Swine farm environmental microbiome: exploring microbial ecology and functionality across farms with high and low sanitary status.

Introduction: Stringent regulations in pig farming, such as antibiotic control and the ban on certain additives and disinfectants, complicate disease control efforts. Despite the evolution of microbial communities inside the house environment, they maintain stability over the years, exhibiting characteristics specific to each type of production and, in some cases, unique to a particular company or farm production type. In addition, some infectious diseases are recurrent in specific farms, while other farms never present these diseases, suggesting a connection between the presence of these microorganisms in animals or their environment. Therefore, the aim of this study was to characterise environmental microbiomes of farms with high and low sanitary status, establishing the relationships between both, health status, environmental microbial ecology and its functionality. Methods: For this purpose, 6 pig farms were environmentally sampled. Farms were affiliated with a production company that handle the majority of the pigs slaughtered in Spain. This study investigated the relationship among high health and low health status farms using high throughput 16S rRNA gene sequencing. In addition, to identify ecologically relevant functions and potential pathogens based on the 16S rRNA gene sequences obtained, functional Annotation with PROkaryotic TAXa (FAPROTAX) was performed. Results and Discussion: This study reveals notable differences in microbial communities between farms with persistent health issues and those with good health outcomes, suggesting a need for protocols tailored to address specific challenges. The variation in microbial populations among farms underscores the need for specific and eco-friendly cleaning and disinfection protocols. These measures are key to enhancing the sustainability of livestock farming, ensuring safer products and boosting competitive edge in the market.

Exploring the Prevalence of Antimicrobial Resistance in Salmonella and commensal Escherichia coli from Non-Traditional Companion Animals: A Pilot Study.

Companion animal ownership has evolved to new exotic animals, including small mammals, posing a new public health challenge, especially due to the ability of some of these new species to harbour zoonotic bacteria, such as Salmonella, and spread their antimicrobial resistances (AMR) to other bacteria through the environment they share. Therefore, the objective of the present pilot study was to evaluate the current epidemiological AMR situation in commensal Escherichia coli and Salmonella spp., in non-traditional companion animal small mammals in the Valencia region. For this purpose, 72 rectal swabs of nine different species of small mammals were taken to assess the antimicrobial susceptibility against 28 antibiotics. A total of one Salmonella enterica serovar Telelkebir 13,23:d:e,n,z15 and twenty commensal E. coli strains were isolated. For E. coli strains, a high prevalence of AMR (85%) and MDR (82.6%) was observed, although neither of them had access outside the household. The highest AMR were observed in quinolones, one of the highest priority critically important antimicrobials (HPCIAs) in human medicine. However, no AMR were found for Salmonella. In conclusion, the results showed that small mammals' commensal E. coli poses a public health risk due to the high AMR found, and the ability of this bacterium to transmit its resistance genes to other bacteria. For this reason, this pilot study highlighted the need to establish programmes to control AMR trends in the growing population of new companion animals, as they could disseminate AMR to humans and animals through their shared environment.

Multidrug-Resistant Commensal and Infection-Causing Staphylococcus spp. Isolated from Companion Animals in the Valencia Region.

The emergence of antimicrobial resistance (AMR) and multidrug resistance (MDR) among microorganisms to commonly used antibiotics is a growing concern in both human and veterinary medicine. Companion animals play a significant role in the epidemiology of AMR, as their population is continuously increasing, posing a risk of disseminating AMR, particularly to strains of public health importance, such as methicillin-resistant Staphylococcus strains. Thus, this study aimed to investigate the prevalence of AMR and MDR in commensal and infection-causing Staphylococcus spp. in dogs and cats in Valencia region. For this purpose, 271 samples were taken from veterinary centers to assess antimicrobial susceptibility against 20 antibiotics, including some of the most important antibiotics for the treatment of Staphylococcus infections, including the five last resort antibiotics in this list. Of all the samples, 187 Staphylococcus spp. strains were recovered from asymptomatic and skin-diseased dogs and cats, of which S. pseudintermedius (≈60%) was more prevalent in dogs, while S. felis (≈50%) was more prevalent in cats. In the overall analysis of the isolates, AMR was observed for all antibiotics tested, including those crucial in human medicine. Furthermore, over 70% and 30% of the strains in dogs and cats, respectively, exhibited MDR. This study highlights the significance of monitoring the trends in AMR and MDR among companion animals. The potential contribution of these animals to the dissemination of AMR and its resistance genes to humans, other animals, and their shared environment underscores the necessity for adopting a One Health approach.

