Bone niches in the regulation of tumour cell dormancy.

Secondary metastases, accounting for 90 % of cancer-related deaths, pose a formidable challenge in cancer treatment, with bone being a prevalent site. Importantly, tumours may relapse, often in the skeleton even after successful eradication of the primary tumour, indicating that tumour cells may lay dormant within bone for extended periods of time. This review summarises recent findings in the mechanisms underlying tumour cell dormancy and the role of bone cells in this process. Hematopoietic stem cell (HSC) niches in bone provide a model for understanding regulatory microenvironments. Dormant tumour cells have been shown to exploit similar niches, with evidence suggesting interactions with osteoblast-lineage cells and other stromal cells via CXCL12-CXCR4, integrins, and TAM receptor signalling, especially through GAS6-AXL, led to dormancy, with exit of dormancy potentially regulated by osteoclastic bone resorption and neuronal signalling. A comprehensive understanding of dormant tumour cell niches and their regulatory mechanisms is essential for developing targeted therapies, a critical step towards eradicating metastatic tumours and stopping disease relapse.

Application of the wildland fire emissions inventory system to estimate fire emissions on forest lands of the United States.

BACKGROUND: Forests are significant terrestrial biomes for carbon storage, and annual carbon accumulation of forest biomass contributes offsets affecting net greenhouse gases in the atmosphere. The immediate loss of stored carbon through fire on forest lands reduces the annual offsets provided by forests. As such, the United States reporting includes annual estimates of direct fire emissions in conjunction with the overall forest stock and change estimates as a part of national greenhouse gas inventories within the United Nations Framework Convention on Climate Change. Forest fire emissions reported for the United States, such as the 129 Tg CO2 reported for 2022, are based on the Wildland Fire Emissions Inventory System (WFEIS). Current WFEIS estimates are included in the Inventory of U.S. Greenhouse Gas Emissions and Sinks: 1990-2022 published in 2024 by the United States Environmental Protection Agency. Here, we describe WFEIS the fire emissions inventory system we used to address current information needs, and an analysis to confirm compatibility of carbon mass between estimated forest fire emissions and carbon in forest stocks. RESULTS: The summaries of emissions from forests are consistent with previous reports that show rates and interannual variability in emissions and forest land area burned are generally greater in recent years relative to the 1990s. Both emissions and interannual variability are greater in the western United States. The years with the highest CO2 emissions from forest fires on the 48 conterminous states plus Alaska were 2004, 2005, and 2015. In some years, Alaska emissions exceed those of the 48 conterminous states, such as in 2022, for example. Comparison of forest fire emission to forest carbon stocks indicate there is unlikely any serious disconnect between inventory and fire emissions estimates. CONCLUSIONS: The WFEIS system is a user-driven approach made available via a web browser. Model results are compatible with the scope and reporting needs of the annual national greenhouse gas inventories.

Adrenocortical carcinoma: selective internal radiation therapy and liver metastases.

Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years' PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation. Significance statement: Adrenocortical carcinoma (ACC) is a rare and aggressive tumour with limited treatments. Once metastatic disease develops, existing standard-of-care treatments offer a dismal overall survival, alongside marked toxicities. Selective internal radiation therapy (SIRT) may represent a new intervention in the treatment paradigm for liver-limited, metastatic ACC. Here, we present the case of a patient treated with multiple rounds of SIRT for relapsed, liver-limited ACC, prolonging survival by several years. Recurrent SIRT led to maintained liver function and no toxicities. Little evidence outlines its use in ACC but further study is certainly warranted to ascertain the value of SIRT, considering the limited treatment landscape that currently exists.

Postvasectomy Semen Analysis Compliance With Utilization of a Mail-In Semen Analysis Kit.

