Study of Canine Distemper Virus Presence in Catalonia's Wild Carnivores through H Gene Amplification and Sequencing.

Canine distemper virus (CDV) is recognised worldwide as an important pathogen in both domestic and wild carnivores. Few data are available on its impact and spread on the wildlife/wildlife-domestic animal-environment interface. This study, aimed at developing a conservation-oriented control strategy, analysed 89 sick or deceased animals from 2019 to 2023 at the Wildlife Rehabilitation Centre in Torreferrussa. RT-PCR and sequencing of the partial H gene were used to detect and analyse CDV in tissues. The total positive percentage was 20.22% (18/89), comprising 13 red foxes (44.8%), 4 European badgers (28.6%), and 1 American mink (4.5%), while 24 Eurasian otters tested negative. Phylogenetic analysis indicated that all of the CDV strains belong to the European lineage. Geographically distant individuals and different species shared the same viral strain, suggesting a strong capacity of CDV for interspecies and long-distance transmission. This calls for further research, particularly focusing on potential impacts of CDV on endangered carnivores.

An Atlas of Surra in Spain: A Tool to Support Epidemiological Investigations and Disease Control.

Trypanosomosis is a global animal issue, causing significant economic losses, particularly in Africa. In Spain, only one pathogenic species, Trypanosoma evansi, has been identified so far. It was first detected in a dromedary camel in the Canary Islands in 1997. Since then, numerous cases of the disease, known as Surra, have been diagnosed, prompting various studies and efforts in control and surveillance. Given the lack of a comprehensive database that consolidates the most relevant data in this area, the development of a national atlas, with a focus on the Canary Islands, to incorporate all available information on T. evansi in Spain became a necessity. For the development of the atlas, a repository was constructed, encompassing a range of datasets and documents spanning from 1997 to 2022. Information from each source, and in particular georeferenced locations and results of blood tests on animals, were extracted and integrated into a comprehensive database. A total of 31 sources were analysed, providing a total of 99 georeferenced locations and 12,433 animal samples. Out of these samples, 601 (mostly from dromedaries) were found to be positive for T. evansi. The Card Agglutination Test for T. evansi (CATT/T. evansi), a serological test, was the most commonly used diagnostic method, and it showed a higher prevalence for all tested animal species. Positive cases were mainly concentrated in the Canary Islands, specifically in the eastern islands, with isolated cases found in the province of Alicante (Iberian Peninsula). This atlas provides an overview of the history and occurrence of Surra in Spain, and it represents a valuable tool for future control initiatives and for research. Still, the need for more studies remains, especially for further testing of potential hosts other than camelids and for the examination of their potential transmission vectors.

Prevalence, antimicrobial resistance, and genetic lineages of nasal Staphylococcus aureus among medical students at a Spanish University: detection of the MSSA-CC398-IEC-type-C subclade.

Medical students could be a potential source of Staphylococcus aureus transmission to patients. This cross-sectional study involved samples collected from both nasal nostrils. Samples were processed for S. aureus recovery; the antimicrobial resistance (AMR) phenotype was determined by disc diffusion assays and the spa types and AMR genotypes by PCR/sequencing. A structured questionnaire was administered to students to collate data related to potential risk factors of nasal colonization. Ninety-eight students were included, 50 % were colonized by S. aureus and 12.2 % by MRSA. The mecA gene was detected in all MRSA isolates. The MSSA-CC398-IEC-type C lineage was found among 16.3 % of nasal carriers, of which t571 was the predominant spa-type. MRSA isolates were ascribed to spa types t2226 (CC5, 12 isolates) and t3444 (new spa type, 1 isolate). All MRSA were multi-drug resistant and MSSA were predominantly resistant to erythromycin-clindamycin (inducible-type, mediated by ermT gene). High rates of S. aureus and MRSA nasal carriages were observed in this study. The predominance of the CC398 lineage among MSSA (emergent invasive lineage) represent a relevant finding of public health concern. The role of medical students as potential source of MRSA and MSSA-CC398 transmissions in hospital and community needs to be elucidated in detail.

Corrigendum: New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation.

[This corrects the article DOI: 10.3389/fnins.2023.1190418.].

Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

Social networks and aggressive attitudes: who is who. Scoping review of the scientific production on their relationships.

Introduction: In the current world, an increasing number of people use social networks as a scenario for socialization, which have come to stay as a part of human development. During this socialization process, violent situations occur all too often, despite their virtuality, and seriously compromises the emotional well-being of the other participants. Based on the work conducted on this subject, the following systematic review aims to establish the state of the art regarding the relationship between moral disengagement, disruptive behavior and emotional intelligence of social network users. Method: A scoping review is carried out, according to the PRISMA-ScR criteria, consulting the WoS, Scopus, Education database, PsycINFO, PsycARTICLES, PLOS one and ScienceDirect databases, from 2021 up to the present day. Results: A total of 999 articles related to the research topic were collected, although the result of research responding to the specific search criteria was reduced to 10. Discussion: The research identified shows that there is a relationship between the level of moral development of social network users and their participation in aggressive online behavior. However, more research is needed, as it has not been demonstrated whether it is the networks that develop or favor the emergence of these attitudes, or simply act as facilitators for their amplified expression.

Unveiling the Secrets of the Stressed Hippocampus: Exploring Proteomic Changes and Neurobiology of Posttraumatic Stress Disorder.

Intense stress, especially traumatic stress, can trigger disabling responses and in some cases even lead to the development of posttraumatic stress disorder (PTSD). PTSD is heterogeneous, accompanied by a range of distress symptoms and treatment-resistant disorders that may be associated with a number of other psychopathologies. PTSD is a very heterogeneous disorder with different subtypes that depend on, among other factors, the type of stressor that provokes it. However, the neurobiological mechanisms are poorly understood. The study of early stress responses may hint at the way PTSD develops and improve the understanding of the neurobiological mechanisms involved in its onset, opening the opportunity for possible preventive treatments. Proteomics is a promising strategy for characterizing these early mechanisms underlying the development of PTSD. The aim of the work was to understand how exposure to acute and intense stress using water immersion restraint stress (WIRS), which could be reminiscent of natural disaster, may induce several PTSD-associated symptoms and changes in the hippocampal proteomic profile. The results showed that exposure to WIRS induced behavioural symptoms and corticosterone levels reminiscent of PTSD. Moreover, the expression profiles of hippocampal proteins at 1 h and 24 h after stress were deregulated in favour of increased inflammation and reduced neuroplasticity, which was validated by histological studies and cytokine determination. Taken together, these results suggest that neuroplastic and inflammatory dysregulation may be a therapeutic target for the treatment of post-traumatic stress disorders.

G4-QuadScreen: A Computational Tool for Identifying Multi-Target-Directed Anticancer Leads against G-Quadruplex DNA.

The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.

New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation.

In recent years, the hypothalamus has emerged as a new neurogenic area, capable of generating new neurons after development. Neurogenesis-dependent neuroplasticity seems to be critical to continuously adapt to internal and environmental changes. Stress is a potent environmental factor that can produce potent and enduring effects on brain structure and function. Acute and chronic stress is known to cause alterations in neurogenesis and microglia in classical adult neurogenic regions such as the hippocampus. The hypothalamus is one of the major brain regions implicated in homeostatic stress and emotional stress systems, but little is known about the effect of stress on the hypothalamus. Here, we studied the impact of acute and intense stress (water immersion and restrain stress, WIRS), which may be considered as an inducer of an animal model of posttraumatic stress disorder, on neurogenesis and neuroinflammation in the hypothalamus of adult male mice, focusing on three nuclei: PVN, VMN and ARC, and also in the periventricular area. Our data revealed that a unique stressor was sufficient to provoke a significant impact on hypothalamic neurogenesis by inducing a reduction in the proliferation and number of immature neurons identified as DCX+ cells. These differences were accompanied by marked microglial activation in the VMN and ARC, together with a concomitant increase in IL-6 levels, indicating that WIRS induced an inflammatory response. To investigate the possible molecular mechanisms responsible for neuroplastic and inflammatory changes, we tried to identify proteomic changes. The data revealed that WIRS induced changes in the hypothalamic proteome, modifying the abundance of three and four proteins after 1 h or 24 h of stress application, respectively. These changes were also accompanied by slight changes in the weight and food intake of the animals. These results are the first to show that even a short-term environmental stimulus such as acute and intense stress can have neuroplastic, inflammatory, functional and metabolic consequences on the adult hypothalamus.

Surveillance and control of Trypanosoma evansi in the canary Islands: A descriptive analysis.

This study examines the occurrence of Surra, a disease caused by Trypanosoma evansi, in camels in the Canary Islands. The 1997 detection of T. evansi in camels in the Canary Islands led to the implementation of an initial control program, resulting in a decrease in prevalence. Following an outbreak in 2014, and due to the impossibility of eradicating it using the conventional measures, a lazaret was set up to separate positive and suspicious animals, in addition to the control measures previously implemented. Stomoxys calcitrans was the only vector captured, and no other animals tested were found to be positive for T. evansi. In November 2019, the last camels that tested serologically positive were detected; however, since February 2018, no camels that tested positive for PCR have been found in the farms were the outbreak was detected, suggesting that the sanitary measures implemented are adequate. The duration of the outbreak control and potential eradication for the disease has yet to be established. This study provides evidence to facilitate the control of African Animal Trypanosomosis in endemic areas of the world, which may contribute to revise the World Organization for Animal Health (WOAH) protocol to implement recommendations of surveillance and control strategies for animal Trypanosomosis in camels.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

BACKGROUND/AIM: The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. MATERIALS AND METHODS: After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. RESULTS: The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). CONCLUSION: In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

Biofilm formation on polyethylene microplastics and their role as transfer vector of emerging organic pollutants.

Microplastic (MP)-colonizing microorganisms are important links for the potential impacts on environmental, health, and biochemical circulation in various ecosystems but are not yet well understood. In addition, biofilms serve as bioindicators for the evaluation of pollutant effects on ecosystems. This study describes the ability of three polyethylene-type microplastics, white (W-), blue (B-), and fluorescent blue (FB-) MPs, to support microbial colonization of Pseudomonas aeruginosa, the effect of mixed organic contaminants (OCs: amoxicillin, ibuprofen, sertraline, and simazine) on plastic-associated biofilms, and the role of biofilms as transfer vectors of such emerging pollutants. Our results showed that P. aeruginosa had a strong ability to produce biofilms on MPs, although the protein amount of biomass formed on FB-MP was 1.6- and 2.4-fold higher than that on B- and W-MP, respectively. When OCs were present in the culture medium, a decrease in cell viability was observed in the W-MP biofilm (65.0%), although a general impairing effect of OCs on biofilm formation was ruled out. Microbial colonization influenced the ability of MPs to accumulate OCs, which was higher for FB-MP. In particular, the sorption of amoxicillin was lower for all bacterial-colonized MPs than for the bare MPs. Moreover, we analysed oxidative stress production to assess the impact of MPs or MPs/OCs on biofilm development. The exposure of biofilms to OCs induced an adaptive stress response reflected in the upregulation of the katB gene and ROS production, particularly on B- and FB-MP. This study improves our understanding of MP biofilm formation, which modifies the ability of MPs to interact with some organic pollutants. However, such pollutants could hinder microbial colonization through oxidative stress production, and thus, considering the key role of biofilms in biogeochemical cycles or plastic degradation, the co-occurrence of MPs/OCs should be considered to assess the potential risks of MPs in the environment.

MRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.

MRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated to the nucleus and activates microphthalmia-associated transcription factor (MITF) activity. In this study, we found that MRGPRX2 triggering led to MITF phosphorylation and increased MITF activity. Therefore, overexpression of LysRS increased MITF activity after MRGPRX2 activation. MITF silencing reduced MRGPRX2-dependent calcium influx and mast cell degranulation. Furthermore, a MITF pathway inhibitor, ML329, impaired MITF expression, calcium influx, and mast cell degranulation. Moreover, drugs such as atracurium, vancomycin, and morphine, reported to induce MRGPRX2-dependent degranulation, increased MITF activity. Altogether, our data show that MRGPRX2 signaling enhances MITF activity, and its abrogation by silencing or inhibition resulted in defective MRGPRX2 degranulation. We conclude that MRGPRX2 signaling involves the LysRS and MITF pathway. Thus, MITF and MITF-dependent targets may be considered therapeutic approaches to treat pathologies where MRGPRX2 is implicated.

MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation.

Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34+-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

Transcriptomic and physiological effects of polyethylene microplastics on Zea mays seedlings and their role as a vector for organic pollutants.

The widespread employment of plastics in recent decades has resulted in the accumulation of plastic residues in all ecosystems. Their presence and degradation into small particles such as microplastics (MPs) may have a negative effect on plant development and therefore on crop production. In this study, the effects of two types of polyethylene MPs on Zea mays seedlings cultured in vitro were analysed. In addition, four organic pollutants (ibuprofen, simazine, sertraline, and amoxicillin) were adsorbed by the MPs to evaluate their capacity as other contaminant vectors. The development of the plants was negatively affected by MPs alone or with the organic compounds. The strongest effect was observed in the W-MPs treatments, with a reduction in leaf and root length near 70%. Chlorophyll content was also differentially affected depending on the treatment. Transcriptome analysis showed that MPs affected gene expression in the roots of maize seedlings. As observed in the physiological parameters analysed, some gene expression changes were associated with specific treatments, such as changes in sugar transport genes in the B-MIX treatment. These results contribute to a better understanding of the molecular mechanisms of plants in regard to plastic stress responses.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors in Locally Advanced Rectal Cancer.

INTRODUCTION: The standard therapy for locally advanced rectal cancer (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study was to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathologic complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS: We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received nCRT based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT was obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ2 or Fisher's exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS: Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50.4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery, 38% had elevated basal NLR (cut-off >1.95), and 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (log-rank, Mantel-Cox 5.165, p = 0.023) and in the high PLR subgroup (log-rank, Mantel-Cox 13.971, p = 0.001). Multivariate analysis showed that PLR (p = 0.006) was a strong significant predictor of DFS. A lower OS was observed in the high NLR and PLR subgroup without significant differences (log-rank, Mantel-Cox 1.245, p = 0.265; 0.578, p = 0.447). No significant differences were obtained in any of the subgroup analysis regarding pCR rates. CONCLUSION: In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.

Antimicrobial resistance patterns of bacteria isolated from chicks of Canarian Egyptian vultures (Neophron percnopterus majorensis): A "one health" problem?

Antimicrobial resistance in Gram-negative bacteria isolated from cloacal samples of chicks of Canarian Egyptian vultures was investigated. Prevalence of Salmonella was also studied. Forty-seven isolates, obtained from 23 animals, were analysed. Escherichia coli (n = 29), Proteus mirabilis (n = 17) and Salmonella spp. (n = 1) were identified using API 20E system. Antimicrobial susceptibility to 13 antibiotics included in nine different categories was determined using disk-diffusion technique. The higher percentages of susceptible E. coli isolates were found for aminoglycosides and cefoxitin, and the lower ones were found for ampicillin, enrofloxacin and tetracycline. Proteus mirabilis isolates were susceptible to most of antimicrobials tested. Multidrug resistance patterns were found in 13 E. coli and four Proteus mirabilis. Salmonella spp. was detected in one chick (4.37%), and the isolate was also resistant to ampicillin and tetracycline. Thirteen E. coli isolates and four Proteus isolates showed a multidrug-resistance pattern, being resistant at least to one antibiotic in three or more different antimicrobial categories. This high level of antibiotic resistance in chickens of an endangered bird may be a limitation for possible treatments of infections in this species, as well as representing a source of resistant bacteria for animal care staff and for other animals in wildlife recovery centres. A "One Health" approach to this problem is necessary to reduce the levels of antimicrobial resistance in wild birds.