Search

Recent research has shown that four-quadrant turbines are required to achieve maximum net energy production in a tidal barrage plant. These turbines can generate electricity in both flow directions and are capable of pumping. An innovative turbine concept is being reviewed in the course of the Eurostars research project Safe*Coast. This project proposes to install a turbine in a reversible cylinder in order to allow for fourquadrant operation. To evaluate the feasibility of the concept, the authors designed a compact low head axial tidal turbine with the aid of CFD simulations. This paper presents the methods used in the design and optimization process of the turbine. It also describes numerically obtained turbine characteristics, and cavitation limits. The most critical requirements of the turbine include high efficiency in turbine and pumping mode and safe cavitation properties. By computing steady state CFD simulations of the turbine stage, an extensive set of geometries was analyzed. The authors optimized the turbine performance by adjusting the meridional section, as well as runner blade and guide vane profiles and angles along with other related parameters. Transient simulations of the whole setup, including the inlet and draft tube geometries, were performed in order to study transient effects. The final design after optimization is a three bladed axial turbine with adjustable guide vanes and a rim generator. The turbine’s symmetrical inlet and outlet geometry and its relative compactness permit its integration in a reversible cylinder. The simulation results are very positive and indicate that all the relevant design criteria are satisfied. As a result, the project will continue into a new phase in which a model of the turbine will be built for physical testing in order to verify the results and to conduct further investigations.

Abstract Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create “Benchmark” to critically evaluate existing tools and find that most function sub-optimally. We thus develop the “Pathway Ensemble Tool” (PET), which outperforms existing methods. Deploying PET, we identify prognostic pathways across 12 cancer types. PET-identified prognostic pathways offer additional insights, with genes within these pathways serving as reliable biomarkers for clinical outcomes. Additionally, normalizing these pathways using drug repurposing strategies represents therapeutic opportunities. For example, the top predicted repurposed drug for bladder cancer, a CDK2/9 inhibitor, represses cell growth in vitro and in vivo. We anticipate that using Benchmark and PET for unbiased pathway discovery will offer additional insights into disease mechanisms across a spectrum of diseases, enabling biomarker discovery and therapeutic strategies.

Abstract Naturally occurring canine invasive urinary carcinoma (iUC) closely resembles human muscle invasive bladder cancer in terms of histopathology, metastases, response to therapy, and low survival rate. The heterogeneous nature of the disease has led to the association of large numbers of risk loci in humans, however most are of small effect. There exists a need for new and accurate animal models of invasive bladder cancer. In dogs, distinct breeds show markedly different rates of iUC, thus presenting an opportunity to identify additional risk factors and overcome the locus heterogeneity encountered in human mapping studies. In the association study presented here, inclusive of 100 Shetland sheepdogs and 58 dogs of other breeds, we identify a homozygous protein altering point mutation within the NIPAL1 gene which increases risk by eight-fold (OR = 8.42, CI = 3.12–22.71), accounting for nearly 30% of iUC risk in the Shetland sheepdog. Inclusion of six additional loci accounts for most of the disease risk in the breed and explains nearly 75% of the phenotypes in this study. When combined with sequence data from tumors, we show that variation in the MAPK signaling pathway is an overarching cause of iUC susceptibility in dogs.

Introduction: For many decades, a common Accreditation Council for Graduate Medical Education (ACGME) citation for community based orthopaedic residency programs has been a lack of scholarly activity. Many obstacles have been cited in the literature for a low output in scholarship, from lack of mentoring and infrastructure, to perceived value of research. In this paper we sought to 1) describe interventions directed toward increasing scholarly activity through our scholarship initiative program (SIP), and 2) provide an objective comparison of the scholarship activity items (SAI) between our pre- and post-intervention periods. Methods: The study period spanned 8 years, evenly split in two: the pre-intervention and post-intervention periods. The intervention date was July 1, 2018, marking the hiring of a new program director who implemented the SIP. The SIP included interventions such as faculty recruitment, culture shift, mentorship, resource awareness and utilization, quarterly research meetings, research requirements, resident recruitment, financial incentives, and public recognition. Results: When comparing the pre- and post-intervention periods, there were significant increases: resident presentations (12–76, p-value 0.028), resident peer-reviewed publications (3–43, p-value 0.029), faculty presentations (4–84, p-value 0.028), unique peer-reviewed publications (5–35, p-value 0.027). There was a trend towards statistical significance in faculty peer-reviewed publications (5–37, p-value 0.055). There was a trend towards higher Impact Factor of the journals of published manuscripts (1.3–1.8), although not statistically significant. Conclusion: Implementation of an SIP at a small community-based orthopaedic residency program significantly increased SAI between the pre- and post-implementation periods. We recommend this SIP as a guide to other residency programs seeking to increase both faculty and resident SAI.

