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Abstract To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p

El mundo actual se encuentra en un vertiginoso desarrollo científico-técnico, que impone complejos procesos de transformaciones sociales e incrementa las necesidades cognitivas de los profesionales mediante diversas vías para su superación. La formación profesional continua del docente universitario ha sido una de las acciones inmediatas para responder a estos retos, sin embargo, la implementación del perfeccionamiento educacional ha evidenciado insuficiencias en el diseño del sistema de superación de los docentes, que han limitado el cumplimiento de las aspiraciones de cada plan de estudio. Así, el presente trabajo se propone como objetivo diseñar un plan de acciones que permita el perfeccionamiento del sistema de superación de los docentes en la Universidad de Camagüey. En consecuencia, se utilizaron los métodos de análisis-síntesis, histórico-lógico y revisión documental que, unido a la modelación favorecieron el diseño e implementación de un plan de acciones de superación profesional y en estrecha vinculación con el trabajo docente-metodológico y científico–metodológico, consideró cinco temáticas identificadas durante el diagnóstico: enseñanza del inglés, uso de las nuevas tecnologías, metodología de la investigación científica, implementación de la Tarea Vida y sistema de educación continua. La propuesta amplía la participación de los docentes en su propia formación y superación continua, toda vez que se aprovechan sus potencialidades para abordar los contenidos identificados como necesidades de aprendizajes, encaminados a garantizar la excelencia del claustro para la dirección del proceso de enseñanza-aprendizaje.

A lack of control of the technological abiotic parameters apparent during cheese manufacture, including temperature and relative humidity, results in this dairy product being prone to mold contamination. Sometimes, inoculant molds are used to obtain the characteristic sensory properties of this type of product. However, during the maturation process, some unwanted molds can colonize the ripening cheese and produce mycotoxins. Mycotoxigenic molds such as Penicillium nordicum and Penicillium verrucosum can colonize ripened cheeses, contaminating them with ochratoxin A (OTA), a nephrotoxic 2B toxin. Thus, the presence of OTA in cheeses could represent a hazard to consumers’ health. This study has evaluated the growth and OTA production of P. nordicum and P. verrucosum on a cheese analogue under simulated ripening conditions of 10 and 15 °C and 0.96 water activity (aw). Ecophysiological, molecular, and analytical tools assessed the mold growth, gene expression, and OTA production under these environmental conditions. Both species were able to effectively colonize the cheese under these ripening conditions. However, neither species expressed the otapks and otanps biosynthetic genes or produced phenotypic OTA. Therefore, these results suggest a relatively low risk of exposure to OTA for consumers of this type of cheese product. The conditions used were thus appropriate for cheese ripening to minimize the potential for contamination with such mycotoxins. An appropriate adjustment of the technological ripening parameters during such cheese manufacture could contribute to OTA-free cheeses.

Fundamento: el uso irracional de medicamentos antibacterianos, no solo ha causado costos innecesarios al sistema de salud, incremento de la resistencia antimicrobiana, sino también un incremento de las reacciones adversas. Objetivo: describir las notificaciones de reacciones adversas a antibacterianos, registradas en la base de datos de farmacovigilancia de Las Tunas, en el período comprendido entre enero y junio de 2023. Métodos: se desarrolló un estudio de farmacovigilancia, observacional, descriptivo y transversal, en el lugar y período antes señalados. El universo estuvo constituido por 408 notificaciones registradas en la base de datos y la muestra por las 69 notificaciones de reacciones adversas a antimicrobianos. Se aplicaron técnicas de estadística descriptiva para el análisis de la información. Resultados: del total de reacciones reportadas a la base de datos, el 17 % correspondió a medicamentos antibacterianos; fueron más frecuentes los reportes de reacciones adversas, en pacientes del sexo femenino (55 %) y en edades menores de 18 años (30,43 %). Los medicamentos que más reportes generaron fueron las cefalosporinas, con un 27,25 % la cefalexina y 7,25 % a cefixime; seguido de las quinolonas, con un 18,84 % el ciprofloxacino y 11,59 % para moxifloxacino. El macrólido azitromicina se reportó en el 14,49 % de las notificaciones. Predominaron las reacciones adversas moderadas (68,12 %), frecuentes (59,4 %) y las catalogadas como probables (69,52 %). El 59,42 % fueron reportadas por médicos. Conclusiones: se caracterizaron las reacciones adversas a los antibacterianos notificadas en la base de datos de farmacovigilancia.

This study focused on the oil extraction from freeze-dried maqui (Aristotelia chilensis) by supercritical fluid extraction with carbon dioxide (SFE-CO2). The basic objective was to optimize the oil yield and the tocopherol concentration. A Box/Behnken experimental design was developed with three processing variables: supercritical pressure (74, 187, and 300 bar), temperature (35, 48, and 60 °C), and extracting time (30, 135, and 240 min). Multiple optimizations, based on the combination of factor levels at 274 bar, 240 min, and 60 °C, led to the highest oil yield and tocopherol values. The validation of the optimized conditions of maqui oil extraction led to an oil yield of 8% and values of 735, 53, and 97 (mg·kg−1 oil) for α-tocopherol, α-tocotrienol, and γ-tocopherol, respectively. A higher concentration of tocopherol compounds was observed when compared to the employment of the conventional extracting method. The optimized SFE-CO2 method led to an oil extract exhibiting higher Hydrophilic-Oxygen Radical Absorbance Capacity (H-ORAC) assay and total phenol content (22 μmol Trolox equivalents·g−1 oil and 28 mg gallic acid equivalents·g−1 oil) than the oil obtained by the conventional procedure. A practical and accurate oil extraction is proposed for obtaining tocopherol-enriched oil including high concentrations of valuable lipophilic antioxidants.

