Glypicans are a family of heparan sulfate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glypicans are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs) and Bone Morphogenetic Proteins (BMPs), among others. In the Hh signalling pathway, glypicans have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix and for its unimpaired reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how glypicans may contribute to it. In this review, we describe the structure, biochemistry and metabolism of glypicans and their interactions with different components of the Hh signalling pathway that are important for the release, transport and reception of Hh.

Alphavirus species are globally distributed zoonoses, primarily transmitted by arthropods. In Costa Rica, Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are endemic. The objective of this study is to detect these viruses in brain samples from equines displaying nervous signs. For this purpose, four published universal RT-PCR methods were compared. The most sensitive and specific RT-PCR method was used to test a total of 70 brain samples, including 40 from bovines and 30 from equines, all exhibiting nervous signs. In the positive cases, eight different brain regions were extracted and tested using this RT-PCR. Positive cases were confirmed through sequencing. Among the four universal RT-PCR assays, Torii RT-PCR demonstrated the highest sensitivity and specificity for diagnosing VEEV and EEEV. Not all assessed brain regions showed DNA amplification. None of the bovine brains was positive and out of the 30 equine brain samples, only four tested positive, and sequencing confirmed two of these samples as VEEV subtype IE. Torii RT-PCR successfully detected VEEV in pools of the hip-pocampus, spinal cord, and basal nuclei, making these brain regions suitable for diagnosing this virus. None of the samples were positive for EEEV.

We present the case of a 35-year-old male with first degree family history of gastric cancer (father diagnosed at the age of 45), that was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates for patients with hematological malignancies due to diagnostic and therapeutic advances. Identification of patients at risk CTRCD is vital to develop preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CTRCD was 17.4 % (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs 13.4% p = 0.017) and previous cardiovascular disease (40% vs 13.3%, p< 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg /L ± 101.02, and 251.518 kg /L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI 1.08-2.93), p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

A mechanical ventilation system is a big support for breathing complications, in which an external solution is quite necessary to keep oxygen compensation in the patients. Its knowledge is well widespread and different equipment has been developed. However, they are very expensive and their quantity in medical centers is not sufficient, especially in Peru. Hence, it has been required to develop new methods to provide oxygen by a low cost equipment; Protofy, a research group from Spain, designed one of the first low cost mechanical ventilation systems which was medically validated by its government. In this sense, a redesign of the mechanical ventilation system was carried out according to the local requirements and available technology, a different airbag resuscitator with different properties and geometry, but maintaining its working concept based on a cam compression mechanism. Sensors and a display were added to improve the performance with a control algorithm for the rotation frequency and to show the ventilation curves over time to the medical staff. It was necessary to develop a mathematical model to relate the behavior between ventilation curves for a patient and physical variables of the design, especially in the epidemic COVID 19, that many countries are dealing with at the time research is being conducted. The mechanical ventilation system was redesigned, fabricated, and tested measuring its ventilation curves over time. Results indicate that this redesign provides a sturdy equipment able to work during a longer lifetime than the original. The replicability of the ventilation curves behavior is assured, while the mechanism dimensions are adapted for a particular airbag resuscitator. The mathematical model of the whole system can predict satisfactorily the ventilation curves over time and was used to provide the air pressure, volume, and flow as a function of the rotation angle measured by sensors.

Abstract: Pasteurella spp. is a gram-negative bacterium that is part of the oral and upper respira-tory tract microbiota of many animals such as canids and felines. In humans it can produce pa-thology primarily associated with animal bites or scratches. In addition, members of this genus, and especially Pasteurella multocida, may also be involved in systemic infections, mainly in im-munocompromised patients in close contact with pets. The aim of this study is to analyse the prevalence and clinical characteristics of infections caused by Pasteurella spp. as well as the sensitivity profile of these isolates obtained in the Microbiology laboratory of the Hospital Can Misses (Ibiza, Ibiza and Formentera Health Area, ASEF) in the period from January 2013 to December 2018. The group of islands of Ibiza and Formentera is known as the Pitiusas Islands. Retrospective descriptive study in which all Pasteurella spp. isolates were analysed in the Microbiology Laboratory of Hospital Can Misses from 1 January 2013 to 31 De-cember 2018. Bacterial identification was performed by Vitek 2 automated biochemical test panel (bioMérieux, Spain) and antimicrobial susceptibility by E-test or antibiotic discs in Mueller-Hinton blood agar, interpreted based on European Committee on An-timicrobial Susceptibility Testing (EUCAST) standards, 2022 version. Medical records were systematically reviewed by collecting demographic data of infected patients, comorbidities, epidemiological data and clinical features of the infection. A total of 22 isolates of Pasterurella spp. were obtained from 22 different patients, 62.8% female, from three different species: 18 P. multocida, 2 P. canis and 2 P. pneumo-tropica. Most isolates came from soft tissue infection samples: 7 wound exudates and 5 abscess material. The antibiotics tested with the highest sensitivity profile were gen-tamicin and cefepime (100% sensitivity). The species most commonly isolated in our environment is P. multocida. Close contact with companion animals, especially cats and dogs, is the main risk factor for Pasteurella spp. infections, although in many cases such contact cannot be established. So Pasteurella spp. infection should be considered a zoonosis in possible emergency, especially in rural areas such as Pitiusas Islands.

We have much to learn from historic buildings. The fact that they are still standing is obvious, but unfortunately often not appreciated. In this paper the results obtained from a series of parametric analyses, where the influence that geometric and mechanical parameters have in the structural response of existing cob walls within an Irish context, are presented. A design of experiments using central composite designs was implemented along with analysis of variance following two computational approaches, namely, finite element method and kinematic limit analysis. As results, a series of response surfaces and parametric equations with which it is possible to compute safety factors and collapse multipliers (within the range of values studied) are provided. Based on the results obtained, it could be concluded that traditional cob walls in Ireland are very robust. Relatively high acceleration values, unlikely to happen in a low seismic hazard region such as Ireland, would be needed to start the collapse mechanisms studied or cause yielding in typical vernacular cob walls. Furthermore, the equations generated with the refined regression models, can be used by practitioners as a first approach to estimate the safety levels of existing cob buildings with similar characteristics.

Several researchers have contemplated deep learning-based post-filters to increase the quality of statistical parametric speech synthesis, which perform a mapping of the synthetic speech to the natural speech, considering the different parameters separately and trying to reduce the gap between them. The Long Short-term Memory (LSTM) Neural Networks have been applied successfully in this purpose, but there are still many aspects to improve in the results and in the process itself. In this paper, we introduce a new pre-training approach for the LSTM, with the objective of enhancing the quality of the synthesized speech, particularly in the spectrum, in a more efficient manner. Our approach begins with an auto-associative training of one LSTM network, which is used as an initialization for the post-filters. We show the advantages of this initialization for the enhancing of the Mel-Frequency Cepstral parameters of synthetic speech. Results show that the initialization succeeds in achieving better results in enhancing the statistical parametric speech spectrum in most cases when compared to the common random initialization approach of the networks.

Podiatric surgeons routinely use electrosurgical devices to cut and coagulate tissue during surgical procedures. Although advances in technology have made electrosurgery increasingly safer for patients and personnel, its use is still poorly understood by those using it and the hazards associated with its use still exist presently. Human error, direct or indirect transfer of electricity to a conductive device, or device malfunction can cause serious adverse events, including burns, electrical shocks, and or fires. Here, we report a rare case of a 43-year-old man who suffered severe burns during hallux valgus surgery. The surgeon and the nursing staff did not notice any injuries during the surgical intervention. This case highlights the need to implement tools to help health professionals improve patient safety during surgery. Based on the case herein reported, a specific checklist was implemented to prevent adverse events related to electrosurgery in our podiatric unit to reduce the risk of electrosurgical complications.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

Mechanical ventilation systems, which are used for breathing support when a person is not able to do it by their own, requires a device for measuring the air flow to the patient in order to monitoring and a assure the magnitude establish by a medical staff. Flow sensors are the conventional devices used for the air flow measuring; however, there were not available in Peru, because of the international demand during COVID-19 pandemic. In this sense, a novel air flow sensor based on orifice plate and an intelligent transducer stage were developed as an integrated design. Advanced methodologies in simulations and experiments using specially designed equipment for this application were carried out. The obtained data was used for a mathematical characterization and dimensions validation of the integrated design. The device was tested in its real working conditions, it was implemented in a breathing circuit connected to a low-cost mechanical ventilation system based on cams. Results indicate that the designed air flow sensor/transducer is a low-cost complete medical device for mechanical ventilators able to provide satisfactorily all the ventilation parameters air flow, pressure and volume over time by measuring the air flow and calculating the others. Furthermore, this device provides directly a filtered equivalent electrical signal for a display or a computer.

This paper is the first of a series of papers which aims to address Islamist violent radicalization from different angles: the nature of violent radicalization in the context of Spain, a comparison between European, North American and Indian violent radicalization, the need to refine territorial radicalization indexes within the context of preventing violent radicalization and the relation between Islamist violent radicalization and other forms of violent radicalization in Europe. This set of articles builds upon the general theoretical framework set by the author on two previous works (García, 2018; 2019). These works are framed under the known conception of three layers of micro, meso and macro factors contributing to violent radicalization processes (McCauley, Moskalenko, 2017). The paper starts by defining Islamist violent radicalization, then it explores different theoretical explanations and finally proposes an explanatory hypothesis that is tested against, on the one hand, data proceeding from different institutional sources in Spain and, on the other, some initial conversations which will become life stories and a in depth interviews to Spanish security officials and people who whether radicalized and regretted or lived very close to others that did it.

