Metagenomic characterization of the equine endometrial microbiome during anestrus.

The equine uterus is highly interrogated during estrus prior to breeding and establishing pregnancy. Many studies in mares have been performed during estrus under the influence of high estrogen concentrations, including the equine estrual microbiome. To date, it is unknown how the uterine microbiome of the mare is influenced by cyclicity; while, the equine vaginal microbiome is stable throughout the estrous cycle. We hypothesized that differences would exist between the equine endometrial microbiome of mares in estrus and anestrus. The aim of this study was two-fold: to characterize the resident endometrial microbiome of healthy mares during anestrus and to compare this with estrus. Double-guarded endometrial swabs were taken from healthy mares during estrus (n = 16) and in the following non-breeding season during anestrus (n = 8). Microbial population was identified using 16S rRNA sequencing. Our results suggest that the equine uterine microbiome in estrus has a low diversity and low richness, while during anestrus, a higher diversity and higher richness were seen compared to estrus. Despite this difference, both the estrus and anestrus endometrial microbiome were dominated by Proteobacteria, Firmicutes, and Bacteroidota. The composition of the microbial community between anestrus and estrus was significantly different. This may be explained by the difference in the composition of the endometrial immune milieu based on the stage of the cycle. Further research investigating the function of the equine endometrial microbiome and dynamics changes within the uterine environment is required.

Effect of Sampling Method on Detection of the Equine Uterine Microbiome during Estrus.

Bacterial endometritis is among the most common causes of subfertility in mares. It has a major economic impact on the equine breeding industry. The sensitivity of detecting uterine microbes using culture-based methods, irrespective of the sample collection method, double-guarded endometrial swab, endometrial biopsy, or uterine low-volume lavage (LVL), is low. Therefore, equine bacterial endometritis often goes undiagnosed. Sixteen individual mares were enrolled, and an endometrial sample was obtained using each method from all mares. After trimming, quality control and decontamination, 3824 amplicon sequence variants were detected in the dataset. We found using 16S rRNA sequencing that the equine uterus harbors a distinct resident microbiome during estrus. All three sampling methods used yielded similar results in composition as well as relative abundance at phyla (Proteobacteria, Firmicutes, and Bacteroidota) and genus (Klebsiella, Mycoplasma, and Aeromonas) levels. A significant difference was found in alpha diversity (Chao1) between LVL and endometrial biopsy, suggesting that LVL is superior at detecting the low-abundant (rare) taxa. These new data could pave the way for innovative treatment methods for endometrial disease and subfertility in mares. This, in turn, could lead to more judicious antimicrobial use in the equine breeding industry.

Per- and polyfluoroalkyl substances (PFAS) contamination in a microtidal urban estuary: Sources and sinks.

This study evaluates PFAS contamination and determines the major drainage sources to a temperate microtidal estuary, the Swan Canning Estuary, in Perth Western Australia. We describe how variability in these sources influences PFAS concentrations within this urban estuary. Surface water samples were collected from 20 estuary sites and 32 catchment sites in June and December from 2016 to 2018. Modelled catchment discharge was used to estimate PFAS load over the study period. Three major catchment sources of elevated PFAS were identified with contamination likely resulting from historical AFFF use on a commercial airport and defence base. Estuary PFAS concentration and composition varied significantly with season and spatially with the two different estuary arms responding differently to winter and summer conditions. This study has found that the influence of multiple PFAS sources on an estuary depend on the historical usage timeframe, groundwater interactions and surface water discharge.

Ketogenic diet enhances the effects of oxycodone in mice.

Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.

Effects of official and unofficial environmental regulations on environmental quality: Evidence from the Yangtze River Economic Belt, China.

Due to the increasing impact of climate change, there is a need to examine the effect of environmental regulation on environmental quality. Consequently, we examine the nonlinear and mediation effects of environmental regulation on environmental quality using panel data of 45 major cities in the Yangtze River Economic Belt, China, from 2013 to 2020. Environmental regulation is divided into official and unofficial environmental regulations according to its formality. The results indicate that an increase of official and unofficial environmental regulations can promote the improvement of environmental quality. In fact, the positive effect of environmental regulation on cities with better environmental quality is greater than that of cities with poorer environmental quality. The implementation of both official and unofficial environmental regulations can improve environmental quality better than the single implementation of either official environmental regulation or unofficial environmental regulation. There are full mediation effects of Gross Domestic Product per capita and technological progress in the positive effects of official environmental regulation on environmental quality. There are also partial mediation effects of technological progress and industrial structure in the positive effects of unofficial environmental regulation on environmental quality. This study assesses the policy effectiveness of environmental regulation and determines the underlying mechanism between environmental regulation and environmental quality to provide a reference for other countries regarding environmental improvement.