Many studies have suggested that the encapsulation of natural antimicrobials increases their antimicrobial activity. In this sense, the objective was to study the inactivation of microorganisms with encapsulated cinnamaldehyde and vanillin (E-CIN and E-VN), in comparison with the unencapsulated antimicrobials (CIN and VN) in protein beverages. Additionally, the microbial response was quantified through mathematical modeling. Cinnamaldehyde and vanillin were encapsulated using whey protein concentrate (WPC) as the encapsulating agent. The effectiveness at inactivating Escherichia coli, Listeria innocua, and Saccharomyces cerevisiae was evaluated in a protein-apple juice beverage during storage (4 °C). Encapsulation increased the effectiveness of cinnamaldehyde, reaching reductions of 1.8, 3.3, and 5.3 log CFU/mL in E. coli, L. innocua, and S. cerevisiae, respectively, while vanillin encapsulation had little effect on antimicrobial activity, reducing by 0.5, 1.4, and 1.1 log cycles, respectively. The combined treatments (E-CIN + E-VN) had an additive effect in reducing E. coli and a synergistic effect against S. cerevisiae. The Gompertz model was more versatile and better described the biphasic curves, whereas the Weibull model complemented the information regarding the spectrum of resistances within the microbial population. In conclusion, the encapsulation of cinnamaldehyde with WPC enhanced its activity. However, further studies are necessary to improve the antimicrobial activity of vanillin.

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Four different concentrations of an aqueous extract of cuttlefish (Sepia spp.) ink (CI) were introduced, respectively, into the packing medium employed during golden seabream (Sparus aurata) canning. The quality parameters of the resulting canned fish were determined and compared to the initial fish and the control canned muscle. An important effect of the CI concentration introduced in the packing medium was proved. The presence in the packing medium of a relatively low CI concentration (CI-2 batch) led to a lower (p < 0.05) lipid oxidation development (fluorescent compound formation), lower (p < 0.05) changes of colour parameters (L* and a* values), and lower (p < 0.05) trimethylamine values in canned fish when compared to control canned samples. Additionally, the two lowest CI concentrations tested led to higher average values of C22:6ω3, ω3/ω6 ratios, and polyene index. On the contrary, the use of the most concentrated CI extract (CI-4 condition) led to a prooxidant effect (higher fluorescence ratio value). In agreement with environmental sustainability and circular economy requirements, the study can be considered the first approach to a novel and valuable use of the current marine byproduct for the quality enhancement of canned fish. On-coming research focused on the optimisation of the CI-extract concentration is envisaged.

Abstract A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Introduction: Penicillin allergy labels (PAL) are common in the hospital setting and are associated with worse clinical outcomes. Desensitization can be a useful strategy for allergic patients when alternative options are suboptimal or not available. The aim was to compare clinical outcomes of patients with PAL managed with antibiotic desensitization vs. those who received alternative non-beta-lactam antibiotic treatments.Methods: A retrospective 3:1 case-control study was performed between 2015–2022. Cases were adult PAL patients with infection who required antibiotic desensitization; controls were PAL patients with infection managed with an alternative antibiotic treatment. Cases and controls were adjusted for age, sex, infection source, and critical or non-critical medical services.Results: Fifty-six patients were included: 14 in the desensitization group, 42 in the control group. Compared to the control group, desensitized PAL patients had more comorbidities, with a higher Charlson index (7.4 vs. 5; p = 0.00) and more infections caused by multidrug-resistant (MDR) pathogens (57.1% vs. 28.6%; p = 0.05). Thirty-day mortality was 14.3% in the desensitized group, 28.6% in the control group (p = 0.24). Clinical cure occurred in 71.4% cases and 54.8% controls (p = 0.22). Four control patients selected for MDR strains after alternative treatment; selection of MDR strains did not occur in desensitized patients. Five controls had antibiotic-related adverse events, including Clostridioides difficile or nephrotoxicity. No antibiotic-related adverse events were found in the study group. In multivariate analysis, no differences between groups were observed for main variables.Conclusion: Desensitization was not associated with worse clinical outcomes, despite more severe patients in this group. Our study suggests that antibiotic desensitization may be a useful Antimicrobial Stewardship tool for the management of selected PAL patients.

Bacteriophage fitness is determined by factors influencing both their replication within bacteria and their ability to maintain infectivity between infections. The latter becomes particularly crucial under adverse environmental conditions or when host density is low. In such scenarios, the damage experienced by viral particles could lead to the loss of infectivity, which might be mitigated if the virus undergoes evolutionary optimization through replication. In this study, we conducted an evolution experiment involving bacteriophage Qβ, wherein it underwent 30 serial transfers, each involving a cycle of freezing and thawing followed by replication of the surviving viruses. Our findings show that Qβ was capable of enhancing its resistance to this selective pressure through various adaptive pathways that did not impair the virus replicative capacity. Notably, these adaptations predominantly involved mutations located within genes encoding capsid proteins. The adapted populations exhibited higher resistance levels than individual viruses isolated from them, and the latter surpassed those observed in single mutants generated via site-directed mutagenesis. This suggests potential interactions among mutants and mutations. In conclusion, our study highlights the significant role of extracellular selective pressures in driving the evolution of phages, influencing both the genetic composition of their populations and their phenotypic properties.

Summary: Breastmilk contains antibodies that could protect breastfed infants from infections. In this work, we examined if antibodies in breastmilk could neutralize SARS-CoV-2 in 84 breastmilk samples from women that were either vaccinated (Comirnaty, mRNA-1273, or ChAdOx1), infected with SARS-CoV-2, or both infected and vaccinated. The neutralization capacity of these sera was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. We found that natural infection resulted in higher neutralizing titers and that neutralization correlated positively with levels of immunoglobulin A in breastmilk. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA-based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contains SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.

IntroductionHost density is one of the main factors affecting the infective capacity of viruses. When host density is low, it is more difficult for the virus to find a susceptible cell, which increases its probability of being damaged by the physicochemical agents of the environment. Nevertheless, viruses can adapt to variations in host density through different strategies that depend on the particular characteristics of the life cycle of each virus. In a previous work, using the bacteriophage Qβ as an experimental model, we found that when bacterial density was lower than optimal the virus increased its capacity to penetrate into the bacteria through a mutation in the minor capsid protein (A1) that is not described to interact with the cell receptor.ResultsHere we show that the adaptive pathway followed by Qβ in the face of similar variations in host density depends on environmental temperature. When the value for this parameter is lower than optimal (30°C), the mutation selected is the same as at the optimal temperature (37°C). However, when temperature increases to 43°C, the mutation selected is located in a different protein (A2), which is involved both in the interaction with the cell receptor and in the process of viral progeny release. The new mutation increases the entry of the phage into the bacteria at the three temperatures assayed. However, it also considerably increases the latent period at 30 and 37°C, which is probably the reason why it is not selected at these temperatures.ConclusionThe conclusion is that the adaptive strategies followed by bacteriophage Qβ, and probably other viruses, in the face of variations in host density depend not only on their advantages at this selective pressure, but also on the fitness costs that particular mutations may present in function of the rest of environmental parameters that influence viral replication and stability.

