Background
Mounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid ...dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE).
Objective
To assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid‐responsive CE.
Animals
Twenty‐four healthy control dogs and 23 dogs with steroid‐responsive CE.
Methods
In this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi‐institutional study where dogs with steroid‐responsive CE were evaluated over time.
Results
The dysbiosis index was increased in dogs with CE (median, 2.5; range, −6.2 to 6.5) at baseline compared with healthy dogs (median, −4.5; range, −6.5 to −2.6; P = .002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%‐99%) compared with healthy dogs (median, 88%; 4%‐96%; P = .049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%‐99%) after 2‐3 months of treatment (median, 94%; range, 1%‐99%; P = 0.0183).
Conclusions and Clinical Importance
These findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid‐responsive CE.
There have been significant advancements in risk identification and treatment for ovarian cancer over the last decade. However, their impact on health services costs is unclear. This study estimated ...the direct health system costs (government perspective) for women diagnosed with ovarian cancer in Australia during 2006-2013, as a benchmark prior to opportunities for precision-medicine approaches to treatment, and for health care planning.
Using cancer registry data, we identified 176 incident ovarian cancers (including fallopian tube and primary peritoneal cancer) in the Australian 45 and Up Study cohort. Each case was matched with four cancer-free controls on sex, age, geography, and smoking history. Costs were derived from linked health records on hospitalisations, subsidised prescription medicines and medical services to 2016. Excess costs for cancer cases were estimated for different phases of care relative to cancer diagnosis. Overall costs for prevalent ovarian cancers in Australia in 2013 were estimated based on 5-year prevalence statistics.
At diagnosis, 10% of women had localised disease, 15% regional spread and 70% distant metastasis (5% unknown). The mean excess cost per ovarian cancer case was $40,556 in the initial treatment phase (≤12 months post-diagnosis), $9,514 per annum in the continuing care phase and $49,208 in the terminal phase (up to 12 months before death). Hospital admissions accounted for the greatest proportion of costs during all phases (66%, 52% and 68% respectively). Excess costs were higher for patients diagnosed with distant metastatic disease, particularly during the continuing care phase ($13,814 versus $4,884 for localised/regional disease). The estimated overall direct health services cost of ovarian cancer in 2013 was AUD$99million (4,700 women nationally).
The excess health system costs of ovarian cancer are substantial. Continued investment in ovarian cancer research, particularly prevention, early detection and more effective personalised treatments is necessary to reduce the burden of disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Societal, economic and scientific interests in knowing where biodiversity is, how it is faring and what can be done to efficiently mitigate further biodiversity loss and the associated loss of ...ecosystem services are at an all‐time high. So far, however, biodiversity monitoring has primarily focused on structural and compositional features of ecosystems despite growing evidence that ecosystem functions are key to elucidating the mechanisms through which biological diversity generates services to humanity. This monitoring gap can be traced to the current lack of consensus on what exactly ecosystem functions are and how to track them at scales beyond the site level. This contribution aims to advance the development of a global biodiversity monitoring strategy by proposing the adoption of a set of definitions and a typology for ecosystem functions, and reviewing current opportunities and potential limitations for satellite remote sensing technology to support the monitoring of ecosystem functions worldwide. By clearly defining ecosystem processes, functions and services and their interrelationships, we provide a framework to improve communication between ecologists, land and marine managers, remote sensing specialists and policy makers, thereby addressing a major barrier in the field.
This paper aims to advance the development of a global biodiversity monitoring strategy by proposing the adoption of a set of definitions and a typology for ecosystem functions, and reviewing current opportunities and potential limitations for satellite remote sensing technology to support the monitoring of ecosystem functions worldwide.