Predictions on multi-class terminal ballistics datasets using conditional Generative Adversarial Networks.

Ballistic impacts are a primary risk in both civil and military defence applications, where successfully predicting the dynamic response of a material or structure to impact crucial to the design of safe and fit-for-purpose protective structures. This study proposes a conditional Generative Adversarial Network (cGAN) architecture that can learn directly from available ballistic data and can be conditioned on additional information, such as class labels, to govern its output. A single Multi-Layer Perceptron (MLP) cGAN architecture is trained on a multi-class ballistic training set consisting of 10 classes labelled 0-9 where each class refers to a ballistic curve with a different ballistic limit velocity, vbl. A total of 5 models are trained on datasets consisting of 5, 10, 15, 20 and 25 samples within each class. For integer class labels 0-9, all cGAN models successfully predict the vbl with a maximum error of 4.12%. Additionally, for non-integer class labels between 0-9 the vbl predictions are similar despite not explicitly appearing in the training set. Moreover, each cGAN model is challenged to generate new samples for class labels that exist beyond the scope of the training set for class labels between 9-20. Four of the models predict the vbl with an error of less than 1.5% in all cases. This study showcases how a cGAN model can learn directly from a multi-class ballistic dataset and generate additional samples representative of that data for classes that do not appear explicitly in the training set.

IL-1ra polymorphisms and risk of epidural-related maternal fever (EPIFEVER-2): study protocol for a multicentre, observational mechanistic cohort study.

BACKGROUND: Laboratory data suggest that insufficient circulating levels of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) are associated with intrapartum inflammation and epidural-related maternal fever, both of which increase the rate of obstetric interventions and antibiotic use during labour. Genetic polymorphisms strongly influence IL-1ra levels in the general population. We aim to examine the association between IL-1ra polymorphisms and epidural-related maternal fever using Mendelian randomization analysis. METHODS: EPIFEVER-2 is a multicentre UK trial enrolling 637 women receiving epidural analgesia for labour. Blood samples obtained no later than four hours after epidural insertion will provide deoxyribonucleic acid for Taqman single-nucleotide polymorphism genotyping for presence/absence of rs6743376, rs1542176 alleles for IL-1ra, to establish the genetic score. The absence of both alleles is associated with the lowest IL-1ra levels. The primary outcome is pyrexia (>38°C) or intrapartum antibiotic administration. Secondary outcomes include mode of delivery, maternal and neonatal healthcare interventions. RESULTS: The EPIFEVER-2 study was prospectively registered (ISRCTN99641204) following ethical approval. Participant recruitment began in May 2021, with 221 women recruited across three centres as of November 21, 2021. CONCLUSIONS: EPIFEVER-2 will generate the largest prospective dataset detailing the incidence and consequences of epidural-related maternal fever. Using Mendelian randomisation analysis, a causative role for lower IL1-ra levels in determining the risk of epidural-related maternal fever and/or antibiotic administration before delivery will be examined.

Protein-, polymer-, and silica-based luminescent nanomaterial probes for super resolution microscopy: a review.

Super resolution microscopy was developed to overcome the Abbe diffraction limit, which effects conventional optical microscopy, in order to study the smaller components of biological systems. In recent years nanomaterials have been explored as luminescent probes for super resolution microscopy, as many have advantages over traditional fluorescent dye molecules. This review will summarize several different types of nanomaterial probes, covering quantum dots, carbon dots, and dye doped nanoparticles. For the purposes of this review the term "nanoparticle" will be limited to polymer-based, protein-based, and silica-based nanoparticles, including core-shell structured nanoparticles. Luminescent nanomaterials have shown promise as super-resolution probes, and continued research in this area will yield new advances in both materials science and biochemical microscopy at the nanometer scale.

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels.

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems.

Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study.

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations.

In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations.

Adult cavernous haemangioma of the vocal cords with a unique presentation of acute respiratory distress: a case report.