The impact of instructional guidance on learning outcomes in higher biomedical education is subject of intense debate. There is the teacher-centered or traditional way of teaching (TT) and, on the other side, the notion that students learn best under minimal guidance (problem-based learning, PBL). Although the benefits of PBL are well-known, there are aspects susceptible to improvement. Hence, a format merging TT and PBL (hybrid-PBL, h-PBL) may advance education in biomedical sciences. Here, we systematically reviewed studies that employed h-PBL in higher biomedical education compared to TT and/or pure PBL. We found that h-PBL resulted in better overall students’ performance and perception than TT or pure PBL. These findings encourage more research on investigating the pedagogical benefits of h-PBL and posit an eclectic system in which the pedagogical tools from TT and PBL are used cooperatively in the best interest of the education and satisfaction of the students.

The aim of this study was to evaluate the effect of an Athletic Performance Program, performed in addition to teams’ regular training routines, on match performance variables in professional football players. Twenty-nine professional football players (age=27.21±4.95 years; body mass=79.56±5.21 kg) of the Spanish First Division (LaLiga) underwent a 10-week training program focused on the development of mobility, stability, strength, and multidirectional running skills. The APP included 5 indoor sessions per week and on-field micro-dosing stimulus in addition to regular training practices. Match performance variables obtained with GPS devices during official matches and jump performance were measured before and after the APP. The APP increased peak running speed (31.1±1.4 vs 32.1±1.0 km/h, P < 0.001, d=1.88), the number of sprints (0.14±0.03 vs 0.16±0.03 sprint/min, P< 0.001, d=1.44) and the sprint distance (6.45±1.43 vs 8.35±1.22 m/min P< 0.001, d=2.49) during the matches. The intervention also increased countermovement jump height (34.1±2.7vs 35.8±2.5 cm, P< 0.001, d=2.20). The APP was effective to improve intense actions during competitive match play in professional football players. Strength and conditioning coaches may consider the use of multicomponent physical training programs included in the usual training week to enhance players’ match running at high intensity.

Smoked cigarette butts (SCB) can be used as precursors to obtain activated carbon (AC) due to their high carbon content related to the presence of cellulose acetate and components that are retained in the tobacco combustion process. In this way, it was analyzed how the process of pyrolysis or formation of char from this residue occurs, for this a study of the kinetics of formation of char is carried out by thermogravimetry, using three heating speeds 5, 10 and 15 °C/min. Based on the data obtained, mathematical models such as Kissenger - Akahira - Sunose (KAS), Starink (STK) and Ozawa - Flynn - Wall (OFW) were used in order to identify thermodynamic parameters through the energy of activation. The char obtained was subjected to an activation treatment with KOH in order to increase the surface area and pore volume, obtaining values of 433 m2/g of BET area and 0.25 cm3/g of micropore volume. Finally, the adsorbent was applied in the removal of Cr (VI) obtaining a Qmax capacity determined by the Langmuir model of 55.8 mg/g.

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed to symptoms relief, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from repurposing of specific compounds with known antiviral activity to the screening of libraries and of natural compounds. The identified antiviral candidates include drugs targeting viral components (structural proteins and enzymes), as well as cellular ones. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

Microbes do not live in isolation but in microbial communities. The relevance of microbial communities is increasing due to the awareness about their biotechnological influences in a huge number of environmental, health and industrial processes. Hence, being able to control and engineer the output of both natural and synthetic communities would be of great interest. However, most of the available methods and biotechnological applications (both in vivo and in silico) have been developed in the context of isolated microbes. In vivo microbial consortia development, i.e. to reproduce the community life conditions in the wet-lab, is extremely difficult and expensive requiring of computational approaches to advance knowledge about microbial communities, mainly with descriptive modelling, and further with engineering modelling. In this review we provide a detailed compilation of available examples of engineered microbial communities as a launch pad for an exhaustive and historical revision of those computational methods devoted so far toward the better understanding, and rational engineering of natural and synthetic microbial communities.

Optoacoustic imaging is an emerging technology that holds great promise for improving general clinical practice since it offers a unique combination of optical absorption contrast, high resolution, and high penetration depth. This combination of factors provides a distinct advantage over alternative imaging modalities in oncology, cardiology, dermatology, or endocrinology among other medical fields. Optoacoustic technology affords the medical practitioner the possibility of visualizing light-absorbing biomolecules like water, lipids, oxy/deoxy hemoglobin, or melanin in deep tissue with relatively cheap and small form factor instruments, without the need of contrast agents or ionizing radiation. Moreover, exogenous fluorescent contrast agents like indocyanine green or methylene blue can also be observed. Driven by its potential for new applications in the clinic, the field has experienced intense changes in the last 20 years. Continuous technological advancements in instrumentation, image formation methods, or acquisition geometries, have led to the development of numerous clinical devices also motivating the creation of several startup companies that aim to translate the technology from the lab to the clinic. Thus, the question arises: how far are we from clinical adoption? In this article, we aim to shed light on such question by reviewing the clinical studies that have been performed in the last 10 years. Our intention is to go beyond the classical review format by providing a brief general overview of the steps that new imaging methods undergo on their journey from the lab to clinical adoption. Then we examine the progress that optoacoustic technology has made on such a journey.

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs under challenging metabolic environments. However, since normal diets provide all AAs at relatively constant levels and ratios, these potentially lethal genetic and metabolic defects are eventually harmless to cancer cells. If we temporarily replace the normal diet of cancer patients with artificial diets in which the levels of specific AAs are manipulated, cancer cells may be unable to proliferate and survive. This article reviews in vivo studies that have evaluated the antitumor activity of diets restricted or supplemented with the 20 proteinogenic AAs, individually and in combinations. It also reviews our recent studies that show that manipulating the levels of several AAs simultaneously can lead to marked survival improvements in mice with metastatic cancers.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

During the pandemic, educational digitization experienced a significant increase. In Mexico, social service is a crucial component of technical and professional training, a phase during which individuals apply the knowledge gained throughout their university education. The aim of this study is to standardize a digital model for the management of social service in the health care sector within health care units. This study employed an analytical, observational, retrospective, and longitudinal approach, involving two groups of trainees: Group A (n=133), utilizing a Non-Digital Model, and Group B (n=50), employing a Digital Model. In Stage I. the model design underwent validation through the Delphi method with a panel of three experts. The model was implemented on a Classroom® digital platform with the integration of the elements 1) a monthly rotation rubric 2) care services rubric 3) clinical cases or nursing process rubric, and 4) innovation project rubric. The validation of the model achieved 100% agreement (K=1). The variables measured for each group included the school of origin, career, unit of assignment, timely enrolment, and timely delivery of rubrics on the platform. The difference between the two groups was measured using Chi-Square. To measure the impact, the difference in the timeliness of the products was considered. From the University of Quintana Roo, the difference was 20.3 vs 34%. According to the Unit of Attachment the most frequent was HGR No. 17 with Group A at 22.5 vs 52%. According to the product the least delivered was Product 4, with 69% vs 81%. Timely enrollment was observed in Group A at 89% vs Group B at 80% p=0.001. Overall timely delivery in Group A was 81% vs Group B at 91% p=0.001 in the first 6 months post-implementation. Demonstrating that the implementation of the digital platform was effective, representing a significant advance in the adaptation of medical education to the circumstances imposed by the pandemic, highlighting the feasibility and effectiveness of digital teaching methods in the training of health professionals.

Introduction: Studies of the socio-economic function of entrepreneurship have emphasized the critical role that entrepreneurial competence and its implementation play at different stages of the education system. In this paper, we seek to determine the entrepreneurial interest of Spanish youth aged between 15 to 18 years of age, who find themselves in the state-regulated education system, at an initial stage in the development of entrepreneurship. A previously validated ad hoc questionnaire was applied through simple random sampling to 1,764 students at a secondary school in Spain. The analysis is done with Artificial Neural Networks (ANN), a technique that reduces the high dimensionality of data through Cooperative Maximum Likelihood Hebbian Learning (CMLHL), applying neurocomputational methods to the educational sciences. Spanish youth expressed a medium level of interest in entrepreneurship. Analysis with ANN shows that education in entrepreneurial competence is an influential aspect of interest in entrepreneurship. As conclusion, educational and curricular reforms must be undertaken to promote the development of entrepreneurial competence at various stages of compulsory education to increase interest in entrepreneurship.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

The sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys, and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced a marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased the survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53 -/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Enteric methane (CH4) emitted by ruminant species is known as one of the main greenhouse gases produced by the agricultural sector. The objective of this study was to evaluate the chemical composition, in vitro gas production, dry matter degradation (DMD), digestibility, CO2 production and CH4 mitigation potential of five tropical tree species with novel forage potential including: Spondias mombin, Acacia pennatula, Parmentiera aculeata, Brosimum alicastrum and Bursera simaruba mixed at two levels of inclusion (15 and 30%) with a tropical grass (Pennisetum purpureum). Crude protein content was similar across treatments (135 g kg-1 DM), while P. purpureum was characterized by a high content of acid detergent fiber (335.9 g kg-1 DM) and B. simaruba by a high concentration of condensed tannins (20 g kg-1 DM). Likewise, A. pennatula and P. aculeata were characterized by a high content of cyanogenic glycosides and alkaloids respectively. Treatments SM30-PP70 (30% S. mombin + 70% P. purpureum) and BA30-PP70 (30% B. alicastrum + 70% P. purpureum) resulted in superior digestibility than P. purpureum, while in the AP30-PP70 (30% A. pennatula + 70% P. purpureum) was lower than the control treatment (P≤0.05). At 24 and 48 h, treatments that contained P. aculeata and B. alicastrum produced higher CH4 ml g-1 DOM than P. purpureum (P≤0.05). The inclusion of B. simaruba at 30% reduced CH4 at 25% compared to P. purpureum. Tropical tree species can improve the nutritional quality of ruminant rations and reduce CH4 emissions to consequently contribute to the development of sustainable ruminant production systems that generate diverse ecosystem services.

