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Objetivo. Estimar el efecto de la pandemia de COVID-19 en la provisión, la utilización, la cobertura y la oportunidad de vacunación en niños menores de 5 años. Método. Se realizó un estudio de cohorte retrospectivo con un componente cuantitativo y un componente cualitativo con dos ciclos rápidos de evaluación. En cada ciclo se aplicaron cuestionarios y entrevistas semiestructuradas a miembros del personal de salud y a madres de menores de cinco años. Los instrumentos exploraron la provisión (disponibilidad de insumos y personal) y utilización (demanda y acceso) del programa de inmunizaciones. Para estimar la cobertura de vacunación se realizó un muestreo aleatorio en menores de cinco años en cinco provincias y se analizaron registros administrativos mensuales del programa para el período 2017-2020. Resultados. Aproximadamente 50% de los informantes percibieron una reducción de personal e insumos para el programa. La demanda de atención se redujo en 26% entre el 2020 y el 2021, explicado principalmente por temor al contagio de COVID-19 en unidades de salud. El acceso a la atención del programa se vio afectado por el cambio de horario, espacios ventilados y atención virtual, que no fue bien aceptado por la población. Solo 50% de menores de 1 año tuvieron esquema completo de vacunación y la mayoría de las vacunas no se aplicaron en forma oportuna. Conclusiones. La pandemia de COVID-19 afectó de manera negativa la provisión de vacunas y la utilización del programa de inmunizaciones; en consecuencia, se intensificó la caída de la coberturas y oportunidad de la vacunación, que alcanzaron niveles subóptimos en menores de cinco años en Ecuador. Esta situación aumentó el riesgo de que los niños contraigan enfermedades prevenibles por vacunación.

Context: Ecuador was one of the most affected counties in Latin America during coronavirus disease 2019 (COVID-19). Its health system already faced financing and organizational problems before the pandemic. Aims: To analyze the effects of the pandemic on the provision and utilization of maternal health services in units of the Public Health of Ecuador as perceived by the health personnel. Material and Methods: This is a mixed methods study with two rapid evaluation cycles. The first cycle collected information during January–March and the second one during April–June, 2021. An online questionnaire and semistructured interviews were applied to professionals involved in the management and provision of maternal health programs. Both instruments explored provision and utilization of maternal health services. Questionnaires were processed using SPSS and descriptive statistics. Interviews were exported to Atlas-Ti and were codified using the explored categories. Results: A total of 207 health workers participated in the first cycle, and 200 in the second one. They recognized that during the pandemic, healthcare personnel were reduced by more than 30% due to the presence of risk factors among them as well as the lack of budget for new contracts. The availability of materials and supplies was also reduced by nearly 50%, mainly due to the lack of budget. The demand for maternal healthcare in public health units was reduced because people feared being infected by COVID-19 and nearly 25% goes to the private sector. Conclusions: The pandemic has had a negative effect on the provision as well as utilization of maternal healthcare services. Nevertheless, health professionals implemented diverse strategies to reduce this negative effect on maternal care.

Hundreds or thousands of Near-Earth Asteroids (NEAs) are discovered every year, so being able to determine their orbits to follow them successfully in the future is essential to warn of the danger they could present. Numerous methods have been developed to improve the precision and efficiency of calculations used in the Initial Orbit Determination (IOD), with Gauss’s method being the benchmark due to its intuitive formulation, comparable precision, and historical importance. Herein, we present the results of the development of a new open access tool to simplify the process of IOD of celestial bodies, specifically, NEAs. This tool was based on a modern implementation, using code written in Python to calculate, propagate, and graph the orbits. The results obtained from the test data exhibited significant accuracy, with the maximum discrepancy not exceeding 1.2% compared to the Horizons System tool, and the average being 0.5%. Furthermore, we found that for the Monte Carlo simulations that the code uses, 5,000 iterations were more than enough to achieve the obtained accuracy.

ABSTRACT The rice husk was chemically treated with acetic acid and calcined at 600 °C, in an uncontrolled atmosphere to obtain the ash (RHA), and in an oxygen-limited atmosphere to produce the biochar (BC). The influence of the thermal treatment on the adsorbent properties for removing cationic (methylene blue) and anionic (methyl orange) dyes was investigated. Both materials showed amorphous structures rich in silica, with acicular morphology and a high roughness. High surface areas (157.2 and 215.5 m²g-1) and pH at the point of zero charge close to neutrality (6.73 and 6.58) for RHA and BC were found, respectively. The anionic dye was adsorbed only by BC due to its contribution to the π- π stacking interaction between the C=C bonds of the adsorbent and the benzene rings of the dye. In contrast, the cationic dye was adsorbed by electrostatic interaction between the Si-O-Si and Si-OH groups of the adsorbents, with the positive charge of the dye. All adsorption isotherms adjusted better to the SIPS model, suggesting adsorption in homogeneous and heterogeneous sites. The observed results suggest good adsorption capacities and the interactions between surface groups on the adsorbents and functional groups of the contaminants are the most important mechanism in the adsorption of dyes of different ionic natures on surfaces derived from rice husk.

BackgroundAdequate nutritional intake plays a crucial role in maximizing skeletal acquisition. The specific effects of a general food restriction and refeeding on fracture healing are yet to be fully understood. The aim of this study was to assess the impact of general food restriction and refeeding on fracture repair.MethodsFifty-four male Wistar Hannover rats were randomly assigned into three groups: (1) Sham: Sham rats with femoral fracture; (2) FRes: Food-restricted rats with fracture, (3) Fres+Ref: Fres rats with refeeding. Following weaning, the FRes and Fres+Ref groups received 50% of the food amount provided to the Shams. In the sixth week of the experiment, all animals underwent a mid-right femur bone fracture, which was subsequently surgically stabilized. Following the fracture, the Fres+Ref group was refed, while the other groups maintained their pre-fracture diet. Bone calluses were analyzed on the fifth-day post-fracture by gene expression and on the sixth-week post-fracture using dual-energy X-ray absorptiometry, morphometry, histomorphometry, immunohistochemistry, computed microtomography, and torsion mechanical testing. Statistical significance was determined at a probability level of less than 0.05, and comparisons were made using the ANOVA test.ResultsFood restriction resulted in significant phenotypic changes in bone calluses when compared to sham rats characterized by deterioration in microstructure (i.e., BV, BV/TV, Tb.N, and Conn.D) reduced collagen deposition, bone mineral density, and mechanical strength (i.e., torque at failure, energy, and stiffness). Moreover, a higher rate of immature bone indicated a decrease in bone callus quality. Refeeding stimulated bone callus collagen formation, reduced local resorption, and effectively restored the microstructural (i.e., SMI, BCa.BV/TV, Tb.Sp, Tb.N, and Conn.D) and mechanical changes (i.e., torque at failure, energy, and angular displacement at failure) caused by food restriction. Despite these positive effects, the density of the bone callus, collagen deposition, and OPG expression remained lower when compared to the shams. Gene expression analysis didn’t evidence any significant differences among the groups.ConclusionsFood restriction had detrimental effects on osseous healing, which was partially improved by refeeding. Based on these findings, new research can be developed to create targeted nutritional strategies to treat and improve fracture healing.

