Canine distemper virus in wildlife in south‐western Europe

[EN] Multi-host pathogens emerging and re-emerging at the wildlife–domestic animal interface affect wildlife management and conservation. This is the case of canine distemper virus (CDV), a paramyxovirus closely related to human measles virus and rinderpest virus of cattle. With an area of 10,603 km2, Asturias region in Atlantic Spain is a hotspot of carnivore diversity, which includes the largest Eurasian brown bear (Ursus arctos arctos) population and one of the largest wolf (Canis lupus) populations in south-western Europe. In 2020–2021, we recorded mortality due to distemper in four carnivore species including three mustelids (Eurasian badger Meles meles, European marten Martes martes and European polecat Mustela putorius) and one canid (red fox, Vulpes vulpes). Clinical signs and pathology were similar across species and consistent with the emergence of a highly pathogenic viral strain, with CDV antigen mainly located in the central nervous system, lungs, spleen and lymph nodes. A molecular study in eight wild carnivore species, also including the Iberian wolf, Eurasian brown bear, American mink (Neovison vison) and stone marten (Martes foina), revealed 19.51% (16/82) of positivity. Phylogenetic analysis demonstrated that CDV belonged to the previously described European lineage. A retrospective serosurvey (2008–2020) showed a high seroprevalence of CDV antibodies (43.4%) in 684 analyzed badgers, indicating a long-term though not stable viral circulation in this multi-host community. The possible triggers of the 2020–2021 outbreak and the implications for carnivore management and conservation are discussed.SISpanishMinisterio de Ciencia; Innovación y Universidades (MCIU); The Agencia Estatal de Investigación (AEI); FEDER co-funded: RTI2018-096010-B-C2

12 Sex-related differential susceptibility to ponatinib-induced cardiotoxicity and its relationship to modulation of notch signalling in a muine model

Abstract Aims Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. Although sex is a risk factor for PON-induced cardiotoxicity in humans, little is known about its mechanisms, in general, and sex-related mechanisms in particular. To determine the mechanisms of sex-related PON-induced cardiotoxicity and identify potential rescue strategies in a murine model. Methods Twenty-four-month-old male and female C57B5 mice were treated with 3 mg/kg/day of PON or vehicle via oral gavage for 28 days, with/without siRNA-Notch1 or siRNA-scrambled via tail vein every 3 days. Results PON + scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells, a higher percentage of senescence-associated β-galactosidase positive senescent cardiac areas, as well as a lower reactivity degree for the survival marker Bmi1 than female counterparts. Proteomics analysis of cardiac tissue showed upstream activation of nitric oxide synthase (NOS) type 2, downstream activation of cell death and production of reactive oxygen species in PON + scrambled siRNA- compared to vehicle or PON + Notch1 siRNA-treated male mice. Upstream analysis showed beta-estradiol activation, while downstream analysis showed activation of cell survival and inhibition of cell death in PON + scrambled siRNA compared to vehicle-treated female mice. PON + scrambled siRNA-treated mice also showed a down-regulation of cardiac actin, which was more marked in male; as well as vessel density, which was more marked in female mice. Female hearts showed a greater extent of cardiac fibrosis than male counterparts at baseline, with no significant changes after PON treatment. In contrast, PON + scrambled siRNA-treated mice had less fibrosis than vehicle or PON + Notch1-siRNA-treated mice. Left ventricular systolic dysfunction shown in PON + scrambled siRNA-treated male mice and—to a lesser extent—by female mice was similarly reversed in both PON + Notch1-siRNA-treated male and female mice (Table 1). Conclusions We found a sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can improve our understanding of sex-related differences and help identify biomarkers in PON cardiotoxicity

Cardiorespiratory and Metabolic Responses to Sinusoidal Exercise of Moderate Intensity: Reliability of the Measurements and the Effects of Fatigue