A new discrete distribution for count data called extended biparametric Waring (EBW) distribution is developed. Its name is related to the fact that, in a specific configuration of its parameters, it can be seen as a biparametric version of the univariate generalized Waring (UGW) distribution, a well-known model for the variance decomposition into three components: randomness, liability and proneness. Unlike the UGW distribution, the EBW can model both overdispersed and underdispersed data sets. In fact, the EBW distribution is a particular case of a UWG distribution when its first parameter is positive; otherwise, it is a particular case of a Complex Triparametric Pearson (CTP) distribution. Hence, this new model inherits most of their properties and, moreover, it helps to solve the identification problem in the variance components of the UGW model. We compare the EBW with the UGW by a simulation study, but also with other over and underdispersed distributions through the Kullback-Leibler divergence. Additionally, we have carried out a simulation study in order to analyse the properties of the maximum likelihood parameter estimates. Finally, some application examples are included which show that the proposed model provides similar or even better results than other models, but with fewer parameters.

Background. Increasing evidence demonstrate that concentration of protein in infant formula >1.9g/100Kcal with high levels of insulinogenic aminoacids is associated with accelerated weight gain, increased fat mass accumulation and risk of adiposity. Purpose of this study was to conduct a systematic review to determine the metabolic effects in infants feed with infant formula optimized in protein. Methods. Systematic review was conducted according PRISMA Statement. RCTs with one intervention group (infant formula with 1.6-1.9gr of protein/100Kcal) and at least one comparative control group (infant formula with >1.9gr of protein/100Kcal) were included. Standardized mean differences (SMD), through random model were calculated. Results. 15 RCT were included. Optimized protein in infant formula was associated with less gain of BMI at 24 months of follow-up (SMD -0.25, IC95% -0.36 to -0.13, p 0.01) and less fat mass accumulation (SMD -0.68, IC95% -0.98 to -0.37, p 0.01). Optimized protein was also associated to less gain of weight, weight/age Z-score, weight/length Z-score, BUN (mmol/dL) and IGF1 (ng/ml). No effect on length/age Z-score was observed. Conclusions. Robust evidence showed optimized protein (1.6gr/100Kcal to 1.9gr/100Kcal) in infant formula is associated with metabolic benefits in infants with less weight gain, BMI and fat mass accumulation.

this article presents the results of implementing existing software tools in the accounting field. The teaching processes regarding the use of Learning and Knowledge Technologies (TAC) in the university environment, and very specifically, in what has to do with the pedagogical integration of the same in the curriculum is deficient and disjointed with the current technological development. Thus, in the different curricula of professional programs of Public Accounting and related, the courses related to computer automation processes are oriented only towards the management of computer science and accounting software and the great diversity of existing applications that would undoubtedly directly benefit the student to know the potential of these in their future accounting practice is not taken into account. Strengthen the various skills of a Public Accountant in training through Learning and Knowledge Technologies (TAC), under the hypothesis of developing skills in the accounting field through TACs. The research was developed using a quantitative approach, an empirical-analytical method, with a type of descriptive research under an experimental design based on G1 x O1 and G2–O2, three phases were defined. In the first phase, the characterization of the existing software tools in the accounting field was carried out. In the second phase, their relevance was determined. In the third phase, performance was evaluated and then classified in a repository. The data obtained were analyzed with parametric analysis techniques through which it was found that the difference in quantitative results in the academic process between the experimental and control groups was statistically significant, which concluded the success of the experimental treatment. The use of CT scans in the classroom by the experimental group resulted in an improvement in their academic performance compared to the control group, strengthening their self-learning processes and facilitating the development of cognitive functions and skills necessary in the exercise of their accounting profession. This research supports and strengthens the work skills developed in the classroom for public accounting students. The tools TAC is developed from the request made by the radiometry laboratory as a first phase and a second phase is necessary for validation with experts.

As entrepreneurial interest is believed to represent a causal factor increasing entrepreneurship, research has begun to explore how family systems affect youth entrepreneurial interests. In the present study, we attempt to identify different types of family influence on the entrepreneurial interests of young people. A questionnaire was used to obtain data from 1,633 Spanish youths, who were 15 to 18 years old, and another questionnaire was used to obtain data from 839 parents. Principal Component Analysis identified unique family types and revealed that they have differential associations to entrepreneurial interest among youths. These findings reaffirm the influence of family on the entrepreneurial ecosystem and the promotion of an entrepreneurial family cuture. This study further suggests that early attention should focus on the detection of entrepreneurial interest among youths so that actions can be implemented in the families of low-interest youths to incentivize an entrepreneurial family culture.

The contents of Education for Sustainable Development (ESD) should be included in teachers’ initial and advanced training programs. In order to determine the key competences for sustainability, creating a Sustainable Consciousness is one of the main foundations. However, there are not many empirical studies that deal with consciousness from education. In this context, e-portfolio appears as a tool that promotes reflection and critical thinking, key competences for consciousness development. This work intends to propose a categorization system to extract types of consciousness and identify trainee teachers’ levels of consciousness. For this research work, of an eminently qualitative nature, we have selected twenty-five portfolios of students in the last year of the School of Education at the University of Macerata (Italy). The qualitative methodological procedure followed allowed to deduce three bases that shape trainee teachers’ consciousness: thinking, representation of reality and type of consciousness. We concluded that the attainment of a Sustainable Consciousness in teachers requires activating and developing higher levels of thinking, as well as a projective and macrostructural representation of reality.

Wildland fires are responsible for large socio-economic impacts. Fires affect the environment, damage structures, threaten lives, cause health issues, and involve large suppression costs. These impacts can be mitigated via accurate fire spread forecast to inform the incident management team. We show that a fire forecast system based on a numerical weather prediction (NWP) model coupled with a wildland fire behavior model can provide this forecast. This is illustrated with the Chimney Tops II wildland fire responsible for large socio-economic impacts. The system is run at high horizontal resolution (111 m) over the region affected by the fire to provide a fine representation of the terrain and fuel heterogeneities and explicitly resolve atmospheric turbulence. Our findings suggest that one can use the high spatial resolution winds, fire spread and smoke forecast to minimize the adverse impacts of wildland fires.

The sympathetic restoration and conservation of built cultural heritage play a significant role in the management and preparedness for future climate scenarios by facilitating adaptive reuse, enhancing cultural resilience, preserving traditional knowledge, and boosting tourism. The importance of restoring damaged heritage sites after an earthquake drew international attention to Nepal after the 2015 Gorka Earthquake. UNESCO established an office in Kathmandu to promote the restoration of tangible and intangible heritage in the area. This included developing structural analyses of buildings with historical and cultural value that due to their nature cannot be intervened with the same methodology as modern buildings. In this paper, the case study of the earthquake-damaged Gopinath temple, is discussed. First, an initial visual inspection phase and the following diagnosis of the structure are discussed. Then, the results from a series of static and dynamic structural analyses performed to determine the safety level of the structure, together with a sensitivity analysis, are presented. A sympathetic intervention proposal capable of increasing the temple safety level and based on the addition of timber plates, has resulted in substantial improvements of the lateral behavior of the structure. The proposed intervention is deemed sustainable and able to increase the resilience of the temple in the face of future hazards.

Speech signals are degraded in real-life environments, product of background noise or other factors. The processing of such signals for voice recognition and voice analysis systems presents important challenges. One of the conditions that make adverse quality difficult to handle in those systems is reverberation, produced by sound wave reflections that travel from the source to the microphone in multiple directions.To enhance signals in such adverse conditions, several deep learning-based methods have been proposed and proven to be effective. Recently, recurrent neural networks, especially those with long and short-term memory (LSTM), have presented surprising results in tasks related to time-dependent processing of signals, such as speech. One of the most challenging aspects of LSTM networks is the high computational cost of the training procedure, which has limited extended experimentation in several cases. In this work, we present a proposal to evaluate the hybrid models of neural networks to learn different reverberation conditions without any previous information. The results show that some combination of LSTM and perceptron layers produce good results in comparison to those from pure LSTM networks, given a fixed number of layers. The evaluation has been made based on quality measurements of the signal's spectrum, training time of the networks and statistical validation of results. Results help to affirm the fact that hybrid networks represent an important solution for speech signal enhancement, with advantages in efficiency, but without a significan drop in quality.

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life for the couple but also to the father-child relationship, mother-child relationship, and well-being of adolescents. This study examined the influence of marital conflict on father-child and mother-child attachment and the psychosocial adjustment (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father-adolescent attachment in situations of family conflict is recommended.

The semi-nonparametric (SNP) modeling of the return distribution has been proved to be a flexible and accurate methodology for portfolio risk management that allows two-step estimation of the dynamic conditional correlation (DCC) matrix. For this SNP-DCC model, we propose a stepwise procedure to compute pairwise conditional correlations under bivariate marginal SNP distributions, overcoming the curse of dimensionality. The procedure is compared to the assumption of Dynamic Equicorrelation (DECO), which is a parsimonious model when correlations among the assets are not significantly different but requires joint estimation of the multivariate SNP model. The risk assessment of both methodologies is tested for a portfolio on cryptocurrencies by implementing backtesting techniques and for different risk measures: Value-at-Risk, Expected Shortfall and Median Shortfall. The results support our proposal showing that the SNP-DCC model has better performance for a smaller confidence level than the SNP-DECO model, although both models perform similarly for higher confidence levels.