Cogeneration systems have been identified as a way to reduce primary energy consumption, especially the ones using fossil fuels. Although this technology has already reached maturity on a medium-to-large scale, it is not very well explored on a micro-scale, especially at a residential level where the market is currently filled with carbon-fueled boilers and combi-boilers. For implementation at a residential level, the organic Rankine cycle has been mentioned as a suitable technology because of its simplicity and thermal/ electrical efficiencies. Despite its performance, one of the most important aspects of these applications is the response time, which is mainly connected to the system’s control. Due to its influence, this study aims to provide insights for developing flexible control strategies and analyze two different control methodologies, a standard PID and a Fuzzy Logic controller, considering the operating conditions of an experimental ORC-based micro-cogeneration test rig.Before being implemented in the test rig, both control methodologies were optimized and tested in a virtual environment in order to avoid the exposure of the test rig to unsafe operating conditions. While both controllers show a reasonable response in operating conditions similar to the ones used in the virtual environment, the Fuzzy Logic approach proved to be more adaptable to changes in the system’s dynamics, which are caused by intrinsic (e.g., unpredicted evaporative phenomena) or external disturbances (e.g., a pressure ratio variation), obtaining an overall better performance. Additionally, the limitations of static PID controllers for complex nonlinear processes, like the ORC, were highlighted by their incapacity to stabilize the system when the organic fluid is diverted from the bypass line to the expansion valve. Conversely, it was concluded that the ability to incorporate expert knowledge and heuristics makes the Fuzzy Logic controller well-suited for ORC systems with uncertain, unstable, and fluctuating behavior.

RESUMO: A introdução de árvores em vias públicas sem conhecer as particularidades de cada espécie geram conflitos com equipamentos urbanos como fiações elétricas, encanamentos, calhas, calçamentos, muros, e postes de iluminação. O poder público é o fundamental responsável por políticas de preservação, recuperação e ampliação dos exemplares arbóreos, dando relevância ao cumprimento dos planos de arborização e devendo também propor novas atualizações dessas normativas. Este trabalho tem por objetivo realizar um levantamento qualitativo, identificando as particularidades de todas as espécies, e a quantificação dos conflitos gerados pela arborização na Avenida Adolf John Terry, localizada no município de Corrente - PI. Para isto, foi feito um levantamento dos indivíduos arbóreos existentes nos canteiros centrais da avenida, assim como a identificação das espécies, realizada por meio do conhecimento popular local, para identificação da denominação popular de cada indivíduo. Dos 78 indivíduos encontrados, prevaleceu as espécies exóticas, no qual observou-se que a maior parte desses indivíduos arbóreos geram conflitos com o meio devido à falta de planejamento e escolha inadequada das espécies. Levando então a geração de vários conflitos com os equipamentos urbanos, como o porte é inadequado das arvores, interferindo na fiação elétrica da avenida. PALAVRAS-CHAVE: Arborização Urbana, Planejamento Urbano e Equipamentos Urbanos. ABSTRACT: The introduction of trees on public roads without knowing the particularities of each species generate conflicts with urban equipment such as electrical wiring, plumbing, gutters, sidewalks, walls and lampposts. The government is the key responsible for preservation policies, recovery and expansion of arboreal specimens, giving importance to the fulfillment of afforestation plans and should also propose new updates of these regulations. This study aims to conduct a qualitative survey, identifying the characteristics of each species and quantify the conflicts generated. by afforestation on Avenue Adolf John Terry, located in the current municipality - PI. For this, a survey was made of existing individual trees in medians Avenue, as well as the identification of species, held by the local popular knowledge for identification of the popular each individual denomination. It was observed that the choice of species and afforestation plan is essential to avoid many losses that can lead to society. KEYWORDS: Urban Afforestation, Urban Planning e Urban Equipment.

Abstract In recent years, machine and deep learning models have attracted significant attention for electricity price forecast in global wholesale electricity markets. Yet, a predominant focus on point forecast in most parts of literature limits the practical application of these models due to the absence of uncertainty quantification. In this study, we first perform an analysis of the electricity price trends in the Mexican wholesale electricity market to determine the influence of key variables. Using independent component analysis and wavelet coherence analysis, we were able to identify primary determinants influencing locational marginal electricity prices. Subsequently, we applied four different models covering the most important algorithms proposed in the literature for electricity price forecast. Our findings revealed that the most accurate forecasting results were achieved using a deep learning‐based method with a decision tree‐based model trailing closely. Finally, we incorporate conformal prediction for uncertainty quantification by calculating the prediction intervals with a target coverage level of 95%. The conformal prediction intervals provide a more comprehensive view of the possible future scenarios, enhancing economic efficiency, risk management, and decision‐making processes. This is particularly important because of the dynamic nature of electricity markets, where prices are strongly influenced by multiple factors.

