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Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (Map). Vaccination is one of the most cost-effective tools for PTB control, although alternative treatments like the probiotic Dietzia have been explored with promising results. Using a rabbit model, we investigated the association of immunological and microbiota profiles in Gut Associated Lymphoid Tissue (GALT) with the effects in protection induced by the administration of Dietzia spp., the commercial vaccine (Silirum ® ) and the combination of both. The treatment with the probiotic diminished inflammation, but failed to control Map burden, suggesting a detrimental effect. Rabbits treated with the probiotic presented the highest rates of tissue lesion extension, although the immunological profile was not suggestive of an inflammatory state. Map load in both vaccinated groups was similar indicating that both treatments are equally effective in eliminating the infection, suggesting the role of vaccination in eliminating the infection prevails over the immunomodulatory effects of the probiotic. There were slight variations in the presence of some taxonomic groups depending on the treatment, highlighting the complexity of microbial interactions and the need to optimise treatment combinations in the context of each disease and animal species.

•Paratuberculosis vaccination extends productive life of dairy cattle.•Paratuberculosis vaccination induces a reduced mortality non-specific effect (NSE)•This NSE fits the expected according to the trained immunity mechanism.•This inactivated vaccine has a positive effect on females.•Extended paratuberculosis vaccination could help reduce antibiotic use. Records of cattle vaccination against paratuberculosis (PTB) have been analyzed to determine whether or not non-specific effect (NSE) on overall mortality similar to that observed in BCG vaccinated humans occurs in animals. The results of a previously reported slaughterhouse study on PTB prevalence were used as a reference on the age incidence of advanced patent (clinical) epidemio-pathogenic forms. In the proper vaccine study, cows in 30 cattle farms in the Basque Country, Spain were followed-up for between 1 and 13 years. Vaccinated groups were composed by 1008 (592 right-censored) animals younger than 3 months treated as calves and by 3761 (3160 right-censored) vaccinated at any older age. Controls were 339 (157 right-censored) and 4592 (2213 right-censored) age matched animals, respectively. Individual last year presence in the annual testing was considered age at culling or death. A survival analysis was carried out according age at vaccination of vaccinated versus non-vaccinated animals. PTB age incidence in the slaughterhouse study was subtracted from the difference between vaccinated and non-vaccinated animals at the same age in order to estimate PTB-specific and non-specific effects. The maximum difference was observed at the 2–3 years interval with a 33.9% mortality reduction in the calf vaccinated group. This corresponded also with the maximum NSE that was 24.5% for a PTB incidence of 9.5%. Overall, vaccination afforded to calves a 26.5% yearly mortality protection, split between 11.1% PTB-specific and 15.4% NSE. These results support a NSE on total mortality associated with PTB vaccination that appeared to persist for up to 6–7 years. This confirms for the first time in an animal field study the innate immune system memory predicted by the recently proposed trained immunity theory. Contrasting the literature, no deleterious effects of killed vaccines on females were observed. Mortality reduction would offset vaccination costs and could improve livestock systems efficiency and potentially reduce antibiotic use. Clinical trial registered with Spanish Agency for Drugs and Sanitary products (AEMPS) as 11/012/ECV.

The early diagnosis of mycoses is important for the institution of an effective antifungal therapy. Detection of antibodies against crude antigenic extracts is one of the standard techniques for the diagnosis of most mycoses. However, while these crude antigenic extracts are relatively easy to obtain, they usually show low reproducibility and are not very specific, since antibodies from patients with different mycoses may show cross-reactivity. The application of molecular biology techniques to the study of fungal antigens has allowed the production of recombinant antigens that may help to solve these problems. The purpose of this review is to discuss the use of recombinant fungal antigens in the diagnosis of mycoses.

