenvironment of growing roots of the seagrasses Halophila ovalis and Zostera muelleri. ROL was restricted to young root tips, indicating that seagrasses will have limited ability to influence sulphide oxidation in bulk sediments. On the microscale, however, ROL corresponded with decreased abundance of potential sulphate-reducing bacteria and decreased sulphide concentrations in the rhizosphere surrounding young roots. Furthermore, roots leaking oxygen had a higher abundance of sulphide-oxidising cable bacteria; which is the first direct observation of these bacteria on seagrass roots. Thus, ROL may enhance both abiotic and bacterial sulphide oxidation and restrict bacterial sulphide production around vulnerable roots, thereby helping seagrasses to colonise sulphide-rich anoxic sediments.

This study linked all claims data for reimbursable medical services and drugs of a cohort of 16,227 Medicaid-eligible recipients diagnosed with schizophrenia residing in the State of Georgia, with the treatment history file and Hospital Medical Information System file of each of the ten Georgia State psychiatric hospitals (Georgia Department of Human Resources [DHR]), which do not routinely bill Medicaid for services rendered. This provided a comprehensive picture of the medical resources consumed for each schizophrenia patient, allowing determination of expenditure use patterns, as well as forecast of future medical costs. Patient-level data were aggregated by category of service and reported as costs per member per month (PMPM). Autoregressive integrated moving average time series models described the temporal pattern of expenditures for 8 years of total cost data and were used to forecast expenditures 5 years into the future. From 1990 to 1997, total cumulative expenditures were over 1.09 billion dollars, expressed in 1995 constant dollars. DHR institutional care dominated the cost of care, but expenditures significantly decreased over time. Apparently offsetting this decrease was an increase in prescription drug cost between 1990 and 1995, from 5.7 percent of total expenditures to 10.5 percent. Total Medicaid and Medicare expenditures in 1995 dollars were relatively constant at approximately 700 dollars PMPM. Prescription expenditures increased from 50 dollars in 1990 to 100 dollars PMPM in 1997 and were projected to increase to 150 dollars in 2002. Expenditures were lower for persons continuously eligible for Medicaid than for the total cohort. Trends include a significant increase in prescription expenditures over time concurrent with decreases in inpatient expenditures and relatively stable changes in community mental health center expenditures.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.

The study analyzed all claims data for reimbursable medical services and drugs rendered to 18- to 50-year-old Medicaid recipients in the State of Georgia over a 3-year period. A cohort of 6,443 schizophrenia patients were identified by inspecting the medical history data for claims indicative of schizophrenia (ICD-9-CM 295.xx). A crude prevalence of 6.02 percent was identified. Use patterns and charges associated with schizophrenia were stratified by major areas of service including ambulatory services, hospitalizations, and pharmacological treatment. The incidence of rehospitalization for chronic schizophrenia patients based on a 12-month hospitalization index format was also identified. Findings are discussed regarding using these data to focus strategies for assessing schizophrenia treatment outcome in relation to treatment cost.

A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.

The association between selenium status and risk of acute myocardial infarction was examined in a multicenter case-control study in 10 centers from Europe and Israel in 1991-1992. Selenium in toenails was assessed for 683 nonfatal male cases with first acute myocardial infarction and 729 controls less than 70 years of age. Median toenail selenium content was 0.553 microgram/g for cases and 0.590 microgram/g for controls. After adjustment for age, center, and smoking, the odds ratio for myocardial infarction in the highest quintile of selenium as compared with the lowest was 0.63 (95 percent confidence interval 0.37-1.07, p for trend = 0.08). The observed inverse trend was somewhat stronger when the authors adjusted for vitamin E status (p = 0.05). Analysis stratified for smoking habits showed an inverse association in former smokers (odds ratio for the 75th-25th percentile contrast = 0.63 (95 percent confidence interval 0.43-0.94)), but not in current smokers (odds ratio = 0.97 (0.71-1.32)) or in those who had never smoked (odds ratio = 1.55 (0.87-2.76)). Analysis stratified by center showed a significant inverse association between selenium levels and risk of myocardial infarction for Germany (Berlin) only (75th to 25th percentile odds ratio = 0.62 (95 percent confidence interval 0.42-0.91)), which was the center with the lowest selenium levels. It appears that the increased risk of acute myocardial infarction at low levels of selenium intake is largely explained by cigarette smoking; selenium status does not appear to be an important determinant of risk of myocardial infarction at the levels observed in a large part of Europe.