The content of polycyclic aromatic hydrocarbons (PAHs) in a traditional Spanish smoked sausage known as ‘Botillo del Bierzo’ was analysed. The determination and quantification of PAH4 (the sum of benzo[a]pyrene, benz[a]anthracene, benzo[b]-fluoranthene and chrysene) in the smoked sausage were performed using GC–MS. The results showed that smoking ‘Botillo del Bierzo’ for 24 h contributes very little to the increase in PAH levels in the product, with no significant differences (p < 0.05). The paprika used in the production of botillo also contributes to PAH content, depending on the paprika’s production process (smoked, low-smoked, mixed paprika (smoked + unsmoked or low-smoked + unsmoked), and unsmoked), with significant differences among them (p < 0.05). Using paprika with a lower PAH content (unsmoked or mixed) enables the production of ‘Botillo del Bierzo’, in accordance with Protected Geographical Indication specifications, with a lower PAH content while maintaining the organoleptic characteristics provided by the paprika. The contamination levels detected in ‘Botillo del Bierzo’ do not pose a risk to consumer health, as the benzo[a]pyrene and PAH4 values are well below the regulatory limits of 5 μg/kg and 30 μg/kg, respectively.

A variety of leaves of different morphological sizes and venation types corresponding to the gymnosperm genus Desmiophyllum have been found in five fossil sites originating from the Barremian to the Cenomanian periods in northeastern Spain over an interval comprising 25 million years that encompasses the Early Cretaceous–Late Cretaceous boundary. These leaves are preserved in various lithologies corresponding to different depositional environments such as lagoonal systems, coastal swamps, deltaic plains, lacustrine environments and fluvial-related deposits. These new data shed light on the morphological and paleoenvironmental variability of Desmiophyllum recorded in the Cretaceous deposits from southwestern Eurasia.

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process.

Background/Objectives: Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. Methods: This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. Results: A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. Conclusions: This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Investigating the antecedents and determinants of entrepreneurial intention is key to understanding the beginning of the entrepreneurial process. There is scarce literature on academic entrepreneurship that identifies the characteristics of an individual in an academic context with the intention of starting a spin-off company. This study explores the association of gender, age, research certification and knowledge area to Academic Entrepreneurial Intention. To this end, data was obtained from the participation of 172 academics at a Mexican university. Through logistic regression, it was possible to find a significant association between age, research certification and certain knowledge areas to academic entrepreneurial intention. This represents a first approximation to identifying the key factors that affect the academic entrepreneurship process, focused particularly on entrepreneurial intention. JEL Codes: L26, M13 Received: 06/03/2024. Accepted: 03/06/2024. Published: 20/06/2024.

Al hablar o escribir acerca de Daniel Alcides Carrión García surge su sacrificio, pero esta noche del 13 de agosto del 2007 dejando de lado cual fue su contribución a la ciencia, me limitaré a exponerles algunas facetas pocas conocidas y hechos que aún faltan rectificar en relación a su biografía y a su entorno familiar.

3D bioprinting is a promising technique for creating artificial tissues and organs. One of the main challenges of bioprinting is cell damage, due to high pressures and tensions. During the biofabrication process, extrusion bioprinting usually results in low cell viability, typically ranging from 40% to 80%, although better printing performance with higher cell viability can be achieved by optimising the experimental design and operating conditions, with nozzle geometry being a key factor. This article presents a review of studies that have used computational fluid dynamics (CFD) to optimise nozzle geometry. They show that the optimal ranges for diameter and length are 0.2 mm to 1 mm and 8 mm to 10 mm, respectively. In addition, it is recommended that the nozzle should have an internal angle of 20 to 30 degrees, an internal coating of ethylenediaminetetraacetic acid (EDTA), and a shear stress of less than 10 kPa. In addition, a design of experiments technique to obtain an optimal 3D bioprinting configuration for a bioink is also presented. This experimental design would identify bioprinting conditions that minimise cell damage and improve the viability of the printed cells.

Italy built its ammasso silo network in the 1930s for two purposes: to stockpile grain and to symbolize fascist power. Much of the network was destroyed in World War II, and over half of the silos still standing are now disused and in disrepair. These structures should be protected and refurbished because they are part of Italy’s historic and agro-industrial heritage and because reusing existing buildings instead of constructing new ones reduces the carbon footprint. To evaluate silo repurposing potential, a method developed for inventorying Spanish silos was adapted and applied to the 30 remaining ammasso silos. The method explores the general features, construction, equipment, and socioeconomic environment of each silo. All extant ammasso silos have machinery for receiving, storing, and dispatching grain, and most have equipment for cleaning, sorting, weighing, and packaging. Vertical-cell silos are challenging to convert, unlike horizontally-oriented silos and other open-plan agro-industrial buildings. Even so, some have already been made over into shops, leisure areas, museums, and even homes. Examples of silo reuse in other countries, such as Spain and Portugal, can offer further useful insights. However, socio-economic indicators suggest that silo repurposing projects are viable only in large population centres.

Objectives: To verify the analytical performance of the HepatoPredict kit, a novel tool developed to stratify Hepatocellular Carcinoma (HCC) patients according to their risk of relapse after a Liver Transplantation (LT). Methods: The HepatoPredict tool combines clinical variables and a gene expression signature in an ensemble of machine-learning algorithms to forecast the benefit of a LT in HCC patients. To ensure the accuracy and reliability of this method, extensive analytical validation was conducted to verify its specificity and robustness. The experiments were designed following the guidelines for multi-target genomic assays such as ISO201395-2019, MIQE, CLSI-MM16, CLSI-MM17, and CLSI-EP17-A. The validation process included reproducibility between operators and between RNA extractions and RT-qPCR runs, and interference of input RNA levels or varying reagent levels. A recently retrained version of the HepatoPredict algorithms was also tested. Results: The validation process demonstrated that the HepatoPredict kit met the required standards for robustness (p > 0.05), analytical specificity (inclusivity of 95 %), and sensitivity (LoB, LoD, linear range, and amplification efficiency between 90 and 110 %). The operator, equipment, input RNA, and reagents used had no significant effect on the HepatoPredict results. Additionally, the testing of a recently retrained version of the HepatoPredict algorithm, showed that this new version further improved the accuracy of the kit and performed better than existing clinical criteria in accurately identifying HCC patients who are more likely to benefit LT. Conclusions: Even with the introduced variations in molecular and clinical variables, the HepatoPredict kit's prognostic information remains consistent. It can accurately identify HCC patients who are more likely to benefit from a LT. Its robust performance also confirms that it can be easily integrated into standard diagnostic laboratories.

