Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.

Microorganisms drive the biogeochemical cycles that link abiotic and biotic processes in the aqueous environment and are intricately associated with plastic debris. The detection of microplastics in water and sediment introduces new concerns as small particle size allows for yet unconsidered pathways for plastics in the food web and element cycles. In this review, we present current knowledge of microbe-plastic interactions and summarize the potential impact of biogeochemical processes on plastic distribution, cycling, transport, and sedimentation. We explore how microbe-plastic interactions influence the exposure of consumers to plastics and plastic degradation products. Key methods used to elucidate biofilm development, microbial biodegradation, and plastic detection in the aqueous environment are discussed. Finally, we comment on potential future questions and research directions needed to further define the role of microorganisms in the environmental fate of microplastics.

Many Caribbean island nations have historically been heavily dependent on imported fossil fuels for both power and transportation, while at the same time being at an enhanced risk from the impacts of climate change, although their emissions represent a very tiny fraction of the global total responsible for climate change. Small island developing states (SIDS) are among the leaders in advocating for the ambitious 1.5°C Paris Agreement target and the transition to 100% sustainable, renewable energy systems. In this work we present three central results. First, we show through GIS mapping of all Caribbean islands the potential for near-coastal deep-water as a resource for Ocean Thermal Energy Conversion (OTEC) and couple these results with an estimate of the countries for which OTEC would be most advantageous due to a lack of other dispatchable renewable power options. Second, hourly data have been utilized to explicitly show the trade-offs between battery storage needs and dispatchable renewable sources such as OTEC in 100% renewable electricity systems, both in technological and economic terms. Finally, the utility of near-shore, open-cycle OTEC with accompanying desalination is shown to enable a higher penetration of renewable energy and lead to lower system levelized costs than those of a conventional fossil fuel system.

The circular economy is an alternative paradigm whose purpose is the protection of the environment, the prevention of pollution and the growth of economic prosperity. This paper covers research which is qualitative in nature but has an exploratory scope through a documentary review, and includes proposals to promote sustainability. A more responsible consumption or use can be achieved by educating the user or consumer to return the product to production or repair through a collection service by way of reverse logistics (recovery of materials), followed by recycling or reuse of the product or its components to then offer these as recovered or recycled products on the market.

Horses’ ability to adapt to new environments and to acquire new information plays an important role in handling and training. Social learning in particular would be very adaptive for horses as it enables them to flexibly adapt to new environments. In the context of horse handling, social learning from humans has been rarely investigated but could help to facilitate management practices. We assessed the impact of human demonstration on spatial problem-solving abilities in horses using a detour task. In this task, a bucket with a food reward was placed behind a double-detour barrier and horses (n = 16) received a human demonstration or no demonstration. Horses were allocated to two test groups of 8 horses each, which experienced the two treatments in a counterbalanced order. We found that horses did not solve the detour task faster with human demonstration. However, both test groups improved rapidly over trials. Our results suggest that horses prefer to use individual rather than social information when being confronted with a spatial problem-solving task.

We evaluated epidemiological evolution and economic impact of COVID-19 pandemic in the European Union (EU) and worldwide, and the effects of control strategies on them. We collected incidence, mortality, and gross domestic product (GDP) data between the first quarter of 2020 and of 2023. Then, we reviewed the effectiveness of the mitigation and zero-COVID control strategies. The statistical analysis was done calculating the incidence rate ratio (IRR) of two rates and its 95% confidence interval (CI). In the EU, COVID-19 presented six epidemic waves. The sixth one at the beginning of 2022 was the biggest. Globally, the biggest wave occurred at the beginning of 2023. Highest mortality rates were observed in the EU during 2020-2021 and globally at the beginning of 2021. In mitigation countries, mortality was much higher than in zero-COVID countries (IRR= 6.82; CI:6.14-7.60; p<0.001). A GDP reduction was observed worldwide, except in Asia. None of the eight zero-COVID countries presented a GDP growth percentage lower than the EU percentage in 2020, and 3/8 in 2022 (p=0.054). COVID-19 pandemic caused epidemic waves with high mortality rates and a negative impact on GDP. The zero-COVID strategy was more effective in avoiding mortality and potentially had less impact on GDP.

The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Organ donors are preserved in warm or cold ischemia. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step and the oxidative stress during the reperfusion step. Different methodologies were developed to prevent or diminish the level of injuries. Preservation solutions were first developed, followed by the addition of chemical compounds. In addition of inhibitors of mitogen activated protein kinase, inhibitors of the proteasome, mesenchymal stem cells started to be used 13 years ago to prevent or diminish the organ’s injuries. Mesenchymal stem cells (e.g bone marrow stem cells, adipose derived stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus on the use of some bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.

Based on rapeseed plantation biodiesel production system requires transportation of goods, like raw materials, machines and tools, and products between various conversion stages of agricultural as well as industrial subsystems. Each transportation step requires consumption of some energy. This consumption, decreases the net amount of energy delivered out of the biofuel production system, and consequently decreases energetic efficiency of the system. The present work deals with computer modelling of the influence of energy consumed on those transport routes on the energetic efficiency of production system. The effects caused by variation of several parameters like fuel consumption and load capacity of transportation means, size of plantation, distribution and sizes of individual fields, distances between fields, as well as plantation yield, and finally the distance between plantation and the industrial facility are studied using the numerical model developed

Tourism is the main economic sector in the Balearic Islands (Spain) and hotel housekeepers (HHs) are a large occupational group, in which stress is becoming a major issue. This study aims at exploring in-depth factors perceived as stressors by HHs and key-informants, and their effects on work-life balance (WLB). A qualitative design with phenomenological approach was used, conducting six focus groups with 34 HHs and 10 individual interviews with key-informants. Results were analyzed adopting the job demands-resources model and a gender perspective. High demands –e.g work overload, time pressure, physical burden...-, lack of enough resources and little control –derived from role conflict, unexpected events...- were the most important factors explaining HHs’ stress. Additionally, this imbalance was perceived as leading to health problems –mainly musculoskeletal disorders-. Working schedule was mentioned as a facilitator to WLB, whereas an imbalance between job demands and resources led to work-home conflict –preventing them from enjoying leisure time-. Multiple roles at work and at home increased their stress. HHs experienced their job as invisible and unrecognised. Regarding practical implications, our recommendations for hotel organization include reducing workload and increasing resources, which would improve the job demands-resource balance, diminish negative mental and physical outcomes and improve WLB.

Fe rich soft magnetic alloys are candidates for applications as magnetic sensors and actuators. These alloys can also be added to hard magnetic compounds to obtain spring magnets. In this work we produce two nanocrystalline Fe-Zr-B-Cu alloys by the powder metallurgy powder technology of mechanical alloying. The increase of the boron content favors the reduction of the crystalline size. Thermal analysis (by differential scanning calorimetry) shows at temperatures between 450 and 650 K wide exothermic processes, associated with the relaxation of tensions of the alloys produced by milling. At high temperatures, a main crystallization peak is found. The apparent activation of this process was determined by Kissinger and isoconversional methods. The values are compared with those found in the scientific literature. Likewise, adapted thermogravimetry permits to determine the Curie temperature. The functional response has been analyzed by hysteresis loop cycles. According to the composition, the decrease of the Fe/B ratio diminishes the magnetic soft behavior.

The objective of this paper is to present a mathematical formalism that states a bridge between Physics and Psychology, concretely between analytical dynamics and personality theory in order to open new insights in this theory. In this formalism energy plays a central role. First, the short-term personality dynamics can be measured by the General Factor of Personality (GFP) response to an arbitrary stimulus. This GFP dynamical response is modelled by a stimulus-response model: an integro-differential equation. The bridge between Physics and Psychology is provided when the stimulus-response model can be formulated as a linear second order differential equation and, subsequently, reformulated as a Newtonian equation. This bridge is strengthened when the Newtonian equation is derived from a minimum action principle, obtaining the current Lagrangian and Hamiltonian functions. However, the Hamiltonian is a non-conserved energy. Then, some changes provide a conserved Hamiltonian function: the Ermakov-Lewis energy. This energy is presented, as well as the GFP dynamical response that can be derived from it. An application case is presented: an experimental design in which 28 individuals consumed 26.51 g of alcohol. This experiment provides an ordinal scale for the Ermakov-Lewis energies that predicts the effect of a single dose of alcohol.

