Latest publications

Microb Genom. 2024 May;10(5). doi: 10.1099/mgen.0.001247.

ABSTRACT

Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a bla CTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. Using a high-throughput bioinformatics pipeline we screened 47 784 isolates for the presence of the P1 lytic replication gene repL, identifying 226 positive isolates from 25 serovars and demonstrating that phage-plasmid elements are more frequent than previously thought. The affinity for phage-plasmids appears highly serovar-dependent, with several serovars being more likely hosts than others; most of the positive isolates (170/226) belonged to S. Typhimurium ST34 and ST19. The phage-plasmids ranged between 85.8 and 98.2 kb in size, with an average length of 92.1 kb; detailed analysis indicated a high amount of diversity in gene content and genomic architecture. In total, 132 phage-plasmids had the p0111 plasmid replication type, and 94 the IncY type; phylogenetic analysis indicated that both horizontal and vertical gene transmission mechanisms are likely to be involved in phage-plasmid propagation. Finally, phage-plasmids were present in isolates that were resistant and non-resistant to antimicrobials. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing.

PMID:38717818 | DOI:10.1099/mgen.0.001247

PLoS One. 2024 May 7;19(5):e0291183. doi: 10.1371/journal.pone.0291183. eCollection 2024.

ABSTRACT

BACKGROUND: Mendelian randomisation (MR) is the use of genetic variants as instrumental variables. Mode-based estimators (MBE) are one of the most popular types of estimators used in univariable-MR studies and is often used as a sensitivity analysis for pleiotropy. However, because there are no plurality valid regression estimators, modal estimators for multivariable-MR have been under-explored.

METHODS: We use the residual framework for multivariable-MR to introduce two multivariable modal estimators: multivariable-MBE, which uses IVW to create residuals fed into a traditional plurality valid estimator, and an estimator which instead has the residuals fed into the contamination mixture method (CM), multivariable-CM. We then use Monte-Carlo simulations to explore the performance of these estimators when compared to existing ones and re-analyse the data used by Grant and Burgess (2021) looking at the causal effect of intelligence, education, and household income on Alzheimer's disease as an applied example.

RESULTS: In our simulation, we found that multivariable-MBE was generally too variable to be much use. Multivariable-CM produced more precise estimates on the other hand. Multivariable-CM performed better than MR-Egger in almost all settings, and Weighted Median under balanced pleiotropy. However, it underperformed Weighted Median when there was a moderate amount of directional pleiotropy. Our re-analysis supported the conclusion of Grant and Burgess (2021), that intelligence had a protective effect on Alzheimer's disease, while education, and household income do not have a causal effect.

CONCLUSIONS: Here we introduced two, non-regression-based, plurality valid estimators for multivariable MR. Of these, "multivariable-CM" which uses IVW to create residuals fed into a contamination-mixture model, performed the best. This estimator uses a plurality of variants valid assumption, and appears to provide precise and unbiased estimates in the presence of balanced pleiotropy and small amounts of directional pleiotropy.

PMID:38713711 | DOI:10.1371/journal.pone.0291183

Lancet. 2024 May 2:S0140-6736(24)00850-X. doi: 10.1016/S0140-6736(24)00850-X. Online ahead of print.

ABSTRACT

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception.

METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period.

FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood.

INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality.

FUNDING: WHO.

PMID:38705159 | DOI:10.1016/S0140-6736(24)00850-X

J Vet Diagn Invest. 2024 May 4:10406387241248594. doi: 10.1177/10406387241248594. Online ahead of print.