Several empirical studies indicate that the lack of financing is one of the main barriers that affects the economic growth of small and medium enterprises (SMEs). The main objective of this investigation was to determine to what extent the economic sector; enterprise size; the characteristics inherent to the enterprise; legal status; the variables linked to the performance of the enterprise; and the attributes of the owner influence the access to bank financing of SMEs in Mexico. Using a discrete response probit regression model, the impact of enterprises characteristics on the probability of obtaining a bank loan was determined. The data collected is from the Enterprise Surveys of Mexico, carried out by the World Bank. The sample of 1,480 enterprises is representative by enterprise size, by economic sector, and by region. The research has a quantitative approach with a correlational scope and a non-experimental and transectional design. One of the main results highlights that the determinants with the greatest influence on access to bank financing are: age, the small size, foreign participation, and the manufacturing sector. These results are consistent with other empirical studies, as well as with the pecking order theory and the financial life cycle theory.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

Introduction and objectives: arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included 8 initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p. (Glu259Glyfs*77) variant in PKP2 gene. The genetic testing employed next-generation sequencing for the index cases, and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years, and a median follow-up of 39 [24-59] months. Worthy of note are the high incidence of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9% respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (4 patients 16.7%) and biventricular (4 patients 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in 8 families of our geographical area in Malaga (Andalusia, Spain), where we can establish a founder effect and describe the clinical and risk characteristics.

The Self-determination theory and The Vallerand's Hierarchical Model has been studied with different types of social factors that can bring different consequences. The purpose of this work was if responsibility and social climate could predict the social and prosocial behaviors and vio-lence. For this, 429 students (M = 11.46, SD = 1.92) participated in this study answering a ques-tionnaire with five variables: school climate, responsibility, motivation, satisfaction of psycholog-ical needs, prosocial and antisocial behaviors and violence. The main results saw that the most part of variables were correlated positive and directly except with antisocial behaviors and vio-lence. On the other hand, prediction model (X2 = 584.145 (98); RMSEA = 0.104 [90% CI = 0.096, 0.112]; TLI = 0.849; CFI = 0.894) showed that responsibility and school climate can predict psy-chological basic needs and these needs, can improve the autonomous motivation and finally have positive consequences improving prosocial behaviors and reducing antisocial behaviors and vio-lence. In conclusion, school climate and responsibility can improve positive consequences to the classroom, specifically, prosocial behaviors and reducing violence and antisocial behaviors.

Proprioception is an essential part of human movement and body awareness. It is the body's perception of its own spatial understanding, which helps us to accurately move our limbs and maintain balance. Purpose: This study aims to provide a comprehensive overview of the current state of knowledge and analyse bibliometric data about proprioception in gymnastics and acrobatics. Methodology: This article consisted of two phases: 1) a bibliometric review (based Web of Science) and 2) a systematic review (Web of Science, PubMed, and Scopus) of literature. "Gymnast*", "propriocep*", were utilized as search terms to find and choose published data. From a total of 164 studies, 30 were included for data extraction (n participants= 1432 of different age, sports, physical activities, and physical condition. Heterogeneity of studies design and assessment make it difficult to interpret the outcomes and the effect of proprioceptive interventions and comparations between samples. Proprioception is difficult to define in gymnastics considering the evidence references and the physiological considerations. Also, assessment tools used do not necessary evaluate proprioception globally considering the senses involved in gymnastics. Gymnastics training enhances joint awareness and force sense, improving proprioception and reducing injury risk. Proprioceptive exercises should be incorporated into gymnastics programs to enhance stability and precision in movements.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

The COVID-19 pandemic brought about a significant change in mobility habits within cities, with a significant decrease in the use of collective urban transport that has only been partially and unevenly reversed. To recover the previous rates of use, many cities are analyzing which characteristics of the urban transport network are hindering this recovery process in order to design actions to promote sustainable mobility. This article shows a study carried out in the city of Almería (Spain), where the operation variables of the municipal bus network have been analyzed (frequency, average vehicle occupancy, length of the lines, urban or suburban character, circularity, nodality or intermodality) to detect what aspects are more determinant on the number of users recovered. The results show that the lines that have recovered the most users in average are suburban lines, as well as the nodal lines that serve key centroids such as the university. Thus, the dependence of users on public transport would be the most important determinant in recovery, more than other variables representative of the service´s intrinsic quality. This result shows that, without compromising the necessary quality of the service, the restrictions on less sustainable transportation alternatives will be those that, to a greater extent, allow for the prompt recovery of the space lost by urban public transportation.

This study aimed to investigate the impact of the establishment of a nursing practice for micropigmentation of the nipple-areola complex at the San Cecilio University Hospital in Granada on women who have undergone unilateral or bilateral mastectomies. Micropigmentation is a procedure for decorating the human body by implanting pigments and dyes at the sub-epidermal level for a temporary duration of several months or years. Methodology: Retrospective descriptive study conducted in the micropigmentation clinic of HUSC-Granada (Spain). The sample consisted of 167 patients: 24 declined the treatment, 3 had second thoughts and cancelled the appointment, and 135 were accepted. Results: The mean age of the women was 53 years (range:35–75 years). Of the patients, 64.1% came from San Cecilio University Hospital in Granada, the rest from Virgen de las Nieves Hospital in Granada (19.6 %), hospitals in the province of Almería (7.2 %), and private hospitals and clinics (9.2 %). In the last two years, 36.4 % of the women had undergone surgery in the last 2 years. Complications arising from this technique are almost nonexistent. Conclusions: A very high number of women accepted the technique, with the highest proportion being those under 48 years of age. It is a technique that has not presented complications; therefore, it would be interesting to study how the application of the technique would affect women's self-esteem and quality of life

Climate change is one of the main issues that humanity is currently facing due to carbon dioxide emissions caused by the use of fossil fuels. Organic Rankine cycles may play an important role in reducing these emissions since they can be operated by using industrial waste heat of renewable energies. The present study presents a comprehensive bibliographic review of organic Rankine cycles. The study not only actualizes previous reviews that mainly focused on basic cycles operating on subcritical or supercritical conditions but also includes the analysis of novel cycles such as two-stage and hybrid cycles and the used fluids. Recuperative and regenerative cycles are more efficient than reheated and basic single-stage cycles. The use of two-stage cycles makes it possible to achieve higher thermal efficiencies and net power outputs of up to 20% and 44%, respectively, compared with those obtained with single-stage cycles. Theoretical studies show that hybrid systems, including Brayton and organic Rankine cycles, are the most efficient; however, they require very high temperatures to operate. Most organic Rankine cycle plants produce net power outputs from 1 kW up to several tens of kW, mainly using microturbines and plate heat exchangers.

Background: Recent advances allow the usage of Augmented Reality (AR) for many medical procedures. We perform different AR-assisted knee surgery techniques using optical surgical navigation with ArUco-type artificial marker sensors. Our study aimed to evaluate the system’s accuracy using an in vitro protocol. We hypothesised that the system’s accuracy was equal to or less than 1mm and 1° for distance and angular measurements, respectively. Methods: Our research was an in-vitro laboratory with a 316 L steel model. We evaluated absolute reliability according to the Hopkins criteria with seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. Results: The accuracy of the system to assess distances had a mean error of 1.203mm and an un-certainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observer almost perfect or perfect. Conclusions: The mean error for the distance’s determination has been statistically larger than 1mm (1.203mm) but with a trivial effect size. The mean error assessing angular values was sta-tistically minor than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

Iberian ham, a traditional Spanish meat product, is renowned for its unique nutritional and sensory attributes, garnering widespread appreciation both domestically and internationally [1]. It is one of the most outstanding Spanish gastronomic treasures, with very special nutritional and sensory properties that make it highly appreciated throughout the world [2]. Recent trends indicate a notable surge in its consumption, a pattern projected to persist [3]. For an enhanced online shopping experience, understanding the specific characteristics and requirements of various consumer segments is crucial. This study aims to scrutinize national Iberian ham consumption patterns and, through survey methodologies, discern the preferences and needs of online consumers purchasing whole Iberian hams. The subsequent cluster analysis will empower suppliers with insights to pinpoint business prospects and craft segment-specific online marketing strategies.

In many regions where drinking water supply is intermittent and unreliable, households adapt by storing water in cisterns or rooftop tanks. Both intermittent supply and stored water can be vulnerable to contamination by microorganisms with deleterious health effects. The Guadalajara Metropolitan Area is a rapidly growing urban center with over five million residents where household storage is nearly ubiquitous. This pilot study was conducted in July 2018 to examine the microbiological quality of drinking water in Guadalajara. Samples were tested for free available chlorine residual, total coliform bacteria, and E. coli. A survey on access to water and public perspectives was also conducted. Water exiting rooftop tanks exceeded regulatory limits for total coliform levels in half of the homes studied. Piped water arriving at two homes had total coliform levels that far exceeded regulatory limits. No E. coli were detected in any of the samples. Only 35% of homes had a chlorine residual between the recommended 0.2 and 1.5 mg/L. Many homes reported unpleasant odors and colors. Only 7% of residents drank the piped water. Future studies are needed, especially during April and May when many homes reported a higher disruption to water service.

Unidentified abortion, of which leptospirosis, brucellosis and ovine enzootic abortion are important factors, is the main cause of disease spread between animals and humans in all agricultural systems in most developing countries. Although there are well-defined risk factors for these diseases, these characteristics do not represent the prevalence of the disease in different regions. This study predicts the unidentified abortion burden from multi-microorganisms in ewes based on artificial neural networks approach and GLM. Methods: A two-stage cluster survey design was conducted to estimate the seroprevalence of abortifacient microorganisms, and to identify putative factors of infectious abortion. Results: Overall seroprevalence of Brucella was 70.7%, while Leptospira spp. was 55.2%, C. abortus 21.9% and B. ovis 7.4%. Serological detection with the 4 abortion-causing microorganisms was determined only in 0.87% of sheep sampled. The best GLM is integrated by serological detection of serovar Hardjo and Brucella ovis in animals of the slopes with elevation between 2600 to 2800 meters above sea level from municipality of Xalatlaco, as well water supply, sheep pen built with materials of metal grids and untreated wood, with dirt and concrete floors, and bed of straw that remained independently associated with infectious abortion in ewes. Approximately 80% of those respondents did not wear gloves or masks to prevent the transmission of the abortifacient zoonotic microorganisms. Conclusions: Sensitizing stakeholders on good agricultural practices could improve public health surveillance. Further studies on the effect of animal-human transmission in such a setting are worthwhile to further support the One Health initiative.