Since the mid-20th century, tourism has become a strategic activity for the economy of the Balearic Islands, causing profound social, territorial and environmental transformations. This fact challenges local society, which must be aware of its environment in order to better face the future challenges posed by this economic activity. With this goal, the official curriculum has been analyzed, making it possible to ascertain the approach with which this subject is taught by the administration and what objectives are set. Furthermore, a review was carried out of the contents of geography textbooks in the third year of ESO and the second year of Baccalaureate, which correspond to the educational stages in which tourism aspects appear. The results obtained represent a fundamental strategic diagnosis in order to improve the teaching and learning of this key activity for the Balearic Islands, giving it more importance and adapting its approach to the current times.

The innate immune system is the first line of defense against pathogens. It’s composition includes barriers, mucus and other substances as well as phagocytic and other cells. The purpose of the paper is to analyze in general grounds the immune system and the body immunity to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen’s average rate of growth. When nonlinearities are added, a reference value for the number of pathogens is set, and a stability condition emerges, which relates strength of regular threats, barrier height and annihilation rate. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The stability condition allows a comparison of immunity in different tissues. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. These statements are formulated at the qualitative level, but may and deserve to be quantitatively checked.

Abstract: Interactions in multicomponent Ni-Cr-Mo-Al-Re model alloy were determined by ab initio calculations in order to investigate the Re doping effect on Haynes 282 alloy. Simulation results provided an understanding of short-range interactions in the alloy and successfully pre-dicted the formation of a Cr and Re-rich phase. The Haynes 282 + 3 % wt. Re alloy was manu-factured using the additive manufacturing Direct Metal Laser Sintering (DMLS) technique, in which the presence of the (Cr17Re6)C6 carbide was confirmed by an XRD study. The results ob-tained provide useful information about the interactions between Ni, Cr, Mo, Al, and Re as a function of temperature. The 5-element model designed can lead to a better understanding of phenomena that occur during the manufacturing or heat treatment of modern, complex, multi-component Ni-based superalloys.

The verticals of 5G, such as the automotive, smart grid and smart cities sectors, will bring lots of new sensors and IoT devices requiring Internet connectivity. Most of these machine-type terminals will be sparsely distributed, covering a very large geographical area and, from time to time, will have to update their software, firmware and/or other relevant data. Given this situation, one viable solution to implement the “Over-the-Air” update of these IoT terminals can be with the aid of GEO satellite systems. However, due to the ultra-dense radio frequency reuse that contemporary High-Throughput Satellite (HTS) systems implement in the access link to serve the IoT terminals, the use of a time-packed Free Space Optical (FSO) link represents a practical solution to avoid the bottleneck that the satellite gateway experiences in the feeder link. The performance of both Detect-and-Forward and Decode-and-Forward relaying strategies are studied, assuming that the single-carrier M-PAM symbols that are transmitted on the optical feeder link are mapped into M-QAM symbols that modulate the multiple subcarriers of the OFDM-based radio access link. In addition, the benefits of encapsulating the NB-IoT frames into DVB-S2(X) satellite frames is also analyzed in detail. The effects of the impairments introduced in both optical feeder and radio access links are characterized in detail, and the end-to-end error correction capabilities of the Modulation and Coding Schemes (MCS) defined in the contemporary releases of the NB-IoT and DVB-S2(X) standards are studied for different working regimes.

Plastid genomes are in general highly conserved given their slow evolutionary rate, thus large changes in their structure are unusual. However, when specific rearrangements are present, they are often phylogenetically informative. Asteraceae is a highly diverse family whose evolution is long driven by polyploidy (up to 48x) and hybridisation, both processes usually complicating systematic inferences. In this study, we have generated one of the most comprehensive plastome-based phylogenies of family Asteraceae, providing information about the structure, genetic diversity, and repeat composition of these sequences. By comparing the whole plastome sequences obtained, we confirmed the double inversion located in the long single copy region, for most of the species analysed (with the exception of basal tribes), a well-known feature for Asteraceae plastomes. We also show that genome size, gene order and gene content are highly conserved along the family. However, species representative of the basal subfamily Barnadesioideae -as well as in the sister family Calyceraceae - are lacking the pseudogene rps19 located in one inverted repeat. The phylogenomic analysis conducted here, based on 63 protein-coding genes, 30 transfer RNA genes and 21 ribosomal RNA genes from 36 species of Asteraceae, are overall consistent with the general consensus for the family’s phylogeny, while resolving the position of tribe Senecioneae and revealing some incongruences at tribe level between reconstructions based on nuclear and plastid DNA data.

We report the results of the characterization of local Monte Carlo (MC) dynamics of an equilibrium bond fluctuation model polymer matrix (BFM), in time interval typical for MC simulations of non-linear optical phenomena in host-guest systems. The study contributes to the physical picture of the dynamical aspects of quasi-binary mosaic states characterized previously in the static regime. The polymer dynamics was studied at three temperatures (below, above and close to the glass transition), using time-dependent generalization of the static parameters which characterize local free volume and local mobility of the matrix. Those parameters play the central role in the kinetic MC model of host-guest systems. The analysis was done in terms of the probability distributions of instantaneous and time-averaged local parameters. The main result is the characterization of time scales characteristic of various local structural processes. Slowing down effects close to the glass transition are clearly marked. The approach yields an elegant geometric criterion for the glass transition temperature. A simplified quantitative physical picture of the dynamics of guest molecules dispersed in BFM matrix at low temperatures offers a starting point for stochastic modeling of host-guest systems.

The paper analyses how between 1956 and 2009 the agrarian metabolism of the Barcelona Metropolitan Region (BMR) has become less functional, losing circularity in biomass flows and in relationship to its landscape. We do so by adopting a Multi-EROI and flow-fund (MuSIASEM) analyses and its nexus with landscape functional structure. The study of agricultural flows of Final Produce, Biomass Reused and External Inputs is integrated with that of land use, livestock, power capacity and population changes between 1956 (at the beginning of the Green Revolution) and 2009 (fully industrialized agriculture). A multi-scale analysis is conducted at the landscape scale (seven districts within the Barcelona metropolitan region) as well as for the functions deployed, within an agroecosystem, by the mutual interactions between its funds (land-uses, livestock and farming population). A complex nexus between land, livestock, dietary patterns and energy needs is shown; we conclude that from the perspective of the circular bioeconomy the agrarian sector has gone worse hand in hand with the landscape functional structure. Therefore, a novel perspective in landscape agroecology is opened

We classify all the topologically non-equivalent phase portraits of the quadratic polynomial differential system dx/dt = (1-2x)(y-x), dy/dt =y (2-g y-(5g-4)x/(g-1)), in the Poincaré disc for all the values of the parameter g in R\{1}. The differential system dx/dt = y-x, dy/dt =y (2-g y-(5g-4)x/(g-1))/(1-2x), when the parameter g in (1,2] models the structure equations of a static star in general relativity in the case of the existence of a homologous family of solutions, being x = m(r)/r where m(r)>= 0 is the mass inside the sphere of radius r of the star, y = 4pi r^2 rho where rho is the density of the star, and t = ln (r/R) where R is the radius of the star. We classify the possible values of m(r)/r and 4pi r^2 rho when r-->0.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

The World Health Organization has developed the Integrated Care of Older People (ICOPE) strategy, a program based on the measurement of intrinsic capacity (IC) as “the composite of all physical and mental attributes on which an individual can draw”. Multicomponent interventions appear to be the most effective approach to enhance IC and to prevent frailty and disability, since adapted physical activity is the preventive intervention that has shown most evidence in the treatment of frailty and risk of falls. Our paper describes the development of a multi-domain group-based intervention addressed to older people living in the community, aimed at improving and/or maintaining intrinsic capacity by means of promoting physical activity, healthy nutrition, and psychological wellbeing in older people. The process of intervention development is described following the Guidance for reporting intervention development studies in health research (GUIDED. The result of this study is the AMICOPE intervention (Aptitude Multi-domain group-based intervention to improve and/or maintain IC in Older PEople) built upon the ICOPE framework and described following the Template for Intervention Description and Replication (TIDieR) guidelines. This study represents the first stage of the UK Medical Research Council framework for developing and evaluating a complex intervention. The next step should be carrying out a feasibility study for the AMICOPE intervention, and in a later stage, assessing the effectiveness in a randomized controlled trial.

The influence of the hot isostatic pressing (HIP) post-processing step on structural and phase changes, porosity healing and mechanical strength in a powder metallurgy Ti35Nb2Sn alloy was studied. Powders were pressed at room temperature at 750 MPa, and then sintered at 1,350°C in a vacuum for 3 h. The standard HIP process at 1,200°C and 150 MPa for 3 h was performed to study its effect on a Ti35Nb2Sn powder metallurgy alloy. The influence of the HIP process and cold rate on density, microstructure, the quantity of interstitial elements, mechanical strength and Young's modulus was investigated. HIP post-processing for 2 h at 1,200°C and 150 MPa led to greater porosity reduction and a marked retention of the β phase at room temperature. The slow cooling rate during the HIP process affected phase stability, with a large amount of α”-phase precipitate, which decreased the titanium alloy’s yield strength.

