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Department of Veterinary Medicine

Cambridge Veterinary School
 

Pat Brooks SCTS in Small Animal Medicine

Job opportunities - Fri, 14/02/2025 - 00:00

SCHOLARSHIP AWARD: £28,738.00 (Subject to change)

A three-year Senior Clinical Training Scholarship in Small Animal Medicine (Residency) is available, to start on 11 August 2025. The training programme covers all aspects of small animal medicine, including cardiology, oncology, medical neurology, diagnostic imaging and clinical pathology, and is approved by the European College of Veterinary Internal Medicine.

The Scholar will register for the Diploma of the European College of Veterinary Internal Medicine. The training programme requires participation in the Department's clinical service, including the out-of-hours rota, in addition to small-group teaching of veterinary students.

An applicant must be a Member of the Royal College of Veterinary Surgeons, or hold a veterinary degree that qualifies them for membership. Completion of an appropriate internship or a minimum of two years' experience in small animal practice, during which you have gained knowledge of UK veterinary regulations and practices, is essential.

Closing date for applications: Midnight on Monday, 10 February 2025.

Interviews will be held early April 2025.

Informal enquiries should be directed to Nick Bexfield, Clinical Director of Small Animal Services, by email: nb289@cam.ac.uk

A SCTS application form (SCTS1) and information pack can be downloaded from the following website: https://www.vet.cam.ac.uk/job

Applicants should supply a completed SCTS Application Form (SCTS1), Curriculum Vitae and Covering Letter giving reasons for wishing to undertake this SCTS in the Department of Veterinary Medicine, University of Cambridge.

Applications should be submitted via e-mail to vetmed@vet.cam.ac.uk with the above documents as one attachment no later than the closing date stated.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a health assessment.

Please note: The ability to take up this Scholarship is contingent upon you being able to evidence your right to work in the UK, or through gaining the right to work via the UK immigration system. Evidence will need to be provided before an offer can be made. Regrettably, this Scholarship is not suitable for sponsorship via the Skilled Worker or Temporary Worker visa routes as the minimum requirements cannot be met.

Modelling the impact and cost effectiveness of universal varicella vaccination in England

Latest publications - Thu, 13/02/2025 - 11:00

Vaccine. 2025 Feb 12;50:126831. doi: 10.1016/j.vaccine.2025.126831. Online ahead of print.

ABSTRACT

INTRODUCTION: Two distinct diseases are attributable to the varicella zoster virus, varicella (chickenpox) and zoster (shingles). This study assesses the impact and cost-effectiveness of a childhood varicella vaccination program in England.

METHODS: We use an age-structured dynamic transmission model and a health economic decision tree. The model incorporates recent data on varicella and zoster epidemiology, including the effects of exogenous boosting on zoster incidence. By simulating various vaccination strategies, including routine and catch-up programs, the study evaluates the potential reduction in varicella and zoster cases due to vaccination and the associated vaccine cost-effectiveness (from the NHS perspective).

RESULTS: We find that a two-dose varicella vaccination program could significantly reduce varicella incidence, potentially achieving near-elimination if high coverage rates are maintained. However, the model also predicts a temporary increase in zoster incidence due to reduced natural boosting from varicella exposure; this is partly mitigated by the current zoster vaccination program and the effect is much less substantial than previously estimated. Cost-effectiveness analyses reveal that all vaccination strategies modelled are cost-effective at typical thresholds, with the routine vaccination scenario being the most economically advantageous. Sensitivity analyses demonstrate that vaccine price and varicella treatment costs are the primary drivers of cost-effectiveness.

CONCLUSION: The study supports the introduction of a childhood varicella vaccination program in England, which offers substantial health benefits and is highly likely to be cost-effective.

PMID:39946866 | DOI:10.1016/j.vaccine.2025.126831

Patient-specific Guides Improve the Accuracy and Safety of Transcondylar Screw Placement-a Cadaveric Study in the Canine Humerus

Latest publications - Tue, 11/02/2025 - 11:00

Vet Comp Orthop Traumatol. 2025 Feb 11. doi: 10.1055/a-2510-3720. Online ahead of print.

ABSTRACT

OBJECTIVES: The goal of this study was to compare the accuracy and safety of a transcondylar screw (TCS) placed using a 3D-printed patient-specific guide (PSG) or a generic aiming device (AD). We hypothesized that PSG is more accurate (i.e., positioning and orientation closer to the optimal trajectory) and safer (reduced incidence of joint violation) than the AD.