Paciente diagnosticada de colitis ulcerosa y artritis reumatoide que está siendo tratada con mesalazina e hidroxicloroquina y que presenta síntomas catarrales similares a los de la COVID-19. El seguimiento farmacoterapéutico (SFT) realizado a la paciente permite asociar estos síntomas con un efecto secundario debido a los medicamentos que toma, consistente en discrasias sanguíneas. La intervención, realizada con el propio estado de situación, para informar al médico, consigue que éste realice modificaciones del tratamiento hasta conseguir el control de la enfermedad mediante disminución de las dosis de los medicamentos utilizados.

ABSTRACT: The yeasts involved in the ripening process of artisanal soft raw ewe milk Protected Designation of Origin (PDO) Torta del Casar and Queso de la Serena cheeses produced in Extremadura, Spain, were isolated throughout their ripening process, strain typed, and characterized for some important technological properties. A total of 508 yeast isolates were obtained and identified by inter-single sequence repeat anchored PCR amplification analysis and subsequent sequencing of the internal transcribed spacer ITS1/ITS2 5.8S rRNA. A total of 19 yeast species representing 8 genera were identified. Debaryomyces hansenii, Pichia kudriavzevii, Kluyveromyces lactis, and Yarrowia lipolytica were the predominant species. We selected 157 isolates, by genotyping and origin, for technological characterization. The evaluation of yeast isolates' growth under stress conditions of cheese ripening showed that 87 presented better performance. Among them, 71 isolates were not able to catabolize tyrosine to produce a brown pigment. Principal component analysis of the biochemical features of these isolates showed that 9 strains stood out, 3 K. lactis strains (2287, 2725, and 1507), 2 Pichia jadinii (1731 and 433), 2 Yarrowia alimentaria (1204 and 2150), Y. lipolytica 2495 and P. kudriavzevii 373. These strains displayed strong extracellular proteolytic activity on skim milk agar as well as an adequate enzymatic profile (strong aminopeptidase and weak protease activity), suggesting their great potential for cheese proteolysis. Extracellular lipolytic activity was mainly restricted to Yarrowia spp. isolates and weakly present in P. kudriavzevii 373 and K. lactis 2725, although enzymatic characterization by API-ZYM (bioMérieux SA) evidenced that all may contribute, at least in part, to the lipolysis process. Moreover, these strains were able to assimilate lactose, galactose, and glucose at NaCl concentrations higher than that usually found in cheese. However, lactate and citrate assimilation were limited to Y. lipolytica 2495, P. kudriavzevii 373, and P. jadinii 433, and may contribute to the alkalinizing process relevant to biochemical processes that take place in the last stages of ripening. By contrast, K. lactis strains showed acidifying capacity and β-galactosidase activity and may take part in the initial stages of ripening, together with lactic acid bacteria. Thus, considering the technological characteristics studied, the 9 selected strains presented biochemical features well suited to their potential use as adjunct cultures, alone or in combination with autochthonous starter bacteria in the cheesemaking process, to overcome the heterogeneity of these PDO cheeses, preserving their unique sensory characteristics.

Abstract Background Levetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view. Methods Different dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam. Results According to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue. Conclusions Conventional dosage regimens of levetiracetam (500–1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 or 6 h) infusions, continuous infusions or the administration of doses higher than the recommended in the summary of product characteristics (> 3000 mg). These new dosage recommendations take into account biopharmaceutical and pharmacokinetic aspects and meet feasibility criteria, which allow them to be transferred to the clinical environment with safety and efficacy. Nevertheless, further clinical studies are needed to confirm these results.

Summary This study aimed to provide insight into the molecular and genetic mechanisms implicated in the responses of Lactobacillus reuteri against the oxidative stress induced by malondialdehyde (MDA) by analysing protein oxidation and assessing the uspA and the dhaT genes. Four experimental groups were evaluated depending on the concentration of MDA added in Man, Rogosa and Sharpe (MRS) broth: Control (L. reuteri), 5 µM (L. reuteri + 5 µM MDA), 25 µM (L. reuteri + 25 µM MDA) and 100 µM (L. reuteri + 100 µM MDA). Three replicates were incubated at 37 °C for 24 h in microaerophilic conditions and sampled at 12, 16, 20 and 24 h. The upregulation of the uspA gene by L. reuteri indicates the recognition of MDA as a potential DNA‐damaging agent. The dhaT gene, encoding a NADH‐dependent‐oxidoreductase, was also upregulated at the highest MDA concentrations. This gene was proposed to play a role in the antioxidant response of L. reuteri. The incubation of L. reuteri with MDA increased the production of ROS and caused thiol depletion and protein carbonylation. L. reuteri is proposed to detoxify pro‐oxidative species while the underlying mechanism requires further elucidation.

The use of underwater recording is widely implemented across different marine ecology studies as a substitute for more invasive techniques. This is the case of the Deep Scattering Layer (DSL), a biomass-rich layer in the ocean located between 400 and 600 m deep. The data processing of underwater videos has usually been carried out manually or targets organisms above a certain size. Marine snow, or macroscopic amorphous aggregates, plays a major role in nutrient cycles and in the supply of organic material for organisms living in the deeper layers of the ocean. Marine snow, therefore, should be taken into account when estimating biomass abundance in the water column. The main objective of this project is to develop a new software application for the automatic detection and analysis of biomass abundance relative to time in underwater videos, taking into consideration small items. The application software is based on a pipeline and client-server architecture, developed in Python and using open source libraries. The software was trained with underwater videos of the DSL recorded with low-cost equipment. A usability study carried out with end-users shows satisfaction with the user-friendly interface and the expected results. The software application developed is capable of automatically detecting small items captured by underwater videos. In addition, it can be easily adapted to a web application.

This study focused on the recovery of valuable lipid compounds from octopus (Octopus vulgaris) by-products. Extraction conditions of total lipids (TLs), phospholipids (PLs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were optimized by employing a Simplex-Lattice design; for it, different relative concentrations of three low-toxicity solvents (ethanol, acetone, and ethyl acetate) were considered. The optimization process was also addressed in reference to fatty acid (FA) ratios (total polyunsaturated FAs/total saturated FAs and total ω3 FAs/total ω6 FAs). The variance analysis of multiple regression data demonstrated that the quadratic model was significant (p < 0.05) for TL, PL, and DHA values and the ω3/ω6 ratio. As a result, the following optimized values were obtained: 113.8 g·kg−1 dry by-products (TLs), 217.3 g·kg−1 lipids (PLs), 22.55 g·100 g−1 total FAs (DHA), and 3.70 (ω3/ω6 ratio). According to the model developed, optimized values were shown to correspond to the following relative solvent concentrations (ethanol/acetone/ethyl acetate): 0.46/0.00/0.54, 0.93/0.07/0.00, 0.83/0.17/0.00, and 0.64/0.00/0.36, respectively. Comparison to yields obtained by the conventional chloroform/methanol method was carried out. A novel strategy based on the employment of low-toxicity solvents is proposed for the extraction of valuable lipid constituents from octopus waste. A different solvent ratio would be necessary according to the lipid compound concerned.

There is a necessity to protect the quality and authenticity of herbs and spices because of the increase in the fraud and adulteration incidence during the last 30 years. There are several aspects that make herbs and spices quite vulnerable to fraud and adulteration, including their positive and desirable sensorial and health-related properties, the form in which they are sold, which is mostly powdered, and their economic relevance around the world, even in developing countries. For these reasons, sensitive, rapid, and reliable techniques are needed to verify the authenticity of these agri-food products and implement effective adulteration prevention measures. This review highlights why spices and herbs are highly valued ingredients, their economic importance, and the official quality schemes to protect their quality and authenticity. In addition to this, the type of frauds that can take place with spices and herbs have been disclosed, and the fraud incidence and an overview of scientific articles related to fraud and adulteration based on the Rapid Alert System Feed and Food (RASFF) and the Web of Science databases, respectively, during the last 30 years, is carried out here. Next, the methods used to detect adulterants in spices and herbs are reviewed, with DNA-based techniques and mainly spectroscopy and image analysis methods being the most recommended. Finally, the available adulteration prevention measurements for spices and herbs are presented, and future perspectives are also discussed.

Fundamento: el conocimiento sobre farmacovigilancia en el personal médico es clave para una correcta identificación y manejo de las reacciones adversas a medicamentos (RAM). Objetivo: determinar el nivel de conocimiento sobre farmacovigilancia del personal médico perteneciente al Policlínico Universitario “Manuel Piti Fajardo”, del municipio Las Tunas, en el período enero-mayo de 2022. Métodos: se realizó un estudio descriptivo de corte transversal en el lugar y periodo de tiempo anteriormente citados. La muestra estuvo constituida por 56 profesionales que respondieron la encuesta aplicada. Resultados: 75 % fueron residentes en medicina general integral; el 85,7 % conocen el modelo de notificación de RAM y solo el 21,4 % ha notificado, coincidiendo con el porciento que ha recibido capacitación. Los principales errores identificados fueron: el 62,5 % consideró que el efecto colateral no es una RAM; el 50 % respondió que para que ocurra una RAM tiene que haber reexposición ante una sensibilización previa; el 41,1 % planteó que para que sea una RAM se requiere que el medicamento se administre a altas dosis; 37,5 % opinan que se notifica la RAM cuando existe seguridad de una relación definitiva y el 33,9 % solo cuando el paciente requiere hospitalización; 42,9 % siempre suspendería el tratamiento y reportaría la RAM; 19,6 % no orienta sobre las posibles RAM a los pacientes. El 33,9 % se actualiza a través de búsqueda en internet. Conclusiones: el nivel de conocimiento sobre farmacovigilancia resultó regular en la mitad del personal médico incluido en el estudio.

Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT.

The study focused on the extraction of valuable lipid compounds from squid (Doryteuthis gahi) waste by a low-toxicity solvent mixture (ethanol/acetone, 50:50, v/v). The effect of the waste weight/solvent volume (WW/SV, g·mL−1) ratio and the number of extractions (NoE) on the total lipid (TL), phospholipid (PL), and tocopherol yields and on the fatty acid (FA) profile (eicosapentaenoic and docosahexaenoic acid contents; polyunsaturated FAs/saturated FAs and ω3/ω6 ratios) was investigated. As a result, an increased NoE led to an increased (p < 0.05) TL yield but a decreased (p < 0.05) proportion of PLs in the lipid extract. Additionally, a lower (p < 0.05) polyunsaturated FA/saturated FA ratio was detected by increasing the NoE. Some differences (p < 0.05) could be outlined as a result of increasing the WW/SV ratio; however, a definite trend for this extraction condition could not be concluded for any of the lipid parameters measured. Yield results were compared to those obtained by the conventional chloroform/methanol procedure. In order to attain an increased yield, the NoE required would depend on the polarity degree of the lipid molecule concerned. All ethanol/acetone extracting conditions tested led to remarkable yields for lipid compounds (PLs, α-tocopherol, ω3 FAs) and FA ratios with healthy, nutritional, and preserving properties.

Grade repetition is an issue with important educational implications. This study analyzes the effect of cognitive variables, socio-economic status, as well as the interaction of socioeconomic status with ethnic origin, on the probability of not repeating. Data were collected to calculate socioeconomic status using the Hollingshead Socioeconomic Index, and the following tests were administered to collect information on cognitive variables: the Primary Mental Aptitude Test (PMA), the Raven's Progressive Matrices Test, and the Wechsler Intelligence for Children Information Scale (WISC IV). The sample consisted of 664 students of Compulsory Secondary Education (ESO), Baccalaureate and intermediate and higher vocational training. The results confirm the predictive power of socioeconomic status. With regard to cognitive variables, significant results were only obtained when the WISC-IV Information Scale was taken as a predictor, this measure being related to crystallized intelligence. The influence of the origin of the students did not yield significant results. There is a clear need for a debate and a rethinking of the issue leading to the identification of new strategies to reduce grade repetition and its negative effects.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease. Our results demonstrate that HHT patients with high bleeding, as determined by a high Epistaxis Severity Score (ESS), do not have prolonged clotting times or alterations in clotting factors. Considering that coagulation is only one of the processes involved in hemostasis, the main objective of this study was to investigate the overall mechanisms of hemostasis in HHT-1 (Eng+/−) and HHT-2 (Alk1+/−) mouse models, which do not show HHT vascular phenotypes in the meaning of spontaneous bleeding. In Eng+/− mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages. In Alk1+/− mice, an overactivation of the fibrinolysis system was observed. These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients' epistaxis.

The hollow protein capsids from a number of different viruses are being considered for multiple biomedical or nanotechnological applications. In order to improve the applied potential of a given viral capsid as a nanocarrier or nanocontainer, specific conditions must be found for achieving its faithful and efficient assembly in vitro. The small size, adequate physical properties and specialized biological functions of the capsids of parvoviruses such as the minute virus of mice (MVM) make them excellent choices as nanocarriers and nanocontainers. In this study we analyzed the effects of protein concentration, macromolecular crowding, temperature, pH, ionic strength, or a combination of some of those variables on the fidelity and efficiency of self-assembly of the MVM capsid in vitro. The results revealed that the in vitro reassembly of the MVM capsid is an efficient and faithful process. Under some conditions, up to ~40% of the starting virus capsids were reassembled in vitro as free, non aggregated, correctly assembled particles. These results open up the possibility of encapsidating different compounds in VP2-only capsids of MVM during its reassembly in vitro, and encourage the use of virus-like particles of MVM as nanocontainers.

Urinary tract infections (UTIs) are extremely common and a major driver for the use of antimicrobials. Calcium fosfomycin is an old antibiotic indicated for the treatment of UTIs; however, data about its urine pharmacokinetic profile are scarce. In this work, we have evaluated the pharmacokinetics of fosfomycin from urine concentrations after oral administration of calcium fosfomycin to healthy women. Moreover, we have assessed, by pharmacokinetic/pharmacodynamic (PK/PD) analysis and Monte Carlo simulations, its effectiveness considering the susceptibility profile of Escherichia coli, the main pathogen involved in UTIs. The accumulated fraction of fosfomycin excreted in urine was around 18%, consistent with its low oral bioavailability and its almost exclusively renal clearance by glomerular filtration as unchanged drug. PK/PD breakpoints resulted to be 8, 16, and 32 mg/L for a single dose of 500 mg, a single dose of 1000 mg, and 1000 mg q8h for 3 days, respectively. For empiric treatment, the estimated probability of treatment success was very high (>95%) with the three dose regimens, considering the susceptibility profile of E. coli reported by EUCAST. Our results show that oral calcium fosfomycin at a dose level of 1000 mg every 8 h provides urine concentrations sufficient to ensure efficacy for the treatment of UTIs in women.

En este artículo se reflexiona sobre la instrumentación del Consentimiento Informado (CI) en investigaciones cualitativas a partir de experiencias de un colectivo de investigadoras de la Facultad de Psicología de la Universidad de la República (Uruguay). Se abordan aspectos históricos sobre el origen del CI contextualizado en los Comités de Ética, ubicando la situación de la Facultad de Psicología de la Universidad de la República. Luego, se profundiza en la ética y en el CI como procesos reflexivos y dialógicos, más allá de los aspectos formales establecidos institucionalmente, y sus particularidades en investigaciones cualitativas desde la Psicología Social Comunitaria. A partir de situaciones particulares, ligadas a investigaciones realizadas por integrantes del colectivo, se reflexiona sobre: a) el rol de las instituciones en la implementación del CI en personas con historias de institucionalización. b) el anonimato y la posibilidad de coautoría. La introducción del CI no es inocua, por ello se piensa en los sentidos que estos procedimientos portan, su incidencia en los vínculos que se establecen en el proceso investigativo y su relación con la ética en la investigación. Las conclusiones versan sobre la necesidad de promover institucionalmente mecanismos para la reflexión, evitando la burocratización de la ética en los procesos de investigación, así como la importancia de la flexibilización y creatividad en cuanto a formas de dar consentimiento en contextos comunitarios.

Objectives: The aim of this study was to assess the influence of renal function, in particular the presence of augmented renal clearance (ARC), on the pharmacokinetics of linezolid in critically ill patients. The effect of continuous infusion on the probability of therapeutic success from a pharmacokinetic/pharmacodynamic (PK/PD) perspective was also evaluated. Methods: Seventeen patients received linezolid (600 mg every 12 h) as a 30-min infusion and 26 as a continuous infusion (50 mg/h). The PK parameters were calculated and the probability of PK/PD target attainment (PTA) was estimated by Monte Carlo simulation (MCS) for different doses administered by intermittent (600 mg every 12 h or 600 mg every 8 h) or continuous infusion (50 mg/h or 75 mg/h). Results: In patients without ARC, the standard dose was adequate to attain the PK/PD target. However, linezolid clearance was significantly higher in ARC patients, leading to sub-therapeutic concentrations. Continuous infusion (50 mg/h) provided concentrations ≥2 mg/l in 70% of the ARC patients. MCS revealed that concentrations ≥2 mg/l would be reached in >90% of patients receiving 75 mg/h. Conclusions: ARC increases linezolid clearance and leads to a high risk of underexposure with the standard dose. Continuous infusion increases the PTA, but an infusion rate of 75 mg/h should be considered to ensure concentrations ≥2 mg/ml. Keywords: Linezolid, Augmented renal clearance, Pharmacokinetic/pharmacodynamics, Critically ill patients, Continuous infusion

The extraction of total lipids and tocopherol compounds from Patagonian squid (Doriteuthis gahi) by-products (viscera, heads, skin, etc.), resulting from squid mantel commercialisation, was studied. An optimisation simplex-lattice design by employing low-toxicity solvents (ethanol, acetone, and ethyl acetate) was carried out taking into account their relative concentrations. The variance analysis of data showed that the quadratic model was statistically significant (p < 0.05); empirical coded equations were obtained as a function of the low-toxicity solvent ratios. The optimised lipid extraction was obtained by employing the 0.642/0.318/0.040 (ethanol/acetone/ethyl acetate) solvent ratio, respectively, leading to an 84% recovery of the total lipids extracted by the traditional procedure. In all extracting systems tested, the presence of α-, γ-, and δ-tocopherol compounds was detected, α-tocopherol being the most abundant. For α-, γ-, and δ-tocopherol compounds, the optimisation process showed that acetone extraction led to the highest concentrations in the lipid extract obtained (2736.5, 36.8, and 2.8 mg·kg−1 lipids, respectively). Taking into account the recovery yield on a by-product basis, the values obtained for the three tocopherols were included in the 88.0–97.7%, 80.0–95.0%, and 25–75% ranges, respectively, when compared to the traditional extraction. This study provides a novel and valuable possibility for α-tocopherol extraction from marine by-products.

Background: In this work, the effect of a selected starter culture of Lactilactobacillus sakei 205 on the evolution of volatile compounds throughout the ripening process and on the final sensorial characteristics of traditional dry-cured fermented “salchichón” was evaluated. Methods: “Salchichón” sausages were prepared, inoculated with L. sakei 205, and ripened for 90 days. Volatile compounds were analyzed throughout the ripening by GC-MS. In the final product, instrumental texture and color were determined. In addition, sensorial analysis was performed by a semi-trained panel. Results: The inoculation of L. sakei 205 does not influence the texture and color parameters of ripened “salchichón”. However, an increase in volatile compounds derived from amino acid catabolism and microbial esterification and a decrease in compounds derived from lipid oxidation, mainly hexanal, were observed throughout the ripening time as a consequence of L. sakei inoculation, which could have a positive effect on the flavor development of the dry-cured fermented “salchichón”. Conclusions: The use of selected strains of lactic acid bacteria (LAB) such as L. sakei 205 as a protective culture could be recommended to improve the quality of traditional “salchichón”.

IntroductionChronic alcohol consumption is known to cause gut dysbiosis (changes in microbiota composition and/or function, disruptive of the normal host–microbiota interactions). However, little is known about the changes that alcohol binge drinking induces in the gut microbiota. Here, we have tested the hypothesis that a protocol of alcohol binge drinking, known to induce neuroinflammation in previous studies, also promotes intestinal dysbiosis, and we explored how oleoylethanolamide (OEA, an acylethanolamide proven to counteract alcohol binge drinking-induced neuroinflammation) pretreatment modulates alcohol-induced dysbiosis.MethodsAlcohol binges were forced by gavage three times per day during 4 consecutive days; OEA pretreatment (intraperitoneal or intragastric) was administered before each alcohol gavage. Stool microbiota composition was assessed by next-generation 16S rRNA gene sequencing, prior and after the 4-day alcohol binge protocol.ResultsAlcohol binge drinking reduced the richness of the gut microbiota and changed the microbial community, reducing Lactobacillus among other genera. Pretreatment with OEA in the alcohol-administered rats decreased the richness, evenness, and Shannon indices to a greater extent with respect to alcohol alone, also changing the community structure. Microbial interactions in the association network were further decreased following OEA administration in the alcohol group, with respect to the water administration. The synergistic interaction between alcohol binge and OEA was affected by the route of administration of OEA, since oral and i.p. administrations differently changed the community structure.ConclusionResults suggest that alcohol binge drinking produces a clear dysbiosis in animals; we observed that the well-known protective actions of OEA in the context of alcohol abuse might not be related to OEA-induced changes in alcohol-induced dysbiosis. These are observational results, and thus, further research will be needed for a complete understanding of the biological significance of the observed changes.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

Obesity is the leading risk factor for developing metabolic (dysfunction)-associated fatty liver disease (MAFLD). The food industry has an essential role in searching for new strategies to improve primary food sources to revert some of the metabolic alterations induced by obesity. There is consistent evidence that long-chain polyunsaturated fatty acids (n-3 LCPUFA) belonging to the n-3 series, i.e., eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) acids, could revert some alterations associated with obesity-induced metabolic diseases. A relevant tool is the synthesis of structured acylglycerols (sAG), which include EPA or DHA at the sn-2 position. On the other hand, it has been reported that a crucial role of antioxidants is the reversion of MAFLD. In this work, we studied the effects of new molecules incorporating gallic acid (GA) into EPA/DHA-rich structured lipids. Mice were fed with a high-fat diet (60%) for three months and were then divided into five groups for supplementation with sAG and sAG structured with gallic acid (structured phenolic acylglycerols, sPAG). sPAG synthesis was optimized using a 2²-screening factorial design based on the response surface methodology (RSM). Our results show that treatment of sPAG was effective in decreasing visceral fat, fasting glycemia, fasting insulin, suggesting that this new molecule has a potential use in the reversal of MAFLD-associated alterations.

Introducción: Rituximab es un anticuerpo monoclonal anti-CD20 quimérico murino/humano capaz de eliminar las células CD20+ de los linfomas. La adición de rituximab a la quimioterapia ha demostrado mejorar los rangos de respuesta y supervivencia libre de progresión en pacientes con linfoma indolente. Realizamos un trabajo que recogiera nuestra experiencia con este fármaco en la terapia de linfomas indolentes en recaída. Materiales y Métodos: Se analizaron 32 pacientes con linfoma indolente CD20+ en recaída tratados con Rituximab como monoterapia o combinado con quimioterapia entre Enero del 2001 y Diciembre del 2005. Requerimientos de inclusión incluían al menos un tratamiento sistémico previo y enfermedad medible. Los objetivos fueron analizar la supervivencia libre de progresión, la respuesta objetiva, y la toxicidad. Resultados: Edad media fue 49 años (rango: 26-71) con prevalencia del sexo femenino. El subtipo histólogico más frecuente fue el folicular (n= 22). La media de terapias previas fue de 2. El índice de respuesta global fue del 75%. La respuesta completa fue 22%, y la parcial 53%. La supervivencia libre de progresión y la global a los 2 años fue del 55% y 69%, respectivamente. La toxicidad severa más frecuente fue la neutropenia y trombocitopenia grado 3-4. Conclusiones: En nuestros pacientes con linfoma indolente en recaída la terapia con Rituximab demostró una alta efectividad, con un nivel de toxicidad aceptable.