Vegetation communities are intricate networks of co-occurring species. Logistical challenges in collecting primary data means research often utilises short-term data from restricted geographical ...areas. In this study, we examine spatiotemporal change in richness and turnover of vascular plants and bryophytes over the last 4000 years at 23 sites in western Eurasia using high-resolution palaeoecological data. We find support for the Latitudinal Diversity Gradient and Altitudinal Diversity Gradient in both the overall vegetation community (arboreal and non-arboreal species) and the shrub and herb sub-community (non-arboreal species only), as well as a significant temporal increase in the gradient of both relationships. There was a temporal increase in (alpha) richness; the rate of turnover was high but temporally consistent for the overall vegetation community and high but decreasing over time for the shrub and herb sub-community. The rate of change in turnover was affected by latitude (steeper negative relationship at higher latitudes) and altitude (steeper negative relationship at lower altitudes). The Diversity-Stability Hypothesis was supported: vegetation communities changed from “lower richness, higher turnover” historically to “higher richness, lower turnover” more recently. Causal mechanisms for these complex interlinked biogeographical patterns remain ambiguous, but likely include climate change, non-native introductions, increasing homogenisation of generalist taxa, landscape simplification, and anthropogenic disturbance. Further research into drivers of the spatiotemporal patterns revealed here is a research priority, which is especially important in the context of biodiversity decline and climate change.
Ventilatory inefficiency during exercise is a key pathophysiological feature of chronic obstructive pulmonary disease. Currently, it is unknown how this physiological marker relates to clinically ...relevant outcomes as resting ventilatory impairment progresses across disease stages. Slope and intercept of the linear region of the ventilation-carbon dioxide output relationship and the ratio between these variables, at the lowest point (nadir), were contrasted in 316 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4 (forced expiratory volume in 1 s, ranging from 148% pred to 12% pred) and 69 aged- and gender-matched controls, Compared to controls, slope and intercept were higher in GOLD stages 1 and 2, leading to higher nadirs (p<0.05). Despite even larger intercepts in GOLD stages 3 and 4, slopes diminished as disease evolved (from mean±sd 35±6 in GOLD stage 1 to 24±5 in GOLD stage 3, p<0.05). As a result, there were no significant differences in nadirs among patient groups. Higher intercepts, across all stages (p<0.01), and to a lesser extent lower slopes in GOLD stages 2-4 (p<0.05), were related to greater mechanical constraints, worsening pulmonary gas exchange, higher dyspnoea scores, and poorer exercise capacity. Increases in the ventilation intercept best indicate the progression of exercise ventilatory inefficiency across the whole spectrum of chronic obstructive pulmonary disease severity.
Abstract
Angular limb deformity (ALD) affects many species of livestock and companion animals. The mechanisms of ALD development are not well understood, but previous research suggests the ...involvement of genetic risk factors. A case-control genome-wide association study (GWAS) was conducted with 40 ALD-affected and 302 unaffected Rambouillet rams and 40,945 single nucleotide polymorphisms (SNPs). Forelimbs of 6 ALD-affected rams were examined and diagnosed with osteochondrosis. Genome-wide or chromosome-wide significant SNPs were positioned exonic, intronic or within the 3′UTR of genes
TSPAN18
,
NRG3
and
NOVA2
, respectively. These genes have previously described roles related to angiogenesis and osteoblast, osteoclast and chondrocyte proliferation and differentiation, which suggests the possibility for their involvement in the pathogenesis of osteochondrosis. Functional consequences of SNPs were evaluated through transcription factor binding site analysis, which predicted binding sites for transcription factors of known importance to bone growth, including SOX6, SOX9 and RUNX2. The identification of genetic risk factors for ALD may help to improve animal welfare and production in Rambouillet, a breed known to be at risk for ALD development. This study proposes genes
TSPAN18
,
NRG3
and
NOVA2
as targets for further research towards understanding the etiology of ALD in Rambouillet sheep.