The cardiorespiratory and metabolic responses to sinusoidal exercise, in which work rate follows an oscillating pattern, have been proposed to assess the effectiveness of the cardiorespiratory adjustments. The repetition of successive sinusoidal periods permits to simultaneously reduce the influence of random fluctuations and accentuate the underlying physiological response. Data analysis has been often performed by overlapping and averaging successive cycles assuming no differences among them, thus excluding the possible presence of fatigue throughout successive cycles. After assessing the reliability of the measurements during sinusoidal exercise, this study sought to investigate the possible differences among subsequent cycles of sinusoidal work. Eleven active volunteers (age: 28±6 yrs., body mass: 73±7 kg; stature: 1.79±0.06 m, maximum oxygen uptake (VO2max): 52 ml·kg−1·min−1) participated to the study that was conducted in accordance with the Basic Principles of the Declaration of Helsinki. After determining individual VO2max and critical power (CP) on a cycle ergometer, they underwent sinusoidal work rates characterized by an amplitude (A), a midpoint (MP) and a period equal to ±50W, 50W below CP and 240s, respectively, up to exhaustion. On a different day, participants repeated the same experimental session for reliability purposes. Expiratory ventilation (VE), oxygen uptake (VO2), carbon dioxide output (VCO2), and heart rate (fH) responses were fitted by the sinewave function that minimized the residuals. A, MP and the time-delay (tD, the latency between mechanical work rate and physiological responses) of all parameters were determined for each cycle. Reliability assessment between day 1 and 2 was expressed as Cronbach’s a and intraclass correlation coefficient (ICC). A one-way ANOVA for repeated measures tested the presence of differences among cycles. Regression analysis was also applied to explore possible relationship between each variables and time. Reliability analysis revealed a very high to high ICC values for most of the parameters, with the exception of A for VO2 and VCO2 and tD for fH (moderate reliability). A of VE and fH response increased and decreased with time, respectively (p<0.05). MP of VE and fH showed a positive regression that led to significantly higher values in the last compared to the first cycle; on the contrary, no changes were observed among cycles in all other MP data. tD was similar in each cycle for all the investigated parameters despite a very slight negative regression found for VCO2. In conclusion, most of the physiological responses to moderate sinusoidal exercise exhibited a high to very high reliability. Some of the cardiorespiratory parameters showed significant changes with time throughout the sinusoidal exercise possibly due to the onset of fatigue. Therefore, an approach that overlaps and averages all the cycles together should not be performed to avoid wrong estimation of physiological responses to sinusoidal exercise, unless the averaging approach involves only the first cycles

Energy cost differences between marathon runners and soccer players: Constant versus shuttle running

Purpose: In the last decades, the energy cost assessment provided new insight on shuttle or constant running as training modalities. No study, though, quantified the benefit of constant/shuttle running in soccer-players and runners. Therefore, the aim of this study was to clarify if marathon runners and soccer players present specific energy cost values related to their training experience performing constant and shuttle running.Methods: To this aim, eight runners (age 34 ± 7.30y; training experience 5.70 ± 0.84y) and eight soccer-players (age 18.38 ± 0.52y; training experience 5.75 ± 1.84y) were assessed randomly for 6’ on shuttle-running or constant-running with 3 days of recovery in-between. For each condition, the blood lactate (BL) and the energy cost of constant (Cr) and shuttle running (CSh) was determined. To assess differences for metabolic demand in terms of Cr, CSh and BL over the two running conditions on the two groups a MANOVA was used.Results:V·O2max were 67.9 ± 4.5 and 56.8 ± 4.3 ml·min−1 kg−1 (p = 0.0002) for marathon runners and soccer players, respectively. On constant running, the runners had a lower Cr compared to soccer players (3.86 ± 0.16 J kg−1m−1 vs. 4.19 ± 0.26 J kg−1 m−1; F = 9.759, respectively; p = 0.007). On shuttle running, runners had a higher CSh compared to soccer players (8.66 ± 0.60 J kg−1 m−1 vs. 7.86 ± 0.51 J kg−1 m−1; F = 8.282, respectively; with p = 0.012). BL on constant running was lower in runners compared to soccer players (1.06 ± 0.07 mmol L−1 vs. 1.56 ± 0.42 mmol L−1, respectively; with p = 0.005). Conversely, BL on shuttle running was higher in runners compared to soccer players 7.99 ± 1.49 mmol L−1 vs. 6.04 ± 1.69 mmol L−1, respectively; with p = 0.028).Conclusion: The energy cost optimization on constant or shuttle running is strictly related to the sport practiced