METHODS: A total of seven pairs of forelimbs were allocated to PSG and AD groups. After CT scanning, the optimal TCS orientation was planned in silico by a surgical specialist, and guides were printed. Using the PSG or AD, a 2.5-mm drill hole was drilled from medial to lateral across the humeral condyle. The positioning of the "planned" and "achieved" drill holes was defined on postoperative CT. The accuracy of TCS positioning and the risk of joint penetration were then calculated for the two groups.

RESULTS: Positioning of the entry and exit holes was significantly more accurate in the PSG group. Differences in screw angulation were not significantly different between groups. Despite the presence of an outlier (caused by incomplete seating of the PSG against the bone), 7 out of 7 screws positioned with PSG were "safe," while 3 out of 7 from the AD group would have violated the joint.

CONCLUSION: Our data confirm the technical superiority of PSG over the AD for placement of a TCS in the humeral condyle.

PMID:39933720 | DOI:10.1055/a-2510-3720

Bone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia

Latest publications - Tue, 11/02/2025 - 11:00

Cell Rep. 2025 Jan 28;44(1):115151. doi: 10.1016/j.celrep.2024.115151. Epub 2024 Dec 28.

ABSTRACT

In acute myeloid leukemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche is unclear. Here, we found that relapsing AML cells increase translation in their bone marrow (BM) niches, where BM mesenchymal stromal cells (BMSCs) become a source of eIF4A-cap-dependent translation machinery that is transferred to AML cells via extracellular vesicles (EVs) to meet their translational demands. In two independent models of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD (internal tandem duplication) and nucleophosmin (NPMc) mutations, protein synthesis levels increase in refractory AML dependent on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, while EVs from BMSCs carrying eIF4A boost AML cell translation and survival. Consequently, eIF4A inhibition synergizes with conventional chemotherapy. Together, these results suggest that AML cells rely on BMSCs to maintain an oncogenic translational program required for relapse.

PMID:39932190 | DOI:10.1016/j.celrep.2024.115151

Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses

Latest publications - Mon, 10/02/2025 - 11:00

Nat Microbiol. 2025 Feb 10. doi: 10.1038/s41564-025-01930-y. Online ahead of print.

ABSTRACT

The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumour mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumour immune responses, and LPS-binding antibiotics and a small-molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumour immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses.

PMID:39929976 | DOI:10.1038/s41564-025-01930-y

Whole genome sequencing identifies novel candidate genetic variants in canine stomatocytosis

Latest publications - Mon, 10/02/2025 - 11:00

Gene. 2025 Feb 8:149314. doi: 10.1016/j.gene.2025.149314. Online ahead of print.

ABSTRACT

Stomatocytosis is a rare spectrum of red blood cell (RBC) disorders. In humans, stomatocytosis is typically caused by genetic changes in specific ion exchange and transport genes. Stomatocytosis has been identified in dogs, however the underlying genetic causes are unknown. Recently, stomatocytosis was reported in a Beagle and Australian Cattle Dog for the first time. Here, whole-genome sequencing (WGS) of these dogs was undertaken to identify candidate genetic variants driving or impacting stomatocytosis. Cases were compared to WGS of 119 controls of several breeds and > 1,000 dogs from public and private datasets. Candidate genes were identified, including genes linked to stomatocytosis in humans: SPTB and KCNN4. Notably, each case carried a different homozygous intronic SNP in SPTB only 24 bases apart (Beagle - chr8:39,194,923; ACD - chr8:39,194,947; CanFam3.1), which were not homozygous in other dogs. Variants with predicted deleterious impact in additional ion transport-related genes were also identified: SLC8A3, DYSF, SLC12A8, INPP5E, SLC1A1, and a novel SLC41A3 genetic change carried by the Australian Cattle Dog. Human and mouse scRNAseq and proteomics data indicate that these candidate genes are expressed in RBCs or their immature precursors. Taken together, these genetic data obtained from spontaneous stomatocytosis in a non-human species provides novel insights and candidate genes for evaluation of rare red cell disorders in humans.