Variation within species is an often‐overlooked aspect of community ecology, despite the fact that the ontogenetic structure of populations influences processes right up to the ecosystem level. ...Accounting for traits at the individual level is an important advance in the implementation of trait‐based approaches in understanding community structure and function. We incorporate individual‐ and species‐level traits into one succinct assemblage structure metric, fractional size, which is calculated as the length of an individual divided by its potential maximum length. We test the implementation of fractional size in demersal fish assemblages along a depth gradient in the deep sea. We use data from an extensive trawl survey at depths of 300–2030 m on the continental slope of the Rockall Trough, Northeast Atlantic, to compare changes in fractional size structure along an environmental gradient to those seen using traditional taxonomic and trait‐based approaches. The relationship between fractional size and depth was particularly strong, with the overall pattern being an increase with depth, implying that individuals move deeper as they grow. Body size increased with depth at the intraspecific and assemblage levels. Fractional size, size structure and species composition all varied among assemblages, and this variation could be explained by the depth that the assemblage occupied. The inclusion of individual‐level traits and population fractional size structure adds to our understanding at the assemblage level. Fractional size, or where an individual is in its growth trajectory, appears to be an especially important driver of assemblage change with depth. This has implications for understanding fisheries impacts in the deep sea and how these impacts may propagate across depths.
SARS-COV-2 has roused the scientific community with a call to action to combat the growing pandemic. At the time of this writing, there are as yet no novel antiviral agents or approved vaccines ...available for deployment as a frontline defense. Understanding the pathobiology of COVID-19 could aid scientists in their discovery of potent antivirals by elucidating unexplored viral pathways. One method for accomplishing this is the leveraging of computational methods to discover new candidate drugs and vaccines
. In the last decade, machine learning-based models, trained on specific biomolecules, have offered inexpensive and rapid implementation methods for the discovery of effective viral therapies. Given a target biomolecule, these models are capable of predicting inhibitor candidates in a structural-based manner. If enough data are presented to a model, it can aid the search for a drug or vaccine candidate by identifying patterns within the data. In this review, we focus on the recent advances of COVID-19 drug and vaccine development using artificial intelligence and the potential of intelligent training for the discovery of COVID-19 therapeutics. To facilitate applications of deep learning for SARS-COV-2, we highlight multiple molecular targets of COVID-19, inhibition of which may increase patient survival. Moreover, we present CoronaDB-AI, a dataset of compounds, peptides, and epitopes discovered either
or
that can be potentially used for training models in order to extract COVID-19 treatment. The information and datasets provided in this review can be used to train deep learning-based models and accelerate the discovery of effective viral therapies.
•Pollen retention on clothing after a period of light or heavy wear is tested.•Retention patterns are complex. Species and fabric characteristics are important.•Standard washing procedures for ...removing pollen from fabric are inconsistent.•These are crucial findings for all forensic investigations using palynology.
Forensic palynology has been important in criminal investigation since the 1950s and often provides evidence that is vital in identifying suspects and securing convictions. However, for such evidence to be used appropriately, it is necessary to understand the factors affecting taphonomic variability (i.e. the variability in the fate of pollen grains before they are found during forensic examination). Here, we test the relative amount of pollen retained on clothing after a period of simulated light or heavy wear based on pollen and fabric characteristics. We also test the efficiency of forensic laboratory protocols for retrieving pollen from fabrics for analysis. There was no statistically significant difference in retention of fresh or dried pollen on any fabric type. There was a substantial difference in pollen retention according to wear intensity, with considerably more pollen being retained after light wear than after heavy wear. Pollen from insect-pollinated species was retained at higher concentrations than pollen from wind-pollinated species. This pattern was consistent regardless of wear intensity but pollination type explained more of the variability in pollen retention after light wear. Fabric type was significantly related to pollen retention, but interacted strongly with plant species such that patterns were both complex and highly species-specific. The efficiency of removing pollen with the standard washing protocol differed substantially according to plant species, fabric type, and the interaction between these factors. The average efficiency was 67.7% but this ranged from 21% to 93%, demonstrating that previous assumptions on the reliability of the technique providing a representative sample for forensic use should be reviewed. This paper highlights the importance of understanding pollen and fabric characteristics when creating a pollen profile in criminal investigations and to ensure that evidence used in testimony is accurate and robust.
We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and ...Treatment of Cancer (EORTC) revised staging proposal.
Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models.
The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival.
This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.
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