Antibiotic resistance (AR) is a growing health concern worldwide and the Arctic represents an understudied region in terms of AR. This study aimed to quantify AR genes (ARGs) from effluent released from a wastewater treatment plant (WWTP) in Iqaluit, Nunavut, Canada, thus creating a baseline reference for future evaluations. Water, sediment, and truncate softshell clam (Mya truncata) tissue samples were compared from the wastewater, the receiving environment of Frobisher Bay, and nearby undisturbed freshwaters. The pharmaceuticals and personal care products (PPCPs) atenolol, carbamazepine, metoprolol, naproxen, sulfapyridine, and trimethoprim were found in the wastewater, but the PPCPs were undetectable in the receiving environment. However, the relative abundances of ARGs were significantly higher in wastewater than in the receiving environment or reference sites. Abundances did not significantly differ in Frobisher Bay compared to undisturbed reference sites. ARGs in clams near the WWTP had similar relative abundances as those from pristine areas. The lack of ARG detection is likely due to Frobisher Bay tides flushing inputs to levels below detection. These data suggest that the WWTP infrastructure does not influence the receiving environment based on the measured parameters; more importantly, further research must elucidate the impact and fate of AR and PPCPs in Arctic communities.

The experiments presented here are based on the reconfiguration of an ancient medicine, Lemnian Earth (LE) (terra sigillata, stamped earth, sphragis), an acclaimed therapeutic clay with a 2500-year history of use. Based on our hypothesis that LE was not a natural material but an artificially modified one involving a clay-fungus interaction, we present results from experiments involving the co-culture of a common fungus, Penicillium purpurogenum (Pp), with two separate clay slurries, smectite and kaolin, which are the principal constituents of LE. Our results show: (a) the leachate of the Pp+smectite co-culture is antibacterial in vitro, inhibiting the growth of both Gram-positive and Gram-negative bacteria; (b) in vivo, supplementation of regular mouse diet with leachates of Pp+smectite increases intestinal microbial diversity; (c) Pp+kaolin does not produce similar results; (d) untargeted metabolomics and analysis of bacterial functional pathways indicates that the Pp+smectite-induced microbiome amplifies production of short-chain fatty acids (SCFAs) and amino acid biosynthesis, known to modulate intestinal and systemic inflammation. Our results suggest that the combination of increased microbial diversity and SCFA production indicates beneficial effects on the host microbiome, thus lending support to the argument that the therapeutic properties of LE may have been based on the potential for modulating the gut microbiome. Our experiments involving reconfigured LE open the door to future research into small molecule-based sources for promoting gut health.

Urothelial carcinoma (UC) is the tenth most diagnosed cancer in humans worldwide. Dogs are a robust model for invasive UC as tumor development and progression is similar in humans and dogs. Recent studies in humans have revealed alterations in urine microbiota in individuals with UC; however, microbial alterations in dogs with UC have not been evaluated. The objective of this pilot study was to compare the urine and fecal microbiota of dogs with UC and matched healthy controls. DNA was extracted from urine and fecal samples followed by 16S rRNA sequencing and analyses using QIIME2 and R. Dogs with UC had significantly decreased microbial diversity (Kruskal–Wallis; Shannon, p = 0.048) and altered microbial composition (PERMANOVA: Unweighted UniFrac, p = 0.011) in urine, but not fecal samples. The relative abundance of Fusobacterium was also increased, although not significantly, in urine and fecal samples of dogs with UC. A comparison of canine and human urine microbiota further revealed similarities in dominant microbial taxa across both host species. This study supports the value of dogs as a model for studies on bladder cancer and urine microbiota, and it provides a foundation for future work exploring host-microbe dynamics in UC carcinogenesis, prognosis, and treatment.

In this study, we determined whether pre-adapting Lactiplantibacillus pentosus strains, isolated from Aloreña green table olives, to vegetable-based edible oils improved their robustness and functionality; this may have great importance on their stress response during fermentation, storage, and digestion. Pre-adapting the strains to the corresponding oils significantly increased their probiotic functionality (e.g., auto-aggregation, co-aggregation with pathogens, and mucin adhesion), although results depended on the strain and the oil used for pre-adaptation. As such, we selected olive-adapted (TO) L. pentosus AP2-16, which exhibited improved functionality, and subjected it to transcriptomic profiling with the aim to understand the molecular mechanisms involved in the adaptation and the increased functionality. Global transcriptomic analysis of oil-adapted (olive or almond) and non-adapted (control) L. pentosus AP2-16 realized that 3,259 genes were expressed, with 2,779 mapped to the reference database. Comparative transcriptomic analysis showed that 125 genes (olive vs. control) and 108 genes (olive vs. almond) became significantly differentially expressed. TO L. pentosus AP2-16 responded by rerouting its metabolic pathways to balance energy production and storage, cell growth and survivability, host interactions (glycoconjugates), and other physiological features. As such, the pre-adaptation of lactobacilli with olive oil switches their transcriptional network to regulate robustness and functionality, possibly representing a novel approach toward the design and manufacture of probiotic products with improved stability and functionality.