Since December 2019, the COVID-19 virus has rapidly spread worldwide, prompting the World Health Organization (WHO) to declare it a pandemic and advocate for the widespread use of face masks to mitigate transmission. In this review, we delve into the potential impact of prolonged face mask use on temporomandibular joint (TMJ) health, an area that has garnered limited attention amidst COVID-19 research. Research has revealed that improper mask fit, and constant readjustment can lead to TMJ abnormalities. Similarly, there is a demonstrated correlation between continuous mask usage and increased incidence of headaches, temporomandibular pain, and diminished quality of life. Many studies have highlighted discomfort in the preauricular area, headaches, TMJ noises, headache, jaw pain, and muscle fatigue, as well as dermatological disorders that have been attributed to prolonged mask wear and its impact on TMJ. Our study catalyzes future research endeavors, urging a deeper exploration of the implications of long-term mask wear, not only in the context of the COVID-19 pandemic but also among occupational groups regularly exposed to extended mask use. By unraveling the complexities of TMJ health in the face of evolving preventive measures, we aim to enhance our understanding and safeguard the well-being of mask-wearers worldwide.

The prevalence of back pain (BP) among children and adolescents has increased over recent years. Some authors advocate promoting back-health education in the school setting. It is therefore important to adopt a uniform suite of assessment instruments to measure the various constructs. The present study aimed to perform a cultural adaptation of a validated measurement instrument (BackPEI), beginning with a translation and cultural adaptation phase, followed by a second phase to test reliability using a test-retest design. The translation and cross-cultural adaptation were performed based on the guidelines. Reliability was tested by applying the questionnaire to 224 secondary school students, at two different times with a 7-day interval between the tests. In general, the Spanish version presented adequate agreement for questions 1–20, with only question 9 achieving a low Kappa range of .312 [-.152- .189]. The question about pain intensity did not show differences between the averages for the test (4.72 ± 2.33) and re-test (4.58 ± 2.37) (p = .333), and the responses for these two tests were highly correlated (ICC= .951 [.928- .966]; p= .0001). Psychometric testing indicated that the Spanish version of the BackPEI is well-adapted and reliable, based on the test-retest design, providing similar results to the original Brazilian version.

During the last 100 years the planet has increased its temperature rapidly, this climate change could bring catastrophic effects for organisms and natural systems. One of the most affected groups is the ectotherms, due to their direct dependence on the environmental temperature. In recent years several studies analyse the effects of temperature and the thermal tolerance on several species of ectotherms. However, there are species whose thermal tolerances are still unknown. Such is the case of critically endangered species the Montseny Brook Newt (Calotriton arnoldi), endemic from the Montseny massif in Spain and whose thermal biology is unknown. Its critical situation makes essential to know its tolerance to cooling, warming and thermopreferendum in water environment where the newt lives. Three experimental procedures were conducted from the western and eastern subpopulations of C. arnoldi considering four classes separately (males, females, juveniles and larvae). The results obtained showed that the CTmax of the species exceeded 31°C, with a significant difference between the two populations. We found that the species tolerates well low temperatures (&lt;1°C), because of the genera Calotriton is adapted to lives in cold waters with temperatures below 15º. Although the thermopreference of the species was expected to trend to cold temperatures, some individuals chose relatively high temperatures, obtaining a range of 11.7°C to 21.6°C. The results presented in this study are an advance in the knowledge of the thermal physiology of this species and support the importance of the temperature of the torrent on its survival. Knowing their thermal limits and their preferred temperature range will help to propose management measures that promote the conservation of streams and its riparian forest cover to mitigate the temperature increase due to climate change.

Municipal Solid Waste Management (MSWM) struggles with significant policy and operational challenges, particularly concerning recyclables collection routes and fleet composition. Within the European Union, phasing out traditional fuel-based vocational vehicles, like garbage trucks, in favor of zero-emission alternatives is mandatory to achieve sustainable development objectives. Integrating electric solid waste collection vehicles into municipal fleets presents challenges due to differences in range, capacity, and noise levels. The emission is even more crucial in the systems where recyclables are collected separately, which requires a greater number of trips to be performed. This study addresses MSWM’s strategic aspect by minimizing the total cost of replacing waste collection vehicles while meeting emission constraints. The Fleet Transition Problem (FTP) was formulated and solved using a MARKAL-based approach. The objective of the FTP and a mixed integer linear program used to solve it is minimizing the overall cost of fleet modernization throughout a multi-phase planning horizon so that the sustainable transition of the fleet can be assured. Computational experiments affirmed the model’s effectiveness in strategizing fleet transition. This research outlines a multi-period model for transitioning to a zero-emission fleet and demonstrates the FTP’s potential for strategic decision-making. Notably, the study observes a consistent reduction in permissible emissions across the planning horizon.

The performance of Integrated Multisatellite Retrievals for GPM (V06B-IMERG) is evaluated at subdaily and daily scale using 10 years of heavy precipitation over a region in the Western Med-iterranean for different temporal aggregations with a dense network of rain gauges. On a half-hourly scale, the contribution of passive microwave (PMW) and infrared (IR) sources in the satellite estimates was considered, as well as the relation of various microphysical properties of cloud tops using Cloud Microphysics (CMIC- NWC SAF) data. IMERG shows a marked tendency to underestimate precipitation compared to rain gauges as the rainfall intensity threshold and temporal resolution increases. Results indicate that the negative bias is weaker when retrievals are due to PMW data. On the other hand, the benefits of filling the PMW gaps of IMERG by including IR information come at the expense of increasing the bias. IMERG performs dramatically better in the presence of precipitating ice clouds compared to warm and mixed phase clouds, which seems to be related with microphysical properties such as cloud optical thickness and cloud top effective radius. This work contributes to the understanding of the factors affecting satellite estimates of extreme precipitation and their relationship with the microphysical characteristics of clouds, which generates added value for further downstream applications and users’ decision making.

The advancement of bioconcrete over cementitious composites has brought us to the application of microbes in the field of construction materials. Certain microbes like bacteria, algae, and fungi have been discussed in the review. The purpose of applying these microbes in the matrix is mainly to enhance the concrete’s strength and other properties such as durability, resistance, and self-healing ability. As these microbes are able to induce calcite biomineralizations, the process is also known as Microbiologically Induced Calcite Precipitation (MICP). Some known microorganisms with their mentioned ability are Bacillus subtilis and Bacillus cohnii (bacteria), Chlorella vulgaris and Spirulina platensis (algae), and Trichoderma reesei, Aspergillus niger, and Neurospora crassa (fungi). The paper provides a “state-of-the-art” review of research into the effects of bioconcrete and discusses the overall methodologies of every medium with their physiological, physicochemical and bioengineering properties in the light of recent researches done so far in the same field.

There is consensus over the fact that urban green areas contribute to the quality of life of their inhabitants. So, efficient city management must assess whether the population has access to green areas and their quality in relation to vegetation, facilities or furnishings, for example. Therefore, the objective set is to establish the environmental justice of urban parks in Tarragona (Spain) by developing a Park Quality Index (PQI) and the sociodemographic characteristics (level of studies, Human Development Index [HDI], home sale and rental prices) of the population living within 300 metres of a park. To prepare this, a GIS-integrated Multi-Criteria Evaluation (MCE) has been produced. The results show that the green areas have low accessibility and availability and that most parks obtain an average-low PQI, with the best- valued aspect being the vegetation and the worst the facilities. As for the degree of environmental justice, a casual relationship emerges between the PQI and the indicators used. The average value of the home sale prices is the one that shows the greatest correlation. These results can be used together with participatory procedures as a basis for identifying places with greater inequality, and for selecting the more effective actions that enable increasing environmental justice with respect to green areas.

