Latest publications

J Infect Dis. 2026 Jan 13:jiag027. doi: 10.1093/infdis/jiag027. Online ahead of print.

ABSTRACT

BACKGROUND: Despite data demonstrating the high prevalence of third-generation cephalosporin resistant gram-negative Enterobacterales (GNE) among children in sub-Saharan Africa, longitudinal descriptions of resistance among these pathogens from Francophone West Africa remain rare.

METHODS: We conducted a retrospective analysis of pathogen-positive children 0-15 years old included in an invasive bacterial infection study at l'Hôpital Gabriel Touré (in Bamako, Mali) from 2005-2023. We aimed to describe changes in pathogen burden and non-Salmonella GNE resistance over time and compare in-hospital mortality between patients with and without non-Salmonella GNE pathogens. Isolates from 2021-2023 underwent whole genome sequencing to identify genes conferring antimicrobial resistance.

RESULTS: Of 3,803 pathogen-positive patients, 392 grew at least one non-Salmonella GNE pathogen. The proportion of pathogen-positive patients with non-Salmonella GNE increased (6% vs. 38%) from 2005-2023. Third-generation cephalosporin and multidrug resistance among non-Salmonella GNE increased from 30% and 55%, respectively, in 2005-2009, to 93% (both) by 2021-2023. Children 0-2 months old from outside Bamako and 3 months-15 years old from and from outside Bamako with non-Salmonella GNE had higher mortality odds (3.17, 95% CI 1.69-5.95; 2.13, 95% CI 1.44-3.14; and 2.25, 95% CI 1.38-3.66, respectively) than similar patients with other pathogens. Sequencing confirmed the presence of the emerging pathogen Pantoea dispersa and revealed genes conferring multidrug resistance.

CONCLUSIONS: Data from this large pediatric referral center in Mali show a high and rising burden of multidrug-resistant gram-negative Enterobacterales. These patterns reflect concerns increasingly reported across sub-Saharan Africa, highlighting the urgency of strengthening antimicrobial access, diagnostics, and stewardship strategies in similar settings.

PMID:41525800 | DOI:10.1093/infdis/jiag027

Gut Microbes. 2026 Dec 31;18(1):2612836. doi: 10.1080/19490976.2026.2612836. Epub 2026 Jan 11.

ABSTRACT

Enteric infections remain a leading global cause of morbidity, mortality and economic loss, increasingly compounded by the rise of antimicrobial resistance. The gut microbiome - spanning bacteria, archaea, fungi, protists and viruses - is now recognized as an important mediator that shapes susceptibility to infection, pathogen expansion and disease severity through mechanisms such as colonization resistance, resource competition and immune modulation. Conversely, the gut microbial community can facilitate enteric infection through other processes such as cross-feeding and horizontal gene transfer. In this review, we synthesize correlative and mechanistic evidence currently available on microbiome-pathogen interactions; outline host, environmental and socioeconomic modifiers that affect disease risk across the life course; and evaluate current clinical applications. We highlight key limitations in the field and identify priority areas for future research to refine causal models of microbiome-pathogen ecology and enable targeted diagnostics and therapeutics for preventing and managing enteric infections.

PMID:41520282 | DOI:10.1080/19490976.2026.2612836

J Feline Med Surg. 2026 Jan 9:1098612X261416013. doi: 10.1177/1098612X261416013. Online ahead of print.

ABSTRACT

OBJECTIVES: Evaluate the association between serum amyloid A [SAA] concentrations and proteinuria in cats without known pre-renal, renal and post-renal causes of proteinuria and to document the magnitude of proteinuria in these cases.

METHODS: Cats with contemporaneous SAA and urine protein: creatinine ratio (UPC) data and without renal azotaemia, evidence of reduced urine concentrating ability, active urine sediment, hyperthyroidism, diabetes mellitus and recent steroid administration were included. Cats with SAA >3.9 µg/dL were classified as having increased SAA. UPC was compared between cats with and without increased SAA using the Mann Whitney U test, comparisons between the proportion of cases classified as proteinuric (UPC>0.4 or UPC >0.2) between the groups were made using the Fisher's Exact test and correlations were assessed using Spearman's correlation coefficient. Multivariable logistic regression analysis was performed to examine the association between SAA and UPC.