Integrons are genetic elements that capture and express antimicrobial resistance genes within arrays, facilitating horizontal spread of multiple drug resistance in a range of bacterial species. The aim of this study was to estimate prevalence for class 1, 2, and 3 integrons in Scottish cattle and examine whether spatial, seasonal or herd management factors influenced integron herd status. We used fecal samples collected from 108 Scottish cattle herds in a national, cross-sectional survey between 2014 and 2015, and screened fecal DNA extracts by multiplex PCR for the integrase genes intI1, intI2, and intI3. Herd-level prevalence was estimated [95% confidence interval (CI)] for intI1 as 76.9% (67.8–84.0%) and intI2 as 82.4% (73.9–88.6%). We did not detect intI3 in any of the herd samples tested. A regional effect was observed for intI1, highest in the North East (OR 11.5, 95% CI: 1.0–130.9, P = 0.05) and South East (OR 8.7, 95% CI: 1.1–20.9, P = 0.04), lowest in the Highlands. A generalized linear mixed model was used to test for potential associations between herd status and cattle management, soil type and regional livestock density variables. Within the final multivariable model, factors associated with herd positivity for intI1 included spring season of the year (OR 6.3, 95% CI: 1.1–36.4, P = 0.04) and watering cattle from a natural spring source (OR 4.4, 95% CI: 1.3–14.8, P = 0.017), and cattle being housed at the time of sampling for intI2 (OR 75.0, 95% CI: 10.4–540.5, P < 0.001). This study provides baseline estimates for integron prevalence in Scottish cattle and identifies factors that may be associated with carriage that warrant future investigation.

Background and purpose: Ultrasound (US) is a non-invasive, non-radiographic imaging technique with high spatial and temporal resolution that can be used for localizing soft-tissue structures and tumors in real-time during radiotherapy (RT) (inter- and intra-fraction). A comprehensive approach incorporating an in-house 3D-US system within RT is presented. This system is easier to adopt into existing treatment protocols than current US based systems, with the aim of providing millimeter intra-fraction alignment errors and sensitivity to track intra-fraction bladder movement. Materials and methods: An in-house integrated US manipulator and platform was designed to relate the computed tomographic (CT) scanner, 3D-US and linear accelerator coordinate systems. An agar-based phantom with measured speed of sound and densities consistent with tissues surrounding the bladder was rotated (0–45°) and translated (up to 55 mm) relative to the US and CT coordinate systems to validate this device. After acquiring and integrating CT and US images into the treatment planning system, US-to-US and US-to-CT images were co-registered to re-align the phantom relative to the linear accelerator. Results: Statistical errors from US-to-US registrations for various patient orientations ranged from 0.1 to 1.7 mm for x, y, and z translation components, and 0.0–1.1° for rotational components. Statistical errors from US-to-CT registrations were 0.3–1.2 mm for the x, y and z translational components and 0.1–2.5° for the rotational components. Conclusions: An ultrasound-based platform was designed, constructed and tested on a CT/US tissue-equivalent phantom to track bladder displacement with a statistical uncertainty to correct and track inter- and intra-fractional displacements of the bladder during radiation treatments. Keywords: Ultrasound guided radiation therapy, Bladder cancer, Multimodal registration, Agar-based tissue equivalent phantom, 3D printing

There is a great need to improve the outlook for people facing urinary bladder cancer, especially for patients with invasive urothelial carcinoma (InvUC) which is lethal in 50% of cases. Improved outcomes for patients with InvUC could come from advances on several fronts including emerging immunotherapies, targeted therapies, and new drug combinations; selection of patients most likely to respond to a given treatment based on molecular subtypes, immune signatures, and other characteristics; and prevention, early detection, and early intervention. Progress on all of these fronts will require clinically relevant animal models for translational research. The animal model(s) should possess key features that drive success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). Experimental animal models, while essential in bladder cancer research, do not possess these collective features to accurately predict outcomes in humans. These key features, however, are present in naturally-occurring InvUC in pet dogs. Canine InvUC closely mimics muscle-invasive bladder cancer in humans in cellular and molecular features, molecular subtypes, immune response patterns, biological behavior (sites and frequency of metastasis), and response to therapy. Thus, dogs can offer a highly relevant animal model to complement other models in research for new therapies for bladder cancer. Clinical treatment trials in pet dogs with InvUC are considered a win-win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. In addition, the high breed-associated risk for InvUC in dogs (e.g., 20-fold increased risk in Scottish Terriers) offers an unparalleled opportunity to test new strategies in primary prevention, early detection, and early intervention. This review will provide an overview of canine InvUC, summarize the similarities (and differences) between canine and human InvUC, and provide evidence for the expanding value of this canine model in bladder cancer research.