Since its adoption in September 2015, the 2030 Agenda has laid the foundations for a model of shared prosperity for a sustainable world. We are going through a complicated pandemic that shows profound inequalities affecting our economies, health, and quality of life. For this reason, our aim in this work is to make known the state of the art of scientific research related to inequality, poverty, and climate change and to propose lines of improvement that can contribute to achieving 3 of the 17 SDGs (End poverty-SDG 1-, Reduce inequality-SDG 10-, and Climate action -SDG 13-), proposed in the 2030 Agenda. To do so, we have used a systematic literature review methodology. The results show that poverty, inequality and climate change is a subject that has been little studied and articulated by researchers, with significant differences between the different areas studied. Topics related to sustainability and economics are those with the highest number of publications (51.7%). The rest are distributed among the 12 existing departments. Another relevant finding is that the effects of climate change are more pressing for more vulnerable populations, including impoverished women from rural areas and children from underdeveloped countries. This is a gender and social inequality that has been little addressed in climate change studies. Food security and energy poverty is another under-exploited aspect in this area. According to the results obtained in this work, we consider that the circular economy could improve these indicators, constituting a line of future research. Thus, one of its main objectives is to eliminate negative externalities, specifically existing social inequalities within the current linear economy model.

In this paper, we introduce a model for the automatic generation of literary sentences in French. It is based on algorithms that we have previously used to generate sentences in Spanish and Portuguese, and on a new corpus consisting of literary texts in French that we have constructed, called [FR]. Our automatic text generation algorithm combines language models, shallow parsing and deep learning, artificial neural networks. We have also proposed and implemented a manual evaluation protocol to assess the quality of the artificial sentences generated by our algorithm, by testing if they fulfill four simple criteria. We have obtained encouraging results from the evaluators for most of the desired features of our artificially generated sentences.

In Mexico, it is estimated that due to the economic system the overexploitation of natural resources, environmental impacts and health have been generated, with high rates of overweight and obesity. This review analyzes the impacts on food safety, environmental health, and the economy in Mexico before and during the COVID-19 contingency. Derived from the analysis, among the lessons learned we can include: the health contingency due to COVID-19 had negative repercussions on food security, environmental health and the economy, which require the promotion of public policies (health, environment and economy) and migrate to a health prevention system and an agroecological model, which includes multidisciplinary and intersectoral interventions (government, academia, researchers, civil society organizations, business groups and citizens themselves) to reform and enforce the right to enjoy adequate food and a healthy environment. The contingency due to COVID19 has shown us that this must go from an ideology to being a reality and the lessons learned will have to focus on promoting an innovative and ethical culture of generating an economy, with a gender balance, resilience to climate change, management transparent technology and a priority in health and this will lead to progress in the food security of the population.

The purpose of this paper is to provide a structural review of the progress made on detection and localization of leaks in pipelines by using approaches based on the Kalman filter. This is, to the best of our knowledge, the first review on the t opic. In particular, it is the first to try to draw the attention of the leak detection community to the important contributions that use the Kalman filter as the core of a computational pipeline monitoring system. Without being exhaustive, we try to gather the results from different research groups and present them in a unified fashion. For this reason, we propose a classification of the current approaches based on the Kalman filter. For each of the existing approaches within this classification, the basic concepts, fundamental results, and relations with the other approaches are discussed in detail. The review starts from a short summary of basic concepts about state observers. Then, a brief history of the use of the Kalman filter for diagnosing leaks is described by mentioning the most outstanding approaches. At last, we briefly discuss some emerging research problems, such as the leak detection in pipelines transporting heavy oils, and we discuss the main challenges and some open problems.

Emotional intelligence can contribute to quality of life and as a health predictor. The aim of this study is to analyze emotional intelligence, quality of life and the correlation factors associated in patients undergoing chronic hemodialysis. A quantitative, observational, cross-sectional design was performed, and one hundred and thirty-eight multi-centers hemodialysis patients were recruited. A battery of questionnaires, including Trait Meta-Mood Scale (TMMS-24), Kidney Disease Quality of Life-Short Form (KDQOL-SF), and an ad-hoc sociodemographic questionnaire, were answered. Sex differences existed when assessing the three dimensions of emotional intelligence: ranked by order, the highest scores in males were in clarity, repair, and attention. However, in females were in repair, clarity, and attention. Males had higher scores than females in emotional role (p=0.045). Younger participants had better scores in all physical functions (p=0.001) and vitality (p=0.038) than older. Moreover, those who had a higher level of education presented better physical function (p=0.027) and higher scores in emotional wellbeing (p=0.036). Finally, in females, emotional attention (p=0.046) and repair (p<0.001) were strongly associated with general health perception. The assessment of emotional intelligence considering sex differences in patients undergoing chronic hemodialysis can be an indicator of quality of life including the use in health interventions.

Nowadays, service sector workers face an increasingly demanding environment in terms of intrapreneurial behaviour due to the key role it plays in the survival of firms and the elimination of threats in the organisational environment. This paper investigates the antecedents of intrapreneurial behaviour in the service sector in southern Spain, analysing the interrelationships between authentic leadership, practised creativity, autonomy and meaningful work. This study employs a quantitative approach through the distribution of a questionnaire. A total of 333 employees in this sector responded to the research questionnaire. The results show that both meaningful work and creativity are direct antecedents of intrapreneurial behaviour. In contrast to these variables, authentic leadership was found to have significant negative effects on intrapreneurial behaviour, although it is essential for promoting employee creativity and autonomy and for fostering the perception of meaningful work. Finally, no significant relationship was found between autonomy and intrapreneurial behaviour. This research provides empirical results that can help broaden the understanding of intrapreneurial behaviour by highlighting the importance of balanced authentic leadership and offering guidance to organisations in designing a work climate that enhances organisational effectiveness.

Nowadays, the combination of fingerprinting methodology with friendly environmental and economical analytical instrumentation are becoming increasingly relevant in the food sector. In this study, a highly versatile portable analyser based on Spatially Offset Raman Spectroscopy (SORS) to obtain the edible vegetable oils (sunflower and olive oils) fingerprints was used to evaluate the capability of such fingerprints, obtained quickly, reliable and without any sample treatment, to discriminate/classify the analysed samples. After data treatment, not only HCA and PCA as unsupervised pattern recognition techniques but also SVM, kNN and SIMCA as supervised pattern recognition techniques, showed that the main effect over the discrimination/classification was associated to those regions of RAMAN fingerprint related to the free fatty acids content, especially oleic and linoleic acid. These facts allowed the discrimination attending to the original raw material used in the oil's elaboration. In all the model established, reliable qualimetric parameters were obtained.

In this paper we deal with the resolution of a fuzzy multiobjective programming problem using the level sets optimization. We compare it to other optimization strategies studied until now and we propose an algorithm to identify possible Pareto efficient optimal solutions.

This article has two objectives. Firstly, we will use the vector variational-like inequalities problems to achieve local approximate (weakly) efficient solutions of Vector Optimization Problem within the novel field of the Hadamard manifolds. Previously, we will introduce the concepts of generalized approximate geodesic convex functions and illustrate them with examples. We will see the minimum requirements under which critical points, solutions of Stampacchia and Minty weak variational-like inequalities and local approximate weakly efficient solutions can be identified, extending previous results from the literature for linear Euclidean spaces. Secondly, we will show an economical application, using again solutions of the variational problems to identify with Stackelberg equilibrium points on Hadamard manifolds and under geodesic convexity assumptions.

Stable isotope concentrations in the soil, rain and ground water have been used to trace the water extraction zones of plants in different environments. The need to identify the plant water use by plants in afforestation programs to control desertification increases the importance of sap water partitioning of plants in sand dune areas. However, the introduction of new plant covers exerts pressure on the water resources and can affect the local soil water conditions. In this study, we analyzed the isotope concentrations in rain, soil, sap, and ground water after the summer of 2010. Two experimental plots established in the Hailiutu catchment (Shaanxi province, northwest China) were selected to gather the water samples between September and October 2010. One plot is dominated by Salix bushes (Salix psammophila C. Wang \& Chang Y. Yang) and the other by the tree species Willow (Salix matsudana Koidz.). The total precipitation at the experimental site was 401 mm/yr during 2010, while 88.7 mm was collected in total for the period September to October. Willow trees transpired 12.82 kg/d being almost three times larger than Salix shrubs (4.57 kg/d). Despite the transpiration rates of both plant species and the few rain events in the region, the soil water beneath the plant covers is not depleted. Stable isotope signature of soil water beneath both covers shows the fractionation front in Salix at 20 cm depth and at Willow at 40 cm depth. However, soil water signature is closer to the groundwater than the collected rain water.

Cogging torque is a pulsating, parasitic and undesired torque ripple intrinsic of the design of a permanent magnet synchronous generator (PMSG), which should be minimized due to its adverse effects: vibration and noise. In addition, as aerodynamic power is low during start-up at low wind speeds in small wind energy systems, the cogging torque must be as low as possible to achieve a low cut-in speed. A novel mitigation technique using compound pre-slotting, based on a combination of magnetic and non-magnetic materials, is investigated. The finite element technique is used to calculate the cogging torque of a real PMSG design for a small wind turbine, with and without using compound pre-slotting. The results show that cogging torque can be reduced by a factor of 48% with this technique, while avoiding the main drawback of the conventional pre-slotting technique: the reduction of induced voltage due to leakage flux between stator teeth. Furthermore, through a combination of pre-slotting and other cogging torque optimization techniques, 84%, cogging torque can be eliminated for a given design.

Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas is a characteristic feature of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.

Irregular female migration to Europe is a growing phenomenon, as more and more women are fleeing their countries of origin due to gender inequality and violence. During the migration process, women experience physical, psychological and social problems that affect their sex lives. The aim of our study is to describe and understand how irregular migrant wom-en living in humanitarian reception centers experience their sexuality at different stages of the migration process. This qualitative phenomenological study collected data through a sixteen in-depth interviews with irregular migrant women between January and February 2023. Data anal-ysis was carried out using ATLAS-ti 23.0 software, from which three themes were extracted: 1) The sexual reality of sub-Saharan women, 2) In search of a better life: take the risk or surrender, and 3) The migrant sexual revolution. The sexual reality of sub-Saharan women is subject to a complex normative order. The migratory process has severe consequences on migrant women's sex life. The sexual needs of irregular migrant women admitted to humanitarian reception cen-ters undergo a process of change that must be understood by healthcare providers in order to make improvements to care provision.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

Natural deep eutectic solvents (NADES) have been shown as selective and environmentally friendly solvents for the extraction of bioactive compounds. However, studies on the solubility of low molecular weight carbohydrates (LMWC) in NADES are scarce. In this work, new solubility data of LMWC in NADES are provided and a new approach based on the use of these solvents for the efficient fractionation of bioactive carbohydrates was explored for the first time. Several mono- and disaccharides and three NADES based on choline chloride (ChCl) and different donors [2-ethylene glycol (EtG), glycerol (Gly) and ethanedioic acid dihydrate (Eth)] were considered. While degradation of carbohydrates, mainly ketoses, was detected with ChCl:Eth due to its acidic nature, ChCl:EtG and ChCl:Gly were found to be useful alternatives for selectively separating bioactive ketoses and their corresponding aldoses (e.g. lactulose/lactose and tagatose/galactose) present in equimolar binary mixtures. In addition, the usefulness of ChCl:EtG for the selective enrichment of lactulose to be used as food ingredient or nutraceutical was proven (from a 25% in the reaction mixture to a 56% in the purified sample). NADES could be used for the selective fractionation of value-added carbohydrates from interfering sugars for several applications including food science, engineering or pharmaceuticals.

The need to carry different items, which become an extra load, is a characteristic of trail running. The aim of this study is to determine physiological-metabolic changes produced by running with extra load. Four male well-trained trail runners completed three treadmill maximal metabolic tests carrying different loads (0% (L0), 5% (L5), and 10% (L10) of their body mass) in a weighted vest. Gasses exchange was monitored to assess ventilatory thresholds 1 (VT1), and 2 (VT2), zone of maximal fat oxidation, and peak oxygen consumption (VO2peak). Heart rate (HR), power and velocity (V) were tracked for comparing their behavior. A repeated measures ANOVA showed significant differences in V (p&lt;.001; ηp2= 0.910) as a limitation for reaching peak velocity (Vpeak) with L10 respect to L0 (p=0.001), and L5 (p=0.011). Power expression showed differences (p=0.068; ηp2= 0.592). It tended to be greater with L10 than L0 (p=0.057), despite achieving lower V. VT2 tended to occur at different %VO2peak (p=0.069; ηp2= 0.591). L5 VT2 was reached at higher %VO2peak than L0 (p=0.062), and L10 (p=0.071). ANOVA also showed a tendency to signification for V at this point (p= 0.098; ηp2= 0.538). In conclusion, L10 seems to limit Vpeak while L5 may delay VT2 expression.

Laser Cladding is one of the leading processes within Additive Manufacturing technologies, a fact which has concentrated an important amount of effort on its development. In regard to the latter, the current study aims to summarize the influence of the most relevant process parameters in the laser cladding processing of single and compound volumes (solid forms) made from AISI 316L stainless steel powders and using a coaxial nozzle for deposition. Process speed, applied laser power and powder flow are considered to be the main variables affecting laser cladding in single clads, meanwhile overlap percentage and overlapping strategy become also relevant when dealing with multiple clads. By means of setting appropriate values of each process parameter, the main goal of this paper is to develop a processing window in which a good metallurgical bond between the delivered powder and substrate is obtained, trying simultaneously to maintain processing times in their lowest value possible. Conventional metallography techniques were performed on the cross sections of the laser tracks to measure the effective dimensions of clads for dilution analysis, height and width for the values of overlap between contiguous clads and layers, and also to analyze them for physical defects such as porosity and cracks. The resulting solid piece was 8 mm high at 800 mm/min.

The principal aim of a spectral observer is twofold: the reconstruction of a signal of time via state estimation and the decomposition of such a signal into the frequencies that make it up. A spectral observer can be catalogued as an online algorithm for time-frequency analysis because is a method that can compute on the fly the Fourier transform (FT) of a signal, without having the entire signal available from the start. In this regard, this paper presents a novel spectral observer with an adjustable constant gain for reconstructing a given signal by means of the recursive identification of the coefficients of a Fourier series. The reconstruction or estimation of a signal in the context of this work means to find the coefficients of a linear combination of sines a cosines that fits a signal such that it can be reproduced. The design procedure of the spectral observer is presented along with the following applications: (1) the reconstruction of a simple periodical signal, (2) the approximation of both a square and a triangular signal, (3) the edge detection in signals by using the Fourier coefficients, (4) the fitting of the historical Bitcoin market data from 2014-12-01 to 2018-01-08 and (5) the estimation of a input force acting upon a Duffing oscillator. To round out this paper, we present a detailed discussion about the results of the applications as well as a comparative analysis of the proposed spectral observer vis-à-vis the Short Time Fourier Transform (STFT), which is a well-known method for time-frequency analysis.

pump as turbine (PAT); computational fluid dynamics; variable rotational nominal speed; OpenFoam.

In this paper we show how to efficiently implement parallel discrete simulations on Multi-Core and GPU architectures through a real example of application: a cellular automata model of laser dynamics. We describe the techniques employed to build and optimize the implementations using OpenMP and CUDA frameworks. We have evaluated the performance on two different hardware platforms that represent different target market segments: high-end platforms for scientific computing, using an Intel Xeon Platinum 8259CL server with48cores and also an NVIDIA Tesla6V100 GPU, both running on Amazon Web Server (AWS) Cloud, and on a consumer-oriented platform, using an Intel Core i9 9900k CPU and an NVIDIA GeForce GTX 1050 TI GPU. Performance results are compared and analysed in detail. We show that excellent performance and scalability can be obtained in both platforms, and we extract some important issues that imply a performance degradation for them. We also found that current Multi-Core CPUs with large core numbers can bring a performance very near to that of GPUs, even similar in some cases.

The state of Oaxaca, Mexico obtained the “Pluma” designation of origin in 2022 and has stood out for the production of specialty coffee. Within its process, roasting is one of the stages that contributes to the physical, chemical and sensory quality of the coffee bean. Therefore, the microstructure and elemental chemical composition of special medium-roasted Coffea arabica L beans from six locations with this denomination were analyzed using Scanning Electron Microscopy. The average values of roughness Rz (25.93±2.69-34.18±1.15 and 13.85±1.66-21.85±6.63) and Ra (5.20±0.47- 8.27±0.82 and 6.55±0.94-11.53±1.65) were obtained at 400 and 2000x, respectively. The roasted Coffea arabica L. beans from MAP and HUA are the ones with the greatest roughness and both are located at a lower altitude compared to the rest. PLU and PTO roasted beans showed the highest physical and structural integrity. In all grains, 6C (66.48-81.14%), 8O (18.86-28.69%) and only 20Ca (4.5%) were found on the outside. This research constitutes a standard of authenticity and microstructural and elemental quality of Coffea arabica L. beans with designation of origin "Pluma".

Abstract: The present work evaluates the feasibility of using volcanic fly ash (VFA), generated by the eruption of the Tajogaite volcano on the island of La Palma (Spain) in 2021, as a precursor in the preparation of cementitious materials with different Portland cement (PC) replacement levels (0%, 30%, 70% and 100%), in the absence (Blended Cement, BC) and presence of an alkaline ac-tivator (Hybrid Alkaline Cement, HAC, and Alkaline Cements, AC). Hydration kinetics (isother-mal conduction calorimetry), paste mechanical strengths and reaction products were character-ised by XRD, FTIR, TG/DTG and BSEM/EDX. The results obtained indicate that the strengths de-veloped by the hybrid alkaline cements (HAC) are higher than those of the blended cements (BC), especially at the age of 2 days, where 25 MPa was obtained with the replacement of 70% PC by VFA. Alkaline cements (AC, 100% VFA) prepared with 8M NaOH solution as activator reached 40 MPa after 2 days. It was observed that in all the binders, depending on the initial composition of the binder mixture and the percentage of replacement and/or activator, VFA reacts to form cementitious gels, C-A-S-H and N-A-S-H type, which supports its use as a mineral addition to blended cement or as a precursor in the preparation of alkaline and hybrid alkaline cements.

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several of their applications require protein engineering, which in turn would greatly benefit from having a reliable structural model of the nanobody of interest. However, as with antibodies, structural modeling of nanobodies is still a challenge. With the rise of artificial intelligence (AI), several methods have been developed in recent years that attempt to solve the problem of protein modeling. In this study, we have compared the performance in nanobody modeling of several state-of-the-art AI-based programs, either designed for general protein modeling, such as AlphaFold2, OmegaFold, ESMFold and Yang-Server, or specifically designed for antibody modeling, such as IgFold, and Nanonet. While all these programs performed rather well in constructing the nanobody framework and CDRs 1 and 2, modeling of CDR3 sill represents a big challenge. Interestingly, tailoring an AI method for antibody modeling does not necessarily translate into better results for nanobodies.