Backyard poultry: exploring non-intensive production systems.

The concept of backyard poultry historically encompassed "food-producing animals." Nevertheless, a recent shift in livestock production paradigms within developed countries is evident, as backyard poultry owners now raise their birds for purposes beyond self-consumption, raising animals in a familiar way, and fostering emotional bonds with them. Because backyard animals are frequently privately owned, and the resulting products are typically not marketed, very little information is available about the demographic profile of backyard owners and information on flocks' characteristics, husbandry, and welfare. Thus, this review aims to clarify the characteristics of backyard poultry, highlighting the prevalent infectious diseases and the zoonotic risk to which farmers are exposed. According to the FAO, there are different types of poultry production systems: intensive, sub-intensive, and extensive. The system conditions, requirements, and the resulting performance differ extensively due to the type of breed, feeding practices, prevalence of disease, prevention and control of diseases, flock management, and the interactions among all these factors. The presence and transmission of infectious diseases in avian species is a problem that affects both the animals themselves and public health. Bacterial (Escherichia coli, Salmonella, Campylobacter, and Mycoplasma), parasitic (helminths, louses, and mites), and viral (Avian influenza, Newcastle, Marek, Infectious Bronchitis, Gumboro, Infectious Laringotracheitis, and Fowlpox) are the most important pathogens involved in backyard poultry health. In addition, Avian influenza, Salmonella, Campylobacter, and E. coli, could be a risk for backyard farmers and/or backyard-derived products consumers. Thus, proper biosecurity implementation measures are mandatory to control them. While the principles and practices of on-farm biosecurity may be well-versed among commercial farmers, hobbyists, and backyard farmers might not be familiar with the necessary steps to protect their flocks from infectious diseases and curb their transmission. This sector represents the fourth category of poultry farming, characterized by the lowest biosecurity standards. Consequently, it is imperative to address the legal status of backyard poultry, educate owners about biosecurity measures, and promote proper veterinary care and disease control.

Phage-Based Biosanitation Strategies for Minimizing Persistent Salmonella and Campylobacter Bacteria in Poultry.

Control strategies to minimize pathogenic bacteria in food animal production are one of the key components in ensuring safer food for consumers. The most significant challenges confronting the food industry, particularly in the major poultry and swine sectors, are antibiotic resistance and resistance to cleaning and disinfection in zoonotic bacteria. In this context, bacteriophages have emerged as a promising tool for zoonotic bacteria control in the food industry, from animals and farm facilities to the final product. Phages are viruses that infect bacteria, with several advantages as a biocontrol agent such as high specificity, self-replication, self-limitation, continuous adaptation, low inherent toxicity and easy isolation. Their development as a biocontrol agent is of particular interest, as it would allow the application of a promising and even necessary "green" technology to combat pathogenic bacteria in the environment. However, bacteriophage applications have limitations, including selecting appropriate phages, legal restrictions, purification, dosage determination and bacterial resistance. Overcoming these limitations is crucial to enhance phage therapy's effectiveness against zoonotic bacteria in poultry. Thus, this review aims to provide a comprehensive view of the phage-biosanitation strategies for minimizing persistent Salmonella and Campylobacter bacteria in poultry.

Multidrug-Resistant Escherichia coli Strains to Last Resort Human Antibiotics Isolated from Healthy Companion Animals in Valencia Region.

Failure in antibiotic therapies due to the increase in antimicrobial-resistant (AMR) bacteria is one of the main threats to public and animal health. In recent decades, the perception of companion animals has changed, from being considered as a work tool to a household member, creating a family bond and sharing spaces in their daily routine. Hence, the aim of this study is to assess the current epidemiological situation regarding the presence of AMR and multidrug resistance (MDR) in companion animals in the Valencia Region, using the indicator bacteria Escherichia coli as a sentinel. For this purpose, 244 samples of dogs and cats were collected from veterinary centres to assess antimicrobial susceptibility against a panel of 22 antibiotics with public health relevance. A total of 197 E. coli strains were isolated from asymptomatic dogs and cats. The results showed AMR against all the 22 antibiotics studied, including those critically important to human medicine. Moreover, almost 50% of the strains presented MDR. The present study revealed the importance of monitoring AMR and MDR trends in companion animals, as they could pose a risk due to the spread of AMR and its resistance genes to humans, other animals and the environment they cohabit.

One Health Approach: Invasive California Kingsnake (Lampropeltis californiae) as an Important Source of Antimicrobial Drug-Resistant Salmonella Clones on Gran Canaria Island.

The increase in the reptile population has led to a rise in the number of zoonotic infections due to close contact with reptiles, with reptile-associated salmonellosis being particularly relevant. California kingsnake invasion not only threatens the endemic reptile population of the island of Gran Canaria (Spain) but also poses serious public health problems by spreading zoonotic pathogens and their antimicrobial resistance (AMR) to the environment. Thus, the aim of this study was to assess the occurrence, genetic diversity, and AMR among Salmonella spp. strains isolated from California kingsnakes in Gran Canaria Island (Spain). Of 73 invasive individuals captured, 20.5% carried Salmonella spp., belonging to different subspecies and serovars, with subsp. salamae as the most abundant. Pulsed-field electrophoresis showed high genetic diversity among subsp. salamae isolates, and among these, 73.3% showed resistance to at least one of the antimicrobials tested. In conclusion, the present study revealed the importance of wild invasive California kingsnakes as reservoirs of drug-resistant Salmonella spp. that could pose a direct threat to livestock and humans. Identification of drug-resistant Salmonella strains in wildlife provides valuable information on potential routes of transmission that involve risks to public and animal health.

Holistic Strategies to Control Salmonella Infantis: An Emerging Challenge in the European Broiler Sector.

Salmonella spp. has been globally recognized as one of the leading causes of acute human bacterial gastroenteritis resulting from the consumption of animal-derived products. Salmonella Enteritidis, S. Typhimurium, and its monophasic variant are the main serovars responsible for human disease. However, a serovar known as S. Infantis has emerged as the fourth most prevalent serovar associated with human disease. A total of 95% of isolated S. Infantis serovars originate from broilers and their derived products. This serovar is strongly associated with an elevated antimicrobial (AMR) and multidrug resistance, a resistance to disinfectants, an increased tolerance to environmental mercury, a heightened virulence, and an enhanced ability to form biofilms and attach to host cells. Furthermore, this serovar harbors genes that confer resistance to colistin, a last-resort antibiotic in human medicine, and it has the potential to acquire additional transferable AMR against other critically important antimicrobials, posing a new and significant challenge to global public health. This review provides an overview of the current status of the S. Infantis serovar in the poultry sector, focusing on its key virulence factors, including its virulence genes, antimicrobial resistance, and biofilm formation. Additionally, novel holistic strategies for controlling S. Infantis along the entire food chain are presented in this review.

Inclusive Culture in Compulsory Education Centers: Values, Participation and Teachers' Perceptions.

This article explores teachers' perceptions concerning educational inclusion as part of an inclusive culture. The study focuses on compulsory education from the teachers' point of view. We used three factors indicated in the "Index of Inclusion": inclusive values, degree of participation in the educational community, and the teachers' perceptions of the educational response offered to SEN students. To comply with the proposed objective, we explored nine variables to understand their influence on the attitudes of teachers and other professionals towards educational inclusion. These variables were gender, age, teaching seniority, educational stage, professional profile, type of center, geographic location of the center, years of experience and characteristics of SEN students, as well as the training received to meet the needs of all students. We found significant differences in the variables of age, educational stage, student characteristics, and training received, and recommendations are provided to address the needs detected.

Antimicrobial Resistance in Companion Animals: A New Challenge for the One Health Approach in the European Union.

Antimicrobial resistance (AMR) and the increase in multi-resistant bacteria are among the most important threats to public health worldwide, according to the World Health Organisation (WHO). Moreover, this issue is underpinned by the One Health perspective, due to the ability of AMR to be transmitted between animals and humans living in the same environment. Therefore, since 2014 different surveillance and control programmes have been established to control AMR in commensal and zoonotic bacteria in production animals. However, public health authorities' reports on AMR leave out companion animals, due to the lack of national programmes and data collection by countries. This missing information constitutes a serious public health concern due to the close contact between companion animals, humans and their surrounding environment. This absence of control and harmonisation between programmes in European countries leads to the ineffectiveness of antibiotics against common diseases. Thus, there is a pressing need to establish adequate surveillance and monitoring programmes for AMR in companion animals and further develop alternatives to antibiotic use in this sector, considering the impact this could have on the gut microbiota. In this context, the aim of this review is to evaluate the current control and epidemiological situations of AMR in companion animals in the European Union (EU), as well as the proposed alternatives to antibiotics.

Faculty of Education Professors' Perception about the Inclusion of University Students with Disabilities.

The recognition of the right to the inclusion of people with disabilities on a global scale has led to progress in the planning and development of policies and programs among different areas. The present work addresses the accessibility barriers to university education as an opportunity for greater inclusion. Universities must facilitate all students' physical, curricular, and relational access and comply with a "reasonable accommodation" policy to allow students with disabilities equal opportunities. The aim is to analyze the barriers that hinder educational inclusion. Four factors are explored: the students' accessibility to facilities and resources; the teachers' willingness to respond to students with disabilities and special educational needs (SEN); the teachers' curricular adjustments to meet those needs; the students' interactions with their peers and professors. We worked with a sample of 201 university professors of teacher training programs in Spain. The results show statistically significant differences in the factors indicated, according to sex, age group, teaching experience, and experience with students who require educational support. According to the study results, a series of recommendations are included to improve the training necessary for university professors to promote inclusive education.

Outpatient parenteral antimicrobial therapy for infective endocarditis in patients over 80 years / Terapia antibiótica domiciliaria endovenosa en pacientes mayores de 80 años con endocarditis infecciosa

Introduction. The incidence of infective endocarditis is progressively increasing, especially in elderly patients. Outpatient parenteral antibiotic therapy (OPAT) is being an excellent alternative for treatment, but advanced age is one of the relative contraindications. The aim of this study is to compare the characteristics and prognosis of patients less or more than 80 years, treated with OPAT. Material and methods. One hundred and ninety four pa-tients were included between 1996 and 2015, 31 of them older than 80 years. Results. The most frequently affected valve is the aortic one, mainly native valves. Most used antibiotics are ceftriaxone, ampicillin, cloxacillin and daptomycin. Differences in surgery (39.9% vs 9.7%, p=0.001) and use of infusion pump (55.2% vs 35.5%; p= 0.044) were observed, under 80 years and older respectively. No differences in readmissions and mortality were observed. Conclusions. OPAT could be considered an effective alternative for appropriately-selected elderly patients with infective endocarditis (AU)

Introducción. La incidencia de la endocarditis infecciosa ha aumentado progresivamente, especialmente en pacientes de edad avanzada. La terapia antibiótica domiciliaria endovenosa (TADE) es una excelente alternativa de tratamiento, aunque la edad avanzada sea en algunas guías una contraindicación relativa. El objetivo de este estudio es comparar las características y el pronóstico de pacientes mayores y menores de 80 años tratados con TADE. Material y métodos. Fueron incluidos 194 pacientes entre los años 1996 y 2015, 31 de ellos con edades superiores a 80 años. Resultados. La válvula más frecuentemente afectada fue la aórtica, especialmente válvulas nativas. Los antibióticos más utilizados fueron la ceftriaxona, ampicilina, cloxacilina y daptomicina. Se observaron diferencias en cirugía (39,9% vs 9,7%, p=0,001) y en uso de bombas de infusión (55,2% vs 35,5%; p= 0,044), en los grupos menores y mayores de 80 años respectivamente. No se observaron diferencias significativas en reingresos y mortalidad. Conclusiones. La TADE podría considerarse una alternati-va adecuada en pacientes de edad avanzada con endocarditis infecciosa adecuadamente seleccionados (AU)

Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin.

Glycogen synthase kinase 3ß (GSK-3ß) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies. We describe here the isolation and biochemical characterization of the marine natural sesquiterpene palinurin as a GSK-3ß inhibitor. Experimental studies performed for characterizing the inhibitory mechanism indicate that GSK-3ß inhibition by palinurin cannot be competed out by ATP nor peptide substrate. Molecular modelling techniques have enabled us to propose an unconventional binding mode to GSK-3ß. Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of palinurin leads to GSK-3ß inhibition. The inhibitory activities determined for a series of structurally related analogues support the proposed binding mode of palinurin, which is the first compound described to target this allosteric site. The results offer new opportunities for designing and developing selective inhibitors with novel mechanisms of action.

Structure-based optimization of oxadiazole-based GSK-3 inhibitors.

Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases ß-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3α and ß, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3α and 17 nM for GSK-3ß. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3α over GSK-3ß, with an IC50 of 35 nM for GSK-3α. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety.

Dolor y distensión abdominal como manifestación inicial de la neuroborreliosis / Abdominal pain and wall distension as the onset form of neuroborreliosis

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Identification of glycogen synthase kinase-3 inhibitors with a selective sting for glycogen synthase kinase-3α.

The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-3α and GSK-3ß to AD pathology and AML is ongoing. Thus, the identification of potent GSK-3α-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-3α inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-3α selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

Evidence for irreversible inhibition of glycogen synthase kinase-3ß by tideglusib.

Tideglusib is a GSK-3 inhibitor currently in phase II clinical trials for the treatment of Alzheimer disease and progressive supranuclear palsy. Sustained oral administration of the compound to a variety of animal models decreases Tau hyperphosphorylation, lowers brain amyloid plaque load, improves learning and memory, and prevents neuronal loss. We report here that tideglusib inhibits GSK-3ß irreversibly, as demonstrated by the lack of recovery in enzyme function after the unbound drug has been removed from the reaction medium and the fact that its dissociation rate constant is non-significantly different from zero. Such irreversibility may explain the non-competitive inhibition pattern with respect to ATP shown by tideglusib and perhaps other structurally related compounds. The replacement of Cys-199 by an Ala residue in the enzyme seems to increase the dissociation rate, although the drug retains its inhibitory activity with decreased potency and long residence time. In addition, tideglusib failed to inhibit a series of kinases that contain a Cys homologous to Cys-199 in their active site, suggesting that its inhibition of GSK-3ß obeys to a specific mechanism and is not a consequence of nonspecific reactivity. Results obtained with [(35)S]tideglusib do not support unequivocally the existence of a covalent bond between the drug and GSK-3ß. The irreversibility of the inhibition and the very low protein turnover rate observed for the enzyme are particularly relevant from a pharmacological perspective and could have significant implications on its therapeutic potential.