PURPOSE: The AUA recommends postvasectomy semen analysis (PVSA) to verify successful vasectomy. However there remains poor patient compliance. We sought to assess whether mail-in PVSA improves patient compliance across a wide range of practice types. MATERIALS AND METHODS: Prospective data were collected on all men who received a Fellow PVSA kit between April 2021 and August 2023 in a nationwide cohort. Date of kit activation, practice type, clinic zip code, and date of kit accession/processing at the lab was collected. Compliance rates for each practice area were reported. χ2 tests of independence, logistic regression models, and multivariable logistic analysis were performed to assess the impact of relevant variables. RESULTS: Overall compliance across all practice areas was 69% following an 18-week period of observation (n = 16,105) and 82% (n = 6687) following a 40-week period. Compliance rates were highest and similar for small urology practices (<5 providers), including Veterans Affairs practices, ranging from 76% to 82% at 18 weeks to 85% to 87% at 40 weeks. Large urology practices had slightly lower compliance rates with 66% at 18 weeks to 80% at 40 weeks. The univariable logistic regression model demonstrated that patients in small urology practices have a 63% greater odds of 26-week compliance, on average, compared to those who receive care in large urology practices (odds ratio 1.63, 95% CI 1.48-1.79). CONCLUSIONS: Fellow's mail-in PVSA offers improved PVSA compliance over previously published data. Improved compliance is seen across all practice types. Despite these successes, there is significant room for improvement to achieve 100% compliance.

Navigating the cultural adaptation of a US-based online mental health and social support program for use with young Aboriginal and Torres Strait Islander males in the Northern Territory, Australia: Processes, outcomes, and lessons.

BACKGROUND: Despite disproportionate rates of mental ill-health compared with non-Indigenous populations, few programs have been tailored to the unique health, social, and cultural needs and preferences of young Aboriginal and Torres Strait Islander males. This paper describes the process of culturally adapting the US-based Young Black Men, Masculinities, and Mental Health (YBMen) Project to suit the needs, preferences, culture, and circumstances of Aboriginal and Torres Strait Islander males aged 16-25 years in the Northern Territory, Australia. YBMen is an evidence-based social media-based education and support program designed to promote mental health, expand understandings of gender and cultural identities, and enhance social support in college-aged Black men. METHODS: Our adaptation followed an Extended Stages of Cultural Adaptation model. First, we established a rationale for adaptation that included assessing the appropriateness of YBMen's core components for the target population. We then investigated important and appropriate models to underpin the adapted program and conducted a non-linear, iterative process of gathering information from key sources, including young Aboriginal and Torres Strait Islander males, to inform program curriculum and delivery. RESULTS: To maintain program fidelity, we retained the core curriculum components of mental health, healthy masculinities, and social connection and kept the small cohort, private social media group delivery but developed two models: 'online only' (the original online delivery format) and 'hybrid in-person/online' (combining online delivery with weekly in-person group sessions). Adaptations made included using an overarching Aboriginal and Torres Strait Islander social and emotional wellbeing framework and socio-cultural strengths-based approach; inclusion of modules on health and wellbeing, positive Indigenous masculinities, and respectful relationships; use of Indigenous designs and colours; and prominent placement of images of Aboriginal and Torres Strait Islander male sportspeople, musicians, activists, and local role models. CONCLUSIONS: This process resulted in a culturally responsive mental health, masculinities, and social support health promotion program for young Aboriginal and Torres Strait Islander males. Next steps will involve pilot testing to investigate the adapted program's acceptability and feasibility and inform further refinement.

Titanium-Titanium Junctions in the Knee Corrode, Generating Damage Similar to the Hip.

