Neoplastic and non-neoplastic lesions in biopsy samples from pet rabbits in Hong Kong: a retrospective analysis, 2019-2022.

Rabbits are popular pets in the urban environment of Hong Kong, ranking third behind cats and dogs. Here we describe the frequency of neoplastic and non-neoplastic lesions in biopsies from pet rabbits submitted to the CityU Veterinary Diagnostic Laboratory between 2019 and 2022, comprising 247 tissue samples from 243 rabbits collected by veterinarians in 19 veterinary clinics. Among the 243 rabbits, there were 128 females (65 spayed), 114 males (54 castrated); sex information was not provided for 1 rabbit. The rabbit breeds included 45 Lionhead, 35 Dwarf, 14 Lop, 11 Dwarf Lop, 5 French Lop, 3 Angora, 2 Dutch, 2 Holland Lop, and 1 each of Netherland Dwarf, Velveteen, Mini Lop, and New Zealand White. The mean ages of rabbits with neoplastic and non-neoplastic lesions were 7.1 and 5.7 y, respectively. The most common neoplastic lesions were adenocarcinoma (26.4%), trichoblastoma (21.4%), sarcoma (9.4%), and thymoma (8.2%). The most common non-neoplastic lesion was uterine cystic endometrial hyperplasia (14.8%), followed by dermal abscess formation in the ventral abdomen or skin of the head (12.5%). Although a broad spectrum of other lesions was described, our findings in biopsies from pet rabbits in Hong Kong are consistent with those in other jurisdictions.

IL-10 dependent adaptation allows macrophages to adjust inflammatory responses to TLR4 stimulation history.

During an infection, innate immune cells must adjust nature and strength of their responses to changing pathogen abundances. To determine how stimulation of the pathogen sensing TLR4 shapes subsequent macrophage responses, we systematically varied priming and restimulation concentrations of its ligand KLA. We find that different priming strengths have very distinct effects at multiple stages of the signaling response, including receptor internalization, MAPK activation, cytokine and chemokine production, and nuclear translocation and chromatin association of NFκB and IκB members. In particular, restimulation-induced TNF-α production required KLA doses equal to or greater than those used for prior exposure, indicating that macrophages can detect and adaptively respond to changing TLR4 stimuli. Interestingly, while such adaptation was dependent on the anti-inflammatory cytokine IL-10, exogenous concentrations of IL-10 corresponding to those secreted after strong priming did not exert suppressive effects on TNF-α without such prior priming, confirming the critical role of TLR4 stimulation history.

Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years.

Aims: This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods: This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results: Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion: Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs.

Background levels of body fluids and DNA on the shaft of the penis and associated underpants in the absence of sexual activity.

This study examines the background of blood, saliva, semen and autosomal DNA on penile swabs and underpants from males in the absence of recent sexual activity. Based on the data collected by the AFSP Body Fluid Forum, the results of this study show that; there is a very low expectation of detecting blood on penile swabs and male underpants; a low expectation of detecting saliva on penile swabs and male underpants; and spermatozoa would be expected in less than a quarter of penile swabs and three quarters of male underpants. As none of the samples had detectable levels of DNA which were suitable for meaningful comparison that did not match the donor or their partner, the expectation of detecting a DNA profile from the cellular background on penile swabs or underpants from a male who has not been involved in recent sexual intercourse is very low. The results of this study are extremely informative when evaluating the significance of blood, saliva, semen and DNA detected on the penile swabs and underpants of males in cases of alleged sexual assault.

Mortality From Combined Fractures of the Atlas (C1) and Axis (C2) in Adults.