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

P22 protein complex in the serodiagnosis of animal tuberculosis: Antigenic stability and cross-reactivity with Corynebacterium pseudotuberculosis infection

The P22 ELISA was recently developed for the serodiagnosis of animal tuberculosis. Herein, the stability of the P22 antigen in different presentations and storage conditions, and the cross-reactivity with Corynebacterium pseudotuberculosis infection in small ruminants were evaluated. For the stability assay, serum samples from cows, sheep, goats, alpacas, badgers, and wild boar were used in the P22 ELISA. The cross-reactivity analysis used sera from sheep and goats with caseous lymphadenitis (CLA). Differences in the immune recognition of P22 were found when the antigen was stored at 40 °C, but without altering the negative or positive status of each sample. P22 ELISA presented 5.71 % cross-reactivity when CLA-positive sheep were evaluated, but no cross-reaction was observed among CLA-positive goat serum samples. This study showed that the P22 protein complex is stable under different formulations and temperatures, and that the assay presents a low cross-reactivity with CLA.This work is a result of the I+D+i research project RTI2018–096010-B-C21, funded by the Spanish MCIN/AEI/10.13039/501100011033/ Ministry of Science, Innovation and the European Regional Development Funds (FEDER Una manera de hacer Europa), and of PCTI 2021–2023 (GRUPIN: IDI2021–000102) funded by Principado de Asturias and FEDER. TDB is a Ph.D. fellow the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES, 88887.511077/2020–00). RDP is a Technological Development fellow from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Proc. 313350/2019–1).Peer reviewe

Identifying invasive species threats, pathways, and impacts to improve biosecurity

Managing invasive species with prevention and early-detection strategies can avert severe ecological and economic impacts. Horizon scanning, an evidence-based process combining risk screening and consensus building to identify threats, has become a valuable tool for prioritizing invasive species management and prevention. We assembled a working group of experts from academic, government, and nonprofit agencies and organizations, and conducted a multi-taxa horizon scan for Florida, USA, the first of its kind in North America. Our primary objectives were to identify high-risk species and their introduction pathways, to detail the magnitude and mechanism of potential impacts, and, more broadly, to demonstrate the utility of horizon scanning. As a means to facilitate future horizon scans, we document the process used to generate the list of taxa for screening. We evaluated 460 taxa for their potential to arrive, establish, and cause negative ecological and socioeconomic impacts, and identified 40 potential invaders, including alewife, zebra mussel, crab-eating macaque, and red swamp crayfish. Vertebrates and aquatic invertebrates posed the greatest invasion threat, over half of the high-risk taxa were omnivores, and there was high confidence in the scoring of high-risk taxa. Common arrival pathways were ballast water, biofouling of vessels, and escape from the pet/aquarium/horticulture trade. Competition, predation, and damage to agriculture/forestry/aquaculture were common impact mechanisms. We recommend full risk analysis for the high-risk taxa; increased surveillance at Florida's ports, state borders, and high-risk pathways; and periodic review and revision of the list. Few horizon scans detail the comprehensive methodology (including list-building), certainty estimates for all scoring categories and the final score, detailed pathways, and the magnitude and mechanism of impact. Providing this information can further inform prevention efforts and can be efficiently replicated in other regions. Moreover, harmonizing methodology can facilitate data sharing and enhance interpretation of results for stakeholders and the general public.</p

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe