Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of ...exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men (
= 5) and age-matched sedentary males (
= 5) at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Following the isolation and enrichment of exosomes from plasma, exosome-enriched preparations were characterized and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed by comparing the baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. While further validation is needed, including measurements of IGF-1/IGF-1 signaling in blood or skeletal muscle, our results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.
Pharmaceuticals, hormones, pesticides, and other bioactive contaminants (BCs) are commonly detected in surface water and bed sediment in urban and suburban areas, but these contaminants are ...understudied in remote locations. In Rocky Mountain National Park (RMNP), Colorado, USA, BCs may threaten the reproductive success and survival of native aquatic species, benthic communities, and pelagic food webs. In 2012–2013, 67 water, 57 sediment, 63 fish, 10 frog, and 12 quality-control samples (8 water and 4 sediment) were collected from 20 sites in RMNP. Samples were analyzed for 369 parameters including 149 pharmaceuticals, 22 hormones, 137 pesticides, and 61 other chemicals or conditions to provide a representative assessment of BC occurrence within RMNP. Results indicate that BCs were detected in water and/or sediment from both remote and more accessible locations in RMNP. The most commonly detected BCs in water were caffeine, camphor, para-cresol, and DEET; and the most commonly detected BCs in sediment were indole, 3-methyl-1H-indole, para-cresol, and 2,6-dimethyl-naphthalene. Some detected contaminants, including carbaryl, caffeine, and oxycodone, are clearly attributable to direct local human input, whereas others may be transported into the park atmospherically (e.g., atrazine) or have local natural sources (e.g., para-cresol). One or more pharmaceuticals were detected in at least 1 sample from 15 of 20 sites. Most of the 29 detected pharmaceuticals are excreted primarily in human urine, not feces. Elevated net estrogenicity was observed in 18% of water samples, and elevated vitellogenin in blood was observed in 12% of male trout, both evidence of potential endocrine disruption. Hormone concentrations in sediment tended to be greater than concentrations in water. Most BCs were observed at concentrations below those not expected to pose adverse effects to aquatic life. Results indicate that even in remote locations aquatic wildlife can be exposed to pharmaceuticals, hormones, pesticides, and other bioactive contaminants.
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•Bioactive contaminants (BCs) in Rocky Mountain NP may threaten native aquatic species.•BCs were detected in water and sediment from both remote and accessible locations.•Detected BCs have natural, local human, atmospheric or multiple sources.•28 pharmaceuticals were detected in water, most excreted primarily in human urine.•12% of male fish had elevated Vtg, 18% of water samples had elevated estrogenicity.
Numerous common pharmaceuticals, including anti-cancer, antiviral and antidiabetic drugs, are derived from traditional plant-derived medicines. With approximately 25,000 species of flora occurring in ...Australia that are adapted to the harsh environment, there is a plethora of novel compounds awaiting research in the context of their medicinal properties. Anecdotal accounts of plant-based medicines used by the Australian Aboriginal and Torres Strait Islander peoples clearly illustrates high therapeutic activity.
This review aims to demonstrate the medicinal potentials of selected native Australian plants based on scientific data. Furthermore, it is anticipated that work presented here will contribute towards enhancing our knowledge of native plants from Australia, particularly in the prevention and potential treatment of disease types such as cancer, microbial and viral infections, and diabetes. This is not meant to be a comprehensive study, rather it is meant as an overview to stimulate future research in this field.
The EBSCOhost platform which included PubMed, SciFinder, Web of Knowledge, Scopus, and ScienceDirect databases were searched for papers using the keywords: medicinal plants, antioxidative, antimicrobial, antibacterial, anticancer, anti-tumor, antiviral or antidiabetic, as well as Australian, native, traditional and plants. The selection criteria for including studies were restricted to articles on plants used in traditional remedies which showed antioxidative potential and therapeutic properties such as anticancer, antimicrobial, antiviral and antidiabetic activity.
Some plants identified in this review which showed high Total Phenolic Content (TPC) and antioxidative capacity, and hence prominent bioactivity, included Tasmannia lanceolata (Poir.) A.C. Sm., Terminalia ferdinandiana Exell, Eucalyptus species, Syzygium species, Backhousia citriodora F.Muell., Petalostigma species, Acacia species, Melaleuca alternifolia (Maiden & Betche) Cheel, Eremophila species, Prostanthera rotundifolia R.Br., Scaevola spinescens R. Br. and Pittosporum angustifolium Lodd. The majority of studies found polar compounds such as caffeic acid, coumaric acid, chlorogenic acid, quercetin, anthocyanins, hesperidin, kaempferol, catechin, ellagic acid and saponins to be the active components responsible for the therapeutic effects. Additionally, mid to non-polar volatile organic compounds such as meroterpenes (serrulatanes and nerol cinnamates), monoterpenes (1,8-cineole and myodesert-1-ene), sesquiterpenes, diterpenes and triterpenes, that are known only in Australian plants, have also shown therapeutic properties related to traditional medicine.
Australian plants express a diverse range of previously undescribed metabolites that have not been given full in vitro assessment for human health potential. This review has included a limited number of plant species of ethnomedicinal significance; hundreds of plants remain in need of exploration and detailed study. Future more elaborate studies are therefore required to screen out and purify lead bioactive compounds against numerous other disease types. This will not only improve our knowledge on the phytochemistry of Australian native flora, but also provide a platform to understand their health-promoting and bioactive effects for pharmaceutical interventions, nutraceuticals, cosmetics, and as functional foods. Finally, plant-derived natural compounds (phytochemicals), as well as plant-based traditional remedies, are significant sources for latent and novel drugs against diseases. Extensive investigation of native medicinal plants may well hold the key to novel drug discoveries.