Study design A retrospective case report of all upper cervical spine fractures diagnosed by CT imaging between 01/01/2013 and 31/12/2015 in NHS Greater Glasgow and Clyde, Scotland. Objective To compare the mortality following combined fractures of the atlas and axis to that of isolated fractures of either vertebra. Background The mortality from axis fractures is well documented in the literature. However, a combined fracture of the atlas and axis is seldom reported, leading to relatively unknown outcomes and mortality. Methods A total of 171 patients with atlas and/or axis fractures. Thirty-three presented with concurrent lower cervical spine fractures and were excluded from further analysis. Kaplan-Meier curves were used to compare survivorship between 108 patients with isolated and 30 with combined fractures. Similar analysis adjusted for comorbidities, including dementia and previous fragility fractures. Results Patients were followed up for 47.3±10.3 months (SD). Patients with isolated atlas fractures were significantly younger than those with an axis or combined fracture. Nearly half (8/17) of combined fracture mortalities occurred within the first 120 days. The mortality at 120 days was 26.7% in the combined fractures group and 18.5% in the isolated fracture group. There was no significant difference in the 120-day and overall mortality between these injury patterns. Furthermore, cognitive impairment and previous fragility fractures bore no significant impact on mortality. Nevertheless, mortality in the combined fracture group with previous fragility fractures did trend to shorter survivorship. Conclusions Patients with combined fractures are older and with the ever-increasing elderly population, the incidence of these injuries is expected to rise. While our data show that the 120-day mortality is proportionally higher in the combined fractures group, no long-term statistically significant difference is demonstrated. This evidence contests the notion that combined fractures of the atlas and axis have higher mortality than isolated injuries of either cervical vertebra.

A Review: Haemonchus contortus Infection in Pasture-Based Sheep Production Systems, with a Focus on the Pathogenesis of Anaemia and Changes in Haematological Parameters.

Haemonchosis is an important cause of anaemia in sheep worldwide, particularly those that are kept in pasture-based systems in warm, high rainfall environments. Potential outcomes vary based on the severity of infection and the sheep's immune response, however, in some sheep infection can lead to death. The consequences of Haemonchus contortus infection mean that it has been well-studied in a range of different farming systems. However, to our knowledge, there has not been a recent review focused on the pathophysiology of anaemia caused by haemonchosis. Thus, this review provides an in-depth discussion of the literature related to the pathophysiology of haemonchosis and associated clinical signs for hyperacute, acute, and chronic haemonchosis. Additionally, haematological and biochemical findings are presented, and various diagnostic methods are assessed.

Genome-resolved metagenomics provides insights into the functional complexity of microbial mats in Blue Holes, Shark Bay.

The present study describes for the first time the community composition and functional potential of the microbial mats found in the supratidal, gypsum-rich and hypersaline region of Blue Holes, Shark Bay. This was achieved via high-throughput metagenomic sequencing of total mat community DNA and complementary analyses using hyperspectral confocal microscopy. Mat communities were dominated by Proteobacteria (29%), followed by Bacteroidetes/Chlorobi group (11%) and Planctomycetes (10%). These mats were found to also harbour a diverse community of potentially novel microorganisms, including members from the DPANN, Asgard archaea and candidate phyla radiation, with highest diversity found in the lower regions (∼14-20 mm depth) of the mat. In addition to pathways for major metabolic cycles, a range of putative rhodopsins with previously uncharacterized motifs and functions were identified along with heliorhodopsins and putative schizorhodopsins. Critical microbial interactions were also inferred, and from 117 medium- to high-quality metagenome-assembled genomes, viral defence mechanisms (CRISPR, BREX and DISARM), elemental transport, osmoprotection, heavy metal resistance and UV resistance were also detected. These analyses have provided a greater understanding of these distinct mat systems in Shark Bay, including key insights into adaptive responses and proposing that photoheterotrophy may be an important lifestyle in Blue Holes.

Eukarya the chimera: eukaryotes, a secondary innovation of the two domains of life?