There is growing evidence that molecular subtypes (e.g. luminal and basal subtypes) affect the prognosis and treatment response in patients with muscle invasive urinary bladder cancer (invasive urothelial carcinoma, iUC). Modeling these subtypes in pre-clinical animal studies is essential, but it is challenging to produce these subtypes, along with other critical host and tumor features, in experimentally-induced animal models. This study was conducted to determine if luminal and basal molecular subtypes are present in naturally-occurring canine iUC, a cancer that mimics the human condition in other key aspects. RNA sequencing was performed on 29 canine treatment naive iUC tissue samples and on four normal canine bladder mucosal samples. Data were aligned to CanFam 3.1, and differentially expressed genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups (n = 13, n = 16). When genes that distinguish basal and luminal subtypes in human cancer (n = 2015) were used to probe genes differentially expressed between normal canine bladder and iUC, 829 enriched signature genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups comprised of 18 luminal subtype tumors and 11 basal subtype tumors. The enriched genes included MMP9, SERPINE2, CAV1, KRT14, and RASA3 in basal tumors, and PPARG, LY6E, CTSE, CDK3, and TBX2 in luminal tumors. In supervised clustering, additional genes of importance in human iUC were identified in canine iUC associated with claudin-low and infiltrated tumors. A smaller panel of genes (n = 60) was identified that distinguished canine luminal and basal iUC with overall 93.1% accuracy. Immune signature patterns similar to those in human iUC were also identified with the greatest enrichment of immune genes being in the basal subtype tumors. These findings provide additional compelling evidence that naturally-occurring canine iUC is a highly relevant and much needed model of human iUC for translational research.

The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 μM and 114 μM for SF767, and 390 μM and 96 μM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 μM and 145 μM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 μM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.

Lactobacillus pentosus MP-10 is a potential probiotic lactic acid bacterium originally isolated from naturally fermented Aloreña green table olives. The entire genome sequence was annotated to in silico analyze the molecular mechanisms involved in the adaptation of L. pentosus MP-10 to the human gastrointestinal tract (GIT), such as carbohydrate metabolism (related with prebiotic utilization) and the proteins involved in bacteria–host interactions. We predicted an arsenal of genes coding for carbohydrate-modifying enzymes to modify oligo- and polysaccharides, such as glycoside hydrolases, glycoside transferases, and isomerases, and other enzymes involved in complex carbohydrate metabolism especially starch, raffinose, and levan. These enzymes represent key indicators of the bacteria’s adaptation to the GIT environment, since they involve the metabolism and assimilation of complex carbohydrates not digested by human enzymes. We also detected key probiotic ligands (surface proteins, excreted or secreted proteins) involved in the adhesion to host cells such as adhesion to mucus, epithelial cells or extracellular matrix, and plasma components; also, moonlighting proteins or multifunctional proteins were found that could be involved in adhesion to epithelial cells and/or extracellular matrix proteins and also affect host immunomodulation. In silico analysis of the genome sequence of L. pentosus MP-10 is an important initial step to screen for genes encoding for proteins that may provide probiotic features, and thus provides one new routes for screening and studying this potentially probiotic bacterium.

Lactobacillus pentosus MP-10, isolated from brines of naturally fermented Aloreña green table olives, exhibited high probiotic potential. The genome sequence of L. pentosus MP-10 is currently considered the largest genome among lactobacilli, highlighting the microorganism's ecological flexibility and adaptability. Here, we analyzed the complete genome sequence for the presence of acquired antibiotic resistance and virulence determinants to understand their defense mechanisms and explore its putative safety in food. The annotated genome sequence revealed evidence of diverse mobile genetic elements, such as prophages, transposases and transposons involved in their adaptation to brine-associated niches. In-silico analysis of L. pentosus MP-10 genome sequence identified a CRISPR (clustered regularly interspaced short palindromic repeats)/cas (CRISPR-associated protein genes) as an immune system against foreign genetic elements, which consisted of six arrays (4-12 repeats) and eleven predicted cas genes [CRISPR1 and CRISPR2 consisted of 3 (Type II-C) and 8 (Type I) genes] with high similarity to L. pentosus KCA1. Bioinformatic analyses revealed L. pentosus MP-10 to be absent of acquired antibiotic resistance genes, and most resistance genes were related to efflux mechanisms; no virulence determinants were found in the genome. This suggests that L. pentosus MP-10 could be considered safe and with high-adaptation potential, which could facilitate its application as a starter culture and probiotic in food preparations.