Laryngeal haemangiomas can commonly be seen in children, and first-line treatment is usually propranolol. However, in adults, cavernous haemangioma of the vocal cord(s) is an extremely rare condition - with this being the only published adult case presenting with acute respiratory distress - the mainstay of treatment is surgical excision under microlaryngoscopy. Presentation in adults can be unpredictable, but primarily consists of hoarseness which can be associated with, dyspnoea, dysphagia, and haemoptysis - and in one documented case stenosis of the aero-digestive tract led to death. Due to these airway difficulties, surgery can often prove challenging. In this study, we explore the unusual case of a previously well 71-year-old gentleman presenting to the Emergency Department, with worsening shortness of breath as his primary complaint. Uniquely, in this case, an awake fibre-optic intubation was undertaken to manage the difficult airway and a microlaryngoscopy was performed. A 20x10x15mm lesion was excised, which had characteristics in keeping with a cavernous haemangioma on microscopic examination.

Evaluating the application of the dual path platform VetTB test for badgers (Meles meles) in the test and vaccinate or remove (TVR) wildlife research intervention project in Northern Ireland.

European badgers (Meles meles) are accepted as a wildlife reservoir host for Mycobacterium bovis, which causes bovine tuberculosis (bTB) in the British Isles. The objective of this study was to evaluate the use of Dual Path Platform (DPP) VetTB test (Chembio Diagnostic Systems Inc., Medford, NY, USA) within a Test and Vaccinate or Remove (TVR) wildlife research intervention project. Blood samples were collected from 456 individual badgers, trapped in 2015 and 2016, and tested in the field with DPP VetTB test using whole blood. Additionally, whole blood and serum samples were taken to the laboratory for further DPP VetTB testing and for gamma interferon (IFN-γ) testing. Swabs were taken from the oropharynx and trachea and submitted for bacteriological culture as were swabs from wounds, if present. Field DPP VetTB test positive badgers were euthanised and underwent post-mortem examination and bTB confirmatory testing. The results demonstrated that the test performed as well in the field using whole blood as DPP Vet TB tests in the laboratory using sera or whole blood, and as well as other established tests for M. bovis. Visual assessment of the DPP VetTB test using serum under laboratory conditions showed a high degree of consistency between raters. Using a relative gold standard (parallel interpretation of IFN-γ assay and oropharyngeal/tracheal sample/culture), sensitivity estimates for the DPP VetTB test using sera and whole blood were 0.5 (95%CI 0.34-0.66) and 0.42 (95%CI 0.24-0.66), respectively. Specificity estimates were 0.95 (95%CI 0.93-0.97) for sera and 0.89 (95%CI 0.86-0.92) for whole blood. Parallel interpretation of Band 1 (MPB83) and Band 2 (CFP-10/ESAT-6) of the DPP VetTB test was not superior to interpretation of Band 1 only. The results give confidence in the reliability and reproducibility of the DPP VetTB test for badgers under field conditions and therefore it is considered appropriate for use in a badger bTB control campaign.

Data Resource: population level family justice administrative data with opportunities for data linkage.

INTRODUCTION: Although there has been considerable progress in the use of administrative data for applied health research, the family justice field lags behind. Better use of administrative data are essential to enhance understanding of how the family justice system is working, as well as the characteristics of, and outcomes for, children and families. The Family Justice Data Partnership (FJDP) supports this aim through analyses of core family justice and linked datasets in the SAIL Databank (Secure Anonymised Information Linkage). Cafcass Cymru provide expert advice for children involved in family court proceedings in Wales, ensuring decisions are made in the best interests of the child. We provide an overview of Cafcass Cymru data. We also describe and illustrate linkage to administrative datasets within SAIL. METHODS: Cafcass Cymru data was transferred to SAIL using a standardised approach to provide de-identified data with Anonymised Linking Fields (ALF) for successfully matched records. Three cohorts were created: all individuals involved in family court applications; all individuals with an ALF allowing subsequent health data linkage; and all individuals with a Residential Anonymised Linking Field (RALF) enabling area-level deprivation analysis. RESULTS: Cafcass Cymru application data are available for child protection matters (public law, range 2011-2019, n=12,745), and child arrangement disputes (private law, range 2005-2019, n=52,023). An 80% data linkage match rate was achieved. 40% had hospital admissions within two years pre or post application; 54% had emergency department attendances and 61% had outpatient appointments. Individuals were more likely to reside in deprived areas regardless of law type. CONCLUSION: Cafcass Cymru data can be accessed through the SAIL Databank. The FJDP will continue to enhance research opportunities for all to better understand the family justice system, and outcomes for those involved, such as health and wellbeing for children and family members.

Core Size does not Affect Blinking Behavior of Dye-Doped Ag@SiO2 Core-Shell Nanoparticles for Super-Resolution Microscopy.