PMID:39929273 | DOI:10.1016/j.gene.2025.149314

Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings

Latest publications - Thu, 06/02/2025 - 11:00

Sci Rep. 2025 Feb 7;15(1):4564. doi: 10.1038/s41598-025-85389-1.

ABSTRACT

Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for controlling bTB. A key requirement for vaccination strategies using BCG is the validation of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in a natural setting. The cattle were tested every 4 months with a skin test and every 2 months with interferon-gamma (IFN-γ) release assays (IGRA) over a year of exposure. Before exposure, the DIVA skin, DIVA IGRA, and tuberculin tests showed 100% specificity in unvaccinated control calves. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had comparable sensitivities of 46% (95% CI 36, 56), 45% (95% CI 35, 55), and 47 (95% CI 37, 57), respectively, when assessed against animals positive by M. bovis culture PCR. The results suggest that test-and-slaughter control strategies using tests with low sensitivity are not expected to be effective in controlling bTB in high-prevalence herds, and highlight an urgent need to improve the sensitivity of diagnostic tests for bTB in these settings.

PMID:39915566 | DOI:10.1038/s41598-025-85389-1

Identification of serotype O3b and high-risk clone ST37 of <em>Klebsiella pneumoniae</em> revealed by comparative genomic analysis

Latest publications - Tue, 04/02/2025 - 11:00

Front Cell Infect Microbiol. 2025 Jan 20;14:1517125. doi: 10.3389/fcimb.2024.1517125. eCollection 2024.

ABSTRACT

BACKGROUND: Epidemiological risk factors such as the demography of a place, environment, food, livestock, and companion animals are known sources of Klebsiella pneumoniae infection. Whole-genome sequencing (WGS) has become a powerful tool to complement traditional microbiological characterization of foodborne pathogens. Moreover, K. pneumoniae has several species complexes (KpSC) and is very difficult to differentiate using routine microbiological methods. The present study aims to investigate the prevalence of K. pneumoniae in fish available in the retail market using WGS.

METHODS: Isolation of K. pneumoniae, identification of K. pneumoniae isolates, and determination of the minimum inhibitory concentration (MIC) were performed. Whole-genome sequencing of K. pneumoniae genomes and phylogenomic analysis were conducted for visual comparison of the genomes. Furthermore, genomes of non-human origin that were submitted from India to the NCBI database were downloaded and included in the comparative analysis.

RESULTS: The findings showed that many antibiotic-resistant genes (ARGs) are prominent, including acrD, BaeR, cpxA, mdtB, mdtC, CRP, H-NS, KpnE, KpnF, KpnG, KpnH, acrA, acrB, marA, ramB, oqxA, oqxB, LptD, and emrR. Four fish-sourced isolates had different blaSHV resistance gene variants. The presence of ARGs for aminoglycosides [aac(3)-IId], fluoroquinolones (oqxA, oqxB), and fosfomycin (fosA5, fosA6) in these K. pneumoniae isolates from fish sources was found. One of the CIFT-K6 isolates had the uncommon serotype of K. pneumoniae O3b with the high-risk clone "ST37." The ST515 sequence type was present in two K. pneumoniae isolates (CIFT-K7 and CIFT-K8), but the O3b serotype and ST192 allele type were present in the CIFT-K10 isolate.

CONCLUSION: To the best of our knowledge, this research study represents the first Indian report of K. pneumoniae linked to fish, specifically the high-risk clone 'ST37' and two other STs, 515 and 192. The most common plasmid type detected in all four isolates was IncFIB, and 75% of the isolates were IncFII and IncHI1B. The prevalence of ARGs linked to efflux pump resistance mechanisms is highlighted by the analysis of genome sequence data.

PMID:39902187 | PMC:PMC11788149 | DOI:10.3389/fcimb.2024.1517125

Demography of the Gambian Epauletted Fruit Bat (<em>Epomophorus gambianus</em>) in Ghana

Latest publications - Fri, 31/01/2025 - 11:00

J Mammal. 2024 Sep 5;106(1):168-177. doi: 10.1093/jmammal/gyae096. eCollection 2025 Feb.