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

The discovery that structurally unique “filamentous integumentary appendages” are associated with several different non-avian dinosaurs continues to stimulate the development of models to explain the evolutionary origin of feathers. Taking the phylogenetic relationships of the non-avian dinosaurs into consideration, some models propose that the “filamentous integumentary appendages” represent intermediate stages in the sequential evolution of feathers. Here we present observations on a unique integumentary structure, the bristle of the wild turkey beard, and suggest that this non-feather appendage provides another explanation for some of the “filamentous integumentary appendages.” Unlike feathers, beard bristles grow continuously from finger-like outgrows of the integument lacking follicles. We find that these beard bristles, which show simple branching, are hollow, distally, and express the feather-type β keratins. The significance of these observations to explanations for the evolution of archosaurian integumentary appendages is discussed. J. Exp. Zool. (Mol. Dev. Evol.) 297B: 27–34, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Uptake of a tetrafluoroborate anion into the centre of a dicopper bis-salicylaldoxime complex causes a major contraction of the cavity and an increase in helicity. [ABSTRACT FROM AUTHOR]

Élie Cartan's classification of the simple Lie algebras over $\mathbb{R}$ is derived quickly from some structure theory over $\mathbb{R}$ and the classification over $\mathbb{C}$. [ABSTRACT FROM AUTHOR]

Abstract The environment disseminates antimicrobial-resistance genes; however, it remains challenging to distinguish whether human activities exacerbate antimicrobial resistance or what is natural. Here, we quantified ~300 resistance-related genes in 200+ Scottish soil samples. Location or land use does not explain gene differences, but nutrient levels reduce gene richness. Elevated levels of metals increased gene richness, and selenium increased transposase levels. Rainfall and persistent organic pollutants also increased transposase relative abundance, possibly promoting conditions conducive to the horizontal transfer of antimicrobial-resistance genes. Selenium and polychlorinated biphenyls were primary factors in gene abundance, while polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and pH influenced gene diversity. Polychlorinated biphenyls are derived from anthropogenic activities, highlighting human activities’ potential impact on gene prevalence. This is the first national-scale, high spatial resolution dataset of antimicrobial-resistance genes in Scottish soils and provides a novel resource on which to build future studies.

Abstract Potentially toxic elements (PTE) from industrial activities remain a global concern for their environmental hazards. In particular, strontium is found in drinking water and food, primarily from contamination from the nuclear industry, petroleum extractions, fireworks, and electronics. Its carbonate form is bioavailable and closely resembles calcium; thus, it has become a health concern, and phytoremediation has often been considered for Sr2+. We toxicologically determined Sr2+ tolerance in Festuca rubra (red fescue) and Trifolium pratense (red clover), and their ability to bio-accumulate strontium was compared to the sorption capacity of the soils. These plants were chosen for their ubiquity and as primary colonisers in soils. Experimentally uncontaminated farm soils from Lanarkshire, Scotland, were used, along with these two common plants. Further, seed-germination and plant-growth assays demonstrated that strontium chloride exposures impact both species (0–40mM; p

Human Campylobacter infections have been associated with chicken and other poultry meat products. Environmental conditions such as temperature and season can affect Campylobacter recoverability from chicken meat products. In the presented study, we sought to investigate the relationship between ambient weather conditions and the isolation of Campylobacter from chicken flocks, as well as the subtype of these isolates. Campylobacter was isolated from the ceca of broilers collected in a commercial processing facility over 7 years, representing 452 flocks. Isolates were subjected to whole-genome sequencing and subtyping by multilocus sequence typing (MLST). Approximately 60% (269/452) of flocks sampled were positive for Campylobacter. There was no significant effect on the presence of detectable Campylobacter by month, season, temperature, or rainfall during grow-out or transportation. Sixty-eight different STs were detected; 45 C. jejuni and 23 C. coli. Diversity as measured by Shannon’s diversity index was higher in the spring and fall than in mid-winter and summer. We concluded that in the warm temperate climate of the Southeastern U.S., seasonality does not affect the rate of Campylobacter isolation from broilers, but the diversity of isolates was higher in the milder spring and fall seasons.