Introduction: In an era of increasing public awareness regarding the pivotal role of nutrition in the onset and progression of chronic degenerative diseases, there is a growing demand for information and assistance pertaining to the intricate relationship between diet and disease. Nutritional practices, therefore, emerge as a fundamental element in the prevention and management of these maladies, necessitating a proactive response from healthcare professionals (HCP). This study sought to evaluate the impact of participation in a Culinary Medicine (CM) program on Mediterranean diet adherence, food management skills, culinary proficiency, and counseling confidence among HCP. Methods: A mixed-methods pilot implementation program (PIP) was meticulously designed and executed, engaging a cohort of 20 HCP recruited from Hospital Clinic Barcelona. The program unfolded at the Alícia Foundation kitchen-lab and encompassed a series of interactive, hands-on sessions that delved into the realms of gastronomy, food management, culinary skills, and culinary diet therapy, with a specific focus on prevalent diseases and their prevention, treatment, and care. Tailored questionnaires were administered to all participants both before and after the PIP. Results: Of the 20 participants, 14 successfully completed the study, comprising 86% women, 86% aged above 40, 71% nurses, and 7% medical doctors. Interestingly, 86% of the participants had previously received nutrition training, whereas only 14% had received culinary training. Following the completion of the program, there was a remarkable improvement in adherence to the Mediterranean diet (p < 0.01). However, no statistically significant improvements were observed in food management and culinary skills or counseling confidence (p > 0.5). Despite the absence of statistical significance, there was a noteworthy trend towards greater advocacy for dietary changes before resorting to medication, along with enhanced confidence in providing nutritional and culinary guidance to patients. Conclusion: The findings from this study underscore the potential of hands-on CM training as a vital component of nutrition education for HCP. While statistically significant improvements in certain domains were not observed, the program did demonstrate its ability to influence attitudes, knowledge, and behaviors related to healthy cooking and eating for both HCP themselves and their patients. Given these promising trends, future studies with a larger sample size must be performed to further elucidate the impact of CM training on HCP and its potential benefits for public health.

In the Quaternary paleosciences, the rationale behind analogical inference presupposes that former natural changes can be explained by causes operating now, although their intensity and rates can vary through time. In this paper we synthesise synthetize the results of different modern analog studies and discuss their value to obtain the best inferences from high resolution past records. This synthesis is based on the following: 1) The monthly monitoring of calcite precipitation reveals a strong connection with primary producers and between-years variability; this precipitation produces a seasonal signal with imprint on varve formation. 2) Clear pollen sedimentation peaks occur in spring/summer and fall/winter that coincide with temperature, precipitation, relative humidity and winds; this pattern converges with the two-layer coupled varves representing the same seasonality. 3) We assess the lake’s contemporary oxygenation dynamics over a three- year period; a combination of sedimentary REDOX proxies revealed different scenarios of oxic/anoxic shifts since 1500 CE. 4) We investigate presence of seasonality in the production/distribution of glycerol dialkyl glycerol tetraethers and derived temperature estimates in soils and particulate matter. Branched glycerol dialkyl glycerol tetraethers signatures and some derived temperature estimates proxies appear to mainly depend on the non-seasonal shifts in soil properties. 5) Currently we examine relationships and similarities between extant phytoplankton and derived pigments in water and traps, and their correspondence with subfossil pigments; some preliminary results are presented here.Keywords: high resolution, endogenic varves, calcite precipitation, pollen sedimentation, meromixis, freshwater glycerol dialkyl tetraether, subfossil pigments, long-term ecology.

The aim of the present study was to measure the apparent absorption of magnesium (Mg) originating from Mg-butyrate. Six mid-lactation Holstein Friesian dairy cows were used with dietary treatments arranged in a cross-over design. Two different diets were fed during the experiment, consisting of a low Mg diet without Mg-butyrate (L-Mg, 3.1g Mg/kg dry matter) or a high Mg diet with Mg-butyrate (H-Mg, 3.9 g Mg/kg dry matter). Cows offered the L-Mg diet ingested 54.7 g Mg/day while the cows fed the H-Mg diets ingested 66.3 g Mg/day (P < 0.001). The fecal excretion of Mg, however, was similar between the two experimental diets (P = 0.174). Consequently, apparent Mg absorption was found to be 7.9 percentage units greater (P = 0.038) when the cows were fed the diet supplemented with Mg-butyrate. The greater Mg absorption after feeding the H-Mg diet was, however, not reflected by a greater urinary Mg concentration (P = 0.228). These results indicate that the availability of Mg from the Mg-butyrate supplemented diet is high (34.1% of intake). The fractional Mg absorption from Mg-butyrate was calculated to be 71.6%. In conclusion, Mg-butyrate is an attractive alternative to supplement dairy rations with Mg.

In relation to organizational performance measurement, there is a growing concern about the creation of value for people, society and the environment. The traditional corporate reporting does not adequately satisfy the information needs of stakeholders for assessing an organization’s past and future potential performance. Practitioners and scholars have developed new non-financial reporting frameworks from a social and environmental perspective, giving birth to the field of Integrated Reporting (IR). The Economy for the Common Good (ECG) model and its tools to facilitate sustainability management and reporting can provide a framework to do it. The present study is the first one that empirically validates such metrics on a sample of 206 European firms. Consequently, it allows knowledge to advance as it checks their statistical validity and reliability.

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Methane and carbon dioxide are the main contributors to global warming, being the methane effect twenty-five times more powerful than carbon dioxide. Although the sources of methane are diverse, it is a very volatile and explosive gas. One way to store the energy content of methane is its conversion to methanol. Methanol is liquid under ambient conditions, easy to transport and, apart from its use as an energy source, it is a chemical platform that can serve as a starting material for the production of various higher value-added products. Accordingly, the transformation of methane to methanol has been extensively treated in the literature, using traditional catalysts as different types of zeolites. However, in the last years, a new generation of catalysts have emerged to carry out this transformation with higher conversion and selectivity, and more importantly, under mild temperature and pressure conditions. These new catalysts typically involve the use of a highly porous supporting material such as zeolite, or more recently, metal-organic frameworks (MOFs) and graphene, and metallic nanoparticles or a combination of different types of nanoparticles that are the core of the catalytic process. In this review, the characteristics, the catalytic mechanisms, reactors, and the main results of these catalysts are presented as a way to overcome the challenges found in traditional catalysts.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID. To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Nowadays, mindfulness-based interventions (MBI) have experimented a remarkable development of studies among childhood and adolescent interventions. For this reason, dispositional mindfulness (DM) measures for children and adolescents have been developed to determine the effectiveness of MBI at this age stage. However, little is known about how key elements of DM (f. e., cognitive de/fusion or experiential avoidance that both conform psychological inflexibility) are involved in the mechanisms of the children and adolescents’ mental health outcomes. This research examined the mediating effect of cognitive fusion between DM and anxiety and other negative emotional states in a sample of 318 Spanish primary-school students (aged between 8 and 16 years, M=11.24, SD=2.19, 50.8% males). Participants completed the AFQ-Y, which is a measure of psychological inflexibility that encompasses cognitive defusion and experiential avoidance; CAMM (DM for children and adolescents), PANAS-N (positive and negative affect measure for children, the Spanish version of PANASC), and STAIC (an anxiety measure for children). The study accomplished ethical standards. As MBI relevant literature has suggested, cognitive defusion was a significant mediator between DM and symptoms of both negative emotions and anxiety in children and adolescents. However, experiential avoidance did not show any significant mediating relationship. Probably, it is needed improvement of the assessment of experiential avoidance. MBI programs for children and adolescents may include more activities for reducing the effects of the cognitive defusion on their emotional distress.

In this work we present some driving strategies for a type of omnidirectional mobile robot, the offset-differential robot. This system presents omnidirectionality while using any type of standard wheels, allowing for applications in all terrain. The work is based on the full kinematic and dynamic analysis of the robot, including the passive elements, to explain some unexpected behaviors that appear during its motion. The stable and unstable behaviors are characterized and some driving strategies are stated in order to achieve the desired performance regarding precise positioning and speed.

Enzymes are in high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users. These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.

Banks have enormous potential in supporting the achievement of sustainable development goals (SDGs) in accordance with their function as financial intermediaries through sustainable lending. However, the average national financing growth for the sustainable business activity category over the past four years is still 12%. The aim of this research is to identify the conditions of sustainable lending at state-owned conventional banks and analyze the influence of the value chain, economic performance and ESG performance on sustainable lending. The research was conducted at state-owned commercial banks in Indonesia. The research utilized a Structural Equation Modeling (SEM). The SEM results of this study describe value chain, ESG performance (environmental, social and governance) and economic performance have direct and positive influences on sustainable lending, of which ESG performance has the biggest influence. As per individual aspect, social orientation gives the biggest contribution toward sustainable lending.