ABSTRACT

We provide the first estimates of survival and reproductive rates for a population of the Gambian Epauletted Fruit Bat Epomophorus gambianus in Ghana. We focused on a large colony of ca. 5,000 bats over 3 years to estimate population parameters including population size, birth rates, survival, and sex ratios for this species. Reproduction chronology was confirmed as seasonal bimodal polyestry, with births occurring in March/April and August/September each year. The estimated birth rate was 0.89 (95% CI = 0.85 to 0.92) per reproductive season. The overall sex ratio (female to male ratio) of the study population was male-dominated (0.69, 95% CI = 0.64 to 0.75), but female-biased for adults (62% female, χ2 1 = 42, P < 0.0001), and showed temporal and age-specific variations. By radiotracking 60 bats for 10 months, we obtained the first estimates of minimum monthly survival for this species as 0.81 (95% CI = 0.74 to 0.86), but this could be an underestimate due to possible undetected emigration of tagged bats.

PMID:39886213 | PMC:PMC11776427 | DOI:10.1093/jmammal/gyae096

Role of inflammasomes in acute respiratory distress syndrome

Latest publications - Thu, 30/01/2025 - 11:00

Thorax. 2025 Jan 30:thorax-2024-222596. doi: 10.1136/thorax-2024-222596. Online ahead of print.

ABSTRACT

Acute respiratory distress syndrome (ARDS) is present in >10% of all people admitted to critical care and is associated with severe morbidity and mortality. Despite more than half a century since its first description, no efficacious pharmacological therapies have been developed, and little progress has been made in improving clinical outcomes. Neutrophils are the principal drivers of ARDS, with their priming and subsequent aberrant downstream functions, including interleukin (IL) 1β and IL-18 secretion, central to the disease pathogenesis. The dominant pathways through which IL-1β and IL-18 are believed to be elaborated are multimeric protein structures called inflammasomes that consist of sensor proteins, adaptor proteins and an effector enzyme. The inflammasome's initial activation depends on one of a variety of damage-associated (DAMP) or pathogen-associated (PAMP) molecular patterns. However, once activated, a common downstream inflammatory pathway is initiated regardless of the specific DAMP or PAMP involved. Several inflammasomes exist in humans. The nucleotide-binding domain leucine-rich repeat (NLR) family, pyrin domain-containing 3 (NLRP3), inflammasome is the best described in the context of ARDS and is known to be activated in both infective and sterile cases. The NLR family, caspase activation and recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have also been implicated in various ARDS settings, as have inflammasome-independent pathways. Further work is required to understand human biology as much of our knowledge is extrapolated from rodent experimental models. Experimental lung injury models have demonstrated beneficial responses to inflammasome, IL-1β and IL-18 blockade. However, findings have yet to be successfully translated into humans with ARDS, likely due to an underappreciation of the central role of the neutrophil inflammasome. A thorough understanding of inflammasome pathways is vital for critical care clinicians and researchers and for the development of beneficial therapies. In this review, we describe the central role of the inflammasome in the development of ARDS and its potential for immunomodulation, highlighting key areas for future research.

PMID:39884849 | DOI:10.1136/thorax-2024-222596

Genomic evaluation of phenotypic antibiotic susceptibility patterns as a surrogate for MRSA relatedness and putative transmission during outbreak investigations

Latest publications - Wed, 29/01/2025 - 11:00

Infect Prev Pract. 2024 Dec 26;7(1):100435. doi: 10.1016/j.infpip.2024.100435. eCollection 2025 Mar.

ABSTRACT

Antibiograms have been used during outbreak investigations for decades as a surrogate for genetic relatedness of Methicillin-resistant Staphylococcus aureus (MRSA). In this study, we evaluate the accuracy of antibiograms in detecting transmission, using genomic epidemiology as the reference standard. We analysed epidemiological and genomic data from 1,465 patients and 1,465 MRSA isolates collected at a single clinical microbiology laboratory in the United Kingdom over a one-year period. A total of 132 unique antibiograms (AB) were identified based on VITEK 2 susceptibility testing, with two profiles (AB1 and AB2) accounting for 698 isolates (48%). We identified MRSA-positive patients with a known hospital or community contact and evaluated the prediction of MRSA transmission based on identical antibiograms. The sensitivity and specificity of identical antibiograms to infer genetically related MRSA isolates (≤25 SNPs) within hospital contacts (presumed transmission events) was 66.4% and 85.5% respectively and 73.8% and 85.7% within community contacts. Reanalysis, where any single drug mismatch in susceptibility results was allowed, increased sensitivity but reduced specificity: 95.2% and 58.8%, respectively, for hospital contacts; and 91.7% and 62.6% for community contacts. Overall, the sensitivity and specificity of identical antibiograms for inferring genetically related MRSA isolates (≤25 SNPs), regardless of epidemiological links, were 49.1% and 87.5%, respectively. We conclude that using an antibiogram with one mismatch can detect most transmission events; however, its poor specificity may lead to an increased workload through the evaluation of numerous pseudo-outbreaks. This study further supports the integration of genomic epidemiology into routine practice for the detection and control of MRSA transmission.

PMID:39877244 | PMC:PMC11772957 | DOI:10.1016/j.infpip.2024.100435

A TTPA deletion is associated with Retinopathy with Vitamin E Deficiency (RVED) in the English Cocker Spaniel Dog

Latest publications - Tue, 28/01/2025 - 11:00

G3 (Bethesda). 2025 Jan 28:jkaf016. doi: 10.1093/g3journal/jkaf016. Online ahead of print.

ABSTRACT

Retinopathy with Vitamin E Deficiency (RVED) is a familial disease in the English Cocker Spaniel (ECS) dog breed. Ophthalmic abnormalities observed in RVED-affected ECS include lipofuscin granule deposition within the tapetal fundus and subsequent retinal degeneration resulting in visual deficits. Affected dogs may also exhibit neurological signs that include ataxia and hindlimb proprioceptive deficit. In all cases, circulating plasma concentrations of α-tocopherol are low. This study sought to investigate the genetic basis of RVED in the ECS breed. We undertook a genome-wide association study comprising 30 ECS with normal fundic examinations aged 6 years or older (controls) and 20 diagnosed with RVED (cases) and identified a statistically associated signal on chromosome 29 (Praw = 1.909×10-17). Whole genome sequencing (WGS) of two cases identified a 102bp deletion in exon 1 of the Alpha Tocopherol Transfer Protein gene (TTPA), truncating the protein by 34 amino acids. The c.23_124del variant segregated with RVED in a total of 30 cases and 43 controls. Variants in TTPA are causal for Ataxia with Vitamin E Deficiency (AVED) in humans which is a phenotypically similar disease to RVED. The identification of the canine variant is extremely significant as the availability of a DNA test will allow for identification of presymptomatic dogs and early therapeutic intervention which may prevent development of retinopathy and improve neurological signs. Breeders can also use the DNA test to efficiently eradicate the disease from this breed.

PMID:39874248 | DOI:10.1093/g3journal/jkaf016

Client Services Administrator

Job opportunities - Mon, 27/01/2025 - 00:00

We have an exciting opportunity for a personable and effective administrator to work in the newly restructured Client Services function of the Queen's Veterinary School Hospital (QVSH). This position is full-time and operates on a rota system to cover the hospital reception's opening hours, which are currently Monday to Friday, 8:00am to 7:00pm.

The Client Service Administrator is the first point of contact within the Small Animal Hospital aiming to provide a first-class customer service, rotating between front desk and telephone to provide all front-of-house services, therefore a friendly, calm and confident communicator is essential. You will be responsible for receiving incoming calls and emails, processing payments, booking appointments, and liaising with clients, referring veterinary practices, QVSH clinicians, nurses and students. You should have experience of working in a busy administrative role, have excellent customer care skills, be numerate, accurate and have an eye for detail.

You must be efficient and experienced in Microsoft Office packages and have the ability to establish professional and effective working relationships with the wider team. Excellent organisation skills, attention to detail and flexibility are all essential parts of the role.

There may also be a requirement to participate in a weekend working, for which additional remuneration will be made in line with the University Policy.

Detailed information about the role and the Department of Veterinary Medicine can be found on our official website: www.vet.cam.ac.uk.

For informal inquiries, please contact the Clinical HR Team via email at qvsh.hr@vet.cam.ac.uk. Kindly include reference PP44848 in your application and all correspondence related to this vacancy.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Closing date for applications: Midnight on Monday, 10 February 2025.

Interviews will be held in late February 2025.

We reserve the right to close this vacancy early if we receive sufficient applications or extend it if we do not receive a sufficient number of applications. Therefore, if you are interested, please submit your application as early as possible.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a health assessment.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Treatment, prognosis, and outcome of dogs treated for rectal plasmacytoma: a multicentric retrospective study

Latest publications - Wed, 22/01/2025 - 11:00

J Am Vet Med Assoc. 2025 Jan 22:1-8. doi: 10.2460/javma.24.10.0666. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to report the outcome and prognosis of canine patients treated medically or surgically for rectal plasmacytomas and to identify factors associated with recurrence, mortality, or progression to multiple myeloma.

METHODS: The databases of 7 referral hospitals were reviewed. The Kaplan-Meier method and Cox proportional hazards analysis were used to determine the association of a range of variables with recurrence and progression-free interval for the surgically treated patients.

RESULTS: 20 dogs were included. Nineteen cases were treated surgically, and 1 case was treated conservatively (analgesia and monitoring). Metastatic lesions were detected in 2 of 20 dogs (10%). Four of 19 dogs (21%) treated surgically developed postoperative complications, 1 major (1 of 19 [5.2%]) and 3 minor (3 of 19 [15.8%]). Tumor recurrence was identified in 6 of 19 dogs (31.5%). The 1-, 2-, and 3-year survival rates were 95%, 72%, and 66%, respectively. None of the variables tested were associated with occurrence of complications. Increased distance from the anus, incomplete surgical margins, and decreasing surgeon experience were associated with an increased risk of recurrence. No progression to multiple myeloma was seen in any of the cases.

CONCLUSIONS: Surgical treatment of rectal plasmacytomas is associated with a low major complication rate and long survival. Metastasis and recurrence rates are significantly higher than previously reported.

CLINICAL RELEVANCE: Conservative surgery leads to long-term survival, but recurrence is common. Future studies should focus on the benefits of adjuvant treatments.

PMID:39842084 | DOI:10.2460/javma.24.10.0666

Isolation of phages infecting the zoonotic pathogen <em>Streptococcus suis</em> reveals novel structural and genomic characteristics

Latest publications - Mon, 20/01/2025 - 11:00

bioRxiv [Preprint]. 2025 Jan 7:2025.01.07.631744. doi: 10.1101/2025.01.07.631744.

ABSTRACT

Bacteriophage research has experienced a renaissance in recent years, owing to their therapeutic potential and versatility in biotechnology, particularly in combating antibiotic resistant-bacteria along the farm-to-fork continuum. However, certain pathogens remain underexplored as targets for phage therapy, including the zoonotic pathogen Streptococcus suis which causes infections in pigs and humans. Despite global efforts, the genome of only one infective S. suis phage has been described. Here, we report the isolation of two phages that infect S. suis: Bonnie and Clyde. The phages infect 58% of 100 S. suis strains tested, including representatives of seven different serotypes and thirteen known sequence types from diverse geographical origins. Clyde suppressed bacterial growth in vitro within two multi-strain mixes designed to simulate a polyclonal S. suis infection. Both phages demonstrated stability across various temperatures and pH levels, highlighting their potential to withstand storage conditions and maintain viability in delivery formulations. Genome comparisons revealed that neither phage shares significant nucleotide identity with any cultivated phages in the NCBI database and thereby represent novel species belonging to two distinct novel genera. This study is the first to investigate the adhesion devices of S. suis infecting phages. Structure prediction and analysis of adhesion devices with AlphaFold2 revealed two distinct lineages of S. suis phages: Streptococcus thermophilus-like (Bonnie) and S. suis-like (Clyde). The structural similarities between the adhesion devices of Bonnie and S. thermophilus phages, despite the lack of nucleotide similarity and differing ecological niches, suggest a common ancestor or convergent evolution, highlighting evolutionary links between pathogenic and non-pathogenic streptococcal species. These findings provide valuable insights into the genetic and phenotypic characteristics of phages that can infect S. suis, providing new data for the therapeutic application of phages in a One Health context.

PMID:39829746 | PMC:PMC11741397 | DOI:10.1101/2025.01.07.631744

Survival of radioiodine treated hyperthyroid cats that are euthyroid and hypothyroid after treatment, and effect of levothyroxine supplementation on survival time of cats with iatrogenic hypothyroidism

Latest publications - Mon, 20/01/2025 - 11:00

J Vet Intern Med. 2025 Jan-Feb;39(1):e17295. doi: 10.1111/jvim.17295.

ABSTRACT

BACKGROUND: Hyperthyroid cats that are azotemic and hypothyroid after surgical or medical treatment have poor outcomes, and supplementation with levothyroxine (LT4) improves survival. However, the effect of LT4 supplementation on survival of nonazotemic, hypothyroid radioiodine (RI)-treated hyperthyroid cats is unknown.

HYPOTHESIS: Radioiodine treated hyperthyroid cats with iatrogenic hypothyroidism or azotemia have shorter survival times than euthyroid, nonazotemic cats and supplementation of LT4 improves survival times of hypothyroid cats.

ANIMALS: One hundred seventeen RI treated hyperthyroid cats.

METHODS: Prospective cohort study. Radioiodine treated cats were screened for azotemia and iatrogenic hypothyroidism using TSH stimulation test; LT4 supplementation was offered to all hypothyroid cats with decision to treat based on owner preference. The log rank test was used to compare survival times between groups, and the Mann-Whitney U test was used to compare age and renal variables. Data are presented as median [range].

RESULTS: Euthyroid azotemic cats (934 [759-2035] days) and nonsupplemented hypothyroid cats (azotemic and nonazotemic combined, 1232 [238-2363] days) had shorter survival times than euthyroid nonazotemic cats (1616 [663-3369] days, P = .003 and P = .002, respectively). Levothyroxine supplemented hypothyroid nonazotemic cats had longer survival times than nonsupplemented hypothyroid nonazotemic cats (1037 [300-2401] days vs 768 [34-1014] days; P = .027). Levothyroxine supplementation was not associated with prolonged survival times in hypothyroid azotemic cats vs nonsupplemented hypothyroid azotemic cats (771 [718-1558] days vs 152 [82-1852] days, respectively, P = .991).

CONCLUSIONS AND CLINICAL IMPORTANCE: Levothyroxine supplementation in nonazotemic cats with iatrogenic hypothyroidism (diagnosed based on TSH stimulation test results) improved survival times, although randomized controlled trials are needed.

PMID:39831449 | DOI:10.1111/jvim.17295

Quaternary Ammonium Compounds: A New Driver and Hidden Threat for <em>mcr-1</em> Prevalence in Hospital Wastewater and Human Feces

Latest publications - Fri, 17/01/2025 - 11:00

Environ Sci Technol. 2025 Jan 16. doi: 10.1021/acs.est.4c11368. Online ahead of print.

ABSTRACT

The emergence of mobile colistin resistance gene mcr-1 has attracted global attention. The prevalence of mcr-1-positive Escherichia coli (MCRPEC) in humans largely decreased following the ban of colistin as an animal growth promoter in China. However, the prevalence of MCRPEC in the hospital environment and the relationship between disinfectants and mcr-1 remain unclear. We found that MCRPEC prevalence was low in the feces of healthy humans attending physical examinations in six hospitals (4.6%, 71/1532) but high in hospital wastewater (50.0%, 27/54). mcr-1 was mainly located on IncI2 (63.0% in wastewater and 62.0% in feces) and IncHI2 plasmids (18.5% in wastewater and 21.1% in feces). High similarity of the mcr-1 context and its carrying plasmids was observed in human and wastewater MCRPEC, with several isolates clustering together. The coexistence of the ESBL gene blaCTX-M with mcr-1 occurred in 19.7% of IncI2 plasmids. Notably, 60.0% of IncHI2 plasmids exhibited co-occurrence of mcr-1 with the disinfectant resistance gene (DRG) qacEΔ1, conferring resistance to quaternary ammonium compounds (QACs). We revealed that QACs, rather than the other two types of disinfectants─ortho-phthalaldehyde (OPA) and povidone-iodine (PVP-I)─select for plasmids carrying both qacEΔ1 and mcr-1 and elevate their conjugative transfer frequency. Monitoring of DRGs in MCRPEC and managing disinfectant use are urgently needed in healthcare settings to mitigate the spread of colistin resistance from hospital environments to inpatients.

PMID:39818750 | DOI:10.1021/acs.est.4c11368

<em>Orthopedia</em> regulates melanocortin 4 receptor transcription and energy homeostasis

Latest publications - Wed, 15/01/2025 - 11:00

Sci Transl Med. 2025 Jan 15;17(781):eadr6459. doi: 10.1126/scitranslmed.adr6459. Epub 2025 Jan 15.