RESULTS: UPC was significantly higher in the increased SAA group than in the normal SAA (0.32 [0.11-1.25] vs. 0.17 [0.08-0.59]; P=0.002) and cats with increased SAA were also more likely to be borderline or overtly proteinuric (UPC >0.2) than cats in the normal SAA group (72% vs. 36%; P=0.02). There was also a moderate positive correlation between UPC and SAA (rs=0.519; P<0.001).

CONCLUSIONS AND RELEVANCE: increased urine protein: creatinine ratio is associated with increased SAA concentrations in cats, although the severity of proteinuria in these cases is usually mild. Systemic inflammation might contribute to proteinuria in some cats, although further studies are required to establish a causal relationship.

PMID:41510759 | DOI:10.1177/1098612X261416013

Infect Immun. 2026 Jan 6:e0011825. doi: 10.1128/iai.00118-25. Online ahead of print.

ABSTRACT

Salmonella enterica infections are a major cause of morbidity and mortality worldwide, especially in sub-Saharan Africa and in the Asian continent, and are increasingly associated with antimicrobial resistance. Salmonella enterica serovars Typhi and Paratyphi A, B, and C cause enteric fever, while non-typhoidal Salmonella serovars (usually Typhimurium and Enteritidis) cause mainly gastroenteritis which can lead to systemic infections. Vaccines are only licensed against S. Typhi, but different combinations are in clinical development to prevent S. Typhi and S. Paratyphi A or S. Typhi and non-typhoidal Salmonella. Here, we describe elements of the pathogenesis of and immunity to Salmonella that are critical to guide the rational design of vaccines. We highlight how the choice of appropriate immunogenic and protective antigens would be essential to achieve the maximum coverage of serovars in a multivalent Salmonella vaccine. The principal vaccines under development at the preclinical and clinical stages are described, together with considerations on the technical and clinical feasibility of moving combination vaccines toward licensure.

PMID:41493384 | DOI:10.1128/iai.00118-25

Br J Pharmacol. 2025 Dec;182 Suppl 1:S259-S306. doi: 10.1111/bph.70233.

ABSTRACT

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of the more detailed information and links available at the www.guidetopharmacology.org website, the printed guide serves as a permanent, citable, point-in-time record, that remains stable despite ongoing updates to the online database. The full contents of this publication can be found at https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70233. The Concise Guides provide expert-curated recommendations of 'Gold Standard' selective pharmacological tools, available either commercially or as donations, which enable the identification of individual drug targets or families of drug targets. While the Concise Guide offers a more streamlined overview, more comprehensive information, including detailed pharmacological profiles and links to multiple online databases, is available through the Guide to Pharmacology website. The 2025/26 edition of the Concise Guide is based on material current as of mid-2025, and supersedes all previous editions, including the 2023/24 Guide, and earlier Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), and as such provides official IUPHAR classification and nomenclature for human drug targets, where applicable. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. Each section includes nomenclature guidance, concise summaries, information of the best available pharmacological tools, key references, and suggestions for further reading.

PMID:41461584 | DOI:10.1111/bph.70233

Br J Pharmacol. 2025 Dec;182 Suppl 1:S24-S151. doi: 10.1111/bph.70230.

ABSTRACT

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of the more detailed information and links available at the www.guidetopharmacology.org website, the printed guide serves as a permanent, citable, point-in-time record, that remains stable despite ongoing updates to the online database. The full contents of this publication can be found at https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70230. The Concise Guides provide expert-curated recommendations of 'Gold Standard' selective pharmacological tools, available either commercially or as donations, which enable the identification of individual drug targets or families of drug targets. While the Concise Guide offers a more streamlined overview, more comprehensive information, including detailed pharmacological profiles and links to multiple online databases, is available through the Guide to Pharmacology website. The 2025/26 edition of the Concise Guide is based on material current as of mid-2025, and supersedes all previous editions, including the 2023/24 Guide, and earlier Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), and as such provides official IUPHAR classification and nomenclature for human drug targets, where applicable. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. Each section includes nomenclature guidance, concise summaries, information of the best available pharmacological tools, key references, and suggestions for further reading.