A substantial body of phenomenological and theoretical work over the last few years strengthens the possibility that the vacuum energy density (VED) of the universe is dynamical, and in particular that it adopts the `running vacuum model' (RVM) form, in which the VED evolves mildly as $\delta \rho_{\rm vac}(H)\sim \nu_{\rm eff} m_{\rm Pl}^2{\cal O}\left(H^2\right)$, where $H$ is the Hubble rate and $\nu_{\rm eff}$ is a (small) free parameter. This dynamical scenario is grounded on recent studies of quantum field theory (QFT) in curved spacetime and also on string theory. It turns out that what we call the `cosmological constant', $\Lambda$, is no longer a rigid parameter but the nearly sustained value of $8\pi G(H)\rho_{\rm vac}(H)$ around (any) given epoch $H(t)$, where $G(H)$ is the gravitational coupling, which can also be very mildly running (logarithmically). Of particular interest is the possibility suggested in past works that such a running may help to cure the cosmological tensions afflicting the $\Lambda$CDM. In the current study, we reanalyze it in full and we find it becomes further buttressed. Using the modern cosmological data, namely a compilation of the latest SNIa+BAO+$H(z)$+LSS+CMB observations, we probe to which extent the RVM provides a quality fit better than the concordance $\Lambda$CDM model, paying particular emphasis on its impact on the $\sigma_8$ and $H_0$ tensions. We utilize the Einstein-Boltzmann system solver \texttt{CLASS} and the Monte Carlo sampler \texttt{MontePython} for the statistical analysis, as well as the statistical DIC criterion to compare the running vacuum against the rigid vacuum ($\nu_{\rm eff} = 0$). On fundamental grounds, $\nu_{\rm eff}$ receives contributions from all the quantized matter fields in FLRW spacetime. We show that with a tiny amount of vacuum dynamics ($|\nu_{\rm eff}|\ll 1$) the global fit can improve significantly with respect to the $\CC$CDM and the mentioned tensions may subside to inconspicuous levels.

This paper presents a script that classify spatial patterns of residential urban growth using a morpho-structural approach. The script performs a combination of variography analysis and morphological closings over buildings possessing a residential function in 2002 and 2017 within a region located in southern France named Centre-Var. The different bounding regions then allow classifying new residential buildings into different categories according to their degrees of clustering/scattering and to their locations regarding existing urban areas. Preliminary results show that this protocol is able to provide useful insights regarding the degree of contribution of each new residential building to different patterns of urban growth (clustered infill, scattered infill, clustered edge-expansion, scattered edge-expansion, clustered leapfrog and scattered leapfrog). Open-access to the script and to the test region data is provided.

Energy transitions are reshaping the global energy system. Such shift has taken the power system to become a critical infrastructure for achieving economic development of every nation in the planet, therefore, guaranteeing its security is crucial, not only for energy purposes but as a part of a national security strategy. This paper presents a multi-dimensional index developed to assess energy security of electrical systems in the long term. This tool, named Power System Security Index (PSIx), and which has been previously used for the evaluation of a country in two different time frames, is applied to evaluate the member countries of the Latin American Energy Organization, located within the Latin America and the Caribbean region, in order to measure their performance on energy security. Mixed results were obtained from the analysis, with clear top performers in the region such as Argentina, while there are others with broad areas of opportunity, as it is the case of Haiti.

(1) Background Diabetic Retinopathy (DR) is the primary cause of poor vision in young adults. Screening for DR is important but many patients do not attend; (2) Methods: We validated an algorithm for predicting DR and its progression by conducting a retrospective study of 11 children in a population of 120,389 T2DM (3) Results: By applying the algorithm to the population showed an AUC of 0.93 (95% CI, 0.92–0.94) for any-DR and 0.90 (95% CI, 0.89–0.91) for referable-DR(4) Conclusions: The algorithm is useful for predicting patients who could develop referable forms of DR and also for any-DR. This would allow a personalized screening plan to be drawn up for each patient.

A relativistic positioning system is a set of four emitters broadcasting their proper times by means of light signals. The four emitter times received at an event constitute the emission coordinates of the event. Covariant quantities associated with relativistic positioning systems are analysed relatively to an observer in Minkowski space-time by splitting them in their relative space-like and time-like components. The location of a user in inertial coordinates from a standard set of emission data (emitted times and satellite trajectories) is solved in the underlying 3+1 formalism. The analytical location solution obtained by Kleusberg for the GPS system is recovered and interpreted in a Minkowskian context.

Stellatolides are natural compounds that have shown promising biological activities, including antitumor, antimicrobial, and anti-inflammatory properties, making them potential candidates for drug development. Chemical Reactivity Theory (CRT) is a branch of chemistry that explains and predicts the behavior of chemical reactions based on the electronic structure of molecules. Conceptual Density Functional Theory (CDFT) and Computational Peptidology (CP) are computational approaches used to study the behavior of atoms, molecules, and peptides. In this study, we present the results of our investigation of the chemical reactivity and ADMET properties of Stellatolides A-H using a novel computational approach called Conceptual DFT-based Computational Peptidology (CDFT-CP). Our study uses CDFT and CP to predict the reactivity and stability of molecules and to understand the behavior of peptides at the molecular level. We also predict the ADMET properties of the Stellatolides A-H to provide insight into their effectiveness, potential side effects, and optimal dosage and route of administration. This study sheds light on the potential of Stellatolides A-H as promising candidates for drug development and highlights the potential of CDFT-CP for the study of other natural compounds and peptides.

Tailed phages are the most abundant and diverse group of viruses on the planet. Yet, the smallest tailed phages display relatively complex capsids and large genomes compared to other viruses. The lack of tailed phages forming the common icosahedral capsid architectures T = 1 and T = 3 is puzzling. Here, we extracted geometrical features from high-resolution tailed phage capsid reconstructions and built a statistical model based on physical principles to predict the capsid diameter and genome length of the missing small tailed phage capsids. We applied the model to 3,348 isolated tailed phage genomes and 1,496 gut metagenome-assembled tailed phage genomes. Four isolated tailed phages were predicted to form T = 3 icosahedral capsids, and twenty-one metagenome-assembled tailed phages were predicted to form T < 3 capsids. The smallest capsid predicted was a T = 4/3 ≈ 1.33 architecture. No tailed phages were predicted to form the smallest icosahedral architecture, T = 1. We discuss the feasibility of the missing T = 1 tailed phage capsids and the implications of isolating and characterizing small tailed phages for viral evolution and phage therapy.

The purpose of this study was to present the challenges faced when implementing a diet and exercise intervention for low-income older Hispanics with type 2 diabetes with an observational study of recruitment, attendance, and characteristics of Hispanic adults with type 2 diabetes in a community congregate meal site pre and post administration of a diet and exercise intervention. This report evaluates retentions and diabetes self-management beliefs Hispanic adults ≥60 years with type 2 diabetes (n=17) at baseline, and completion of the six-month intervention in terms of the Health Belief Model. There was limited interest in controlling diabetes with diet and exercise. Major barriers included lack of perceived vulnerability to diabetes complications and a belief that medication alone is sufficient to stabilize blood glucose. Environmental barriers included lack of transportation, access to exercise groups, access grocery stores, and limited ability to pay for healthy foods. A lesson learned from this intervention was that the diet and exercise intervention given was insufficient as a cue to action for this population interventions to engage low-income, older Hispanics with diabetes in diet and exercise need to consider strategies to overcome barriers such as health beliefs, transportation issues, lack of access to nutritious food and group exercise classes.

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effec-tiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influ-enza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; ap-plied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, pub-lication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed us-ing a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season and risk of bias. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017-2018 influenza season. The arVE was 3% (-01 to 7%) in the 2018-2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

Indole-3-acetic acid (IAA) is a key vegetative hormone that plays crucial roles in plant growth and development. In this study, the effect of the exogenous application of IAA as a biostimulant in the cultivation of onions (Allium cepa) was investigated. Different IAA concentrations were evaluated to determine their effects on onion growth and chemical parameters. Various physical and chemical parameters such as total fresh weight, plant height, chlorophyll content, nitrates, total phenols, and antioxidant capacity (DPPH) were analyzed. The results revealed that exogenous application of IAA had a significant impact on onion growth and quality. Specifically, it was found that certain concentrations of IAA fostered a greater fresh weight of the bulb, an increase in the levels of phenolic compounds and a greater DPPH. However, the onion response to IAA was dependent on the concentration. In conclusion, the present study provides evidence that the exogenous application of IAA as a biostimulant can improve onion growth and quality. These results are relevant for the development of sustainable agricultural practices and could be oriented towards crop improvement.

Aggregative multicellularity occurs when dispersed cells join together to form a highly cooperative unit, in contrast to clonal multicellular organisms formed by cells that remain in contact after descent from a single cell. Because aggregative groups may include non-relatives, aggregative multicellular organisms should be particularly vulnerable to the rise of cheater cells that take advantage of social goods without paying the costs, reducing cooperation, and even threatening extinction. We review the key mechanisms by which aggregative multicellular organisms control cheaters with a focus on the best studied aggregative organisms, Myxococcus xanthus and Dictyostelium discoideum. These include various passive and active mechanisms to maintain high relatedness within aggregates, to enforce cooperation on aggregate members, and the costs of cheating on other key functions. Ultimately, aggregative multicellular organisms are not that different from clonal organisms descended from a single cell.