La malacoplaquia tiene afinidad especial por el tracto urinario, casi todos los casos en vejiga y aproximadamente el 80-90% tiene cultivos positivos para organismos gramnegativos, la mayoría de los pacientes presentan cierto grado de inmunocompromiso, es importante tenerla en cuenta en pacientes con dichas características aun cuando los estudios de extensión implican otra patología. El porcentaje de falsos positivos en biopsias prostáticas de lesiones categorizadas como PI-RADS (Prostate Imaging-Report and Data System) 5 no es despreciable, sin embargo no es común encontrarlo como diagnóstico diferencial. Paciente de 69 años sin inmunocompromiso, quien presenta inicialmente retención aguda de orina y antígeno prostático específico elevado (8.35 ng/ml), complicado con choque séptico urinario. En la resonancia magnética multiparamétrica se identificó absceso prostático asociado a lesión PI-RADS 5 en zona periférica prostática, biopsiada con diagnóstico histopatológico de malacoplaquia. Es una patología granulomatosa rara, puede ocurrir en cualquier parte del cuerpo, sin embargo la primera vez que se describió la localización prostática fue en 1959, por Carruthers. El conocimiento y sospecha de una entidad inflamatoria, benigna y rara como la malacoplaquia prostática, incluso en el contexto un paciente no inmunocomprometido, con una lesión caracterizada como PI-RADS 5 puede prevenir el mal diagnóstico y sobretratamiento de estos pacientes.

For a long time, electrical signaling was neglected at the expense of signaling studies in plants being concentrated with chemical and hydraulic signals. Studies conducted in recent years have revealed that plants are capable of emitting, processing, and transmitting bioelectrical signals to regulate a wide variety of physiological functions. Many important biological and physiological phenomena are accompanied by these cellular electrical manifestations, which supports the hypothesis about the importance of bioelectricity as a fundamental ‘model’ for response the stresses environmental and for activities regeneration of these organisms. Electrical signals have also been characterized and discriminated against in genetically modified plants under stress mediated by sucking insects and/or by the application of systemic insecticides. Such results can guide future studies that aim to elucidate the factors involved in the processes of resistance to stress and plant defense, thus aiding in the development of successful strategies in integrated pest management. Therefore, this mini review includes the results of studies aimed at electrical signaling in response to biotic stress. We also demonstrated how the generation and propagation of electrical signals takes place and included a description of how these electrical potentials are measured.

Objetivo: Determinar la prevalencia de los principales factores de riesgo asociados a contractura capsular posterior a mamoplastia de aumento en un centro de referencia. Método: Estudio retrospectivo de 210 pacientes en el que se registraron variables sociodemográficas, escala clínica de Baker y resultados histopatológicos. Resultados: Se realizó el análisis estadístico de 210 pacientes; el 98.1% fueron mujeres. La edad promedio fue de 47 años (± 11), el índice de masa corporal 25 kg/m2 (± 10) y el inicio de los síntomas 13 años (± 8.5). Factores sociodemográficos: labores domésticas 63.3%. Alcoholismo 70% y tabaquismo 65.7%. El principal motivo de consulta fue dolor más deformidad, en el 81.6%. Los factores de riesgo con significancia estadística fueron el antecedente de traumatismo, con un 83.3% (p = 0.004), y el plano subglandular, con un 73.8% (p = 0.0115). Histopatología: cápsula fibrosa 81.4%. Conclusiones: La prevalencia de los factores de riesgo descritos es similar a lo reportado en la literatura. Solo para el antecedente de traumatismo y el plano subglandular hubo significancia estadística.

Mycoplasma hyopneumoniae (Mhyo) is the causative agent of porcine enzootic pneumonia (EP), as well as one of the main pathogens involved in the porcine respiratory disease complex. The host–pathogen interaction between Mhyo and infected pigs is complex and not completely understood; however, improving the understanding of these intricacies is essential for the development of effective control strategies of EP. In order to improve our knowledge about this interaction, laser-capture microdissection was used to collect bronchi, bronchi-associated lymphoid tissue, and lung parenchyma from animals infected with different strains of Mhyo, and mRNA expression levels of different molecules involved in Mhyo infection (ICAM1, IL-8, IL-10, IL-23, IFN-α, IFN-γ, TGF-β, and TNF-α) were analyzed by qPCR. In addition, the quantification of Mhyo load in the different lung compartments and the scoring of macroscopic and microscopic lung lesions were also performed. Strain-associated differences in virulence were observed, as well as the presence of significant differences in expression levels of cytokines among lung compartments. IL-8 and IL-10 presented the highest upregulation, with limited differences between strains and lung compartments. IFN-α was strongly downregulated in BALT, implying a relevant role for this cytokine in the immunomodulation associated with Mhyo infections. IL-23 was also upregulated in all lung compartments, suggesting the potential involvement of a Th17-mediated immune response in Mhyo infections. Our findings highlight the relevance of Th1 and Th2 immune response in cases of EP, shedding light on the gene expression levels of key cytokines in the lung of pigs at a microscopic level.

Abstract Background Potential functional variants (PFVs) can be defined as genetic variants responsible for a given phenotype. Ultimately, these are the best DNA markers for animal breeding and selection, especially for polygenic and complex phenotypes. Herein, we described the identification of PFVs for complex phenotypes (in this case, Feed Efficiency in beef cattle) using a systems-biology driven approach based on RNA-seq data from physiologically relevant organs. Results The systems-biology coupled with deep molecular phenotyping by RNA-seq of liver, muscle, hypothalamus, pituitary, and adrenal glands of animals with high and low feed efficiency (FE) measured by residual feed intake (RFI) identified 2,000,936 uniquely variants. Among them, 9986 variants were significantly associated with FE and only 78 had a high impact on protein expression and were considered as PFVs. A set of 169 significant uniquely variants were expressed in all five organs, however, only 27 variants had a moderate impact and none of them a had high impact on protein expression. These results provide evidence of tissue-specific effects of high-impact PFVs. The PFVs were enriched (FDR