ABSTRACT

Liver lobe torsion has been reported in many species, with frequent reports in rabbits. Here we describe caudate liver lobe torsion and concurrent necrohemorrhagic typhlocolitis in a Patagonian mara (syn: Patagonian cavy, Patagonian hare, Dolichotis patagonum). Following acute death, postmortem examination findings included torsion of the hepatic caudate process, which had fibrous adhesions to the pancreas indicating chronicity. The cecal apex and proximal 30 cm of colon had regionally reddened serosa and diffusely roughened and reddened mucosa with brown-red and granular luminal contents. Key histologic findings included massive necrosis of the torsed hepatic caudate lobe, consistent with infarction, necrotizing hepatitis in remaining areas of liver, necrohemorrhagic typhlocolitis, adrenocortical necrosis and hemorrhage, and renal tubular degeneration and necrosis with tubular casts. Bacterial culture of cecal contents yielded pure growth of Salmonella spp. Death was attributed to toxemia or bacteremia resulting from Salmonella spp. infection, as the hepatic lobe torsion appeared chronic. It was undetermined if the liver lobe torsion predisposed to gastrointestinal compromise and infection. Patagonian maras have some anatomical similarities to rabbits and are highly cursorial, not dissimilar to hares, Lepus spp. We speculate that these characteristics may increase the likelihood of hepatic caudate lobe torsion in this species.

PMID:38702955 | DOI:10.1177/10406387241248594

Sci Rep. 2024 May 3;14(1):10226. doi: 10.1038/s41598-024-60377-z.

ABSTRACT

Tracheal pooling for Mycoplasma hyopneumoniae (M. hyopneumoniae) DNA detection allows for decreased diagnostic cost, one of the main constraints in surveillance programs. The objectives of this study were to estimate the sensitivity of pooled-sample testing for the detection of M. hyopneumoniae in tracheal samples and to develop probability of M. hyopneumoniae detection estimates for tracheal samples pooled by 3, 5, and 10. A total of 48 M. hyopneumoniae PCR-positive field samples were pooled 3-, 5-, and 10-times using field M. hyopneumoniae DNA-negative samples and tested in triplicate. The sensitivity was estimated at 0.96 (95% credible interval [Cred. Int.]: 0.93, 0.98) for pools of 3, 0.95 (95% Cred. Int: 0.92, 0.98) for pools of 5, and 0.93 (95% Cred. Int.: 0.89, 0.96) for pools of 10. All pool sizes resulted in PCR-positive if the individual tracheal sample Ct value was < 33. Additionally, there was no significant decrease in the probability of detecting at least one M. hyopneumoniae-infected pig given any pool size (3, 5, or 10) of tracheal swabs. Furthermore, this manuscript applies the probability of detection estimates to various real-life diagnostic testing scenarios. Combining increased total animals sampled with pooling can be a cost-effective tool to maximize the performance of M. hyopneumoniae surveillance programs.

PMID:38702379 | DOI:10.1038/s41598-024-60377-z

mBio. 2024 Apr 29:e0058124. doi: 10.1128/mbio.00581-24. Online ahead of print.

ABSTRACT

Recombination of short DNA fragments via horizontal gene transfer (HGT) can introduce beneficial alleles, create genomic disharmony through negative epistasis, and create adaptive gene combinations through positive epistasis. For non-core (accessory) genes, the negative epistatic cost is likely to be minimal because the incoming genes have not co-evolved with the recipient genome and are frequently observed as tightly linked cassettes with major effects. By contrast, interspecific recombination in the core genome is expected to be rare because disruptive allelic replacement is likely to introduce negative epistasis. Why then is homologous recombination common in the core of bacterial genomes? To understand this enigma, we take advantage of an exceptional model system, the common enteric pathogens Campylobacter jejuni and C. coli that are known for very high magnitude interspecies gene flow in the core genome. As expected, HGT does indeed disrupt co-adapted allele pairings, indirect evidence of negative epistasis. However, multiple HGT events enable recovery of the genome's co-adaption between introgressing alleles, even in core metabolism genes (e.g., formate dehydrogenase). These findings demonstrate that, even for complex traits, genetic coalitions can be decoupled, transferred, and independently reinstated in a new genetic background-facilitating transition between fitness peaks. In this example, the two-step recombinational process is associated with C. coli that are adapted to the agricultural niche.IMPORTANCEGenetic exchange among bacteria shapes the microbial world. From the acquisition of antimicrobial resistance genes to fundamental questions about the nature of bacterial species, this powerful evolutionary force has preoccupied scientists for decades. However, the mixing of genes between species rests on a paradox: 0n one hand, promoting adaptation by conferring novel functionality; on the other, potentially introducing disharmonious gene combinations (negative epistasis) that will be selected against. Taking an interdisciplinary approach to analyze natural populations of the enteric bacteria Campylobacter, an ideal example of long-range admixture, we demonstrate that genes can independently transfer across species boundaries and rejoin in functional networks in a recipient genome. The positive impact of two-gene interactions appears to be adaptive by expanding metabolic capacity and facilitating niche shifts through interspecific hybridization. This challenges conventional ideas and highlights the possibility of multiple-step evolution of multi-gene traits by interspecific introgression.