Mountain systems within the Mediterranean region, e.g. the Pyrenees, are very sensitive to climate change. In the present study, we quantified the magnitude of extreme precipitation events and the number of days with torrential precipitation (daily precipitation ≥ 100 mm) in all the rain gauges available in the Pyrenees for the 1981-2015 period, analyzing the contribution of the synoptic scale in this type of events. The easternmost (under the Mediterranean influence) and north-westernmost (under Atlantic influence) areas of the Pyrenees registered the highest number of torrential events. The heaviest events are expected in the eastern part, i.e. 400 mm day-1 for a return period of 200 years. Northerly advections over the Iberian Peninsula, which present a low zonal index, i.e. im-plying a stronger meridional component, give rise to torrential events over the western Pyrenees; and easterly advections favour extreme precipitation over the eastern Pyrenees. The air mass travels a long way, from the east coast of North America, bringing heavy rainfall to the western Pyrenees. In the case of the torrential events over the eastern Pyrenees, the air mass causing the events in these areas is very short and originates in the Mediterranean Basin. The NAO index has no influence upon the occurrence of torrential events in the Pyrenees, but these events are closely related to certain Mediterranean teleconnections such as the WeMO

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

The Nocturnal Bottleneck explains how mammals evolved from their reptilian ancestors after inverting the chronotype, form diurnal to nocturnal. Pre-mammals traded-off the excellent visual system of their ancestors for improvements in audition and in olfactory telencephalon, needed for efficient orientation in the dark. This was how the mammalian nocturnal telencephalic wakefulness was born. However, the modified visual system of those pre-mammals became sensitive to the dangerous diurnal light and the exposure would involve a high risk of blindness and death. Therefore, pre-mammals had to remain immobile with closed eyes hidden in lightproof burrows during light time. This was the birth of the mammalian sleep. Typical reptiles distribute their wake time cycling between Basking Behavior, to attain the preferred body temperature, and poikilothermic Goal Directed Behavior, to perform life sustaining tasks. These cycles persisted during the new mammalian sleep. However, as the behavioral output had to be blocked during light time, the paralyzed reptilian Basking Behavior and Goal Directed Behavior cycles became the NREM and REM cycles, respectively. This was how NREM and REM cycles remained incorporated within the mammalian sleep. After the Cretaceous-Paleogene extinction, the environmental pressure for nocturnal life was softened, allowing high variability in chronotype and sleeping patterns. This permitted some mammalian groups, e.g., primates, to begin the quest for diurnal wake.Concluding, sleep constituted an additional bottleneck in the mammalian evolution. The reduced population of pre-mammals that was able to develop sleep during light time, including NREM and REM, became full mammals and survived; the remainder perished.

Waste glycerol can be subjected to various processing operations, including purification and re-fining, to obtain glycerol of appropriate purity. In addition, alternative methods of utilising waste glycerol are also being sought, e.g. by converting it into other valuable chemical products or biofuels. Therefore, various technologies are being developed to utilise this type of waste effectively and sustainably. The production of value-added products from waste glycerol is an important issue that determines the improvement of the economic viability of biofuel production and corresponds to the model of a waste-free and emission-free circular economy. This paper characterised the mechanisms and evaluated the efficiency of existing methods of microbiological utilisation of waste glycerol into liquid biofuels, including biodiesel, bioethanol and biobutanol, and identified further directions for the production of value-added products. In addition, a bibliographical analysis of publications re-lated to the production of liquid fuels and economically valuable products from glycerol was carried out, the progress of research and application work was assessed and directions for future research were identified.

Atherosclerosis (ATH) and Coronary Artery Disease (CAD) are chronic inflammatory diseases with an important genetic background which derive from the cumulative effect of multiple common risk alleles, most of them located in genomic non-coding regions. These complex diseases behave as non-linear dynamical systems that show a high dependence on their initial conditions, so that long-term predictions of disease progression are unreliable. One likely possibility is that the non-linear nature of ATH could be dependent on non-linear correlations in the structure of the human genome. In this review we show how Chaos theory analysis highlighted genomic regions that shared specific structural constraints that could have a role in ATH progression. These regions were shown to be enriched in repetitive sequences of the Alu family, genomic parasites which colonized the human genome, which show a particular secondary structure and have been involved in the regulation of gene expression. We also review the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms by which the Alu elements could alter the inflammatory homeostasis. We devise especial attention to their relationship with the lncRNA ANRIL, the strongest risk factor for ATH, their role as miRNA sponges, and their ability to interfere with the regulatory circuitry of the NF-kB response. We aim to characterize ATH as a non-linear dynamic system in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

In the last decade, probably in response to global changes and environmental crisis, the use of the term “social-ecological system” (SES) in the scientific literature has been growing. This is certainly a sign of the recognition of the need and importance of transdisciplinary research. Here, we explore whether the use of the term is a buzzword, or it actually represents a key concept toward the integration of social and ecological research. We compiled a data base of publications (N = 1289) that mentioned SES in title, keywords and abstract. Subsequently, we analyzed: authors affiliations, type of work (conceptual, empirical, review), study site, prevailing human use, temporal and spatial scales of analysis, kind of variables analyzed (socioeconomic, biophysical), and the method/s used to integrate them. We detected four time spans in the use of the term (1975–1997, 1998–2006, 2007–2012, 2013–2016). Our results suggest that SES is a widely invoked concept to study the interface between social and ecological systems. Most works show some common elements such as the analysis of resilience, ecosystem services, sustainability, governance and adaptive management. However, the majority of studies does not study SES as a whole, integrating both social and ecological variables and their feedback loops. We consider that SES is still a concept in construction in order to build a necessary framework to integrate social and ecological sciences. For a robust evolution we recommend to focus on 1. a conscious, discussed and agreed effort of scientists to conduct transdisciplinary research needed to study SES; 2. developing methodological tools for the true integration of social and ecological data.

This study delves into the realm of heuristic evaluation within usability testing, focusing on refining and applying a tailored algorithm that simplifies the implementation of the Analytic Hierarchy Process for heuristic prioritization. Addressing the prevalent challenge of disparate evaluation methodologies and the absence of a standardized process in usability testing, our research introduces a novel method that leverages the Analytic Hierarchy Process alongside a bespoke algorithm. This algorithm utilizes transitive properties for pairwise comparisons, significantly reducing the evaluative workload. This innovative approach facilitates the estimation of heuristic relevance irrespective of the number of items per heuristic or the item scale and streamlines the overall evaluation process. In addition to rigorous simulation testing of the tailored algorithm, we applied our method in a practical scenario, engaging seven usability experts in evaluating a web interface. This empirical application underscored our method’s capacity to diminish the requisite comparison count and spotlight areas of improvement for critically weighted yet underperforming heuristics. The outcomes of this study underscore the efficacy of our approach in enhancing the efficiency and organization of heuristic evaluations, paving the way for more structured and effective usability testing methodologies in future research endeavors.

Pigs are a social species and they stablish hierarchies for a better use of resources and to reduce conflicts. However, in pig production, the opportunities for growing can differ in dominant and subordinate animals. In the present study a system was tested to perform a Dominance versus Subordinate test in growing pigs to investigate how the hierarchy affects feeding behaviour, growth and gut microbiota assessed in faeces. 64 animals housed in eight different pens were used, with four castrated males and four females in each one, weighing 18kg at arrival and maintained during the whole growing period, until 140 kg. Three stool samplings were obtained from the animals directly from the anus to avoid contamination of the faeces on 58, 100 and 133 days after the start of the study to investigate the microbiota composition. The dominant animals had higher gains during the growing period that the subordinate. In addition, they were performing more visits to the feeder throughout the day. Differential abundance patterns were observed in five bacterial genera, Oliverpabstia, Peptococcus, and Faecalbacterium being more abundant in dominant animals and Holdemanella and Acetitomaculum being overrepresented in subordinate ones. This microbial biomarker accurately classified dominant versus subordinate groups of samples with an AUC of 0.92.