One of the most significant events in the evolution of life is the origin of the eukaryotic cell, an increase in cellular complexity that occurred approximately 2 billion years ago. Ground-breaking research has centered around unraveling the characteristics of the Last Eukaryotic Common Ancestor (LECA) and the nuanced archaeal and bacterial contributions in eukaryogenesis, resulting in fundamental changes in our understanding of the Tree of Life. The archaeal and bacterial roles are covered by theories of endosymbiogenesis wherein an ancestral host archaeon and a bacterial endosymbiont merged to create a new complex cell type - Eukarya - and its mitochondrion. Eukarya is often regarded as a unique and distinct domain due to complex innovations not found in archaea or bacteria, despite housing a chimeric genome containing genes of both archaeal and bacterial origin. However, the discovery of complex cell machineries in recently described Asgard archaeal lineages, and the growing support for diverse bacterial gene transfers prior to and during the time of LECA, is redefining our understanding of eukaryogenesis. Indeed, the uniqueness of Eukarya, as a domain, is challenged. It is likely that many microbial syntrophies, encompassing a 'microbial village', were required to 'raise' a eukaryote during the process of eukaryogenesis.

Absence of serological or molecular evidence of Leptospira infection in farmed swine in the Hong Kong Special Administrative Region.

Leptospirosis is an important zoonotic disease with several maintenance host species including swine. A cross sectional survey was undertaken between January to October 2020 to investigate the prevalence of leptospirosis in farmed swine in the Hong Kong Special Administrative Region (HKSAR) of China. Serum samples were collected from swine on seven farms (15 swine per farm; ten multiparous sows and five twelve-week-old weaners), while kidney samples were collected from 64 swine submitted for routine post-mortem (26 farms; average 2.4 swine per farm, range 1-6). Microscopic agglutination tests (MAT) to a panel of 24 Leptospira antigens did not reveal any evidence of seroconversion at a titre of 1:100. Polymerase chain reaction (PCR) testing of the kidney samples for Leptospira DNA did not detect any evidence of infection. Bayesian methods were used to compute the probability that the leptospirosis prevalence in farmed swine in the HKSAR was <3%, given none of the 105 swine sampled were positive on the MAT. The results of this study demonstrate no serological or molecular evidence of leptospirosis in farmed swine in the HKSAR. Subsequent statistical analysis supports the conclusion that the prevalence of leptospirosis in farmed swine in the HKSAR is negligible at present.

Microbial dark matter filling the niche in hypersaline microbial mats.

BACKGROUND: Shark Bay, Australia, harbours one of the most extensive and diverse systems of living microbial mats that are proposed to be analogs of some of the earliest ecosystems on Earth. These ecosystems have been shown to possess a substantial abundance of uncultivable microorganisms. These enigmatic microbes, jointly coined as 'microbial dark matter' (MDM), are hypothesised to play key roles in modern microbial mats. RESULTS: We reconstructed 115 metagenome-assembled genomes (MAGs) affiliated to MDM, spanning 42 phyla. This study reports for the first time novel microorganisms (Zixibacterial order GN15) putatively taking part in dissimilatory sulfate reduction in surface hypersaline settings, as well as novel eukaryote signature proteins in the Asgard archaea. Despite possessing reduced-size genomes, the MDM MAGs are capable of fermenting and degrading organic carbon, suggesting a role in recycling organic carbon. Several forms of RuBisCo were identified, allowing putative CO2 incorporation into nucleotide salvaging pathways, which may act as an alternative carbon and phosphorus source. High capacity of hydrogen production was found among Shark Bay MDM. Putative schizorhodopsins were also identified in Parcubacteria, Asgard archaea, DPANN archaea, and Bathyarchaeota, allowing these members to potentially capture light energy. Diversity-generating retroelements were prominent in DPANN archaea that likely facilitate the adaptation to a dynamic, host-dependent lifestyle. CONCLUSIONS: This is the first study to reconstruct and describe in detail metagenome-assembled genomes (MAGs) affiliated with microbial dark matter in hypersaline microbial mats. Our data suggests that these microbial groups are major players in these systems. In light of our findings, we propose H2, ribose and CO/CO2 as the main energy currencies of the MDM community in these mat systems. Video Abstract.