PMID:41461581 | DOI:10.1111/bph.70230

Vet Rec. 2025 Dec 26. doi: 10.1002/vetr.70169. Online ahead of print.

ABSTRACT

BACKGROUND: During lambing, 10% iodine is often used to protect neonatal navel and ear tag sites. The evidence for its effectiveness is sparse. Recently, a specific navel barrier solution (NBS) was developed. Here, an in vivo field trial compared the two treatments.

METHODS: Ten farms reported data from 6840 lambs. The navel and ear tag sites of alternate lambs were treated with usual care-iodine or NBS. Usual care-iodine was 10% iodine for all navels and for most ear tag sites.

RESULTS: Mortality was 8.36% for the usual care-iodine group and 9.34% for the sub-group where only iodine was used for navel and ear tag sites. It was 6.51% for NBS (p < 0.004 vs. iodine groups). Mixed-effect generalised linear modelling gave an adjusted odds ratio (OR) for mortality of 0.76 for NBS (95% confidence interval [CI]: 0.63-0.91; p = 0.003). Spraying navels was inferior to dipping them for survival (OR 2.14; 95% CI: 1.11-4.09; p = 0.02). Farmers did not report differences in joint ill between the groups.

LIMITATIONS: For practical implementation, the study was non-blinded and pseudorandomised. Non-appearance of a lamb at the week 8 weighing event was taken as a sensitive and objective proxy for death.

CONCLUSION: Optimal navel and ear tag site application during lambing efficiently protects against neonatal deaths. NBS is superior to 10% iodine, and dipping outperforms spraying for improvement of lamb survival.

PMID:41454551 | DOI:10.1002/vetr.70169

Front Endocrinol (Lausanne). 2025 Nov 25;16:1699831. doi: 10.3389/fendo.2025.1699831. eCollection 2025.

ABSTRACT

SCOPE: Adipocyte-derived extracellular vesicle (EV) lipid cargo reflects the obese metabolic state. Nevertheless, it is currently unknown whether the adipocyte-derived EV lipid profile is influenced by saturated fatty acid overload. This study investigated if palmitic acid (PA) affected human Simpson-Golabi-Behmel syndrome (SGBS) adipocyte insulin sensitivity and the repercussions on the EV fatty acid cargo secreted by these cells.

METHODS: Adipocytes were treated with 500 or 1,000 μM of PA, and cytotoxicity was assessed using the lactate dehydrogenase assay. Thereafter, cells were treated with 1,000 μM of PA for 48 h, followed by the assessment of triglyceride accumulation and adipokine expression. Insulin signaling, NF-κβ activation, and stearoyl-CoA desaturase-1 (SCD) abundance were assessed by Western blot. EVs were isolated via ultracentrifugation, and the intracellular as well as the EV fatty acid profile was characterized using gas chromatography coupled to a flame ionization detector.

RESULTS: Neither 500 nor 1,000 μM of PA did not elicited a cytotoxic effect on SGBS adipocytes. PA promoted adipocyte hypertrophy without hampering insulin signaling or triggering the activation of NF-κβ. However, PA increased intracellular and EV SFA content and raised intracellular oleic acid (OA) levels in parallel with the upregulation of SCD, while it decreased OA content in EVs.

CONCLUSIONS: Active lipid sorting within EVs may be an additional mechanism underpinning intercellular communication by which adipocytes inform other cells about their metabolic status. However, further studies are warranted to evaluate the effects of EV lipid cargo on recipient cells.

PMID:41377945 | PMC:PMC12685657 | DOI:10.3389/fendo.2025.1699831

Blood Adv. 2025 Dec 9;9(23):6234-6235. doi: 10.1182/bloodadvances.2025018018.

NO ABSTRACT

PMID:41364450 | DOI:10.1182/bloodadvances.2025018018

Microb Genom. 2025 Dec;11(12). doi: 10.1099/mgen.0.001589.