Dye-doped nanoparticles have been investigated as bright, luminescent labels for super -resolution microscopy via localization methods. One key factor in super-resolution is the size of the luminescent label, which in some cases results in a frame shift between the label target and the label itself. Ag@SiO2 core-shell nanoparticles, doped with organic fluorophores, have shown promise as super-resolution labels. One key aspect of these nanoparticles is that they blink under certain conditions, allowing super-resolution localization with a single excitation source in aqueous solution. In this work, we investigated the effects of both the Ag core and the silica (SiO2) shell on the self-blinking properties of these nanoparticles. Both core size and shell thickness were manipulated by altering the reaction time to determine core and shell effects on photoblinking. Size and shell thickness were investigated individually under both dry and hydrated conditions and were then doped with a 1 mM solution of Rhodamine 110 for analysis. We observed that the cores themselves are weakly luminescent and are responsible for the blinking observed in the fully-synthesized metal-enhanced fluorescence nanoparticles. There was no statistically significant difference in photoblinking behavior-both intensity and duty cycle-with decreasing core size. This observation was used to synthesize smaller nanoparticles ranging from approximately 93 nm to 110 nm as measured using dynamic light scattering. The blinking particles were localized via super-resolution microscopy and show single particle self-blinking behavior. As the core size did not impact blinking performance or intensity, the nanoparticles can instead be tuned for optimal size without sacrificing luminescence properties.

Longitudinal dynamics of herd-level Mycobacterium bovis MLVA type surveillance in cattle in Northern Ireland 2003-2016.

Investigating genetically-structured diversity in pathogen populations over time is important to better understand disease maintenance and spread. Herd-level surveillance of Mycobacterium bovis genotypes (multi-locus VNTR analysis types, MLVA types) from all culture-confirmed bovine tuberculosis (TB) herd cases was undertaken in Northern Ireland (NI), generating an unparalleled, longitudinal, population-level 14-year survey for this pathogen. Across this population, 295 genetically-distinct M. bovis MLVA types were identified in the 19,717 M. bovis isolates surveyed. Of these, the most frequent was MLVA type 002 (23.0%); 151 MLVA types were represented more than once, in groups ranging from 2 to 4438 isolates. Only 23 MLVA types were isolated in all 14 years. Investigating inter-annual frequency of M. bovis MLVA types, examples of statistically-significant expansions (MLVA types 002, 004, 006, 009 and 027), contractions (MLVA types 001, 007 and 011) and maintenance (MLVA types 003 and 005) were disclosed, during a period of fluctuating bovine TB herd-level incidence at the NI scale. The fixed period frequency distribution of MLVA types remained highly right-skewed. Novel VNTR copy number variant MLVA types (N = 242; an average of 17 per annum) were identified throughout the survey. The MLVA type distribution in the landscape was not random; MLVA types showed statistically-significant geographical localization and strong spatial associations with Divisional Veterinary Office (DVO) regions. There was also evidence of differential risk of particular MLVA types across breeds (Holstein/Friesian vs. other), age-class, and sex and some evidence of an association between the number of animals testing positive for bovine TB during the disclosing test and particular MLVA types, although there was substantial variation.

Practical implementation of robust MR-thermometry during clinical MR-guided microwave ablations in the liver at 1.5 T.

Practical non-invasive equipment modifications and effective acquisition methods to achieve robust and reliable real-time MR thermometry for monitoring of clinical hepatic microwave ablations were implemented. These included selection of the microwave generator location (inside versus outside the MR scan room), the number of radiofrequency chokes added to the microwave generator's coaxial lines, and the use of copper wool to maximize their electrical grounding. Signal-to-noise ratio (SNR) of MR thermometry images of a small fluid-filled phantom acquired during activation of microwave antenna were used to evaluate image quality as a function of each modification. SNR measurements corresponding to both locations of the microwave generator were comparable and so it was located outside the MR scan room. For this location, addition of one RF choke on the power and four chokes on the sensor coaxial lines was found to be optimal, corresponding to a 68% increase in SNR. Furthermore, image quality strongly depended on the proper electrical grounding of the power and sensor lines. SNR ratio (relative to SNR of baseline images) during activation of microwave generator was found to be 0.49 ±â€¯0.28 without adequate grounding, and 0.88 ±â€¯0.08 with adequate grounding (p = 0.002, Student's t-test). These SNR measurements were sufficiently sensitive to detect issues related to equipment performance and hence formed part of the quality assurance testing performed prior to each clinical treatment. Incorporating these non-invasive approaches resulted in significant improvements to image quality and, importantly while maintaining the clinical integrity of the microwave system which is of paramount importance in a highly regulated healthcare environment.