BACKGROUND: Previous studies identified corrosion between the modular tibial components of total knee arthroplasty (TKA) devices. In this study, we investigated the damage modes present in titanium-titanium (Ti-Ti) junctions in the knee. We asked: under typical in vivo cyclic loading conditions, will the same alloy damage modes from TKA devices resemble those documented in the hip? METHODS: A total of 50 paired titanium alloy tibial baseplates and stems were collected and semi-quantitatively analyzed using Goldberg corrosion scoring. To characterize damage, a subsection of moderately and severely corroded components was sectioned and imaged using scanning electron and digital optical microscopy. RESULTS: Of the 100 device components, 95% showed visual evidence of corrosion. The initial contact area between the stem and bore generally occurred 3 mm from the stem taper base. Scanning electron microscopy revealed four damage modes, including oxide film formation, crevice corrosion, selective dissolution, and pitting. CONCLUSIONS: Each of the damage modes identified in modular Ti-Ti tibial junctions was previously reported by total hip arthroplasty retrieval studies. Cumulatively, our results suggest that mechanically assisted crevice corrosion promoted this damage in vivo.

Mid-term outcomes using a 'kinematic retaining' total knee replacement - A multicentre prospective study at five years follow-up.

Background: Although total knee replacement (TKR) surgery has succeeded in improving pain and deformity, a proportion of patients remain incompletely satisfied with their outcome. This prospective study aims to assess the survivorship, clinical, and radiological outcomes using a novel 'kinematic retaining' (KR) implant. Methods: 156 patients underwent TKR surgery for primary osteoarthritis using the Physica KR implant at three European Centres. Patients were followed up for five years using both radiographic and clinical evaluations. Results: Within 6 months post-operatively, 79.4% and 85.9% had good-excellent clinical and functional KSS values, this was maintained to 76.9% and 79.5% at five years. Mean Knee Society Score (KSS) improvement at 5 years was 32.8 (from 23 to 40) and 37.4 (from 30 to 50) (p < 0.01). All Knee Injury and Osteoarthritis Outcome Score (KOOS) sub-scores showed statistically significant improvement from before surgery at a mean of 34.7 (SD ± 16.1) to a mean of 86.6 (SD ± 16.1) at five years. The mean Oxford Knee Score (OKS) was 43.7 (±5.6), with over 80% of the patients having a good-excellent outcome at five years. OKS improved significantly by six weeks after surgery (p < 0.01) and remained constant throughout the 5-year follow-up. Visual Analogue Score (VAS) Satisfaction scores improved significantly after the post-operative time point of six weeks. From 1 year to 5 years, the average VAS was over 85 mm. The Forgotten Joint Score (FJS) increased from 64.5 at 1 year to 79.2 at 5 years after surgery (p < 0.01). No progressive adverse radiographic features were noted. Two patients were revised during the study period: one for infection and the other for aseptic loosening. Conclusions: This novel 'kinematic retaining' knee prosthesis has shown exceptional clinical and patient-reported improvements, with a remarkable 99.4% survivorship (95.5-99.9) at five years.

Adapting pest management strategies to changing climates for the redlegged earth mite, Halotydeus destructor.

As climate change continues to modify temperature and rainfall patterns, risks from pests and diseases may vary as shifting temperature and moisture conditions affect the life history, activity, and distribution of invertebrates and diseases. The potential consequences of changing climate on pest management strategies must be understood for control measures to adapt to new environmental conditions. The redlegged earth mite (RLEM; Halotydeus destructor [Tucker]) is a major economic pest that attacks pastures and grain crops across southern Australia and is typically controlled by pesticides. TIMERITE® is a management strategy that relies on estimating the optimal timing (the TIMERITE® date) for effective chemical control of RLEM populations in spring. In this study, we assessed the efficacy of control at the TIMERITE® date from 1990 to 2020 across southern Australia using a simulation approach that incorporates historical climatic data and field experimental data on life history, seasonal abundance, and population level pesticide responses. We demonstrate that moisture and temperature conditions affect the life history of RLEM and that changes in the past three decades have gradually diminished the efficacy of the TIMERITE® strategy. Furthermore, we show that by incorporating improved climatic data into predictions and shifting the timing of control to earlier in the year, control outcomes can be improved and are more stable across changing climates. This research emphasises the importance of accounting for dynamic environmental responses when developing and implementing pest management strategies to ensure their long-term effectiveness. Suggested modifications to estimating the TIMERITE® date will help farmers maintain RLEM control outcomes amidst increasingly variable climatic conditions.