Abstract Inflammatory states and body composition changes are associated with a poor prognosis in many diseases, but their role in coronavirus disease 2019 (COVID-19) is not fully understood. To assess the impact of low skeletal muscle radiodensity (SMD), high neutrophil-to-lymphocyte ratio (NLR) and a composite score based on both variables, on complications, use of ventilatory support, and survival in patients with COVID-19. Medical records of patients hospitalized between May 1, 2020, and July 31, 2020, with a laboratory diagnosis of COVID-19 who underwent computed tomography (CT) were retrospectively reviewed. CT-derived body composition measurements assessed at the first lumbar vertebra level, and laboratory tests performed at diagnosis, were used to calculate SMD and NLR. Prognostic values were estimated via univariate and multivariate logistic regression analyses and the Kaplan–Meier curve. The study was approved by the local Institutional Review Board (CAAE 36276620.2.0000.5404). A total of 200 patients were included. Among the patients assessed, median age was 59 years, 58% were men and 45% required ICU care. A total of 45 (22.5%) patients died. Multivariate logistic analysis demonstrated that a low SMD (OR 2.94; 95% CI 1.13–7.66, P = 0.027), high NLR (OR 3.96; 95% CI 1.24–12.69, P = 0.021) and both low SMD and high NLR (OR 25.58; 95% CI 2.37–276.71, P = 0.008) combined, were associated with an increased risk of death. Patients who had both low SMD and high NLR required more mechanical ventilation (P

Abstract Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies.

Three-dimensional printing in the field of additive manufacturing shows potential for customized medicines and solving gaps in paediatric formulations. Despite successful clinical trials, 3D printing use in pharmaceutical point-of-care is limited by regulatory loopholes and a lack of Pharmacopoeia guidelines to ensure quality. Semi-solid extrusion is a 3D printing technology that stands out for its versatility, but understanding the fluid dynamics of the semi-solid mass is critical. The aim of this research is to look into the advantages of instrumenting a 3D printer with a semi-solid extrusion motor-driven printhead, which is able to record the printing pressure over time, for in situ characterization of the semi-solid mass and quality evaluation of dosage forms. Four formulations using hydrochlorothiazide as the active pharmaceutical ingredient and several excipients were used. Their flow properties were studied at different printing speeds and temperatures using traditional techniques (rheometer and Texture Analyzer) and the proposed semi-solid extrusion motor-driven printhead incorporated into a printing platform. In addition, the influence of printing speed in the printing process was also evaluated by the study of printing pressure and printlet quality. The results demonstrated the similarities between the use of a Texture Analyzer and the semi-solid extrusion motor-driven. However, the latter enables temperature selection and printing speed in accordance with the printing process which are critical printing parameters. In addition, due to the incorporation of a sensor, it was possible to conclude, for the first time, that there is a link between changes in essential printing parameters like printing speed or formulations and variations in printing pressure and printlet quality attributes such as the energy require to obtain a single dosage unit, weight or diameter. This breakthrough holds a lot of potential for assuring the quality of 3D printing dosage forms and paving the way for their future incorporation into point-of-care settings.

A retrospective study of microbiological laboratory results from 2020 to 2022, obtained from a veterinary diagnostic laboratory of the island of Gran Canaria, Spain, focused on canine otitis cases, was performed. The objective of this study was to analyze the pathogen distribution, antimicrobial susceptibility, prevalence of multidrug resistant phenotypes and the role of coinfections in otitis cases in order to provide up-to-date evidence that could support effective control strategies for this prevalent pathology. A total of 604 submissions were processed for the diagnosis of canine external otitis. Of the samples analyzed, 472 were positive for bacterial or fungal growth (78.1%; 95% CI: 74.8–81.4%). A total of 558 microbiological diagnoses were obtained, divided in 421 bacterial (75.4%; 95% CI: 71.8–79.0%) and 137 fungal (24.6%; 95% CI: 20.9–28.1%) identifications. Staphylococcus pseudintermedius, Malassezia pachydermatis and Pseudomonas aeruginosa were the most prevalent microorganisms detected in clinical cases of otitis. High level antimicrobial resistance was found for Pseudomonas aeruginosa (30.7%), Proteus mirabilis (29.4%), Staphylococcus pseudintermedius (25.1%) and Escherichia coli (19%). Multidrug-resistant phenotypes were observed in 47% of the bacteria isolated. In addition, a 26.4% prevalence of methicillin-resistant Staphylococcus pseudintermedius was detected. The high prevalence of antimicrobial resistant phenotypes in these bacteria highlights the current necessity for constant up-to-date prevalence and antimicrobial susceptibility data that can support evidence-based strategies to effectively tackle this animal and public health concern.

Fall armyworm (FAW, Spodoptera frugiperda) is a polyphagous and migratory lepidopteran pest insect in field crops and is notoriously invasive worldwide. In large portions of the Americas, its populations are managed using transgenic maize or cotton varieties producing insecticidal proteins from Bacillus thuringiensis (Bt), primarily Vip3Aa pyramided with Cry Bt proteins. We determined the susceptibility of FAW field populations from locations pressured with such maize hybrids for over five years. We used time–mortality bioassays with F1 third-instar larvae of six geographically distinct populations collected in maize fields of a tropical agricultural region encompassing four Brazilian states. We maintained the neonate progeny from the field populations on an artificial diet until the third instar, and then determined their survival curves on the foliage of three Vip3Aa/Cry-producing Bt maize hybrids. Death of the mid-size, third-instar FAWs occurred relatively rapidly, with larval mortality rates reaching 98–100% in less than five days regardless of Bt maize hybrid. However, median survival time (ST50) for the larvae differed among the populations, with the lowest and highest ST50 values occurring for PI-Cr (42 h, 1.75 d) and PI-Ur populations (66–90 h, 2.75–3.75 h), respectively. Therefore, the F1 third-instar larvae of FAW populations were largely susceptible to Vip3Aa/Cry-producing maize foliage, and the most contrasting susceptibility occurred in the insects from Piauí state, Brazil. These results indicate that progeny of FAWs from areas highly pressured with Vip3Aa/Cry Bt maize hybrids are killed on maize foliage producing Vip3Aa and Cry Bt proteins despite field reports of increased leaf damage by the larvae in some locations. This research informs decision making for Bt-crop resistance management by producers, technicians, and researchers in local, regional, and world agriculture.