ABSTRACT

Campylobacter jejuni is a commensal bacterium that colonizes livestock and wild animals and is responsible for more than 80% of campylobacteriosis cases in humans, which all ultimately have an animal source. Its high genome plasticity and recombination rate allow it to adapt to multiple hosts and lead to the rapid emergence of lineages, some of which can be antibiotic resistant. Our aim in this study was to examine the population structure of Campylobacter in California and assess its differentiation between animal hosts and humans. We sequenced 69 human clinical isolates of C. jejuni from California and collected a dataset of human and animal Californian genomes to contextualize them. By comparing groups of isolates, we detected significant levels of differentiation between the human and animal Californian isolates. Through phylogenetic reconstruction, we demonstrated that, as expected, the human C. jejuni clinical isolates were derived from both avian and ruminant sources but represented a distinct subset of those populations. By identifying the genomic regions that were contributing to population differentiation amongst the host groups, we were able to identify protein variants potentially responsible for host adaptation and propensity to cause infection in humans.

PMID:41359477 | DOI:10.1099/mgen.0.001589

Vet Rec. 2025 Dec 4. doi: 10.1002/vetr.5775. Online ahead of print.

ABSTRACT

BACKGROUND: Biosecurity is the primary defence against diseases such as avian influenza (AI) for poultry farms. This research reviews online resources to assess the availability and topics shaping biosecurity advice for poultry farmers.

METHODS: A rapid scoping review examined biosecurity guidelines available to UK poultry farmers on 10 websites (www.gov.uk; www.gov.scot; www.gov.wales; www.bfrepa.co.uk; www.nfuonline.com; www.britishpoultry.org.uk; www.redtractor.org.uk; www.bvpa.co.uk; www.bva.co.uk; www.britisheggindustrycouncil.com). Webpages were analysed against key criteria, including topics and levels of detail.

RESULTS: Ultimately, 174 webpages were analysed. Government websites housed many pages relevant to poultry biosecurity, while assurer and trade union sites contained fewer. There was a broad consensus across websites on the topics covered, with hygiene and administrative guidance included on the largest number of webpages. Most webpages contained only limited or some relevant details, often repeating key messages rather than offering comprehensive implementation guidance. Pages with extensive detail were linked to regularly and appeared early in search results.

LIMITATIONS: Northern Ireland's government website was not reviewed.

CONCLUSION: Many webpages advising on poultry farm biosecurity exist. They often highlighted the importance of hygiene measures and administrative actions. However, the lack of detailed implementation guidance may present challenges for farmers seeking to learn how to implement good biosecurity.

PMID:41346186 | DOI:10.1002/vetr.5775

Nat Commun. 2025 Dec 2;16(1):10415. doi: 10.1038/s41467-025-66564-4.

ABSTRACT

Staphylococcus aureus colonises the nose in humans, with individuals defined as persistent, intermittent or non-carriers. Unlike the gut microbiome, the nasal microbiome has not been studied in large numbers of people. Here, we define the nasal microbiome in ~1100 individuals from the CARRIAGE study (ISRCTN: ISRCTN10474633) and combine with S. aureus culture data. We identify seven community state types (CST), including two CSTs more common in females. Approximately 70% of those who are persistently colonised with S. aureus have a CST dominated by S. aureus, while non-carriers are distributed across the other six CSTs. Intermittent carriers are not a unique state but have microbiomes that resemble non- or persistent carriers. Persistent carriage is positively associated with S. aureus abundance, and negatively associated with three Corynebacterium species, Dolosigranulum pigrum, Staphylococcus epidermidis, and Moraxella catarrhalis; the microbiome can be exploited with machine learning to accurately predict the persistence of S. aureus colonisation. Finally, we find that certain S. aureus lineages are better adapted to colonisation than others. Our data provides a comprehensive view of the nasal microbiome with respect to S. aureus colonisation, describing two key states: a S. aureus dominated CST in which S. aureus shapes the microbiome, and CSTs in which S. aureus is rare or absent.

PMID:41330943 | DOI:10.1038/s41467-025-66564-4

BMC Biol. 2025 Dec 2. doi: 10.1186/s12915-025-02477-4. Online ahead of print.

ABSTRACT

BACKGROUND: The interconnectedness of human, animal, and environmental health drives emerging threats, such as antimicrobial-resistant pathogens. The widespread use of the same antimicrobials in both human and livestock may play a role in interspecies bacterial transmission by disrupting natural microbial communities and creating an environment favouring resistant bacteria. Pigs and poultry receive high levels of antimicrobials and are reservoirs of multidrug-resistant bacteria, including Streptococcus suis, a zoonotic pig pathogen. S. suis detection in non-porcine hosts, particularly poultry, raises a critical question: is this due to transient spillover or does it represent sustained host jumps and adaptation?

RESULTS: Analysing over 3000 S. suis genomes from a diverse range of hosts-including pigs, wild boar, humans, cats, dogs, cattle, fish, otter, and birds-we identify a multidrug-resistant lineage, distinct from the lineage responsible for most zoonoses, that has undergone multiple host jump events into birds. Unlike transmission to humans, which is exclusively derived through contacts with pigs, we find evidence of S. suis adaptation to birds. This includes phylogenetic persistence, independent acquisition of bird-specific mobile genomic islands, enhanced survival in chicken versus pig blood, and subsequent transmission from poultry to wild birds.

CONCLUSIONS: While chickens may not be a source of zoonotic S. suis infections, shared antibiotic usage in pigs and poultry may have promoted host jumps of multidrug-resistant S. suis, leading to onward transmission to wild bird populations. Our results suggest that antibiotic use in livestock production may promote transmission of antimicrobial-resistant bacteria to other hosts, thereby expanding the ecological range of bacterial pathogens.

PMID:41327274 | DOI:10.1186/s12915-025-02477-4

Curr Microbiol. 2025 Dec 1;83(1):54. doi: 10.1007/s00284-025-04621-3.

ABSTRACT

Proteus mirabilis is a foodborne and environmental pathogen causing catheter-associated urinary tract infections (CAUTIs) with antimicrobial resistance (AMR) and virulence. As the potential of Indian strains remains underexplored, whole-genome sequence (WGS) data of 18 strains were analyzed for AMR, virulence, and genetic relatedness. The disc diffusion method assessed phenotypic AMR. Genomic DNA sequencing was performed on Illumina MiSeq platform, followed by quality control, read assembly, gap closure, and annotation using software tools. Various tools were used to predict antimicrobial resistance genes (ARGs), resistome, virulence, mobile genetic elements (MGEs), pathogenicity, single nucleotide polymorphisms (SNPs), and plasmids. Phylogenetic analysis based on SNPs was performed using maximum likelihood (ML) and neighbor-joining (NJ) methods. All isolates showed resistance to tetracycline but were sensitive to gentamicin, amoxicillin/clavulanic acid, and streptomycin. Genome sizes ranged from 3,824 to 4,296 kb (average 3691.6 ± 164.3) and 5-26 ARGs per isolate. Common intrinsic resistance genes, including tetJ, tet(D), K. pneumoniae KpnF, and amphenicol resistance genes (cat and catA4) were present in all but one isolate. Predominant ARGs were linked to tetracycline, quinolone, cephalosporin, cephamycin, penam, quaternary ammonium compounds, and glycopeptide groups present in MGEs. Isolates contained numerous virulence genes (n = 4785) across 10 categories. The average SNP count was 4114.27 ± 3216.91, with four isolates showing no SNPs. Phylogenetic analysis revealed diversity (D= -1.6910, P = 0.0047) among 86 reference strains. Ongoing monitoring through WGS analysis is essential for understanding and managing infections caused by this pathogen.

PMID:41324717 | DOI:10.1007/s00284-025-04621-3

Cell. 2025 Nov 28:S0092-8674(25)01251-6. doi: 10.1016/j.cell.2025.11.002. Online ahead of print.

ABSTRACT

The combination of innate immune activation and metabolic disruption plays critical roles in many diseases, often leading to mitochondrial dysfunction and oxidative stress that drive pathogenesis. However, mechanistic regulation under these conditions remains poorly defined. Here, we report a distinct lytic cell death mechanism induced by innate immune signaling and metabolic disruption, independent of caspase activity and previously described pyroptosis, PANoptosis, necroptosis, ferroptosis, and oxeiptosis. Instead, mitochondria undergoing BAX/BAK1/BID-dependent oxidative stress maintained prolonged plasma membrane contact, leading to local oxidative damage, a process we termed mitoxyperiosis. This process then caused membrane lysis and cell death, termed mitoxyperilysis. mTORC2 regulated the cell death, and mTOR inhibition restored cytoskeletal activity for lamellipodia to retract and mobilize mitochondria away from the membrane, preserving integrity. Activating this pathway in vivo regressed tumors in an mTORC2-dependent manner. Overall, our results identify a lytic cell death modality in response to the synergism of innate immune signaling and metabolic disruption.

PMID:41317732 | DOI:10.1016/j.cell.2025.11.002

Sci Rep. 2025 Nov 28;15(1):42641. doi: 10.1038/s41598-025-26710-w.

ABSTRACT

Rift Valley fever (RVF) and brucellosis are serious zoonotic diseases with significant public health and economic consequences. In livestock, both diseases are associated with abortions that are not routinely reported as part of disease surveillance. We piloted a community-driven call centre initiative in Isingiro District, Uganda, from March to June 2023, aimed at facilitating the reporting of livestock abortions. The community call centre was promoted through stakeholder engagements, social media campaigns, and targeted sensitisation materials.Over three months, we received 53 alerts reporting 423 livestock abortions. We investigated 78% of these alerts and collected 200 serum samples. Of these, 184 samples were tested via ELISA for RVF virus antibodies (IgG and IgM), while all 200 were screened for anti-Brucella (IgG) antibodies using validated commercial kits. The proportion of aborting livestock testing positive for IgG antibodies to Rift Valley fever virus (RVFV) was 38% [95% CI 29-47] in cattle, 33% [95% CI 14-61] in sheep, and 20% [95% CI 12-31] in goats. For IgM, sheep showed the highest proportion at 8% [95% CI 1-35], followed by cattle at 2% [95% CI 1-6]. Further analysis showed that cattle had a 2.9-fold elevated odds of RVF IgG seropositivity relative to sheep and goats (OR = 2.9, 95% CI 1.27-7.07, P = 0.014). The proportion of aborting livestock testing positive for IgG antibodies to brucellosis was 36% [95% CI 25-49] in goats and 16% [95% CI 11-23] in cattle, with no evidence of antibodies found in the sampled sheep.Our pilot study revealed high seropositivity to RVFV and brucellosis in cattle, sheep, and goats that had recently experienced abortions. This study demonstrates that early reporting of abortions by communities, followed by immediate collection of samples for diagnosis, could facilitate early detection and response to outbreaks. Furthermore, the response registered at the call centre by livestock owners has the potential for collaborative efforts to establish disease reporting and surveillance, thereby enabling more timely interventions.

PMID:41315575 | DOI:10.1038/s41598-025-26710-w

Am J Vet Res. 2025 Nov 24:1-9. doi: 10.2460/ajvr.25.07.0267. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the investigation, management, and outcome, including medication adverse effects, of nonassociative immune-mediated polyarthritis cases when referred to different specialist disciplines.

METHODS: A retrospective observational review of medical records from 4 United Kingdom referral centers (2018 through 2022) was conducted. Dogs were included if they had nondegenerative neutrophilic inflammation in synovial fluid from > 2 joints and associated disease was not evident. Data on clinical signs, diagnostic tests, treatment, and adverse effects were collected. Remission at 12 months and relapse were recorded.

RESULTS: 83 dogs met the inclusion data. Cases referred to internal medicine underwent more diagnostic procedures, received lower initial prednisolone doses, and were more commonly prescribed adjunctive immunosuppressives compared to neurology (effect size, 0.35; 95% CI, 0.1 to 0.57:OR, 4.7; 95% CI, 0.6 to 216) and orthopedics (effect size, 0.26; 95% CI, 0.02 to 0.53:OR, 4.0; 95% CI, 0.5 to 185). There was no significant difference in the frequency of adverse effects with prednisolone dose, referral service, or adjunct immunosuppressant use. Remission at 12 months was not significantly associated with referral service, corticosteroid dose, or adjunctive immunosuppressant use.