Abstract Mycobacterium avium subsp. paratuberculosis (Map) is the underlying pathogen causing bovine paratuberculosis (PTB), an enteric granulomatous disease that mainly affects ruminants and for which an effective treatment is needed. Macrophages are the primary target cells for Map, which survives and replicates intracellularly by inhibiting phagosome maturation. Neutrophils are present at disease sites during the early stages of the infection, but seem to be absent in the late stage, in contrast to healthy tissue. Although neutrophil activity has been reported to be impaired following Map infection, their role in PTB pathogenesis has not been fully defined. Neutrophils are capable of releasing extracellular traps consisting of extruded DNA and proteins that immobilize and kill microorganisms, but this mechanism has not been evaluated against Map. Our main objective was to study the interaction of neutrophils with macrophages during an in vitro mycobacterial infection. For this purpose, neutrophils and macrophages from the same animal were cultured alone or together in the presence of Map or Mycobacterium bovis Bacillus-Calmette-Guérin (BCG). Extracellular trap release, mycobacteria killing as well as IL-1β and IL-8 release were assessed. Neutrophils released extracellular traps against mycobacteria when cultured alone and in the presence of macrophages without direct cell contact, but resulted inhibited in direct contact. Macrophages were extremely efficient at killing BCG, but ineffective at killing Map. In contrast, neutrophils showed similar killing rates for both mycobacteria. Co-cultures infected with Map showed the expected killing effect of combining both cell types, whereas co-cultures infected with BCG showed a potentiated killing effect beyond the expected one, indicating a potential synergistic cooperation. In both cases, IL-1β and IL-8 levels were lower in co-cultures, suggestive of a reduced inflammatory reaction. These data indicate that cooperation of both cell types can be beneficial in terms of decreasing the inflammatory reaction while the effective elimination of Map can be compromised. These results suggest that neutrophils are effective at Map killing and can exert protective mechanisms against Map that seem to fail during PTB disease after the arrival of macrophages at the infection site. Competing Interest Statement The authors have declared no competing interest. Footnotes * Improved version of the manuscript.

Purpose In recent years, the need for a more appropriate prescription of medications in the older population has emerged as a significant public health concern. In this study, we aimed to evaluate the prevalence of potentially inappropriate medications (PIM) in hospitalized adults aged ≥ 75. Patients and methods This was a retrospective descriptive observational study of patients at 16 hospitals in Spain. The study population included inpatients aged ≥ 75 admitted during a 7-day period (May 10 to 16, 2021). Data were obtained from the pharmacy databases of the participating hospitals. The list of PIMs was based on the Beers, STOPP-START, EU-PIM and PRISCUS criteria. Results A total of 4,183 patients were included. PIMs were detected in 23.5% ( N  = 1,126) of the cohort. The prevalence rates at the participating hospitals ranged from 10% to 42.5%. The PIM/patient ratio was 1.2. The most common PIMs were midazolam, dexketoprofen, diazepam, and doxazosin, all of which (except for doxazosin) were more common in women. Benzodiazepines accounted for 70% of all PIMs. In 35% of cases, the PIMs were initiated before hospital admission. Of the 818 PIMs initiated during hospitalization, the two most common were benzodiazepines (49%) and anti-inflammatory drugs (25%). At discharge, only 4.9% of the PIMs initiated during the hospital stay were still prescribed. Conclusion In this population of older hospitalized patients, the overall prevalence of PIMs was moderate. However, the prevalence rate at the participating hospitals was highly variable. In most cases, PIMs prescribed prior to hospitalization for chronic conditions were not withdrawn during the hospital stay. No significant increase in PIMs was observed from pre-admission to post-discharge. These findings underscore the need for multidisciplinary interventions to optimize the pharmaceutical treatment in older adults in the hospital setting to reduce the consequences of PIMs in patients.

L’enquête menée dans des brigades territoriales de gendarmerie interroge l’articulation entre genre et position sociale dans un métier au centre des structures de pouvoir de genre, en tant que métier d’ordre, et de référence pour les attentes de promotion sociale des classes populaires. L’analyse de constructions alternatives du métier par rapport au modèle viril et populaire montre la place décisive des qualifications scolaires. Virilité et capital culturel dessinent deux pôles au sein de l’espace social des gendarmes où se négocient les relations de pouvoir en termes de classe et de genre. This study conducted in local rural and peri-urban police squads ( brigades territoriales de gendarmerie ) questions the articulation between gender and social status in a profession at the heart of gender power structures, as a law enforcement profession, as well as a model for social advancement expectations among the working-classes. The analysis of alternative constructions of the profession in relation to the common manly model shows the critical importance of school qualifications. Manliness and cultural capital make up two focal points within the social space of the police noncommissioner officers (gendarmes) where class- and gender-based power relations are negotiated.

II s'agit de réaliser des aliments concentrés (20-40 p. 100 d'eau), consommables directement, stables sur le plan microbiologique et chimique, équilibrés nutritionnellement, et pouvant remplacer des repas (déplacements, camping, snacks, etc.). Avec des pectines méthoxylées, il a été possible d'obtenir un gel pectique (pH 3,5) de type pâte de fruits, mais contenant 20 p. 100/m.s. de protéines et moins de saccharose. L'activité de l'eau (Aw) est de 0,75-0,78, pour une teneur en eau de 25 p. 100, du fait de l'addition de sirop de glucose et de sorbitol. Après 4 mois d'entreposage à 20 ou 38 °C en sachets d'aluminium, il n'y a pas de développement de moisissures (même avec ensemencement préalable), et pratiquement pas de modifications de saveur, texture ou Aw. Avec des pectines déméthoxylées, des aliments gélifiés plus riches en eau (35 p. 100), plus souples, moins acides (pH 4,3) et encore moins riches en sucres ont été préparés (protéines 26 p. 100, glucides 34 p. 100, lipides 15 p. 100/m.s.). L'Aw est abaissée à 0,84 par addition d'agents humectants (saccharose, glycérol, sorbitol, acide citrique, citrate et chlorure de sodium). Des gels d'amidon (40 p. 100 d'amidon/m.s.) de pH inférieur à 4,5, contenant protéines et lipides, ont été aromatisés avec des poudres de légumes. Pour 30 p. 100 d'eau et avec des agents humectants, l'Aw est de 0,84-0,88. La texture évolue favorablement ou non selon la nature de l'amidon utilisé. Par la technologie des fromages fondus, nous avons réalisé des gels protéiques possédant, soit une Aw réduite (0,84; 38 p. 100 d'eau) par addition d'agents humectants, mais une texture souple analogue à celle d'une crème de gruyère, soit une même Aw réduite, avec une teneur en amidon de 26 p. 100/m.s., et une texture proche de celle de l'emmenthal. The aim of this study was to prepare concentrated foods (20-40 p. 100 water), edible as such, chemically and microbiologically stable, nutritionally balanced, and which could be used as meal substitutes (travel, camping, snacks, etc.). With high methoxyl pectins, it was possible to obtain a pectic gel (pH 3,5), similar to a fruit jelly, but containing 20 p. 100 d.w. protein, and less sucrose. Water activity (Aw) was 0,750,78, for a 25 p. 100 water content, as a result of adding glucose syrup and sorbitol. After 4 months storage at 20 or 38 °C in aluminium pouches, no mold growth was detected (even following prior inoculation) nor practically any change in flavor, texture or Aw. With low methoxyl pectins, gel foods richer in water (35 p. 100), softer, less acid (pH 4,3) and containing even less sugars have been prepared (26 p. 100 d.w. protein, 34 p. 100 carbohydrates, 15 p. 100 lipids). Aw was lowered to 0,84 by adding humectants (sucrose, glycerol, sorbitol, citric acid, sodium citrate and chloride). Starch gels (40 p. 100 starch/d.w.), of pH less than 4,5, containing proteins and lipids, were flavored with végétale powders. For 30 p. 100 water and with humectants, Aw was 0,84-0,88. The texture changes more or less favorably with time according to the nature of the starch used. Using the technology of processed cheeses, protein gels were made with either of the following characteristics: 1° A reduced Aw (0,86, for 38 p. 100 water) by adding humectants, but with a soft texture similar to that of a processed swiss cheese ; 2° The same reduced Aw, with a starch content of 26 p. 100/d.w., and a harder texture, comparable to that of Emmenthal cheese.