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Treatment advances over the past five decades have resulted in significant improvements in survival from childhood cancer. Although survival rates are relatively high, social disparities in outcomes ...have been sometimes observed. In a population-based study, we investigated social inequalities by sex and deprivation in treatment receipt in childhood cancer in Ireland. Cancers incident in people aged 0 to 19 during 1994 to 2012 and treatments received were abstracted from the National Cancer Registry Ireland. Multivariable modified Poisson regression with robust error variance (adjusting for age, and year) was used to assess associations between sex and deprivation category of area of residence at diagnosis and receipt of cancer-directed surgery, chemotherapy or radiotherapy. Three thousand seven hundred and four childhood cancers were included. Girls were significantly less likely than boys to receive radiotherapy for leukemia overall (relative risk RR = 0.70; 95% confidence interval CI = 0.50-0.98), and acute lymphoblastic leukemia specifically (RR = 0.54; 95% CI = 0.36-0.79), and surgery for central nervous system (CNS) overall (RR = 0.83; 95% CI = 0.74-0.93) and other CNS (RR = 0.76; 95% CI = 0.60-0.96). Girls were slightly less likely to receive chemotherapy for non-Hodgkin lymphoma and surgery for Hodgkin lymphoma (HL), but these results were not statistically significant. Children residing in more deprived areas were significantly less likely to receive chemotherapy for acute myeloid leukemia or surgery for lymphoma overall and HL, but more likely to receive chemotherapy for medulloblastoma. These results may suggest social inequalities in treatment receipt for childhood cancers. Further research is warranted to explore whether similar patterns are evident in other childhood cancer populations and to better understand the reasons for the findings.
Tobacco use accounts for 30% of all cancer-related deaths worldwide and 20% in the US, despite effective, evidence-based interventions for reducing tobacco use and tobacco-related cancers and deaths. ...In 2012, to reduce the burden of tobacco-related cancer and associated population-level risks across Texas, The University of Texas MD Anderson Cancer Center initiated the EndTobacco® program to promote statewide cancer control activities. We created evidence-based initiatives, established selection criteria, and implemented actions involving policy, education, and tobacco treatment services. As a result, EndTobacco has supported, educated, and convened local and state coalitions in policymaking; provided tobacco treatment education to health professionals; implemented Texas’ only certified tobacco treatment training program; and led an initiative to enhance the tobacco-free culture of the state’s publicly funded university system. Supported by commitments from MD Anderson, we developed and implemented evidence-based actions for tobacco control tailored to the center’s mission, values, expertise, resources, and partnerships. By 2021, the adult smoking rate in Texas dropped from 19.2% (2014) to 13.2%. Contributors to this drop include state tobacco control policies, programs and services from multiple agencies and associations, and EndTobacco activities that complement the statewide effort to prevent youth smoking initiation and increase quit attempts among youth and adults.
As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age ...and stage at diagnosis.
Data from 386 870 patients diagnosed during 2010-2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, RESULTS: (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage).
Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.
Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been ...made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of
pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.
Introduction
Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of ...the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics.
Methods
Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays.
Results
There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (
P
< 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (
r
2
) of the BAL-to-serum comparisons was mostly low except for TNF-α (
r
2
= 0.73) when assuming a simple (linear) relationship.
Conclusion
This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.
Abstract Objectives Productivity costs constitute a substantial proportion of the total societal costs associated with cancer. We compared the results of applying two different analytical methods—the ...traditional human capital approach (HCA) and the emerging friction cost approach (FCA)—to estimate breast and prostate cancer productivity costs in Ireland in 2008. Methods Data from a survey of breast and prostate cancer patients were combined with population-level survival estimates and a national wage data set to calculate costs of temporary disability (cancer-related work absence), permanent disability (workforce departure, reduced working hours), and premature mortality. Results For breast cancer, productivity costs per person using the HCA were €193,425 and those per person using the FCA were €8,103; for prostate cancer, the comparable estimates were €109,154 and €8,205, respectively. The HCA generated higher costs for younger patients (breast cancer) because of greater lifetime earning potential. In contrast, the FCA resulted in higher productivity costs for older male patients (prostate cancer) commensurate with higher earning capacity over a shorter time period. Reduced working hours postcancer was a key driver of total HCA productivity costs. HCA costs were sensitive to assumptions about discount and growth rates. FCA costs were sensitive to assumptions about the friction period. Conclusions The magnitude of the estimates obtained in this study illustrates the importance of including productivity costs when considering the economic impact of illness. Vastly different results emerge from the application of the HCA and the FCA, and this finding emphasizes the importance of choosing the study perspective carefully and being explicit about assumptions that underpin the methods.
Inferences of hearing capabilities and audition-related behaviours in extinct reptiles and birds have previously been based on comparing cochlear duct dimensions with those of living species. ...However, the relationship between inner-ear bony anatomy and hearing ability or vocalization has never been tested rigorously in extant or fossil taxa. Here, micro-computed tomographic analysis is used to investigate whether simple endosseous cochlear duct (ECD) measurements can be fitted to models of hearing sensitivity, vocalization, sociality and environmental preference in 59 extant reptile and bird species, selected based on their vocalization ability. Length, rostrocaudal/mediolateral width and volume measurements were taken from ECD virtual endocasts and scaled to basicranial length. Multiple regression of these data with measures of hearing sensitivity, vocal complexity, sociality and environmental preference recovered positive correlations between ECD length and hearing range/mean frequency, vocal complexity, the behavioural traits of pair bonding and living in large aggregations, and a negative correlation between ECD length/rostrocaudal width and aquatic environments. No other dimensions correlated with these variables. Our results suggest that ECD length can be used to predict mean hearing frequency and range in fossil taxa, and that this measure may also predict vocal complexity and large group sociality given comprehensive datasets.
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