This paper presents a quantum formulation for classical abstract dynamical systems (ADS), defined by coupled sets of first order differential equations. They are referred as “abstract” because their dynamical variables can be of different interrelated nature, not necessarily corresponding to physics, such as populations, socioeconomic variables, behavioural variables, etc. A first order classical Hamiltonian in canonical moments can be derived for ADS by using Dirac’s dynamics for singular Hamiltonian systems. And also a corresponding first order Schrödinger equation (which involves the existence of a system Planck constant particular of each system) can be derived from this Hamiltonian. However, Bohm and Hiley’s reinterpretation of quantum mechanics produces no further information about the mathematical formulation of ADS. However, a second order classical Hamiltonian in canonical moments can be also derived for ADS, as well as a corresponding second order Schrödinger equation. In this case, Bohm and Hiley’s reinterpretation of quantum mechanics provides a quantum Hamiltonian that does provide the quantum formulation for ADS, which provides new quantum variables interrelated dynamically with the classical variables. An application case is presented: the one-dimensional autonomous system given by the logistic dynamics, where the differences between the classical and the quantum trajectories are highlighted.

Objectives: A wealth of literature has established risk factors for social isolation among older people, however much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.

Three types of wakefulness appeared along the vertebrate’s phylogeny and ontogeny: spinal-rhombencephalic in fish, brainstem-diencephalic in reptiles and cortical in mammals, in which the paralyzed spinal-rhombencephalic wake and the brainstem-diencephalic wake remain as REMS and NREMS The spinal-rhombencephalic and cortical types of wake are inherently anti-homeostatic. Animals must forage, reproduce, and survive to predation disregarding the environmental circumstances, hence temporarily forgetting the homeostatic regulation. After fulfilling the vital functions, the brainstem-diencephalic wake recovers the homeostatic control. The phasic signs of REMS are adaptive in immature mammals, serving for demanding heat, milk and defense to their mother. These advantages outweigh the REMS' poikilostasis in infants. The adults’ poikilostasis of REMS is harmless in thermoneutral environments but is mal-adaptive in aquatic environments in which REMS is reduced or even disappears. These exceptions explain the anomalous examples of REMS. An on-off hypothalamic switch homeostatically regulates the entrance and exit from REMS. Furthermore, the vital phasic signs of REMS depend on a second pontine proportional homeostatic control. Altogether, they regulate the expression of REMS.

The Japanese city presents a certain number of peculiarities in the organization of its physical space (weak zoning regulations, fast piecemeal destruction/reconstruction of buildings and blocks, high compacity, incremental reorganization). Compared to countries where urban fabrics are more perennial and easily distinguishable (old centers, modern planned projects, residential areas, etc.), in Japanese metropolitan areas we often observe higher heterogeneity and more complex spatial patterns. Even within such a model, it should be possible to recognize the internal organization of the physical city. The aim of this paper is thus to study the spatial structure of the contemporary Japanese city, generalizing on the case study of Osaka and Kobe. In order to achieve this goal, we will need to identify urban forms at different local scales (building types, urban fabrics) and to analyze them at a wider scale to delineate morphological regions and their structuring of the overall layout of the contemporary Japanese city. Several analytical protocols are used together with field observations and literature. The results, and more particularly the building and urban fabrics types and their location within the Osaka-Kobe metropolitan area, are interpreted in the light of Japanese history and model of urbanization. A synoptic graphical model of an urban morphological structure based upon Osaka is produced and proposed as an interpretative pattern for the Japanese metropolitan city in general.

Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain dynamics or computer traffic have been shown to display noisy behaviour consistent with a critical state between order and disorder. Living close to the critical point can have a number of adaptive advantages and it has been conjectured that evolution could select (and even tend to) these critical states. One way of approaching such state is by means of so-called self-organized criticality (SOC) where the system poises itself close to the critical point. Is this the case of living cells? It is difficult to test this idea given the enormous dimensionality associated with gene and metabolic webs. In this paper, we present an alternative approach: to engineer synthetic gene networks displaying SOC behaviour. This is achieved by exploiting the presence of a saturation (congestion) phenomenon of the ClpXP protein degradation machinery in E. coli cells. Using a feedback design that detects and then reduces ClpXP congestion, a {\em critical motif} is built from a two-gene network system, where SOC can be successfully implemented. Both deterministic and stochastic models are used, consistently supporting the presence of criticality in intracellular traffic. The potential implications for both cellular dynamics and designed intracellular noise are discussed.

The new SARS-CoV-2 coronavirus has brought with it an increase in the use of digital platforms and an exponential increase in the number of scientific papers worldwide. The purpose of this study is to show a global overview of the digital transformation from 1975 to the present (2021). The main collection of the Web of Science database was used to retrieve global scientific production on digital transformation. Bibliometric indicators of production, visibility, impact, and collaboration were analyzed to assess research progress on the topic. The results show that digital transformation is a construct of recent development, increasingly relevant and transdisciplinary, with a clear growth after the declaration of the global COVID-19 pandemic.

Background The high incidence of diverticulitis and hemorrhoidal proctitis episodes in the population imposes an important healthcare and economic burden. Aim To determine the association between intake of certain plant foods and diverticulitis and hemorrhoidal proctitis episodes. Methods Case-control study with quantitative food frequency questionnaire focusing on selected plant foods and derived products. These were grouped by main chemical components into: ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods like curcumin. We quantified intake according to 24-h recall, either on a 1-4 scale (no intake, low, moderate, high intake) or as the number of units consumed (e.g. cups of tea/coffee, n of oranges or lemons); this value was multiplied by the number of reported intake days per week (1-7). Overall intake was expressed as a continuous variable obtained by successively multiplying the score for each food category, and the result was transformed into a common logarithm (range 0.3 to 27.7). Cases and controls were compared using the chi-squared test, student’s t test, odds ratio (OR) and 95% confidence interval (CI), and predictive analysis (multiple logistic regression). Results The sample included 410 cases and 401 controls, who were similar in mean age and gender distribution. The mean score for overall intake of included plant foods was 6.3 points (standard deviation [SD] 4.5), and this was significantly higher in cases (8.5 points, SD 5.3) than in controls (4.1 points, SD 1.2; p < 0.001). Overall intake was similar in cases presenting diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (> 7 points) compared to controls (OR 13.2, 95% CI 8.3 to 20.8, p < 0.001). Predictive logistic regression models showed that the chemical food group most closely associated with diverticulitis and hemorrhoidal proctitis was capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. The OR for age was near the null value. Neither alliin nor miscellaneous food groups showed any association. Conclusions High, frequent consumption of some plant foods and derived products increases the risk of presenting symptoms of diverticulitis and hemorrhoidal proctitis.

To investigate whether high body mass index (BMI) increases the risk of recurrence and corre-lates with higher glucose uptake in recurrent lesions in post-menopausal female patients with breast cancer. The hospital database was searched to retrieve breast cancer patients, who had undergone an [18F]FDG PET/CT scan before neoadjuvant chemotherapy and curative-intent sur-gery. BMI was calculated at the baseline [18F]FDG PET/CT scan. There was a median follow-up of 5 years after the baseline PET/CT scan to identify: recurrence in the breast (T_rec); lymph nodes (N_rec); distant locations (M_rec). Furthermore, SUVmax was measured in the sites of recur-rence. A chi-square test was used to investigate any difference in the frequency of any recur-rence, T_rec, N_rec, and M_rec between overweight women (BMI≥25 kg/m2) and women with a BMI<25 kg/m2 (p<0.05). SUVmax, was compared using a t-test (p<0.05) between the two groups. A total of post-menopausal 142 women (BMI: 26.84±5.59; 84 overweight and 58 with normal weight) were retrieved. There were 48 recurrences at the follow-up. The chi-square test demon-strated in overweight women an increased frequency of any recurrence (35 vs. 13; p=0.025) and T_rec (15 vs. 2; p=0.018) and a higher T_rec SUVmax (4.74±2.90 vs. 1.85 ± 0.63; p=0.09) compared to women with a BMI<25 kg/m2. BMI seems to correlate with an increased rate of recurrence, espe-cially in the breast, and a higher glucose uptake in post-menopausal patients with recurrent breast cancer.

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single site lymphoma, 17% had regional lymphoma and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

Agriculture has been experiencing a difficult situation because of limiting factors in its production, Natural biostimulants (NBs) have emerged as a novel alternative. This study reviews NBs produced through Solid-State Fermentation (SSF) from organic waste, focusing on the processes and production methods. The aim is to highlight their potential for improving agricultural productivity and promoting sustainable agriculture. Through a literature review, the effects of NBS on crops were examined, as well as the challenges associated with their production and application. The importance of standardizing production processes, optimizing fermentation conditions, and assessing their effects on different crops is emphasized. Furthermore, future research areas are identified, such as enhancing production efficiency and evaluating the effectiveness of SSF-produced NBS in different agricultural systems. In conclusion, SSF-produced NBS offers a promising alternative for sustainable agriculture, but further research and development are needed to maximize its efficacy and enable large-scale implementation.