PMID:38683013 | DOI:10.1128/mbio.00581-24

Biol Trace Elem Res. 2024 Apr 24. doi: 10.1007/s12011-024-04175-8. Online ahead of print.

ABSTRACT

Silicon (Si) may be a mineral beneficial for bone health. Pregnancy and lactation have major impacts on maternal bone metabolism as bone minerals, including calcium (Ca), are required for growth of the foetus and for milk production. Like urinary Ca excretion, Si excretion has been reported to be high in pregnant women, but there are no data post-partum and during lactation. The aim of the present study was to investigate the urinary excretion of Si (U-Si), from the third trimester of pregnancy until 18 months post-partum, and in relation to the length of lactation, to determine if changes in U-Si are associated with changes in areal bone mineral density (aBMD). This longitudinal study included 81 pregnant women, of whom 56 completed the study. Spot urine samples were collected at the third trimester and at 0.5, 4, 12, and 18 months post-partum and were analysed for Si and Ca by ICP-OES. The aBMD was measured post-partum at lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Women lactating for 4-8.9 and ≥ 9 months had significantly higher U-Si at 4 months post-partum, compared with the third trimester. No significant longitudinal differences in U-Si were found after correcting for creatinine. Changes in U-Si and in aBMD were not correlated, except at the lumbar spine from 0.5 to 12 months post-partum in the women lactating for 4-8.9 months. Taken together, our results suggest that there is a possibility that U-Si increases post-partum in women lactating for 4 months or longer, although it is not related to changes in aBMD.

PMID:38656681 | DOI:10.1007/s12011-024-04175-8

Front Pharmacol. 2024 Apr 9;15:1369489. doi: 10.3389/fphar.2024.1369489. eCollection 2024.

ABSTRACT

Introduction: Pulmonary arterial hypertension (PAH) is characterised by endothelial dysfunction and pathological vascular remodelling, resulting in the occlusion of pulmonary arteries and arterioles, right ventricular hypertrophy, and eventually fatal heart failure. Targeting the apelin receptor with the novel, G protein-biased peptide agonist, MM07, is hypothesised to reverse the developed symptoms of elevated right ventricular systolic pressure and right ventricular hypertrophy. Here, the effects of MM07 were compared with the clinical standard-of-care endothelin receptor antagonist macitentan. Methods: Male Sprague-Dawley rats were randomised and treated with either normoxia/saline, or Sugen/hypoxia (SuHx) to induce an established model of PAH, before subsequent treatment with either saline, macitentan (30 mg/kg), or MM07 (10 mg/kg). Rats were then anaesthetised and catheterised for haemodynamic measurements, and tissues collected for histopathological assessment. Results: The SuHx/saline group presented with significant increases in right ventricular hypertrophy, right ventricular systolic pressure, and muscularization of pulmonary arteries compared to normoxic/saline controls. Critically, MM07 was as at least as effective as macitentan in significantly reversing detrimental structural and haemodynamic changes after 4 weeks of treatment. Discussion: These results support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.

PMID:38655187 | PMC:PMC11035786 | DOI:10.3389/fphar.2024.1369489

Nat Med. 2024 Apr 22. doi: 10.1038/s41591-024-02922-x. Online ahead of print.

NO ABSTRACT

PMID:38649779 | DOI:10.1038/s41591-024-02922-x

Comput Struct Biotechnol J. 2024 Apr 10;23:1522-1533. doi: 10.1016/j.csbj.2024.04.019. eCollection 2024 Dec.