Myocardial inflammation after elective percutaneous coronary intervention.

OBJECTIVE: It is well established that inflammation plays a central role in the sequelae of percutaneous coronary intervention (PCI). Most of the studies to date have focused on the inflammatory reaction affecting the vessel wall after angioplasty. However, there are data to suggest that the main foci of inflammation are in fact in the myocardium beyond the vessel wall. The main aim of our study was to investigate the myocardial inflammation after elective, uncomplicated angioplasty with cardiovascular magnetic resonance (CMR) enhanced by ultrasmall superparamagnetic particles of iron oxide (USPIO) and also blood biomarkers. This is the first study to report such findings after elective angioplasty. METHODS: We assessed patients undergoing elective angioplasty for stable angina with USPIO-enhanced CMR two weeks after the procedure and compared the results with those of healthy volunteers who constituted the control group. We excluded patients with previous myocardial infarction, previous PCI, or any significant inflammatory condition. All patients also underwent blood biomarker testing at baseline (pre-PCI), 4 h, and two weeks later. RESULTS: A total of five patients and three controls were scanned. There was a small absolute increase, although statistically insignificant, in R2∗ values in the PCI area compared with either remote myocardium from the same patient (PCI area [left anterior descending artery (LAD)] vs remote myocardium [circumflex area]: 19.3 ± 10.8 vs 9.2 ± 7.9, p = 0.1) or healthy myocardium from healthy volunteers (PCI area [LAD] vs healthy myocardium [LAD]: 19.3 ± 10.8 vs 12.2 ± 4.0, p = 0.2). PTX3 and IL-6 were the only biomarkers that changed significantly from baseline to 4 h and 2 weeks. Both biomarkers peaked at 4 h. CONCLUSION: We used USPIO-enhanced CMR for the first time to assess myocardial inflammation after elective, uncomplicated PCI. We have demonstrated a small numerical increase in inflammation, which was not statistically significant. This study opens the way for future studies to use this method as a means to target inflammation.

Health Related Quality of life Amongst Refugees: A meta Analysis of Studies Using the SF-36.

The health of refugees has been widely documented, as has the impact of a range of factors throughout the migration journey from being exposed to violence to the impacts of immigration detention. This study adds to our understanding of health-related quality of life amongst refugees and asylum seekers by evaluating health-related quality of life as measured by the Short-Form 36 (SF-36) Health Survey using meta-analysis. The aims of this study were to (1) provide a summary and overview of health-related quality of life (as measured by the SF-36), including the extent to which this varies and (2) explore the factors that influence health-related quality of life (as measured by the SF-36) amongst refugees and asylum seekers. A search was undertaken of MEDLINE, CINAHL, PSYCINFO and SCOPUS, returning 3965 results. Papers were included if they sampled refugees (or asylum seeker or those with refugee-like experiences) and used the SF-36 (or its variants) as an outcome measure. Mean scores and standard deviations were pooled using a random effects model. The pooled sample size was 18,418. The pooled mean scores for the SF-36 physical summary measures was 54.99 (95% CI 46.01-63.99), while the mental health summary measure was 52.39 (95% CI 43.35-61.43). The pooled mean scores for each of the sub-scales ranged from 49.6 (vitality) to 65.54 (physical functioning). High heterogeneity was found between both summary measures and all sub-scales. In comparison to SF-36 results from general populations in high and middle income countries, these results suggest that refugee quality of life is generally poorer. However, this varied substantially between studies. One issue that is not well clarified by this review are the factors that contributed to health-related quality of life.

Transoceanic pathogen transfer in the age of sail and steam.