IntroductionThe domestic dog, Canis familiaris, is quickly gaining traction as an advantageous model for use in the study of cancer, one of the leading causes of death worldwide. Naturally occurring canine cancers share clinical, histological, and molecular characteristics with the corresponding human diseases.MethodsIn this study, we take a deep-learning approach to test how similar the gene expression profile of canine glioma and bladder cancer (BLCA) tumors are to the corresponding human tumors. We likewise develop a tool for identifying misclassified or outlier samples in large canine oncological datasets, analogous to that which was developed for human datasets.ResultsWe test a number of machine learning algorithms and found that a convolutional neural network outperformed logistic regression and random forest approaches. We use a recently developed RNA-seq-based convolutional neural network, TULIP, to test the robustness of a human-data-trained primary tumor classification tool on cross-species primary tumor prediction. Our study ultimately highlights the molecular similarities between canine and human BLCA and glioma tumors, showing that protein-coding one-to-one homologs shared between humans and canines, are sufficient to distinguish between BLCA and gliomas.DiscussionThe results of this study indicate that using protein-coding one-to-one homologs as the features in the input layer of TULIP performs good primary tumor prediction in both humans and canines. Furthermore, our analysis shows that our selected features also contain the majority of features with known clinical relevance in BLCA and gliomas. Our success in using a human-data-trained model for cross-species primary tumor prediction also sheds light on the conservation of oncological pathways in humans and canines, further underscoring the importance of the canine model system in the study of human disease.

Background: Digital technology has emerged as a useful tool for preoperative and postoperative patient engagement and for remote patient monitoring. Smartphones are equipped with motion-sensing technology, and apps can be designed which use these features to create a simple method for measuring range of motion. The purpose of this study was to determine the accuracy of digital technology in assessing knee range of motion using a smartphone app, compared to traditional goniometric measurements in an office setting. Methods: Fifty-three (53) patients in a clinical practice were enrolled between October 2019 and March 2020. Three separate measurements were taken during the patient encounter: (1) the surgeon, (2) the app, and (3) the physical therapist. Intraclass correlations were computed to assess the agreement between (1) the surgeon and app and (2) that between the physical therapist and surgeon. Results: When measuring flexion, the correlation between either the surgeon or therapist with the app was good, whereas the comparison between the surgeon and therapist was moderate. All extension measurement comparisons, between the app, surgeon, and therapist, showed moderate correlation. Limits of agreements showed that 80% of the difference between surgeon and app is within 10 degrees for extension and 11 degrees for flexion. Body mass index did not affect the accuracy of the measurements. Conclusion: Digital app measurements were comparable to measurements made by either a surgeon or physical therapist with a manual goniometer in the clinical setting and may be beneficial for measuring and monitoring patients’ range of motion remotely.

BackgroundEarly detection and intervention research is expected to improve the outcomes for patients with high grade muscle invasive urothelial carcinoma (InvUC). With limited patients in suitable high-risk study cohorts, relevant animal model research is critical. Experimental animal models often fail to adequately represent human cancer. The purpose of this study was to determine the suitability of dogs with high breed-associated risk for naturally-occurring InvUC to serve as relevant models for early detection and intervention research. The feasibility of screening and early intervention, and similarities and differences between canine and human tumors, and early and later canine tumors were determined.MethodsSTs (n=120) ≥ 6 years old with no outward evidence of urinary disease were screened at 6-month intervals for 3 years with physical exam, ultrasonography, and urinalysis with sediment exam. Cystoscopic biopsy was performed in dogs with positive screening tests. The pathological, clinical, and molecular characteristics of the “early” cancer detected by screening were determined. Transcriptomic signatures were compared between the early tumors and published findings in human InvUC, and to more advanced “later” canine tumors from STs who had the typical presentation of hematuria and urinary dysfunction. An early intervention trial of an oral cyclooxygenase inhibitor, deracoxib, was conducted in dogs with cancer detected through screening.ResultsBiopsy-confirmed bladder cancer was detected in 32 (27%) of 120 STs including InvUC (n=29, three starting as dysplasia), grade 1 noninvasive cancer (n=2), and carcinoma in situ (n=1). Transcriptomic signatures including druggable targets such as EGFR and the PI3K-AKT-mTOR pathway, were very similar between canine and human InvUC, especially within luminal and basal molecular subtypes. Marked transcriptomic differences were noted between early and later canine tumors, particularly within luminal subtype tumors. The deracoxib remission rate (42% CR+PR) compared very favorably to that with single-agent cyclooxygenase inhibitors in more advanced canine InvUC (17-25%), supporting the value of early intervention.ConclusionsThe study defined a novel naturally-occurring animal model to complement experimental models for early detection and intervention research in InvUC. Research incorporating the canine model is expected to lead to improved outcomes for humans, as well as pet dogs, facing bladder cancer.