ABSTRACT

The complex relationships between gastrointestinal (GI) nematodes and the host gut microbiota have been implicated in key aspects of helminth disease and infection outcomes. Nevertheless, the direct and indirect mechanisms governing these interactions are, thus far, largely unknown. In this proof-of-concept study, we demonstrate that the excretory-secretory products (ESPs) and extracellular vesicles (EVs) of key GI nematodes contain peptides that, when recombinantly expressed, exert antimicrobial activity in vitro against Bacillus subtilis. In particular, using time-lapse microfluidics microscopy, we demonstrate that exposure of B. subtilis to a recombinant saposin-domain containing peptide from the 'brown stomach worm', Teladorsagia circumcincta, and a metridin-like ShK toxin from the 'barber's pole worm', Haemonchus contortus, results in cell lysis and significantly reduced growth rates. Data from this study support the hypothesis that GI nematodes may modulate the composition of the vertebrate gut microbiota directly via the secretion of antimicrobial peptides, and pave the way for future investigations aimed at deciphering the impact of such changes on the pathophysiology of GI helminth infection and disease.

PMID:38633385 | PMC:PMC11021794 | DOI:10.1016/j.csbj.2024.04.019

R Soc Open Sci. 2024 Apr 17;11(4):231875. doi: 10.1098/rsos.231875. eCollection 2024 Apr.

ABSTRACT

Tasmanian devils are endangered by a transmissible cancer known as Tasmanian devil facial tumour 1 (DFT1). A 2020 study by Patton et al. (Science 370, eabb9772 (doi:10.1126/science.abb9772)) used genome data from DFT1 tumours to produce a dated phylogenetic tree for this transmissible cancer lineage, and thence, using phylodynamics models, to estimate its epidemiological parameters and predict its future trajectory. It concluded that the effective reproduction number for DFT1 had declined to a value of one, and that the disease had shifted from emergence to endemism. We show that the study is based on erroneous mutation calls and flawed methodology, and that its conclusions cannot be substantiated.

PMID:38633353 | PMC:PMC11022658 | DOI:10.1098/rsos.231875

Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2403206121. doi: 10.1073/pnas.2403206121. Epub 2024 Apr 17.

ABSTRACT

Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One of the genes found to be under strong evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an arabinosyltransferase required for the biosynthesis of the cell envelope lipoglycan, lipoarabinomannan (LAM). To assess the impact of patient-derived embC mutations on the physiology and virulence of M. abscessus, mutations were introduced in the isogenic background of M. abscessus ATCC 19977 and the resulting strains probed for phenotypic changes in a variety of in vitro and host cell-based assays relevant to infection. We show that patient-derived mutational variations in EmbC result in an unexpectedly large number of changes in the physiology of M. abscessus, and its interactions with innate immune cells. Not only did the mutants produce previously unknown forms of LAM with a truncated arabinan domain and 3-linked oligomannoside chains, they also displayed significantly altered cording, sliding motility, and biofilm-forming capacities. The mutants further differed from wild-type M. abscessus in their ability to replicate and induce inflammatory responses in human monocyte-derived macrophages and epithelial cells. The fact that different embC mutations were associated with distinct physiologic and pathogenic outcomes indicates that structural alterations in LAM caused by nonsynonymous nucleotide polymorphisms in embC may be a rapid, one-step, way for M. abscessus to generate broad-spectrum diversity beneficial to survival within the heterogeneous and constantly evolving environment of the infected human airway.

PMID:38630725 | DOI:10.1073/pnas.2403206121

Microb Genom. 2024 Apr;10(4). doi: 10.1099/mgen.0.001235.

ABSTRACT

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019. We included samples from in-patients, clinic out-patients, people reviewed in the Emergency Department and healthcare workers screened by Occupational Health. We sequenced the first MRSA isolate from 823 consecutive individuals, defined their pairwise genetic relatedness, and sought epidemiological links in the hospital and community. Genomic analysis of 823 MRSA isolates identified 72 genetic clusters of two or more isolates containing 339/823 (41 %) of the cases. Epidemiological links were identified between two or more cases for 190 (23 %) individuals in 34/72 clusters. Weekly genomic epidemiology updates were shared with the IPC team, culminating in 49 face-to-face meetings and 21 written communications. Seventeen clusters were identified that were consistent with hospital MRSA transmission, discussion of which led to additional IPC actions in 14 of these. Two outbreaks were also identified where transmission had occurred in the community prior to hospital presentation; these were escalated to relevant IPC teams. We identified 38 instances where two or more in-patients shared a ward location on overlapping dates but carried unrelated MRSA isolates (pseudo-outbreaks); research data led to de-escalation of investigations in six of these. Our findings provide further support for the routine use of genomic epidemiology to enhance and target IPC resources.