Abstract In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats protected the kidney in streptozotocin-induced diabetes. It reduced albuminuria, glomerular hypertrophy, and glomerular expression of collagen IV and fibronectin, as well as markers of kidney inflammation, when compared to sedentary diabetic rats. These effects were associated with elevation in muscle FNDC5/irisin and activity of AMPK in the diabetic kidney. However, the beneficial effects of exercise were lost when the diabetic rats were treated with CycloRGDyK, that in the bone it has been described as an irisin receptor blocker. In cultured human tubular (HK-2) cells, treatment with recombinant irisin counteracted the effect of high glucose in a dose-dependent manner. Irisin, per se, also activated AMPK in HK-2 cells. It is concluded that in diabetes, the renal protective effect of exercise may be mediated by the irisin/AMPK pathway.

This work presents a micromachining process that allows the creation of hierarchical, matryoshka-like MEMS structures that can be used for multi-axis sensing. This novel vibration multi-axis MEMS sensor based on the capacitive open-loop operation can be widely deployed in the structural monitoring systems due to its simple fabrication and operating principle. The device is composed by a double proof-mass hierarchical design with separate sets of electrodes for in-plane differential measurements. The operation principle of this multi-axis device relies on the fact that accelerations in the zz direction will induce a change in the overlapping area of the xx and yy sensing electrodes, extracted from the single-ended capacitance measurement, while xx and yy accelerations will yield a differential capacitance change. To sense the direction of zz accelerations (capacitance decrease independently of the direction), out-of-plane parallel-plates were added to the device using suspended metallic membranes. The devices were fabricated through an in-house process using a seven-mask dicing-free MEMS process on a 10 μm-thick SOI wafer. The proposed devices were successfully validated using a two-degrees of freedom (DoF) setup that induces external accelerations in the three-orthogonal axes and reads the resulting output voltage of the device. It then possible to conclude that using the proposed fabrication process, it is possible to successfully produce functional multi-structure SOI-based devices that integrate suspended metallic membranes.

Objectives and methods: The objective of this study was to identify problems related to oxygen therapy in hospitalized adults in the literature. The systematic review was developed to identify problems related to oxygen therapy in hospitalised adults and classify them by means of an expert panel using the Pharmaceutical Care Network Europe, version 9.1. Results: Of the 2,618 articles initially identified for the systematic review, 18 met the eligibility criteria, of which five were carried out in Australia (5/18; 27.7%), and the most frequent study design was clinical trial (5/18; 27.7%). An analysis by the expert panel identified hyperoxia as the main cause of patients’ problems (17/18; 94.4%), and no DRP (drug-related problem) was classified as P1.1 (no treatment effect medication, despite the correct use) or P3.2 (unclear problem or complaint: further clarification is required). Studies show that problems related to oxygen therapy are mostly associated with high doses, often caused by failures in the care process such as errors in prescriptions and failures in administration and monitoring of use. Conclusions: the results reinforce the need for the involvement of all members of the multidisciplinary team in the care of patients on oxygen. In addition, the role of the pharmacist in establishing protocols for use with the team, in the standardisation of the system for prescribing medicinal gases, in the validation of medical prescriptions, and in the pharmacotherapeutic follow-up can contribute to the quality and safety of the services provided by health institutions.

The milpa system is the basis of traditional agriculture in Mesoamerica. It is based on a polyculture of maize (Zea mays L.), bean (Phaseolus spp.) and squash (Cucurbita spp.) and is associated with a great diversity of crops and wild species. The milpa has great cultural and historical importance but can also be highly productive and provide sufficient and healthy diets for smallholder farmers. The milpa system is practiced less and less however, mainly due to socioeconomic changes, but also due to a lack of agronomic knowledge adapted to current conditions. To provide a starting point for new agronomic research, we reviewed the scientific literature to identify the current knowledge on milpa agronomy and determine research priorities to further improve the system. Given the wide diversity of conditions under which milpa is practiced, agronomic research is lacking, but indicates that improvements to the milpa can be made in all aspects of the milpa. 176 research articles on the milpa system were found in databases, of which 61 treated agronomic research. The main agronomic topics described in literature are crop variety, soil fertility management, weed management and productivity. Most research has focused only on maize and studies reporting on the associated crops are scarce. More research on all aspects of the milpa is needed to understand and improve the agronomy of the system under the changing conditions of modern agriculture. Reducing the workload associated with the milpa, as well as soil fertility and weed management can be identified as research priorities.

The quality of drug products may be affected from manufacture to dispensing, particularly at high temperature and humidity as in Mauritania. This country is not included in the World Health Organization reports on poor quality products due to the lack of a qualified laboratory and monitoring system. Ensuring the quality of medicine is even more relevant in the case of diseases such as Tuberculosis, due to its high prevalence, complex treatment and continuous bacterial resistance. The aim was to develop a monitoring system to assess the quality of antituberculosis drugs products, by the substandard detection based on European and United States Pharmacopeial recommendations regarding quality control. In addition to studying the influence of accelerated storage conditions (40 ± 2°C/75 ± 5% relative humidity) on their qualities and comparing the dissolution profiles to contrast the quality. 18 antituberculosis drug products were taken from Europe and Mauritania, and quality was studied through visual inspection and according to the compliance of the mass uniformity, uniformity of dosage units, dissolution, disintegration and friability pharmacopeial tests. Furthermore, a dissolution profile comparison was carried out to examine quality. A stability study was conducted to assess the influence of climatic conditions on the content and the dissolved amount of the active pharmaceutical ingredients, which were determined by an ultra-performance liquid chromatography system. As result, 69.3% of 13 Mauritanian formulations had a substandard quality mainly due to non-compliance with the test for friability or content uniformity of these medicines. All European drug products complied with pharmacopeia specifications. In addition, storage conditions affected the dissolution rate of ethambutol and the uniformity of the 4 antituberculosis combination drug products.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

5-hydroxymethylfurfural (HMF) oxidation in aqueous media using visible photocatalysis is a green and sustainable route for the valorization of lignocellulosic biomass derivatives. Several semiconductors have already been applied for this purpose; however, the use of Poly(heptazine imides), which has high crystallinity and a special cation exchange property that allows the replacement of the cation held between the layers of C3N4 structure by transition metal ions (TM), remains scarce. In this study, PHI(Na) was synthesized using a melamine/NaCl method and used as precursor to prepare metal (Fe, Co, Ni, or Cu)-doped PHI catalysts. The catalysts were tested for selective oxidation of HMF to 2,5-diformylfuran (DFF) in water and O2 atmosphere under blue LED radiation. The catalytic results revealed that the 0.1 wt% PHI(Fe) catalyst is the most efficient photocatalyst while higher Fe loading (1 and 2 wt%) favors the formation of Fe3+ clusters, which are responsible for the drop in HMF oxidation. Moreover, the 0.1 wt% PHI(Fe) photocatalyst has strong oxidative power due to its efficiency in H2O2 production, thus boosting the generation of nonselective hydroxyl radicals (●OH) via different pathways that can destroy HMF. We found that using 50 mM, the highest DFF production rate (393 μmol·h−1·g−1) was obtained in an aqueous medium under visible light radiation.