First case of feline cryptococcosis in Hong Kong, caused by Cryptococcus neoformans.

A nine-year-old domestic short hair cat was presented for a nasal planum mass, nasal discharge, hyporexia and weight loss. On physical examination nasal proliferative and ulcerative lesions and submandibular lymphadenopathy were identified. Cytology, histopathology, fungal culture, antigen serology and MALDI-TOF confirmed cryptococcal rhinitis with regional mandibular lymph node involvement due to Cryptococcus neoformans infection. This is the first reported case of cryptococcosis in a feline patient in Hong Kong.

Bayesian Network Modeling Applied to Feline Calicivirus Infection Among Cats in Switzerland.

Bayesian network (BN) modeling is a rich and flexible analytical framework capable of elucidating complex veterinary epidemiological data. It is a graphical modeling technique that enables the visual presentation of multi-dimensional results while retaining statistical rigor in population-level inference. Using previously published case study data about feline calicivirus (FCV) and other respiratory pathogens in cats in Switzerland, a full BN modeling analysis is presented. The analysis shows that reducing the group size and vaccinating animals are the two actionable factors directly associated with FCV status and are primary targets to control FCV infection. The presence of gingivostomatitis and Mycoplasma felis is also associated with FCV status, but signs of upper respiratory tract disease (URTD) are not. FCV data is particularly well-suited to a network modeling approach, as both multiple pathogens and multiple clinical signs per pathogen are involved, along with multiple potentially interrelated risk factors. BN modeling is a holistic approach-all variables of interest may be mutually interdependent-which may help to address issues, such as confounding and collinear factors, as well as to disentangle directly vs. indirectly related variables. We introduce the BN methodology as an alternative to the classical uni- and multivariable regression approaches commonly used for risk factor analyses. We advise and guide researchers about how to use BNs as an exploratory data tool and demonstrate the limitations and practical issues. We present a step-by-step case study using FCV data along with all code necessary to reproduce our analyses in the open-source R environment. We compare and contrast the findings of the current case study using BN modeling with previous results that used classical regression techniques, and we highlight new potential insights. Finally, we discuss advanced methods, such as Bayesian model averaging, a common way of accounting for model uncertainty in a Bayesian network context.

Introducing a drift and diffusion framework for childhood growth research.

Background: Growth trajectories are highly variable between children, making epidemiological analyses challenging both to the identification of malnutrition interventions at the population level and also risk assessment at individual level. We introduce stochastic differential equation (SDE) models into child growth research. SDEs describe flexible dynamic processes comprising: drift - gradual smooth changes - such as physiology or gut microbiome, and diffusion - sudden perturbations, such as illness or infection. Methods: We present a case study applying SDE models to child growth trajectory data from the Haydom, Tanzania and Venda, South Africa sites within the MAL-ED cohort. These data comprise n=460 children aged 0-24 months. A comparison with classical curve fitting (linear mixed models) is also presented. Results: The SDE models offered a wide range of new flexible shapes and parameterizations compared to classical additive models, with performance as good or better than standard approaches. The predictions from the SDE models suggest distinct longitudinal clusters that form distinct 'streams' hidden by the large between-child variability. Conclusions: Using SDE models to predict future growth trajectories revealed new insights in the observed data, where trajectories appear to cluster together in bands, which may have a future risk assessment application. SDEs offer an attractive approach for child growth modelling and potentially offer new insights.

The Vulnerability of Microbial Ecosystems in A Changing Climate: Potential Impact in Shark Bay.