PMID:38630616 | DOI:10.1099/mgen.0.001235

Nat Food. 2024 Apr 11. doi: 10.1038/s43016-024-00921-2. Online ahead of print.

ABSTRACT

Farming externalities are believed to co-vary negatively, yet trade-offs have rarely been quantified systematically. Here we present data from UK and Brazilian pig production systems representative of most commercial systems across the world ranging from 'intensive' indoor systems through to extensive free range, Organic and woodland systems to explore co-variation among four major externality costs. We found that no specific farming type was consistently associated with good performance across all domains. Generally, systems with low land use have low greenhouse gas emissions but high antimicrobial use and poor animal welfare, and vice versa. Some individual systems performed well in all domains but were not exclusive to any particular type of farming system. Our findings suggest that trade-offs may be avoidable if mitigation focuses on lowering impacts within system types rather than simply changing types of farming.

PMID:38605128 | DOI:10.1038/s43016-024-00921-2

Hemasphere. 2024 Apr 4;8(4):e65. doi: 10.1002/hem3.65. eCollection 2024 Apr.

NO ABSTRACT

PMID:38577479 | PMC:PMC10993146 | DOI:10.1002/hem3.65

Science. 2024 Mar 29;383(6690):eadl3962. doi: 10.1126/science.adl3962. Epub 2024 Mar 29.

ABSTRACT

Bacillus Calmette-Guérin (BCG) is a routinely used vaccine for protecting children against Mycobacterium tuberculosis that comprises attenuated Mycobacterium bovis. BCG can also be used to protect livestock against M. bovis; however, its effectiveness has not been quantified for this use. We performed a natural transmission experiment to directly estimate the rate of transmission to and from vaccinated and unvaccinated calves over a 1-year exposure period. The results show a higher indirect efficacy of BCG to reduce transmission from vaccinated animals that subsequently become infected [74%; 95% credible interval (CrI): 46 to 98%] compared with direct protection against infection (58%; 95% CrI: 34 to 73%) and an estimated total efficacy of 89% (95% CrI: 74 to 96%). A mechanistic transmission model of bovine tuberculosis (bTB) spread within the Ethiopian dairy sector was developed and showed how the prospects for elimination may be enabled by routine BCG vaccination of cattle.

PMID:38547287 | DOI:10.1126/science.adl3962

Lancet Glob Health. 2024 Apr;12(4):e563-e571. doi: 10.1016/S2214-109X(23)00603-4.

ABSTRACT

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered.

METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up.

FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]).

INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption.

FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

PMID:38485425 | DOI:10.1016/S2214-109X(23)00603-4

Nat Commun. 2024 Feb 29;15(1):1864. doi: 10.1038/s41467-024-45793-z.

ABSTRACT

Early-life human gut microbiome is a pivotal driver of gut homeostasis and infant health. However, the viral component (known as "virome") remains mostly unexplored. Here, we establish the Early-Life Gut Virome (ELGV), a catalog of 160,478 non-redundant DNA and RNA viral sequences from 8130 gut virus-like particles (VLPs) enriched or bulk metagenomes in the first three years of life. By clustering, 82,141 viral species are identified, 68.3% of which are absent in existing databases built mainly from adults, and 64 and 8 viral species based on VLPs-enriched and bulk metagenomes, respectively, exhibit potentials as biomarkers to distinguish infants from adults. With the largest longitudinal population of infants profiled by either VLPs-enriched or bulk metagenomic sequencing, we track the inherent instability and temporal development of the early-life human gut virome, and identify differential viruses associated with multiple clinical factors. The mother-infant shared virome and interactions between gut virome and bacteriome early in life are further expanded. Together, the ELGV catalog provides the most comprehensive and complete metagenomic blueprint of the early-life human gut virome, facilitating the discovery of pediatric disease-virome associations in future.