In traditional soft ripened cheeses made with raw milk, the use of protective cultures is infrequent. In the present work, the effect of selected (for their activity against Listeria monocytogenes) protective cultures of Lactocaseibacillus casei 116 and Lactococcus garvieae 151 was evaluated, on the evolution of volatile compounds throughout the ripening and on the final sensory characteristics of traditional soft ripened “Torta del Casar” cheese. For this, both strains were separately inoculated in raw cheeses and ripened for 90 days. The selected LAB strains did not affect physicochemical parameters, including texture and color of the ripened cheeses. However, they could have a positive effect on the aroma, for the generation of methyl branched acids and for the reduction in compounds derived from β-oxidation of fatty acids. Thus, these protective cultures, in addition to contributing to their safety, could improve quality of the ripened cheeses.

A critical issue to understanding how populations adapt to new selective pressures is the relative contribution of the initial standing genetic diversity versus that generated de novo. RNA viruses are an excellent model to study this question, as they form highly heterogeneous populations whose genetic diversity can be modulated by factors such as the number of generations, the size of population bottlenecks, or exposure to new environment conditions. In this work, we propagated at nonoptimal temperature (43 °C) two bacteriophage Qβ populations differing in their degree of heterogeneity. Deep sequencing analysis showed that, prior to the temperature change, the most heterogeneous population contained some low-frequency mutations that had previously been detected in the consensus sequences of other Qβ populations adapted to 43 °C. Evolved populations with origin in this ancestor reached similar growth rates, but the adaptive pathways depended on the frequency of these standing mutations and the transmission bottleneck size. In contrast, the growth rate achieved by populations with origin in the less heterogeneous ancestor did depend on the transmission bottleneck size. The conclusion is that viral diversification in a particular environment may lead to the emergence of mutants capable of accelerating adaptation when the environment changes.

Resumen: Introducción: El análisis del líquido sinovial (LS) es una herramienta importante en el diagnóstico de pacientes con artritis idiopática juvenil (AIJ). Pacientes y métodos: Análisis retrospectivo de las características citológicas del LS obtenido de pacientes con AIJ en el periodo 2008-2016. Resultados: Se analizaron 102 LS de 59 pacientes. El 66% fueron mujeres y la forma clínica más frecuente fue la AIJ oligoarticular persistente (52,5%). La mediana de edad al inicio fue de 5 años (RIC 2,4-11,8). El LS generalmente era de características inflamatorias (mediana leucocitos 11.757/mm3; RIC 4.543-18.800) con predominio de polimorfonucleares (PMN, 61%; RIC 30-75). Ocho pacientes (14%) presentaron recuentos inferiores a 2.000 cél/mm3, con predominio de mononucleares (80%), mientras que 3 pacientes (5%) presentaron recuentos superiores a 50.000 cél/mm3, con predominio de PMN (90%). No se encontraron diferencias en los recuentos celulares entre las distintas formas de AIJ. La mediana del recuento de leucocitos de pacientes positivos para ANA fue un 20% inferior a la de niños negativos para ANA (9.340 vs. 11.600/mm3; p = 0,23). La proporción de PMN en LS tendía a aumentar conforme se incrementaba la VSG (p

Introduction: Synovial fluid (SF) analysis is an important tool for the diagnosis of patients with juvenile idiopathic arthritis (JIA). Patients and methods: A retrospective analysis was carried out of cytological features of SF samples obtained from patients with JIA during the period 2008–2016. Results: A total of 102 SF samples from 59 patients were analysed. JIA was more common in females (66%). The most frequent form was persistent oligoarticular JIA (52.5%). The median age at onset was 5 years (IQR 2.4–11.8). SF usually showed an inflammatory pattern (median white blood cells count 11,757/mm3; IQR 4,543–18,800), with a predominance of polymorphonuclear (PMN) cells (61%; IQR 30–75). Eight patients (14%) had white blood cells counts of less than 2000 cells/mm3, with predominance of mononuclear cells (80%), whereas 3 patients (5%) had white blood cells counts higher than 50,000 cells/mm3, with a predominance of PMN cells (90%). Synovial white blood cells count did not show significant differences among the different forms of JIA. The median synovial white blood cells count in ANA-positive patients was 20% lower than in ANA-negative (9,340 vs. 11,600/mm3; P = .23). The proportion of PMN increased with increasing levels of ESR (P

Abstract Background Angiogenesis can occur under pathological conditions when stimuli such as inflammation, vascular obstruction or hypoxia exist. These stimuli are present in cardiopulmonary dirofilariosis (Dirofilaria immitis). The aim of this study was to analyze the capacity of D. immitis antigens to modify the expression of angiogenic factors and trigger the formation of pseudocapillaries (tube-like structures) in an in vitro model of endothelial cells. Methods The expression of VEGF-A, sFlt, mEndoglin and sEndoglin in cultures of canine microvascular endothelial cells stimulated with extract of adult worms of D. immitis obtained from an untreated dog (DiSA) and from a dog treated for 15 days with doxycycline (tDiSA), was determined by using commercial kits. The capacity of pseudocapillary formation was evaluated analyzing cell connections and cell groups in Matrigel cell cultures stimulated with DiSA and tDiSA. In both cases non-stimulated cultures were used as controls. Results First, we demonstrated that worms obtained from the dog treated with doxycycline showed a significantly lower amount of Wolbachia (less than 60%) than worms removed from the untreated dog. Only DiSA was able to significantly increase the expression of the proangiogenic factor VEGF-A in the endotelial cells cultures. None of the D. immitis extracts modified the expression of sFlt. tDiSA extract was able to modify the expression of the endoglins, significantly decreasing the expression of the pro-angiogenic mEndoglin and increasing the anti-angiogenic sEndoglin. The formation of pseudocapillaries was negatively influenced by tDiSA, which reduced the organization and number of cellular connections. Conclusions The ability of antigens from adult D. immitis worms to modify the expression of pro and anti-angiogenic factors in endotelial cell cultures was demonstrated, as well as the trend to form pseudocapillaries in vitro. The capacity of stimulation may be linked to the amount of Wolbachia present in the antigenic extracts.