The potential impact of climate change on eukaryotes, including humans, has been relatively well described. In contrast, the contribution and susceptibility of microorganisms to a changing climate have, until recently, received relatively less attention. In this review, the importance of microorganisms in the climate change discourse is highlighted. Microorganisms are responsible for approximately half of all primary production on earth, support all forms of macroscopic life whether directly or indirectly, and often persist in "extreme" environments where most other life are excluded. In short, microorganisms are the life support system of the biosphere and therefore must be included in decision making regarding climate change. Any effects climate change will have on microorganisms will inevitably impact higher eukaryotes and the activity of microbial communities in turn can contribute to or alleviate the severity of the changing climate. It is of vital importance that unique, fragile, microbial ecosystems are a focus of research efforts so that their resilience to extreme weather events and climate change are thoroughly understood and that conservation efforts can be implemented as a response. One such ecosystem under threat are the evolutionarily significant microbial mats and stromatolites, such as those present in Shark Bay, western Australia. Climate change models have suggested the duration and severity of extreme weather events in this region will increase, along with rising temperatures, sea levels, and ocean acidification. These changes could upset the delicate balance that fosters the development of microbial mats and stromatolites in Shark Bay. Thus, the challenges facing Shark Bay microbial communities will be presented here as a specific case study.

Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells.

An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release. Supplementation of mouse neural stem cells (mNSCs) with dextrin-growth factor conjugates led to greater and prolonged proliferation compared to unbound EGF/bFGF controls, with no detectable apoptosis after 7 days of treatment. Immunocytochemical detection of neural precursor (nestin) and differentiation (Olig2, MAP2, GFAP) markers verified that controlled release of dextrin-conjugated growth factors preserves stem cell properties of mNSCs for up to 7 days. These results show the potential of dextrin-growth factor conjugates for localized delivery of bioactive therapeutic agents to support stem cell expansion and differentiation, and as an adjunct to direct neuronal repair.

Review of Diagnostic Procedures and Approaches to Infectious Causes of Reproductive Failures of Cattle in Australia and New Zealand.

Infectious causes of reproductive failure in cattle are important in Australia and New Zealand, where strict biosecurity protocols are in place to prevent the introduction and spread of new diseases. Neospora caninum ranks highly as an important cause of reproductive wastage along with fungal and bacterial infections. Brucella, a leading cause of abortion elsewhere in the world, is foreign, following successful programs to control and eradicate the disease. Leptospirosis in cattle is largely controlled by vaccination, while Campylobacter and Tritrichomonas infections occur at low rates. In both countries, Bovine Viral Diarrhea virus (BVDV) infection rates as the second most economically important disease of cattle and one that also has an effect on reproduction. Effective disease control strategies require rapid diagnoses at diagnostic laboratories. To facilitate this process, this review will discuss the infectious causes of reproductive losses present in both countries, their clinical presentation and an effective pathway to a diagnosis.

Perspectives on Current Challenges and Opportunities for Bovine Viral Diarrhoea Virus Eradication in Australia and New Zealand.

This review outlines the history of bovine viral diarrhoea virus (BVDV) and the current situation in Australia and New Zealand. BVDV has been reported as present in cattle from both countries for close to 60 years. It rates as the second most economically significant disease afflicting cattle, and is highly prevalent and spread throughout the beef and dairy industries. While other cattle diseases have been the subject of government control and eradication, infection with BVDV is presently not. Eradication has been undertaken in many other countries and been judged to be a good investment, resulting in positive economic returns. Presently, Australia and New Zealand have adopted a non-compulsory approach to control schemes, initiated and managed by farmers and veterinarians without the ultimate goal of eradication. Moving towards eradication is possible with the infrastructure both countries possess, but will require additional resources, coordination, and funding from stakeholders to move to full eradication.

The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1.

The mechanisms that determine whether a neural progenitor cell (NPC) reenters the cell cycle or exits and differentiates are pivotal for generating cells in the correct numbers and diverse types, and thus dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that doublesex- and mab-3-related transcription factor a2 (Dmrta2, also known as Dmrt5) plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into postmitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function is linked to the regulation of Hes1 and other proneural genes, as demonstrated by genome-wide RNA-seq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study thus establishes a link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.

Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A.

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions.