Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with Mycobacterium Bovis.

Mycobacterium bovis (Mb) is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling Mb infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFNÉ£) and its use in bovine selective breeding programs have not been explored. In the current study, IFNÉ£ production was measured using a specific IFNÉ£ ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the peripheral blood samples collected from the animals included in the study was genotyped with the EuroG Medium Density bead Chip, and the genotypes were imputed to whole-genome sequences. A genome-wide association analysis (GWAS) revealed that the IFNÉ£ in response to bPPD was associated with a specific genetic profile (heritability = 0.23) and allowed the identification of 163 SNPs, 72 quantitative trait loci (QTLs), 197 candidate genes, and 8 microRNAs (miRNAs) associated with this phenotype. No negative correlations between this phenotype and other phenotypes and traits included in the Spanish breeding program were observed. Taken together, our results define a heritable and distinct immunogenetic profile associated with strong production of IFNÉ£ in response to Mb.

Volatile biomarkers of Gram-positive bacteria of clinical relevance as a tool for infection diagnosis.

AIM: Volatile organic compounds (VOCs) are being studied as potential biomarkers in many infections. Therefore, this study aimed to analyze the volatile profile of three Gram-positive bacteria of clinical relevance to identify potential volatile biomarkers that allow their differentiation. METHODS AND RESULTS: L. monocytogenes, S. aureus, and E. faecalis clinical isolates were inoculated in a thioglycollate medium until grown. Then, VOCs were extracted by solid-phase microextraction, and the data obtained were subjected to multivariate analysis. According to our results, there was a high production of aldehydes in E. faecalis. In the case of alcohols, they only increased in L. monocytogenes, while ketones were produced significantly in all three bacteria, mainly due to acetoin. Acids were produced significantly in E. faecalis and L. monocytogenes. CONCLUSIONS: Potential biomarkers of L. monocytogenes could be 1-butanol and 2-methylbutanoic acid. In the case of E. faecalis, the VOC most related to its presence was nonanal. Lastly, potential biomarkers of S. aureus could be isoamyl butanoate and methionol, although some pyrazines have also been associated with this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of potential biomarkers of these clinically relevant bacteria could open the way for the diagnosis of these infections through the analysis of volatile compounds.

Does compartmental resection really impact retroperitoneal soft tissue sarcomas? A retrospective analysis from a Single Referral Center.

BACKGROUND: The treatment of choice for retroperitoneal soft tissue sarcomas (RPS) is surgical resection; the outcomes with more radical surgeries, notably compartmental resection, remains a subject of debate. Arguments against it, include the complexity of the technique and high morbidity. MATERIALS AND METHODS: A retrospective analysis of cases treated in a single center from January 2010 to December 2019 is presented. Two time periods were evaluated: 2010-2015 and 2016-2019, corresponding to before and after the implementation of routine compartmentectomy. We evaluated the short- and long-term outcomes of compartmental resection compared to limited surgeries through a multivariate analysis of prognostic factors. RESULTS: A total of 176 cases were included, of which 102 met the inclusion criteria. The sex distribution was similar. The average age was 52.9 years, and the average tumor size was 24.5 cm. The most frequent histology was liposarcoma (65.7%), followed by leiomyosarcoma (12.7%), and malignant peripheral nerve sheath tumor (8.8%). The median follow-up period was 40 months. We found a lower local recurrence in the group treated in the recent period (compartmentectomy) 42.3% vs 20% p = 0.007. The median overall survival (OS) was 38.7 months, and there was no difference in distant recurrence between the two time periods. Postoperative morbidity was higher in the recent period (25% vs 10% p 0.041), with no difference in 30-day mortality. CONCLUSIONS: The implementation of extensive surgery, specifically compartmentectomy, for retroperitoneal sarcomas has been linked to reduced local recurrence. We recommend considering this surgical approach for RPS in alignment with current expert consensus guidelines, as highlighted by the updated TARPSWG consensus.

Association between High Interferon-Gamma Production in Avian Tuberculin-Stimulated Blood from Mycobacterium avium subsp. paratuberculosis-Infected Cattle and Candidate Genes Implicated in Necroptosis.

The mechanisms underlying host resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are largely unknown. In the current study, we hypothesize that cows with an ability to produce higher levels of interferon-gamma (IFNÉ£) might control MAP infection more successfully. To test this hypothesis, IFNÉ£ production was measured using a specific IFNÉ£ ELISA kit in avian purified protein derivative (aPPD)-stimulated blood samples collected from 152 Holstein cattle. DNA isolated from peripheral blood samples of the animals included in the study was genotyped with the EuroG Medium-Density Bead Chip, and the genotypes were imputed to whole-genome sequencing. A genome-wide association analysis (GWAS) revealed that high levels of IFNÉ£ in response to the aPPD were associated with a specific genetic profile (heritability = 0.64) and allowed the identification of 71 SNPs, 40 quantitative trait loci (QTL), and 104 candidate genes. A functional analysis using the 104 candidate genes revealed a significant enrichment of genes involved in the innate immune response and, more specifically, in necroptosis. Taken together, our results define a heritable and distinct immunogenetic profile associated with the production of high IFNÉ£ levels and with the capacity of the host to lyse MAP-infected macrophages by necroptosis.

Gemelos siameses toracopagos, reporte de caso / Thoracopagus conjoined twins, case report

Los gemelos toracópagos están unidos de hecho como se dice cara a cara por el pecho y suelen compartir uno o varios órganos y en este caso y en particular el corazón. Existen casos reportados hace años atrás en las que algunos suelen compartir el hígado el diafragma e incluso intestino, y obviamente la piel o puente tisular. En este reporte de caso se trata de una paciente multigesta, y producto de su tercera gestación que fue diagnosticada como embarazo gemelar tora copago o (siamés toraco pago). La cual fue captada inicialmente en un primer nivel de atención proveniente del área rural y derivada a segundo nivel en nuestra ciudad para su reevaluación por especialidad de gineco-obstetricia utilizando como herramienta diagnóstica un equipo ultrasonográfico de alta gama.

Clinical and Ecological Impact of an Educational Program to Optimize Antibiotic Treatments in Nursing Homes (PROA-SENIOR): A Cluster, Randomized, Controlled Trial and Interrupted Time-Series Analysis.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are recommended in nursing homes (NHs), although data are limited. We aimed to determine the clinical and ecological impact of an ASP for NHs. METHODS: We performed a cluster, randomized, controlled trial and a before-after study with interrupted time-series analyses in 14 NHs for 30 consecutive months from July 2018 to December 2020 in Andalusia, Spain. Seven facilities implemented an ASP with a bundle of 5 educational measures (general ASP) and 7 added 1-to-1 educational interviews (experimental ASP). The primary outcome was the overall use of antimicrobials, calculated monthly as defined daily doses (DDD) per 1000 resident days (DRD). RESULTS: The total mean antimicrobial consumption decreased by 31.2% (-16.72 DRD; P = .045) with respect to the preintervention period; the overall use of quinolones and amoxicillin-clavulanic acid dropped by 52.2% (P = .001) and 42.5% (P = .006), respectively; and the overall prevalence of multidrug-resistant organisms (MDROs) decreased from 24.7% to 17.4% (P = .012). During the intervention period, 12.5 educational interviews per doctor were performed in the experimental ASP group; no differences were found in the total mean antimicrobial use between groups (-14.62 DRD; P = .25). Two unexpected coronavirus disease 2019 waves affected the centers increasing the overall mean use of antimicrobials by 40% (51.56 DRD; P < .0001). CONCLUSIONS: This study suggests that an ASP for NHs appears to be associated with a decrease in total consumption of antimicrobials and prevalence of MDROs. This trial did not find benefits associated with educational interviews, probably due to the coronavirus disease 2019 pandemic. Clinical Trials Registration. NCT03543605.

Factors that characterize oleotourists in the province of Córdoba.

Oleotourism (olive oil tourism) is a new form of gastronomic tourism that satisfies increasingly challenging tourist demand, especially in the wake of the pandemic and for tourists who seek not only quality food products but also a safe environment to enjoy their chosen activity. Córdoba is a province in southern Spain where olives play a very important role, accounting for 50% of its cultivated area, and whose agricultural activity can be complemented with tourism due to its 189 oil mills that can welcome visitors for oil tasting. However, this type of tourism is not seeing an expected boom. This research analyzes, through a varimax analysis, the factors that attract and drive oleotourists as well as the components of such tourism. As a result, four principal components related to tourists and tourism offers were obtained, finding a high degree of satisfaction of oleotourist with the routes explored as well as a lack of knowledge of this type of tourism in international markets.

Effect of processing parameters on texture and variant selection of as-built 300 maraging steel processed by laser powder bed fusion.

Among the materials that might be manufactured with laser powder bed fusion (LPBF), one can highlight maraging steels, with excellent weldability, strength and fracture toughness. However, the effects of the processing parameters and the mechanisms governing the as-built texture are not clear yet. A recent publication showed a low texture index in the prior austenite, in contrast to other alloys subjected to LPBF with the same strategy. Authors suggested several hypotheses, although no conclusions were drawn. This work aims to investigate these findings by using a 300 maraging steel processed under different conditions, i.e. different printer, powder layer thickness and laser emission mode. To do so, X-Ray Diffraction, Electron Backscattered Diffraction and Scanning Electron Microscopy have been used. Results show that the heat treatment intrinsic to the LPBF process does not affect the prior austenite grains, whose texture and morphology remain unchanged throughout the process. Also, for the studied ranges, the microstructure texture is not related to the powder layer thickness or to the laser emission mode, although it could be affected by the laser power or the scan strategy. Finally, a low degree of variant selection has been observed, where the selected variants are those that contribute to a martensite cubic rotated texture.

Ultrasensitive and rapid identification of ESRI developer- and piperacillin/tazobactam-resistant Escherichia coli by the MALDIpiptaz test.

BACKGROUND: The excessive use of piperacillin/tazobactam (P/T) has promoted the emergence of P/T-resistant Enterobacterales. We reported that in Escherichia coli, P/T contributes to the development of extended-spectrum resistance to ß-lactam/ß-lactamase inhibitor (BL/BLI) (ESRI) in isolates that are P/T susceptible but have low-level resistance to BL/BLI. Currently, the detection of P/T resistance relying on conventional methods is time-consuming. To overcome this issue, we developed a cost-effective test based on MALDI-MS technology, called MALDIpiptaz, which aims to detect P/T resistance and ESRI developers in E. coli. METHODS: We used automated Clover MS Data Analysis software to analyse the protein profile spectra obtained by MALDI-MS from a collection of 248 E. coli isolates (91 P/T-resistant, 81 ESRI developers and 76 P/T-susceptible). This software allowed to preprocess all the spectra to build different peak matrices that were analysed by machine learning algorithms. RESULTS: We demonstrated that MALDIpiptaz can efficiently and rapidly (15 min) discriminate between P/T-resistant, ESRI developer and P/T-susceptible isolates and allowed the correct classification between ESRI developers from their isogenic resistance to P/T. CONCLUSION: The combination of excellent performance and cost-effectiveness are all desirable attributes, allowing the MALDIpiptaz test to be a useful tool for the rapid determination of P/T resistance in clinically relevant E. coli isolates.

Ferrimagnetic Clusters as the Origin of Anomalous Curie-Weiss Behavior in ZnFe2O4 Antiferromagnetic Susceptibility.

Different studies carried out in the last three decades on the magnetic susceptibility of the spinel ZnFe2O4 ferrite have revealed the positive character of its Curie-Weiss temperature, contradicting its observed antiferromagnetic behavior which is characterized by a well-defined susceptibility peak centered around the Neel temperature (10 K). Some approaches based on ab initio calculations and mixture of interactions have been attempted to explain this anomaly. This work shows how for very low values of the inversion parameter, the small percentage of Fe atoms located in tetrahedral sites gives rise to the appearance of ferrimagnetic clusters around them. Superparamagnetism of these clusters is the main cause of the anomalous Curie-Weiss behavior. This finding is supported experimentally from the thermal dependence of the inverse susceptibility and its evolution with the degree of inversion.

Enotourism in Southern Spain: The Montilla-Moriles PDO.

The profile of tourists during the COVID-19 pandemic is changing toward those seeking health, safety and quality products. One of the modalities that best adapts to these needs is gastronomic tourism and, within this segment, wine tourism (enotourism), which can be enjoyed in many areas across the world. The great diversity of grapes, climates, terrains and winemaking processes gives rise to an enormous variety of wines that ensures that no two wines are alike. The current situation of the tourism market necessitates enhancing the uniqueness of areas that offer differentiated products, helping to position such locations as benchmarks for gastronomic tourism. Gastronomic routes provide a way to unify and benefit rural areas through the recently increased demand of tourists seeking to experience regional foods. In this study, the Montilla-Moriles Wine Route is analyzed with the objective of forecasting the demand (using autoregressive integrate moving average, ARIMA models), establishing a tourist profile and calculating the probability that a wine tourist is satisfied with the visit based on their personal characteristics (logit model). The results obtained indicate a slight increase (3.6%) in wine tourists with a high degree of satisfaction, primarily derived from the gastronomic or catering services of the area, from the number of wineries visited, from the treatment received and from the age of the tourist. Consequently, a high percentage of these tourists recommend the route. By increasing the demand for enotourism in this area and applying the results obtained, marketing initiatives could be established, particularly for wine festivals to improve this tourist segment and generate wealth in that area.

Unveiling the Hidden Entropy in ZnFe2O4.

The antiferromagnetic (AFM) transition of the normal ZnFe2O4 has been intensively investigated with results showing a lack of long-range order, spin frustrations, and a "hidden" entropy in the calorimetric properties for inversion degrees δ ≈ 0 or δ = 0. As δ drastically impacts the magnetic properties, it is logical to question how a δ value slightly different from zero can affect the magnetic properties. In this work, (Zn1-δFeδ)[ZnδFe2-δ]O4 with δ = 0.05 and δ = 0.27 have been investigated with calorimetry at different applied fields. It is shown that a δ value as small as 0.05 may affect 40% of the unit cells, which become locally ferrimagnetic (FiM) and coexists with AFM and spin disordered regions. The spin disorder disappears under an applied field of 1 T. Mossbauer spectroscopy confirms the presence of a volume fraction with a low hyperfine field that can be ascribed to these spin disordered regions. The volume fractions of the three magnetic phases estimated from entropy and hyperfine measurements are roughly coincident and correspond to approximately 1/3 for each of them. The "hidden" entropy is the zero point entropy different from 0. Consequently, the so-called "hidden" entropy can be ascribed to the frustrations of the spins at the interphase between the AFM-FiM phases due to having δ ≈ 0 instead of ideal δ = 0.

Impact of the COVID-19 Pandemic on Survival in the Patients With the Intra-Abdominal Infections.

Objective: To analyze the availability and access to the hospital for the patients with intra-abdominal infections (IAIs) by Escherichia coli (E. coli) as a result of the coronavirus disease 2019 (COVID-19) pandemic and the impact of these changes in the diagnosis and their effects on the death of these patients. Methods: Two prospective observational cohorts of the patients with IAI by E. coli were conducted in 2016 (the pre-COVID-19, n = 108) and in 2020 (during the COVID-19, n = 96) at the University Hospital of Seville, Spain. The demographic and clinical variables of the patients were collected and analyzed. The patients were followed-up for 120 days, until the hospital discharge or death. The bivariate and multivariate analyses were performed. Results: Both the cohorts were homogeneous according to age, sex, emergency surgery cause, immunosuppression, neutropenia, acquisition type, and previous intervention. The patients attended during the COVID-19 had significantly higher Charlson comorbidity index and the more McCabe score, required more emergency surgery, had more severe infections with the higher rates of septic shock and sepsis, and the presence of additional care support such as a nasogastric tube. They were diagnosed later; the time intervals between the symptoms onset (SO) to the first medical contact or surgical intervention (SI) and between the first medical contact to the admission or SI were significantly higher. The death rates during the COVID-19 and the pre-COVID-19 were 16.7 and 6.5%, respectively (p = 0.02). Finally, the multivariate analysis in both the cohorts together identified the patients diagnosed during the COVID-19, the longer period from SO to SI, septic shock, and the Charlson comorbidity index as the independent factors associated with death. Conclusion: This study showed the impact of the COVID-19 pandemic on the clinical outcome and death due to IAI with an extension of the time between SO and SI.

Improved extraction of carrageenan from red seaweed (Chondracantus canaliculatus) using ultrasound-assisted methods and evaluation of the yield, physicochemical properties and functional groups.

Red seaweed Chondracanthus canaliculatus, an underexploited algae species, was used as a potential source for the obtaining of carrageenan. Seaweed was treated under alkaline conditions using ultrasound alone or combined with conventional procedures, to improve the yield extraction. Color, syneresis behavior, water retention capacity, and functional groups of the gelling and non-gelling fractions of carrageenan were determined; these properties were compared with those of commercial carrageenans named A and B. Ultrasound alone or with heat significantly (p < 0.05) increased the yield extraction up to 41-45% and influenced color parameters, in comparison with conventional treatments. Functional groups kappa and iota, and alginates, were confirmed in both carrageenan fractions. Syneresis behavior was well fitted to a third-degree polynomial equation within days 1 to 6, after which, it reached a plateau. While, the use of ultrasound at room temperature gave carrageenan properties more similar to those of the commercial carrageenan type A.

Interdependent Oxidation of Eicosapentaenoic Acid and Docosahexaenoic Acid in Isada Krill Oil Encapsulated with Maltodextrin by Spray-drying.

The major polyunsaturated fatty acids in krill oil extracted from Euphausia pacifica, known as Isada on the Sanriku coast, are eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid. A kinetic model was proposed to explain the relationship between the fractions of unoxidized EPA (Y E) and unoxidized DHA (Y D) in the oil spray-dried with maltodextrin and stored at 25, 50, and 70℃. The relationship between Y E and Y D during storage was independent of the temperature and could be expressed using the proposed model. This indicated that the oxidation of EPA and DHA in krill oil was interdependent.

Synthesis and Characterization of a Nearly Single Bulk Ti2AlN MAX Phase Obtained from Ti/AlN Powder Mixture through Spark Plasma Sintering.

MAX phases are an advanced class of ceramics based on ternary carbides or nitrides that combine some of the ceramic and metallic properties, which make them potential candidate materials for many engineering applications under severe conditions. The present work reports the successful synthesis of nearly single bulk Ti2AlN MAX phase (>98% purity) through solid-state reaction and from a Ti and AlN powder mixture in a molar ratio of 2:1 as starting materials. The mixture of Ti and AlN powders was subjected to reactive spark plasma sintering (SPS) under 30 MPa at 1200 °C and 1300 °C for 10 min in a vacuum atmosphere. It was found that the massive formation of Al2O3 particles at the grain boundaries during sintering inhibits the development of the Ti2AlN MAX phase in the outer zone of the samples. The effect of sintering temperature on the microstructure and mechanical properties of the Ti2AlN MAX phase was investigated and discussed.

Utilidad de la citometría de flujo para la detección de Pseudomonas aeruginosa productoras de metalobetalactamasas / Utility of flow citometry for detecting metallo-beta-lactamase-producing Pseudomonas aeruginosa

RESUMEN Con el objetivo de determinar la utilidad de la citometría de flujo para la detección de Pseudomonas aeruginosa productoras de metalobetalactamasas (MBL), se estudiaron aislamientos de P. aeruginosa genotípicamente caracterizados del cepario del laboratorio de Epidemiología Molecular y Genética de la Universidad Nacional Mayor de San Marcos. Se analizaron 29 aislamientos (17 productoras de MBL y 12 no productoras de MBL) con el kit de viabilidad celular FACSCalibur (Becton Dickinson). Se utilizaron dos tratamientos, uno con meropenem y el otro con meropenem-EDTA. Usando la razón de aumento de fluorescencia en las células no vivas, se demostró una diferencia significativa entre las productoras de MBL y las no MBL, considerando como punto de corte una razón >1,6. Se determinó una sensibilidad de 94,1% y una especificidad del 100%. La citometría de flujo constituye una alternativa para la detección de P. aeruginosa productora de MBL.

ABSTRACT In order to determine the utility of flow cytometry for detecting metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa, we used genotypically characterized P. aeruginosa isolates from the Molecular Epidemiology and Genetics Laboratory of the Universidad Nacional Mayor de San Marcos. A total of 29 isolates (17 MBL-producing and 12 non-MBL-producing) were analyzed with the FACSCalibur (Becton Dickinson) cell viability kit. Two treatments were used, one with meropenem and the other with meropenem-EDTA. A significant difference between MBL and non-MBL-producing P. aeruginosa was demonstrated using the fluorescence ratio in non-living cells, considering a cut-off point of >1.6. We determined a sensitivity of 94.1% and a specificity of 100%. Flow cytometry represents an alternative for the detection of MBL-producing P. aeruginosa.

Dilatometric and Microstructural Study of Martensite Tempering in 4% Mn Steel.

This paper presents the results of martensite tempering resistance in 4% Mn steel. The material was quenched and tempered at 350 °C for 15, 30, and 60 min. The analysis of the quenching and tempering was carried out using dilatometric and microstructural approaches. The phase composition was assessed using X-ray diffraction. The Ms temperature and tempering progress were simulated using JMatPro software. The dilatometric analysis revealed a small decrease in the relative change in length (RCL) during tempering. This decrease was connected to the precipitation kinetics of cementite within the martensite laths. The microstructure investigation using a scanning electron microscope showed a very small amount of carbides, even for the longest tempering time. This showed the high tempering resistance of the martensite in medium-Mn steels. The hardness results showed an insignificant decrease in the hardness depending on the tempering time, which confirmed the high tempering resistance of martensite.

A New Roadway Eventual Obstacle Detection System Based on Computer Vision.

A new roadway eventual obstacle detection system based on computer vision is described and evaluated. This system uses low-cost hardware and open-source software to detect and classify moving elements in roads using infra-red and colour video images as input data. This solution represents an important advancement to prevent road accidents due to eventual obstacles which have considerably increased in the past decades, mainly with wildlife. The experimental evaluation of the system demonstrated that the proposed solution detects and classifies correctly different types of moving obstacles on roads, working robustly under different weather and illumination conditions.

Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients.

BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.