ABSTRACT

Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of MC4R in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates Mc4r transcription. Deletion of Otp in PVN neurons during development or adulthood reduced Mc4r expression, causing increased food intake and obesity. In humans, four of the five carriers of rare predicted functional OTP variants in UK Biobank had obesity. To explore a causal role for human OTP variants, we generated mice with a loss-of-function OTP mutation identified in a child with severe obesity. Heterozygous knock-in mice exhibited hyperphagia and obesity, reversed by treatment with an MC4R agonist. Our findings demonstrate that OTP regulates mammalian energy homeostasis and enable the diagnosis and treatment of individuals with obesity due to OTP deficiency.

PMID:39813316 | DOI:10.1126/scitranslmed.adr6459

The mutational landscape of Staphylococcus aureus during colonisation

Latest publications - Mon, 13/01/2025 - 11:00

Nat Commun. 2025 Jan 13;16(1):302. doi: 10.1038/s41467-024-55186-x.

ABSTRACT

Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution. Here we applied a genome-wide mutation enrichment approach to a genomic dataset of 3060 S. aureus colonization isolates from 791 individuals. Despite limited within-host genetic diversity, we observed an excess of protein-altering mutations in metabolic genes, in regulators of quorum-sensing (agrA and agrC) and in known antibiotic targets (fusA, pbp2, dfrA and ileS). We demonstrated the phenotypic effect of multiple adaptive mutations in vitro, including changes in haemolytic activity, antibiotic susceptibility, and metabolite utilisation. Nitrogen metabolism showed the strongest evidence of adaptation, with the assimilatory nitrite reductase (nasD) and urease (ureG) showing the highest mutational enrichment. We identified a nasD natural mutant with enhanced growth under urea as the sole nitrogen source. Inclusion of 4090 additional isolate genomes from 731 individuals revealed eight more genes including sasA/sraP, darA/pstA, and rsbU with signals of adaptive variation that warrant further characterisation. Our study provides a comprehensive picture of the heterogeneity of S. aureus adaptive changes during colonisation, and a robust methodological approach applicable to study in host adaptive evolution in other bacterial pathogens.

PMID:39805814 | DOI:10.1038/s41467-024-55186-x

Routine childhood rabies pre-exposure prophylaxis can be cost effective in low- and middle-income countries

Latest publications - Sun, 12/01/2025 - 11:00

Vaccine. 2025 Jan 11;47:126703. doi: 10.1016/j.vaccine.2024.126703. Online ahead of print.

ABSTRACT

BACKGROUND: Pre-exposure prophylactic rabies vaccination (PrEP) is advised for travellers to countries with high rabies incidence, but rarely available for local residents. Some studies suggest poor cost-effectiveness of PrEP in such settings, but have generally focused upon post-exposure prophylaxis (PEP) cost savings as the main benefit of PrEP, without considering lives saved by PrEP efficacy.

METHODS: We compared incremental cost-effectiveness ratios (ICERs) of use of rabies PrEP, against an alternative of using only PEP, by adapting a decision-tree model previously used to inform Gavi's investment in rabies PEP. We consider scenarios including: a range of PrEP efficacies in individuals unable to access PEP; PrEP costs significantly below current prices (through single-dose approaches, inclusion in childhood vaccination schedules, increased manufacturing volume and/or new low-cost products); and variable rabies exposure risk and PEP access. We also present results from a simplified model, designed for ease of understanding.

RESULTS: Modelled ICERs were <1000 USD per quality adjusted life year (QALY) across a range of plausible combinations of rabies exposure risk, PEP access, PrEP cost and PrEP efficacy. If PrEP efficacy exceeds 50 % over 15 years, we estimate ICERs <500 USD/QALY where rabies incidence ≥3 per 100,000 per year and cost of vaccination is ≤5 USD/child. Under scenarios with lower rabies incidence of around 0.3 per 100,000 per year, due either to more limited exposure or greater access to PEP, ICERs <3000 USD may still be achieved even if PrEP efficacy is as low as 30 %.

CONCLUSIONS: Routine childhood PrEP may be cost-effective in settings with modest willingness-to-pay, and rabies exposure risks plausible across much of Africa and South Asia. Cost-effectiveness requires low-cost PrEP regimes and some efficacy of PrEP in individuals unable to access PEP. Under such conditions, PrEP may be an attractive additional tool in the fight against rabies.

PMID:39799849 | DOI:10.1016/j.vaccine.2024.126703