Semi-solid extrusion (SSE) is a three-dimensional printing (3DP) process that involves the extrusion of a gel or paste-like material via a syringe-based printhead to create the desired object. In pharmaceuticals, SSE 3DP has already been used to manufacture formulations for human clinical studies. To further support its clinical adoption, the use of a pressure sensor may provide information on the printability of the feedstock material in situ and under the exact printing conditions for quality control purposes. This study aimed to integrate a pressure sensor in an SSE pharmaceutical 3D printer for both material characterization and as a process analytical technology (PAT) to monitor the printing process. In this study, three materials of different consistency were tested (soft vaseline, gel-like mass and paste-like mass) under 12 different conditions, by changing flow rate, temperature, or nozzle diameter. The use of a pressure sensor allowed, for the first time, the characterization of rheological properties of the inks, which exhibited temperature-dependent, plastic and viscoelastic behaviours. Controlling critical material attributes and 3D printing process parameters may allow a quality by design (QbD) approach to facilitate a high-fidelity 3D printing process critical for the future of personalized medicine.

Se presenta un estudio de los petroglifos sedentes que posee la “Sala de Arqueología” de la Universidad de Oriente (Cuba), que fueron aserrados de sus sitios originales y convertidos en piezas de colección. Se aplicaron procedimientos de recopilación y consulta de referentes históricos documentales, y el análisis traceológico por microscopía digital y obtención de moldes sintéticos. Documentamos así un conjunto de nueve petroglifos, cuya información era desconocida en la literatura rupestrológica cubana. Como resultado, se reafirma su origen precolonial y se establece su similitud tipológica con los de otros sitios del oriente cubano. Se documenta que la tendencia al aserrado y extracción de petroglifos se expandió por el extremo oriental de Cuba, a partir de las acciones de Mark R. Harrington, entre 1915 y 1919. Se concluye que dichas piezas deben proceder de las regiones de Maisí y Baracoa, y que, en la actualidad, existen condiciones favorables para la identificación y localización de los sitios de procedencia, a partir del registro de cortes que hoy se posee y los levantamientos de los moldes de áreas de corte que se obtuvieron en esta investigación.

Background: Helicobacter pylori (H. pylori) infection and chronic dyspepsia represent significant medical burdens in the developing world. An accurate assessment of the prevalence of chronic dyspepsia, as well as of the effectiveness of population-based screening and eradication of H. pylori are warranted. Objectives: We determined the prevalence of H. pylori and chronic dyspepsia within the general adult population in a region of eastern Uganda. Independent predictors of H. pylori infection were assessed. Finally, we evaluated the efficacy of standard triple therapy on H. pylori eradication. Methods: Of 400 randomly selected adult residents in eastern Uganda, 376 were administered a validated, chronic dyspepsia questionnaire and provided a stool sample for H. pylori testing. H. pylori-positive participants were given standard triple therapy and monitored for medication adherence. The efficacy of triple therapy on H. pylori eradication was determined by fecal antigen testing after treatment. Log-linear and logistic regression analyses identified predictors of H. pylori positivity and eradication failure. Results: H. pylori prevalence within the study population was 48%. The prevalence of chronic dyspepsia was 87%. The presence or severity of dyspepsia did not predict H. pylori infection. However, a higher level of education was an independent predictor of H. pylori infection. Standard triple therapy resulted in ∼90% eradication. Missing at least four doses of any of the triple therapy medications over the 14-day course predicted eradication failure. Conclusions: In our study population, chronic dyspepsia did not predict H. pylori infection, though clinical suspicion for this prevalent pathogen should nonetheless remain high. Population-based screening and adherence to triple therapy are effective at eradicating H. pylori within this region.

Abstract Excessive alcohol consumption is considered a risk factor for bone health, as it causes a reduction in mass and increases the risk of fracture. However, the determination of bone mineral density (BMD) has not always been an adequate predictor of bone fragility. Thus, the hypothesis arises that chronic alcohol consumption interferes with collagen synthesis and the quality of bone trabeculae, with consequent bone fragility. Groups: Control (n = 6; water intake only during the entire study period); Ethanol (n = 6; ingestion of ethyl alcohol according to the protocol for inducing chronic alcohol consumption). The chronic alcohol consumption model did not cause a significant change in BMD, but there was a significant reduction of 20% in the thickness of the bone trabeculae and of 1.56% in the collagen located in the neck region of immature rat femurs. Although there was no significant change in the mineral matrix, the changes in the organic matrix were able to provide a significant reduction in bone strength. The results suggest harmful effects of alcohol intake on the bone quality of young adult animals and draw attention to the need to also consider methods for the diagnosis of collagen as an element of bone fragility.

Over the years, there has been an increase in the consumption of drugs, particularly antibiotics. Amoxicillin (AMX) is considered one of the most widely used antibiotics, causing resistance in microorganisms in the ecosystem where it is found. Additionally, it has been cataloged among the drugs under surveillance by the European Commission since 2020. The present work studies the efficiency of AMX degradation by photolysis and heterogeneous solar photocatalysis processes under different reaction pH levels (3.5, 4.15, 7 and 9) and observing the influence of different doses of H2O2 (nil and 4 mM), as an oxidizing agent. TiO2 P25 was used as photocatalyst, impregnated in glass supports of 0.1 and 1 m2 in flat plate reactors (FPR). A 2 × 2 × 4 statistical analysis carried out after repeated measurements to determine the relationship between the different parameters involved (process, H2O2 dose, and pH). The kinetics of the AMX degradation reaction showed the best rate constant (KphC = 0.10 min−1) under acidic medium conditions (pH 4.15), without addition of H2O2, and by heterogeneous photocatalysis when using a 1 m2 FPR to achieve 100% COD removal. ANCOVA showed significant differences (p < 0.05) in the use of H2O2 for the first minutes of the reaction and in the different FPR surfaces.