In the centuries following Christopher Columbus's 1492 voyage to the Americas, transoceanic travel opened unprecedented pathways in global pathogen circulation. Yet no biological transfer is a single, discrete event. We use mathematical modeling to quantify historical risk of shipborne pathogen introduction, exploring the respective contributions of journey time, ship size, population susceptibility, transmission intensity, density dependence, and pathogen biology. We contextualize our results using port arrivals data from San Francisco, 1850 to 1852, and from a selection of historically significant voyages, 1492 to 1918. We offer numerical estimates of introduction risk across historically realistic ranges of journey time and ship population size, and show that both steam travel and shipping regimes that involved frequent, large-scale movement of people substantially increased risk of transoceanic pathogen circulation.

In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii.

OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant Enterobacterales, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB. METHOD: A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0-64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined. RESULTS: An AVI concentration-dependent reduction in CAZ MIC was observed (r2 = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r2 > 0.96). Bacterial suppression was observed >24 hours with the serum exposure, but not that from the ELF. CONCLUSION: Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.

Discovery and In Vivo Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity.

PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties. Bioisosteric replacement of the original thiazole guanidine headgroup, spirocyclization of the isoindolinone amide scaffold to both configurationally and conformationally lock the bioactive form, and fine-tuning of the potency, MTA cooperativity, and DMPK properties through specific substitutions of the azaindole headgroup were conducted. We have identified an orally available in vivo lead compound, 28 ("AZ-PRMT5i-1"), which shows sub-10 nM PRMT5 cell potency, >50-fold MTA cooperativity, suitable DMPK properties for oral dosing, and significant PRMT5-driven in vivo efficacy in several MTAP-deficient preclinical cancer models.

The microbial composition of pancreatic ductal adenocarcinoma: A systematic review of 16S rRNA gene sequencing.

BACKGROUND: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. MATERIALS AND METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. RESULTS: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies. CONCLUSION: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

Man versus machine: cost and carbon emission savings of 4G-connected Artificial Intelligence technology for classifying species in camera trap images.

Timely and accurate detection and identification of species are crucial for monitoring wildlife for conservation and management. Technological advances, including connectivity of camera traps to mobile phone networks and artificial intelligence (AI) algorithms for automated species identification, can potentially improve the timeliness and accuracy of species detection and identification. Adoption of this new technology, however, is often seen as cost-prohibitive as it has been difficult to calculate the cost savings or qualitative benefits over the life of the program. We developed a decision tool to quantify potential cost savings associated with incorporating the use of mobile phone network connectivity and AI technologies into monitoring programs. Using a feral cat eradication program as a case study, we used our decision tool to quantify technology-related savings in costs and carbon emissions, and compared the accuracy of AI species identification to that of experienced human observers. Over the life of the program, AI technology yielded cost savings of $0.27 M and when coupled with mobile phone network connectivity, AI saved $2.15 M and 115,838 kg in carbon emissions, with AI algorithms outperforming human observers in both speed and accuracy. Our case study demonstrates how advanced technologies can improve accuracy and cost-effectiveness and improve monitoring program efficiencies.

The importance of 'place' and its influence on rural and remote health and well-being in Australia.

AIMS: This article explores the crucial role of 'place' as an ecological, social and cultural determinant of health and well-being, with a focus on the benefits and challenges of living rurally and remotely in Australia. CONTEXT: The health system, including health promotion, can contribute actively to creating supportive environments and places that foster health and well-being among individuals residing in rural and remote locations. For First Nations peoples, living on Country, and caring for Country and its people, are core to Indigenous worldviews, and the promotion of Aboriginal and Torres Strait Islander health and well-being. Their forced removal from ancestral lands has been catastrophic. For all people, living in rural and remote areas can deliver an abundance of the elements that contribute to a 'liveable' community, including access to fresh air, green and blue space, agricultural employment, tight-knit communities, a sense of belonging and identity, and social capital. However, living remotely also can limit access to employment opportunities, clean water, affordable food, reliable transport, social infrastructure, social networks and preventive health services. 'Place' is a critical enabler of maintaining a healthy life. However, current trends have led to a reduction in local services and resources, and increased exposure to the impacts of climate change. APPROACH: This commentary suggests ideas and strategies through which people in rural and remote locations can strengthen the liveability, resilience and identity of their communities, and regain access to essential health care and health promotion services and resources. CONCLUSION: Recommended strategies include online access to education, employment and telehealth; flexible provision of social infrastructure; and meaningful and responsive university-health service partnerships.