PMID:38424077 | DOI:10.1038/s41467-024-45793-z

J Small Anim Pract. 2024 Feb 27. doi: 10.1111/jsap.13707. Online ahead of print.

ABSTRACT

OBJECTIVES: To observe the occurrence of postanaesthetic respiratory complications and to determine their prevalence and risk factors in dogs undergoing brachycephalic obstructive airway syndrome surgery.

MATERIALS AND METHODS: Data from 199 clinical records were retrospectively analysed. Univariable logistic regression followed by multivariable logistic regression was used to identify associations between the dependent variables (set as the postoperative respiratory complications observed in the study dogs) and various independent covariates. The quality of model-fit was assessed using the likelihood ratio test. P≤0.05 was considered statistically significant.

RESULTS: Four postoperative respiratory complications were observed: hypoxaemia (n=10/199; 5%), dyspnoea requiring tracheal re-intubation (n=13/199, 7%), dyspnoea requiring tracheostomy (n=10/199, 5%) and aspiration pneumonia (n=12/199, 6%). Univariable logistic regression showed an association between postoperative aspiration pneumonia and increasing body condition score and American Society of Anaesthesiology classification; however, when these covariates were evaluated in the multivariable model significance was not maintained. Risk factors for tracheostomy were preoperative and postoperative aspiration pneumonia (odds ratio: 9.52, 95% confidence interval: 1.56 to 57.93) and increasing brachycephalic obstructive airway syndrome grade (odds ratio: 4.65, 95% confidence interval: 0.79 to 27.50).

CLINICAL SIGNIFICANCE: High brachycephalic obstructive airway syndrome grade and aspiration pneumonia, either developing peri-operatively or as pre-existing condition, may represent risk factors for postoperative tracheostomy. Preoperative diagnosis of aspiration pneumonia may further increase the risk of postoperative complications.

PMID:38413137 | DOI:10.1111/jsap.13707

Vet J. 2024 Feb 22:106085. doi: 10.1016/j.tvjl.2024.106085. Online ahead of print.

ABSTRACT

Previous studies have shown that the most reliable external conformational risk factor of whether a brachycephalic dog will develop Brachycephalic Obstructive Airway Syndrome (BOAS) is the status of nostril stenosis, assessed as a static observation using the brachycephalic nostril grading scheme. The nostrils however are a dynamic structure, opening further when the dog is exercising, sniffing or panting. The hypothesis of this study was that brachycephalic dogs with open or mildly stenotic nostrils are more likely to have nostril mobility whilst dogs with moderately or severely stenotic nostrils are more likely to have immobile nostrils. A retrospective study of dogs presented for BOAS assessment at two UK referral centres between 2012-2020 was performed. Data extracted included nares stenosis status and nares mobility. A mesocephalic pilot control group was recruited from a third referral centre. Statistical analysis was performed with χ2, Cochran-Armitage, spearman's rho and linear-by-linear tests as appropriate. Of the 974 brachycephalic dogs included in the study: 124 had open nostrils (68.5% mobile); 212 mildly stenotic nostrils (58.5% mobile); 379 moderately stenotic nostrils (35% mobile) and 259 severely stenotic nostrils (19.3% mobile). The nostril stenotic status was significantly associated with nostril wing mobility (χ2 =135.55; P<0.0001). When considering open and mildly stenotic (considered acceptable) nostrils versus moderate and severely stenotic nostrils, mobility was 62% versus 25.5% (χ2= 135.88; P = <0.0001). All 27 mesocephalic dogs had nostril mobility. Brachycephalic dogs with moderate and severely stenotic nares have reduced nasal mobility compared to brachycephalic dogs with mildly stenotic and open nares. Data is further evidence that dogs with moderately and severely stenotic nares should not be bred.

PMID:38401643 | DOI:10.1016/j.tvjl.2024.106085