The prenatal environment is recognized as crucial for the postnatal performance in cattle. In tropical regions, pregnant beef cows commonly experience nutritional restriction during the second half of the gestation period. Thus, the present study was designed to analyze the genotype by prenatal environment interaction (G × Epn) and to identify genomic regions associated with the level and response in growth and reproduction-related traits of beef cattle to changes in the prenatal environment. A reaction norm model was applied to data from two Nelore herds using the solutions of contemporary groups for birth weight as a descriptor variable of the gestational environment quality. A better gestational environment favored weights until weaning, scrotal circumference at yearling, and days to first calving of the offspring. The G × Epn was strong enough to result in heterogeneity of variance components and genetic parameters in addition to reranking of estimated breeding values and SNPs effects. Several genomic regions associated with the level of performance and specific responses of the animals to variations in the gestational environment were revealed, which harbor QTLs and can be exploited for selection purposes. Therefore, genetic evaluation models considering G × Epn and special management and nutrition care for pregnant cows are recommended.

ObjectiveTo investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.Methods148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.ResultsOur results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).ConclusionsDiabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.

Este artículo explora el canon implícito presupuesto en la Poética de Aristóteles al objeto de identificar a los autores de épica y tragedia a los que este tratado reconoce como modélicos y en función de qué criterios. Se estudia igualmente cuáles son las obras concretas de esos autores que se presentan como canónicas en la Poética. Se concede también atención a las semejanzas y diferencias entre el canon implícito de Aristóteles y el alejandrino.

El Geoparque Mundial de la UNESCO Montañas do Courel cuenta con yacimientos paleontológicos paleozoicos que van desde el Cámbrico hasta el Carbonífero. En la actualidad, se está llevando a cabo un proceso de búsqueda y catalogación de yacimientos con fósiles marinos paleozoicos que ha generado una base de datos, la cual ha permitido y permitirá ponerlos en valor, así como mejorar su mejor protección y preservación. Además, mediante la musealización de algunos de los fósiles del Geoparque en el Museo Geológico de Quiroga, se cumple uno de los objetivos del geoparque, que es el acercamiento de la Geología a la sociedad.

3D printing technology can be used to develop individualized medicines in hospitals and pharmacies, allowing a high degree of personalization and the possibility to adjust the dose of the API based on the quantity of material extruded. The main goal of incorporating this technology is to have a stock of API-load print cartridges that could be used at different storage times and for different patients. However, it is necessary to study the extrudability, stability, and buildability of these print cartridges during storage time. A paste-like formulation containing hydrochlorothiazide as a model drug was prepared and distributed in five print cartridges, each of which was studied for different storage times (0 h–72 h) and conditions, for repeated use on different days. For each print cartridge, an extrudability analysis was performed, and subsequently, 100 unit forms of 10 mg hydrochlorothiazide were printed. Finally, various dosage units containing different doses were printed, taking into account the optimized printing parameters based on the results of the extrudability analysis carried out previously. An appropriate methodology for the rapid development of appropriate SSE 3DP inks for pediatrics was established and evaluated. The extrudability analysis and several parameters allowed the detection of changes in the mechanical behavior of the printing inks, the pressure interval of the steady flow, and the selection of the volume of ink to be extruded to obtain each of the required doses. The print cartridges were stable for up to 72 h after processing, and orodispersible printlets containing 6 mg to 24 mg of hydrochlorothiazide can be produced using the same print cartridge and during the same printing process with guaranteed content and chemical stability. The proposed workflow for the development of new printing inks containing APIs will allow the optimization of feedstock material and human resources in pharmacy or hospital pharmacy services, thus speeding up their development and reducing costs.

Infectious mastitis is the most prevalent health problem in dairy cattle that can result in permanent economic losses on dairy farms. The micronised purified flavonoid fraction (MPFF) is a biocompatible active polyphenolic compound derived from flavonoid glycosides which exhibits several antimicrobial, anti-inflammatory, and phlebotonic properties. The goal was to assess the effects of an alternative therapy for mastitis based on MPFF intramammary infusions in late lactation in dairy cows naturally infected by Staphylococcus spp. The California Mastitis Test (CMT scores) was performed to detect mastitis-positive quarters in twelve dairy farms. All cows were screened for immune response by measuring somatic cell counts (SCCs; cells/mL) in milk samples from each quarter. In addition, bacteriological identification, pathogenic bacterial isolates, and total bacterial counts (TBCs; CFU/mL) were assessed before (day 0, last milking day) and after (day 3 post-calving) MPFF application. Antimicrobial sensitivity patterns of the pathogenic isolated bacteria were evaluated. Finally, cure rates (%) were determined for each MPFF treatment. Around 15 mastitis-related genera were isolated. Staphylococcus aureus (25.2%) and coagulase-negative Staphylococci (CNS; 22.4%) were the most prevalent pathogens. No statistical differences were observed in SCCs and TBCs after low, medium, and high MPFF dose administration in S. aureus-positive mastitis cases (p > 0.05). However, differences were observed in SCCs and TBCs after medium and high MPFF dose administration in CNS-positive quarters (p < 0.05). The pathogenic bacteria isolate reduction after MPFF applications showed a dose-response fashion (p < 0.01) while isolates obtained from controls and low MPFF-treated quarters remained similar, irrespective of the pathogen (p > 0.05). Sensitivity patterns were variable, although S. aureus remained resistant, irrespective of the MPFF dose. However, CNS showed a dose-response sensitivity pattern. Finally, the cure rate (%) on day 3 post-partum improved significantly using medium and higher MPFF doses in CNS-positive quarters (p < 0.05). In conclusion, MPFF treatment was found to be more effective for CNS-positive cases in the late lactation due to noticeable dose-specific responses regarding somatic cells, bacterial counts, sensitivity patterns, and cure rates in dairy cattle.