The presence and fate of antimicrobial residues in the environment is a subject of growing concern. Previous researchers have demonstrated the persistence of residues in soil and water. Additionally, antimicrobial resistance is a growing concern, particularly to public health, animal health and economic development. In this study, a low cost, commercial blood glucose meter was explored as the basis for detecting antimicrobial residues in conjunction with a microorganism sensitive to this residue. A microbial bioassay was developed based on the metabolic response of Geobacillus stearothermophilus, a sensitive bacteria used in the determination of antimicrobial residues in food products, by measuring changes in glucose as a result of metabolic activity. After optimizing experimental conditions, this sensing strategy was tested using bacterial cultures in the presence of colistin, a last-resort antibiotic used for human and animal health. Growth of G. stearothermophilus was measurable as a change in glucose concentration after 2–4 h incubation at 60 °C, when LB media was supplemented with 100 mg/dL of glucose. The lowest measured colistin concentration that resulted in inhibition of growth was 1 mg/L colistin and an increase in lag phase resulted at 100 µg/L colistin. To increase the sensitivity of the assay, we then added a sub-inhibitory concentration of chloramphenicol to the media and found that growth inhibition could be achieve at a lower colistin concentration of 8 µg /L. These results provide a promising basis for a future low-cost sensor to identify antimicrobial residues from environmental samples in the field.

Urothelial carcinoma (UC) comprises up to 2% of all naturally occurring neoplasia in dogs and can be challenging to diagnose. MicroRNAs (miRNAs) have been reported to be dysregulated in numerous diseases, including neoplasia. MiRNA expression has been evaluated in human UC, but there is limited information regarding the miRNA transcriptome of UC in dogs. Our study aimed to evaluate differential miRNA expression in bladder tissue collected from normal canine urothelium and canine invasive UC (iUC) to elucidate the dysregulated pathways in canine UC. Next-Generation RNA sequencing (RNA-Seq) was performed for dogs with UC (n = 29) and normal canine urothelium (n = 4). Raw RNA data were subjected to normalization, and pairwise comparison was performed using EdgeR with Benjamini-Hochberg FDR multiple testing correction (p < 0.05; >2-fold change) comparing tissue samples of normal urothelium to canine iUC samples. Principal component analysis and hierarchical cluster analysis were performed. MiRNA of FFPE tissue samples of separate iUC (n = 5) and normal urothelium (n = 5) were used to evaluate five miRNAs using RT-qPCR. Pathway analysis was performed utilizing miRWalk, STRING database, and Metascape utilizing KEGG pathways and GO terms databases. Twenty-eight miRNAs were differentially expressed (DE) by RNA-Seq. RT-qPCR confirmed that four miRNAs are significantly downregulated in UC compared to healthy urothelial samples (miR-105a, miR-143, miR-181a, and miR-214). Principal component analysis and hierarchical cluster analysis showed separation between miRNAs in iUC and the control group. The DE miRNAs are most often associated with gene silencing by miRNA, miRNAs in cancer, and miRNAs involved in DNA damage responses. Proteins involved include HRAS, KRAS, ARAF, RAF1, MAPK1, MAP2K1, MAPK3, FGFR3, EGFR, HBEGF, RASSF1, E2F2, E2F3, ERBB2, SRC, MMP1, and UP3KA. The differential expression of miRNAs in canine iUC compared to normal canine urothelial tissue indicates that these markers should be further evaluated for their potential role as diagnostic and therapeutic targets.

Abstract Background Invasive urothelial carcinoma (iUC) is highly similar between dogs and humans in terms of pathologic presentation, molecular subtypes, response to treatment and age at onset. Thus, the dog is an established and relevant model for testing and development of targeted drugs benefiting both canine and human patients. We sought to identify gene expression patterns associated with two primary types of canine iUC tumors: those that express a common somatic mutation in the BRAF gene, and those that do not. Methods We performed RNAseq on tumor and normal tissues from pet dogs. Analysis of differential expression and clustering, and positional and individual expression was used to develop gene set enrichment profiles distinguishing iUC tumors with and without BRAFV595E mutations, as well as genomic regions harboring excessive numbers of dysregulated genes. Results We identified two expression clusters that are defined by the presence/absence of a BRAFV595E (BRAFV600E in humans) somatic mutation. BRAFV595E tumors shared significantly more dysregulated genes than BRAF wild-type tumors, and vice versa, with 398 genes differentiating the two clusters. Key genes fall into clades of limited function: tissue development, cell cycle regulation, immune response, and membrane transport. The genomic site with highest number of dysregulated genes overall lies in a locus corresponding to human chromosome 8q24, a region frequently amplified in human urothelial cancers. Conclusions These data identify critical sets of genes that are differently regulated in association with an activating mutation in the MAPK/ERK pathway in canine iUC tumors. The experiments also highlight the value of the canine system in identifying expression patterns associated with a common, shared cancer.