CONCLUSIONS: The management of nonassociative immune-mediated polyarthritis varies significantly across specialist disciplines. Despite differences in treatment strategies, adverse effects were common and not significantly associated with corticosteroid dose or adjunct use.

CLINICAL RELEVANCE: Further controlled prospective studies should focus on optimizing treatment protocols to improve outcomes and minimize complications in this challenging disease.

PMID:41289689 | DOI:10.2460/ajvr.25.07.0267

Nat Commun. 2025 Nov 20;16(1):10222. doi: 10.1038/s41467-025-65023-4.

ABSTRACT

Impaired mitochondrial bioenergetics in macrophages promotes hyperinflammatory cytokine responses, but whether inherited mtDNA mutations drive similar phenotypes is unknown. Here, we profiled macrophages harbouring a heteroplasmic mitochondrial tRNAAla mutation (m.5019A>G) to address this question. These macrophages exhibit combined respiratory chain defects, reduced oxidative phosphorylation, disrupted cristae architecture, and compensatory metabolic adaptations in central carbon metabolism. Upon inflammatory activation, m.5019A>G macrophages produce elevated type I interferon (IFN), while exhibiting reduced pro-inflammatory cytokines and oxylipins. Mechanistically, suppression of pro-IL-1β and COX2 requires autocrine IFN-β signalling. IFN-β induction is biphasic: an early TLR4-IRF3 driven phase, and a later response involving mitochondrial nucleic acids and the cGAS-STING pathway. In vivo, lipopolysaccharide (LPS) challenge of m.5019A>G mice results in elevated type I IFN signalling and exacerbated sickness behaviour. These findings reveal that a pathogenic mtDNA mutation promotes an imbalanced innate immune response, which has potential implications for the progression of pathology in mtDNA disease patients.

PMID:41266309 | DOI:10.1038/s41467-025-65023-4

Parasitology. 2025 Nov 20:1-3. doi: 10.1017/S0031182025101273. Online ahead of print.

NO ABSTRACT

PMID:41261533 | DOI:10.1017/S0031182025101273

Pain Rep. 2025 Nov 14;10(6):e1360. doi: 10.1097/PR9.0000000000001360. eCollection 2025 Dec.

ABSTRACT

INTRODUCTION: Microglia and astrocytes are believed to play a central role in the pathogenesis of neuropathic pain (NeP). These glial cells are commonly identified by the expression of ionized calcium-binding adaptor molecule 1 (IBA1) for microglia and glial fibrillary acidic protein (GFAP) for astrocytes. Under pathological conditions, astrocytes and microglia undergo both morphological and transcriptional changes, which may promote shifts in functions that can have both protective and detrimental effects on the surrounding neuroparenchyma. Like humans, the dog breed Cavalier King Charles Spaniels (CKCSs) suffers from heritable syringomyelia (SM) which in both species is associated with NeP.

OBJECTIVES: To investigate the potential role of IBA1 and GFAP-positive cells in the dorsal horn in CKCSs with SM and NeP.

METHODS: Using NanoString GeoMx technology, we conducted spatial transcriptomic analyses on spinal cord dorsal horns from CKCSs with SM and NeP.

RESULTS: Several differentially expressed genes were identified in dogs with SM and NeP. Cells positive for IBA1 showed upregulation of inflammatory genes as well as a downregulation of immune functions, while GFAP-positive cells indicated different states of reactivity. Pathway analyses indicated that the PI3K-Akt signaling pathway may be involved in the generation of NeP in CKCSs with SM.

CONCLUSION: These findings provide new insights into the complex molecular changes in dorsal horn IBA1 and GFAP-rich areas in the presence of NeP and SM. The findings of this study serve as a foundation for future research that may facilitate new understandings of NeP mechanisms.

PMID:41255848 | PMC:PMC12622671 | DOI:10.1097/PR9.0000000000001360