Using first-principles molecular dynamics (FPMD), we performed numerical simulations at 300 K to explore the interaction of a 2D MoS2 surface and a platinum atom, calculating the optical properties of the resulting material. The pristine MoS2 is a semiconductor with a gap of around 1.8 eV. The Pt atom is chemisorbed by the surface with an adsorption energy of −1.718 eV. With the adsorption of the Pt atom, the material remains a semiconductor, and its energy band gap reduces to 1.04 eV. But changes in the material's energy band structure imply substantial changes in its optical properties. The energy band structure of the 2D MoS2 with a sulfur vacancy VS shows that the material becomes a conductor, and there are significant changes in its optical properties. We also found that the Pt atom chemisorbs in a sulfur vacancy of the material, with an adsorption energy of −4.1164 eV. After the adsorption of Pt atoms in the sulfur vacancy, the material becomes a semiconductor with a band gap of 1.06 eV, and the changes in the optical absorption and reflectivity are significant.

An easier method for the calibration of differential drive robots is presented. Most of the calibration is done on-board and it is not necessary to expend too much time taking note of the robot's position. The calibration method does not need a big free space to perform the tests. The bigger space is just in a straight line, which is easy to find. Results with the proposed method are compared with those from UMB as a reference, and they show very little deviation while the proposed calibration is much simpler.

There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model to study renal disease. We developed a protocol to measure GFR in conscious swine with the plasma clearance of iohexol. We used two groups: testing and validation, of 8 animals each. Ten milliliters of iohexol (6.47 g) were injected by the marginal auricular vein and blood samples (3 ml) were collected from the orbital sinus at different points after injection. GFR was determined considering two models: two-compartments (CL2: all samples) and one-compartment (CL1: the last six samples). In the testing group, CL1 overestimated CL2 by ~30%: CL2=245±93 and CL1=308±123 ml/mn. This error was corrected by a first order polynomial quadratic equation to CL1, which was considered the simplified method: SM=-47.909+(1.176xCL1)–(0.00063968xCL1²). SM showed narrow limits of agreement with CL2, and a concordance correlation of 0.97 and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples avoiding urine collection. Finally, it portends a significant improvement in animal-welfare conditions and handling necessities in experimental trials.

(1) Background: the use of force by Public and Private Security Forces is currently an issue of great relevance because of the potential injuries that any excessive use of force by either the active or passive subjects or a deficit in the real mastery of the appropriate Physical Intervention Techniques (PIT) may cause. For this reason, certain traditionally used Physical Intervention Techniques have been questioned by scientific research studies and punished by justice. On the other hand, certain media have dealt with this matter in a biased and unfair manner by broadcasting videos where the use of force by police officer is displayed out of context. As a consequence, this problem has been brought under the spotlight, causing general uneasiness of the communities and rapidly spreading over social networks while favoring all sorts of parallel judgments. (2) Research method: A suit equipped with 19 Inertial Measurement Units (IMU) and a Biomechanics of Bodies software application for the Marras’ analysis of the data collected on trajectory, trunk twisting velocity, its sagittal angle, load, nature and severity of the injuries associated to the different intervention techniques that have been examined. (3) Results: according to the data registered, the implementation of Operational Tactical Procedures (OTP) reduces the probability of injuries and leads to a more satisfactory outcome. (4) Conclusions: the implementation of Operational Tactical Procedures, to-gether with the awareness on the risks associated to the excessive use of force by Public and Private Security Forces and Bodies, could reduce the risk of injuries suffered by both officers and citizens.

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.

Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Results: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. Conclusions: The cytotoxicity of ethanol can explain the epidemiological association between mouthwash use and oral cancer. Recent findings indicate that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, we will force the stem cells of the oral cavity to divide more often than usual and our risk of developing oral cancer will probably increase.Clinical significance: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol containing mouthwashes when advising their patients.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

The objective of this study is to identify how demographic characteristics (gender, age, seniority at work, and educational level) are related to the entrepreneurial behavior of companies. To comply with the above, a quantitative, transversal, and non-experimental research was carried out, which consisted in applying an instrument to 262 managers of Small and Medium Enterprises (SMEs) in a northern city in Mexico. The collected information was analyzed in the software SPSS, version 26 with statistical testing by the Mann-Whitney and Kruskal-Wallis. The main findings dermore highly educated managers are those who contribute to this behavior of the studied companies, while gender and seniority at work are not differentiating elements in relation to the above. This research generates different possibilities of studies to be carried out in large companies from other sectors, as well as to include behavioral characteristics as study variables.

In this study, a novel binary nanocomposite system based on TiO₂-SiO₂ was functionalized with trimethylolpropane triacrylate (TMPTA) and characterized by XPS and XRD. Results revealed that TiO₂-SiO₂ nanoparticles were covalently functionalized. Functionalized nanoparticles at low concentrations (0.1 wt% and 0.5 wt%) were dispersed in acrylic acid acting as a polymer matrix. Nanocomposite coatings analysis demonstrate to achieve superhydrophilic properties as well as very good optical characteristics. Water contact angle characterization showed the functionalization effect by achieving a superhydrophilic behavior with a contact angle less than 5°. UV-Vis measurements demonstrated high optical transmittance above 95% for the coatings. Based on the obtained results a mechanism describing the chemical interactions of the constituents responsible for the synergy in the nanocomposite as well as the morphological play role in the behavior are presented.

Some evidence suggests that personality types are a useful construct to understand stress and coping. However, further research is needed, especially on academic stress. Our aim was to explore how personality types and gender relate to coping strategies for academic stress and perceived coping efficacy. A total of 810 university psychology students completed the NEO-FFI Inventory and the Coping Strategies Inventory. Post-hoc tests for MANOVA and ANOVA were performed, where personality types and gender were treated as predictors and use of coping strategies and perceived coping efficacy as criteria. Finally, a one-way ANOVA followed by post hoc comparisons was performed to analyse the associations between personality types and perceived coping efficacy. Those with personality types combining low neuroticism with high conscientiousness chose the most adaptive coping strategies and showed the highest levels of perceived coping efficacy, while those whose personality types combined high neuroticism with low conscientiousness opted for maladaptive coping strategies and presented the lowest level of perceived coping efficacy. As for gender, women chose emotional expression more frequently. The personality type classification provided useful information on individual differences in coping with academic stress, which can help guide specific strategies to manage it.

Starch is a biopolymer with wide potential for the generation of new biodegradable packages due to its high availability and low price. However, due to its weak functional properties, it is necessary to limit the interaction of some hydroxyl, and to evaluate blends with other polymers to improve their performance. Glycerol plasticized acetylated corn starch films were developed by the casting method, and the impact of incorporating chitosan (TPS:CH) at various proportions (75:25, 50:50, and 25:75 v/v) was studied. The effect of the chitosan ratios on the films' physical, mechanical, water vapor barrier, and thermal properties was evaluated. Chitosan protonated amino groups promote the formation of intermolecular bonds, improving the tensile strength, the thermal stability, the water adsorption capacity, and the gas barrier of starch films. Where the film composed of TPS25-CH75 was the one that presented the best barrier to water vapor. These composite films are a good option for development of biodegradable packaging.

A pathway frequently altered in cancer is glutaminolysis where glutaminase (GA) catalyses the main step: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 may function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We have reviewed the literature to highlight the critical roles of GLS and GLS2 to restrain ROS and regulate both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes and also by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy to dual activate ferroptosis and inhibit cancer cell growth in a ROS-mediated mechanism.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

(1) Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians; (2) Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", and "drug-related problems” and “negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)”; (3) Results: A total of 59 references were recovered and after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications; (4) Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medication affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds from natural origin is increasing. Several countries have initiatives in place to construct and maintain compound databases that are representative of their diversity. Examples are Brazil, France, Panama and recently Vietnam. Herein, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. It is reported the profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints. BIOFACQUIM is freely available.

In commercial terms, Virgin Olive Oil (VOO) is considered an exceptional food of excellent sensory and nutritional quality, for its taste and genuine odour and, as well as for its bioactive compounds, of a great interest for the health. This quality can be affected by oxidative degradation, chemical as well as enzymatic (activity of oxidative endogenous enzymes from polyphenol oxidase and peroxidase olive fruit type), of essential components during extraction and conservation of VOO. In the bibliography, the reduction of oxygen during the malaxation process and the storage of the oil has been studied in different ways. However, research about the reduction of oxygen in the crushing of olive fruit, malaxation of the paste and/or both at the same time in “real extraction condition” is scarce. The reduction of oxygen has been compared to control conditions (concentration of atmospheric oxygen of 21%). Batches of 200 kg of olive fruit, Picual cultivar, were used and the following treatments were applied: Control (21% O2 Mill - 21% O2 Mixer), “IM-NM”: Inerted milling -Normal malaxation (6.5% O2 Mill-21% O2 Mixer), “NM-IM”: Normal milling-Inerted malaxation (21% O2 Mill-4 % O2 Mixer) and “IM-IM”: Inerted milling-Inerted malaxation (5.5% O2 Mill-10% O2 Mixer). The parameters of commercial quality covered by Regulation: free acidity, peroxide value and absorbency in ultra-violet (k 232 and k270) did not suffer any change in relationship to the control, the oils belong to the comercial category of “Extra virgin olive oil”. The phenolic compounds are involved in the distinctive bitter and purgent taste and, their healthy properties and their oxidative stability, increased with the downsizing amounts of oxygen regarding control and the IM-NM, NM-IM and IM-IM treatments with an average of 4, 10 and 20 %, respectively. By contrast, total volatile compounds decrease between a 10-20 % in all oxygen reduction treatments. The volatile compounds arising from lipoxygenase pathway, which are responsable for the green and fruity notes of VOO, also decreased their concentration with the treatments, between 15-20%. The results show how the reduction of oxygen in the milling and malaxation stages of olive fruit can modulate the content of phenols, volatile compounds, carotenoids and chlorophyll pigments of the VOO avoiding the degradation of compound with sensorial and nutritional interest.