Gene supplementation therapy with plasmid DNA (pDNA) represents one of the most promising strategies for the treatment of monogenic diseases such as Fabry disease (FD). In the present work, we developed a solid lipid nanoparticles (SLN)-based non-viral vector with a size below 100 nm, and decorated with galactomannan (GM) to target the liver as an α-Galactosidase A (α-Gal A) production factory. After the physicochemical characterization of the GM-SLN vector, cellular uptake, transfection efficacy and capacity to increase α-Gal A activity were evaluated in vitro in a liver cell line (Hep G2) and in vivo in an animal model of FD. The vector showed efficient internalization and it was highly efficient in promoting protein synthesis in Hep G2 cells. Additionally, the vector did not show relevant agglutination of erythrocytes and lacked hemolytic activity. After the systemic administration to Fabry mice, it achieved clinically relevant α-Gal A activity levels in plasma, liver, and other organs, importantly in heart and kidneys, two of the most damaged organs in FD. This work shows the potential application of GM-decorated lipidic nanocarries for the treatment of FD by pDNA-based gene augmentation.

The components of metabolic syndrome (MetS) and hepatogastrointestinal diseases are widespread worldwide, since many factors associated with lifestyle and diet influence their development and correlation. Due to these growing health problems, it is necessary to search for effective alternatives for prevention or adjuvants in treating them. The positive impact of regulated microbiota on health is known; however, states of dysbiosis are closely related to the development of the conditions mentioned above. Therefore, the role of prebiotics, probiotics, or symbiotic complexes has been extensively evaluated; the results are favorable, showing that they play a crucial role in the regulation of the immune system, the metabolism of carbohydrates and lipids, and the biotransformation of bile acids, as well as the modulation of their central receptors FXR and TGR-5, which also have essential immunomodulatory and metabolic activities. It has also been observed that they can benefit the host by displacing pathogenic species, improving the dysbiosis state in MetS. Current studies have reported that paraprobiotics (dead or inactive probiotics) or postbiotics (metabolites generated by active probiotics) also benefit hepatogastrointestinal health.

El presente trabajo analiza el tratamiento de los llamados “monstrous births” en los tratados de obstetricia ingleses redactados a lo largo del siglo XVII. El estudio que proponemos demostrará que se puede distinguir un primer grupo de tratados con descripciones detalladas acompañadas de ilustraciones, propias de baladas y panfletos de carácter popular y con una marcada intención sensacionalista, y un segundo grupo de tratados con un interés genuino por este tipo de malformaciones que revelan la voluntad científica de la literatura médica del momento.

Se presenta el caso de un hombre de 31 años, con historia de fibrilación auricular paroxística, a quien se realizó exitosamente una ablación por radiofrecuencia de venas pulmonares guiada por un sistema de mapeo tridimensional EnSiteTM. Tres meses después del procedimiento presentó hemoptisis y dolor torácico de características pleuríticas, motivo por el cual se le realizó una angiotomografía computarizada coronaria que evidenció una estenosis grave de la vena pulmonar superior izquierda y una estenosis moderada de la vena inferior izquierda. El paciente fue sometido a angioplastia con balón, con la cual se normalizó la perfusión pulmonar.

The objective of this work was to obtain glass-ceramics from stable glasses, with a composition of barium, lead, and potassium titanate phases, for use as semiconductors. For this purpose, the glass-ceramic technique was used to control crystal growth and obtain a fine-grained microstructure. Various glasses containing K2O, PbO, BaO, Al2O3, B2O3, and TiO2 were prepared using a melt-quenching method. X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed a single amorphous phase of all samples. Infrared spectra confirmed the presence of B-O bonds stretching vibrations of (B3O6)3− boroxol rings and BO3 triangles, as well as Ti-O stretching vibrations of (TiO6/2) and (AlO6/2) octahedral units. Thermal analyses confirmed the presence of one or more crystallization peaks in the range of 700 to 744 °C. On this base, they were heat-treated to promote crystal growth. XRD and SEM detected Ba4Ti12O27, Ti7O13, and BaTiO3 phases, homogeneously distributed throughout the material with fine crystallite size. In addition, crystallized glasses’ (glass-ceramics) properties were determined; the density values were 2.8–3.55 g/cm3; the chemical resistance to acidic and basic media was low; and the band-gap values were in the range of 2.88 to 3.05 eV. These results suggest that crystallized glasses may have application in photocatalysis.

Listeria monocytogenes is one of the most important foodborne pathogens. This microorganism is a serious concern in the ready-to-eat (RTE) meat and dairy-ripened products industries. The use of lactic acid bacteria (LAB)-producing anti-L. monocytogenes peptides (bacteriocins) and/or lactic acid and/or other antimicrobial system could be a promising tool to control this pathogen in RTE meat and dairy products. This review provides an up to date about the strategies of use of LAB and their metabolites in RTE meat products and dairy foods by selecting the most appropriate strains, by analysing the mechanism by which they inhibit L. monocytogenes and methods of effective application of LAB, and their metabolites in these kinds of products to control this pathogen throughout the processing and storage. The selection of LAB with anti-L. monocytogenes activity allows to dispose of effective strains in meat and dairy-ripened products, achieving reductions form 2–5 logarithmic cycles of this pathogen throughout the ripening process. The combination of selected LAB strains with antimicrobial compounds, such as acid/sodium lactate and other strategies, as the active packaging could be the next future innovation for eliminating risk of L. monocytogenes in meat and dairy-ripened products.