Computationally-accelerated prediction of polyester-melamine coatings degradation to design sustainable organically-coated steels for outdoor applications.

This work implements computational chemistry as a screening tool to aid in the coating and resin formulation process. Conceptual Density Functional theory (DFT) reactivity descriptors like the global chemical hardness and the dual descriptor Fukui function identify the tendency of polyester-melamine coatings to undergo electrophilic and nucleophilic attack during weathering exposure. Coatings were subjected to natural and accelerated weathering tests, with periodic infrared spectroscopy, colour, and gloss measurements to assess for the degree of changes brought about through photodegradation. It was found that the number of attack sites in the atomistic models, when weighted as a function of the polyester : crosslinker ratio, effectively ranked the degradation of different coating systems upon weathering. This ranking matched the performance of the coatings subjected to both accelerated and natural weathering, showing affinity with naturally weathered samples, and matching in all areas. The results were shown to demonstrate significant correlation, being over R 2 = 0.8 for 7 of the 8 measured areas, and greater than R 2 = 0.9 for 6 compared areas. Comparison of computationally derived and experimentally acquired results showed that the performance of naturally weathered samples was matched across all areas by the computational rankings, showing superior correlation than that observed between natural and accelerated weathering tests. This indicates that the method utilised within this work provides a novel, cost-effective alternative to evaluate the projected performance of selected coatings, while enabling a computationally accelerated platform for more sustainable low-degradation coatings without the requirement of long-term weathering tests.

Detection of Leptospira kirschneri in a short-beaked common dolphin (Delphinus delphis delphis) stranded off the coast of southern California, USA.

BACKGROUND: Pathogenic Leptospira species are globally important zoonotic pathogens capable of infecting a wide range of host species. In marine mammals, reports of Leptospira have predominantly been in pinnipeds, with isolated reports of infections in cetaceans. CASE PRESENTATION: On 28 June 2021, a 150.5 cm long female, short-beaked common dolphin (Delphinus delphis delphis) stranded alive on the coast of southern California and subsequently died. Gross necropsy revealed multifocal cortical pallor within the reniculi of the kidney, and lymphoplasmacytic tubulointerstitial nephritis was observed histologically. Immunohistochemistry confirmed Leptospira infection, and PCR followed by lfb1 gene amplicon sequencing suggested that the infecting organism was L.kirschneri. Leptospira DNA capture and enrichment allowed for whole-genome sequencing to be conducted. Phylogenetic analyses confirmed the causative agent was a previously undescribed, divergent lineage of L.kirschneri. CONCLUSIONS: We report the first detection of pathogenic Leptospira in a short-beaked common dolphin, and the first detection in any cetacean in the northeastern Pacific Ocean. Renal lesions were consistent with leptospirosis in other host species, including marine mammals, and were the most significant lesions detected overall, suggesting leptospirosis as the likely cause of death. We identified the cause of the infection as L.kirschneri, a species detected only once before in a marine mammal - a northern elephant seal (Mirounga angustirostris) of the northeastern Pacific. These findings raise questions about the mechanism of transmission, given the obligate marine lifestyle of cetaceans (in contrast to pinnipeds, which spend time on land) and the commonly accepted view that Leptospira are quickly killed by salt water. They also raise important questions regarding the source of infection, and whether it arose from transmission among marine mammals or from terrestrial-to-marine spillover. Moving forward, surveillance and sampling must be expanded to better understand the extent to which Leptospira infections occur in the marine ecosystem and possible epidemiological linkages between and among marine and terrestrial host species. Generating Leptospira genomes from different host species will yield crucial information about possible transmission links, and our study highlights the power of new techniques such as DNA enrichment to illuminate the complex ecology of this important zoonotic pathogen.