A The guinea pig value chain in Jauja, Peru, has been developed through the application of productive projects, institutional strengthening and implementation of the principles of responsible investment in agriculture and food systems (CFS-RAI). The actors in this chain have been showing economic improvements, representativeness and participation, characteristics that make them the key human capital for development. To improve the performance of the actors in the sustainable rural development of the territory of Jauja, Peru, the research carried out an evaluation of the competencies and capacities for project management in 46 actors linked to the business programme on the CFS-RAI Principles, representing 1,094 people in the guinea pig value chain in Jauja, using the Working With People (WWP) model and empirical instruments based on the Octagon method, International Project Management Association (IPMA) competencies, performance evaluation carried out by experts, attitudinal evaluation and the Business Model Canvas. The results have helped to structure the actors of the value chain, who show an intermediate mastery of project management competencies (2.73/5), institutional capacities in development (2.89/7) and a growing organizational management performance (26.2/100). In addition, trust and proactivity have been generated among the actors in the chain, with an interest in continuing with the implementation of the CFS-RAI Principles in order to achieve sustainability in their productive projects with commercial innovation. The results have allowed us to generate the design of an innovative programme for the development of competencies, which balances the three dimensions of IPMA competencies (perspective, person and practice) in connection with the CFS-RAI Principles. Both processes complement the strengthening of human capital in agrifood value chains through sustainable project management and contributing to sustainable development in the region.

INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.

Premenstrual syndrome is characterized by pain and symptoms affecting the women´s quality of life. We aimed to evaluate the safety and effectiveness of an oral fixed dose combination containing naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg tablet (Analgen Fem®) during the routine clinical practice. A prospective, open-label, multicenter, observational post-marketing study was conducted from December 2017 to December 2019 including 270 women older than 18 years. Primary endpoint was the proportion of adverse events, meanwhile the pain intensity, premenstrual syndrome symptoms, and patient proportion with a pain score reduction by at least 50% were secondary endpoints. The mean age of population was 28.9 ± 8.8 years. Among the 270 women, 8 (3%) experienced 10 adverse events. These were headache (5/8), gastritis (2/8) dyspepsia (1/8), diarrhea (1/8) and nausea (1/8). The investigator discontinued the study medication in 3/8 patients because of adverse events. The median of differences between the pain intensity at baseline and at last observation (-4.5, 95%CI; -5, -4) demonstrated that naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg fixed dose combination reduced pain intensity (p<0.001). In addition, the proportion of patients with pain reduction by at least 50% at the end of the treatment was 70.7%. The study demonstrated that this drug represents a safe and tolerated treatment, reducing pain intensity and premenstrual symptoms.

The analytical method for the calculation of the properties of a bolted connection established by the structural Eurocodes proposes the T-stub as a component for the characterization of the tension and compression zones in moment joints. In this article, a review of the state of the art on the T-stub component is developed, where the works developed since it was initially defined, and from the perspectives of formulation, experimentation and numerical simulation are summarized and discussed. Additionally, possible future lines of work are proposed.

Glycosylation, the most significant modification of proteins, plays an essential role in cellular processes. Congenital disorders of glycosylation (CDG) are multisystemic diseases resulting from mutations affecting glycosylation steps. Diagnosis of CDG relies on biochemical assays, such as isoelectric focusing. Despite its significance, CDG cases remain unreported in Cuba due to the lack of implemented diagnostic methods. This study aimed to evaluate transferrin glycoforms for diagnosing congenital N-glycosylation defects. We conducted a cross-sectional descriptive study using serum samples from 17 patients stored at the National Center for Medical Genetics of Cuba for suspected CDG. Results revealed abnormal glycosylation patterns in 7 patients, suggesting congenital N-glycosylation defects. We conclude that the implementation of transferrin glycoform analysis could pioneer a preliminary diagnosis of CDG in Cuba.

Smart cities will have a strong impact on the future of renewable energies as terms like sustainability and energy saving will be more common. In this sense, both of wind and hydrokinetic compact-size turbines, can play an important role in urban communities by providing energy to nearby consumption points in an environmentally suitable way. This work presents the experimental evaluation for a vertical-axis turbine Darrieus type, operating in an open-field wind tunnel and a confined water channel. Power and characteristic curves have been obtained for all test conditions, also the effect of turbine blockage has been evaluated under blockage values ranging from 6.8% to 35%. The peak power coefficient for the confined flow condition reached a value of 0.31 which is 1.5 times higher than the peak one for the experimental open field condition at the same Reynolds number and a blockage of 20%. Finally, two blockage correction equations have been applied to the water channel tests, which gave values quite similar to the results obtained from the wind tunnel.

The purpose of this research has been to analyze the organizational structures of the different federations and entities representing the modalities of trail-running, skyrunning and mountain running and how they have settled in the current sports landscape. The main task of these entities is to act as hosts of the legally established modalities, both internationally and nationally, applying their respective regulations and statutes unilaterally. Through an in-depth review of the different regulations, statutes and current articles of all the organizations that represent the different disciplines, we can observe how a sport modality that seems to be the same is nevertheless distant in its execution (regulations, championships, classifications, systems of points, ...) and that has led to the international level being established in different sport modalities (trail-running and skyrunning) and at the level of the Spanish territory, it has led to an administrative dispute to know who has the powers to approve the sports competitions.

On 11 March 2020, the COVID-19 emergency was declared and a large number of patients were admitted to the ICUs. Consequently, ICUs had to recruit nurses from other units as well as Nursing students without working experience in critical patients care. Since Critical nursing competence is crucial to avoid medical errors, the aim of this study was, to describe the level of safety and nursing competence in critical patient care of recruited nurses and students, during the COVID-19 pandemic in ICUs. A cross-sectional descriptive study of 66 participants using the validated competency assessment questionnaire for nurses in hospital care (COM-VA©) was performed. Our results showed that the level of safety perceived in critical patients care by the students on placement in ICUs and mentors scored higher than the rest of the participants. Interestingly, whereas the participant’s COM-VA© score indicated a level of competence good enough to work autonomously, the supervisor/mentor’s COM-VA© evaluation showed that only the group of students on placement obtained this level of competency. Altogether, we found that students on placement in ICU possesses a higher level of safety and COM-VA© scores than the rest of participants probably due to the close support of the mentor.

The anthropogenic deterioration of aquatic ecosystems affects water resources due to agricultural malpractices, pollution from domestic septic tanks, recreational activities, and poor watershed management, among others. This study examines the management of Las Curias Reservoir (176,974 m2), San Juan, Puerto Rico, post the 2016 arrival of the invasive aquatic fern Salvinia molesta. In December 2019, a community-led initiative introduced the Cyrtobagous salviniae weevil, an effective biological control agent for S. molesta, and commenced a mechanical removal campaign using an aquatic harvester. Limnological sampling (September 2019 to March 2022) and drone flights were employed to measure physicochemical and floating plant cover changes, respectively, in the reservoir. Monitoring of weevils in the reservoir demonstrated a rapid establishment and dispersal, which resulted in visible damage including browning of plants and eventually sinking of entire mats. By January 29, 2021, 71% (125,652 m2) of the reservoir surface was covered by salvinia. In 2022, the reservoir recorded an average dissolved oxygen concentration of 2.38 mg/L -1 (± 0.021, n = 144), the highest in the study period and indicative of ecosystem recovery. After three years of control efforts, dissolved oxygen, pH, and specific conductance returned to levels recorded prior to Salvinia molesta introduction. This ecosystem recovery, a first in Puerto Rico, could be attributed to an early use of mechanical control and a long-term impact of biological control.

Secondary metabolites from Hibiscus sabdariffa have been used to prevent different diseases. Roselle Hibiscus is known for being rich in phenolic bioactive compounds. The extraction conditions are directly related to the chemical composition and then to the overall bioactivity of the extract. In this study, a Box Behnken experimental design has been used to optimize the antioxidant activity, considering four variables: the ethanol:water ratio, the temperature, the extraction time, and the solvent:solid ratio. The experiment comprises 27 experiments and 3 repetitions at the central point. The results are described by surface response analysis and a second-degree polynomial equation. The model explains 87% of the variation in the response. The maximum antioxidant activity is yielded when 1% solids are extracted in 35.5% ethanol at 60°C for 33 min. Finally, a nutritional functional supplement of 495 µmol Trolox Equivalent (TE) antioxidant capacity was prepared with the optimized extract.

We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (detected with the comet assay). Cells deficient in the DNA repair pathway nucleotide excision repair (NER) were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. The combinations of AzGalp with either oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also displayed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.

Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. So far, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of periodontally-healthy individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. Matching AD patients (n=6) and controls (n=6) were enrolled at the International Center for Clinical Studies, Santiago, Chile. Complete dermatological and periodontal evaluations (involving the collection of GCF samples) were made. The levels of 35 proteases were analyzed using a human protease antibody array. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8 and Neprilysin/CD10, aspartyl-binding Cathepsin E, and serin-binding Protein convertase9 and uPA/Urokinase proteases were lower in moderate/severe AD patients compared to controls (p<0.05). No inter-group differences in the levels of the other 28 proteases were found. MMP8, Cathepsin E and ADAM9 were the biomarkers with the highest sensitivity and specificity regarding the detection of AD (p < 0.05). The area under receiver operating characteristic (ROC) curve for MMP-8+ADAMP-9 was 0.90. In conclusion, differences in the protease profile between AD and control patients associated with MMP8, Cathepsin E and ADAM9. MMP8, ADAM9 and Cathepsin E may be useful as combined diagnostic and therapeutic biomarkers of moderate/severe AD.