Objective To develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30‐second fast‐paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities. Methods Twenty females with symptomatic knee OA (mean age [SD] 58.30 [8.05] years) and 20 age‐ and sex‐matched asymptomatic controls (57.25 [8.71] years) participated in the study. Participants completed questionnaires of demographic and clinical data, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36‐item Short Form Health Survey (SF‐36) followed by 30SFW performance. Participants returned 2‐7 days later and performed the 30SFW again. Results The knee OA group reported function that was worse than controls (all KOOS subscales; P < 0.0001). The 30SFW intrarater and interrater reliability were excellent [ICC(2,1) = 0.95‐0.99]. Knee OA participants walked a shorter distance in the 30SFW than controls (mean [SD]: OA 44.4 m [9.5 m]; control 58.1 m [7.8 m]; P < 0.0001). Positive strong correlations were found between the 30SFW and the KOOS–Activity of Daily Living, SF‐36‐Physical Functioning, and SF‐36‐Physical Health Composite scores (P < 0.0001). A nonsignificant, weak correlation between 30SFW and SF‐36‐Mental Health scores was present (r = 0.32, P = 0.05). Conclusion The 30SFW has excellent intrarater and interrater reliability. The 30SFW demonstrated excellent known groups, convergent, and discriminant validity as a measure of short‐distance walking ability in persons with knee OA. Clinicians and researchers should consider using the 30SFW to quantify walking ability in persons with knee OA and assess walking ability change.

We aimed to better understand resistome and virulome patterns on animal and process-area surfaces through a pig slaughterhouse to track possible contamination within the food production chain. Culture-dependent methods revealed high levels of microbial contamination, corresponding to mesophilic and pathogenic bacteria on both the animal and process-area surfaces mainly in the anesthesia (AA and AS) zone followed by “scorching and whip” (FA and FS) zone and also in the end products. To evaluate the potential risk of antibiotic resistance and virulence determinants, shotgun metagenomic DNA-sequencing of isolates from selected areas/products uncovered a high diversity and richness of antibiotic resistance genes (ARGs): 55–62 genes in the anesthesia area (AA and AS) and 35–40 in “animal-arrival zone” (MA and MS). The “scorching and whip” (FA and FS) area, however, exhibited lowered abundance of ARGs (1–6), indicating that the scalding and depilating process (an intermediate zone between “anesthesia” and “scorching and whip”) significantly decreased bacterial load by 1–3 log10 but also diminished the resistome. The high prevalence of antibiotic-inactivating enzyme genes in the “animal-arrival zone” (60–65%) and “anesthesia” area (56%) were mainly represented by those for aminoglycoside (46–51%) and lincosamide (14–19%) resistance, which did not reflect selective pressures by antibiotics most commonly used in pig therapy—tetracyclines and beta-lactams. Contrary to ARGs, greater number of virulence resistance genes were detected after evisceration in some products such as kidney, which reflected the poor hygienic practices. More than 19 general virulence features—mainly adherence, secretion system, chemotaxis and motility, invasion and motility were detected in some products. However, immune evasion determinants were detected in almost all samples analyzed from the beginning of the process, with highest amounts found from the anesthesia area. We conclude that there are two main sources of contamination in a pig slaughterhouse: the microorganisms carried on the animals’ hide, and those from the evisceration step. As such, focussing control measures, e.g., enhanced disinfection procedures, on these contamination-source areas may reduce risks to food safety and consumer health, since the antibiotic and virulence determinants may spread to end products and the environment; further, ARG and virulence traits can exacerbate pathogen treatments.

The distribution and quantification of tetracycline, sulfonamide and beta-lactam resistance genes were assessed in slaughterhouse zones throughout meat chain production and the meat products; this study represents the first to report quantitatively monitor antibiotic resistance genes (ARG) in goat and lamb slaughterhouse using a culture independent approach, since most studies focused on individual bacterial species and their specific resistance types. Quantitative PCR (qPCR) revealed a high prevalence of tetracycline resistance genes tetA and tetB in almost all slaughterhouse zones. Sulfonamide resistance genes were largely distributed, while beta-lactam resistance genes were less predominant. Statistical analysis revealed that resistant bacteria, in most cases, were spread by the same route in almost all slaughterhouse zones, except for tetB, blaCTX and blaTEM genes, which occurred in few zones as isolated 'hot spots.' The sum of all analyzed ARG indicated that slaughterhouse surfaces and end products act as reservoirs of ARG, mainly tet genes, which were more prevalent in slaughtering room (SR), cutting room (CR) and commercial meat products (MP). Resistance gene patterns suggest they were disseminated throughout slaughterhouse zones being also detected in commercial meat products, with significant correlations between different sampling zones/end products and total resistance in SR, CR and white room (WR) zones, and also refrigerator 4 (F4) and MP were observed. Strategically controlling key zones in slaughterhouse (SR, CR and WR) by adequate disinfection methods could strategically reduce the risks of ARG transmission and minimize the issues of food safety and environment contamination.