Background: Frailty assessment allows the identification of patients at risk of death, and it is a challenge in both emergency departments and support wards. The aim here was to study the ability of the Frail-VIG Index (FI-VIG) in order to discriminate frailty groups of older adults and garner its correlation with mortality in an emergency department short-stay unit (2) Methods: Our observational, single-center, prospective study consecutively included patients over 65-years-old admitted to the unit between March 1, 2021, and April 30, 2021. (3) Results: A total of 302 patients were included (56% women), with a mean age of 83 ± 8 years, and 39.1% of them had a functional disability whilst 16.5% of them had dementia. A total of 174 patients (58%) met the frailty criteria (FI-VIG ≥0.2): 111 (63.8%) had mild frailty (FI-VIG 0.2 - 0.36), 52 (29.9%) had moderate frailty (FI-VIG 0.36 - 0.55), and 11 (6.3%) had advanced frailty (FI-VIG >0.55). Mortality at 30 days, 6 months, and 1 year was analyzed: no frailty was 6.3%, 10.8%, and 12.5%, respectively; mild frailty was 10.8%, 22.5%, and 22.5%, respectively; moderate frailty was 25%, 34.6%, and 42.3%, respectively; and advanced frailty was 36.4%, 54.5%, and 3.6%, respectively. This shows the significant differences between the groups (1-year mortality p<0.001). Mild frailty vs. non-frail HR was 2.47 (95%CI 1.12 - 5.46), moderate frailty vs. non-frail HR was 6.93 (95%CI 3.16 - 15.23), and advanced frailty vs. non-frail HR was 11.29 (95%CI 3.54 - 36.03). The mean test time was 7 minutes. (4) Conclusions: There was a strong correlation between frailty degree and mortality at 1, 6, and 12 months. FI-VIG Index is a fast and easy-to-use tool in this setting, and its routine implementation in SSUs could enable early risk stratification in order to detect vulnerable patients with specific needs.

The increading emission of carbon dioxide to the atmosphere has urged the scientific community to investigate alternatives to alleviate such emissions being the principal contributor to the greenhouse gas effect. One major alternative is carbon capture and utilisation (CCU) towards the production of value-added chemicals using diverse technologies. This work aims at the study of the catalytic potential of different cobalt-derived nanoparticels for methanol syntheis from carbon dioxide hydrogenation. Thanks to its abundance and cost-efficacy, cobalt can serve as an economical catalyst compared to noble-metal-based catalysts. In this work, we present a systematic comparison among different cobalt and cobalt oxide nanocomposites in terms of their efficiency as catalysts for carbon dioxide hydrogenation to methanol as well as how different supports can enhance their catalytic capacity. The oxygen vacancies in the cerium oxide act as carbon dioxide adsorption and activation sites, which facilitates a higher methanol production yield.

This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries have been tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance have been determined. Results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with previous studies results, to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.

The 3D/3D+ multidimensional geriatric assessment tool provides an optimal model of emergency care for patients aged 75 and over who attend the Emergency Department (ED). The baseline, or static, component (3D) stratifies the degree of frailty prior to the acute illness, while the current, or dynamic, component (3D+) assesses the multidimensional impact caused by the acute illness and helps to guide the choice of care facility for patients upon their discharge from the ED. The objective of this study was to evaluate the prognostic value of the 3D/3D+ to predict short- and long-term adverse outcomes in ED patients aged 75 years and older. Multivariable logistic regression models were used to identify the predictors of mortality 30 days after 3D/3D+ assessment. Two hundred and seventy-eight patients (59.7% women) with a median age of 86 years (interquartile range: 83-90) were analysed. According to the baseline component (3D), 83.1% (95%CI: 78.2-87.3) presented some degree of frailty. The current component (3D+) presented alterations in 60.1% (95%CI: 54.1-65.9). The choice of care facility at ED discharge indicated by the 3D/3D+ was considered appropriate in 96.4% (95%CI: 93.0-98.0). Thirty-day all-cause mortality was 19.4%. Delirium and functional decline were the dimensions on the 3D/3D+ that were independently associated with 30-day mortality. These two dimensions had an area under receiver operating characteristic of 0.80 (95%CI: 0.73-0.86) for predicting 30-day mortality. 3D/3D+ enhances the provision of comprehensive care by ED professionals, guides them in the choice of patients’ discharge destination, and has a prognostic validity that serves to establish future therapeutic objectives.

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

The objective of this study was to evaluate the potential benefits of feeding spray-dried porcine plasma (SDPP) to pigs infected with African swine fever virus (ASFV). Two groups of twelve weaned pigs each were fed with CONVENTIONAL or 8% SDPP enriched diets. Two pigs (trojans)/group) were injected intramuscularly with the pandemic ASFV (Georgia 2007/01) and comingled with the rest of the pigs (1:5 trojan:naïve ratio) to simulate a natural route of transmission. Trojans developed ASF and died within the first week after inoculation but contact pigs did not develop ASF, viremia or seroconversion. Therefore, three more trojans per group were introduced to optimize the ASFV transmission (1:2 trojan:naïve ratio). Blood, nasal and rectal swabs were weekly harvested and at end of the study, ASFV-target organs collected. After the second exposure, rectal temperature of conventionally fed contact pigs increased >40.5˚C while fever was delayed in the SDPP contact pigs. Additionally, PCR Ct values in blood, secretions and tissue samples were significantly lower (P<0.05) for CONVENTIONAL compared to SDPP contact pigs. Under these study conditions, contact exposed pigs fed SDPP had delayed ASFV transmission and reduced virus load, likely by enhanced specific T-cell priming after the first ASFV-exposure.

Cognitive networks have evolved to cope with uncertain environments in order to make reliable decisions. Such decision making circuits need to respond to the external world in efficient and flexible ways, and one potentially general mechanism of achieving this is grounded in critical states. Mounting evidence has shown that brains operate close to such critical boundaries consistent with self-organized criticality (SOC). Is this also taking place in small-scale living systems, such as cells? Here we explore a recent model of engineered gene networks that have been shown to exploit the feedback between order and control parameters (as defined by expression levels of two coupled genes) to achieve a SOC state. We suggest that such SOC motif could be exploited to generate adaptive behavioral patterns and might help design fast responses in synthetic cellular and multicellular organisms.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Background: Tuberculosis (TB) continues to be a serious public health threat that affects the most vulnerable population. Patients who are LTFU after TB diagnosis still represent one of the biggest challenges to TB control. Method: In this prospective observational study, we aimed to identify and analyse the risk factors associated with LTFU among TB patients who started first-line TB treatment in the Sanatorium Hospital in Luanda. Result: A total of 113 patients with TB were included between August 2018 and September 2019. Seventy-six (67.3%) patients were cured, 27 (23.9%) were LTFU, 5 (4.4%) died, 4 (3.5%) were transferred and 1 (0.9%) presented a treatment failure. After excluding those dead, transferred or who failed to treatment, we observed that severe TB at the time of diagnosis (OR 9.24, 95% CI 2.18-39.04) and food insecurity were significantly associated with LTFU (OR 5.96, 95% CI 1.66-21.41). Conclusion: The findings of our study are of enormous value to understand the reasons for the LTFU of patients with TB and can guide polices and facilitate designing measures to allow better adherence, and therefore, greater treatment success

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

Blood-based biomarkers are much-needed diagnostic and prognostic tools for ALS. Canine degenerative myelopathy (DM) is recognized animal disease model to study the biology of human ALS. Serum derived exosomes are potential carrier that transport intercellular hormone-like messengers, together with their stability as carrier of proteins and RNA, make them ideal as biomarkers for a variety of diseases and biological processes. We study exosomal TDP-43 pattern as a surrogate biomarker that reflects biochemical changes in central nervous system. We isolated exosomes from canine serum using commercial exosome isolation reagents. TDP-43 and SOD1 profile in spinal cord homogenate lysate and that of serum-derived exosomes were found elevated in dogs with DM. We conclude levels of spinal cord TDP-43 and serum-derived exomes were similar in TDP-43 profiling, which warrant further investigation of disease sensitivity and specificity for establishing as a blood-based biomarker in canine DM.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

Mediterranean catchments are characterized by significant spatial and temporal hydrological variability caused by the interaction of natural as well human-induced abiotic and biotic factors. This study investigates the (non-)linearity rainfall-runoff relationship at multiple temporal scales in representative small Mediterranean catchments (i.e., < 10 km2) to achieve a better understanding of the hydrological response. Rainfall-runoff relationship was evaluated in 44 catchments at annual and event –203 events in 12 of these 44 catchments– scales. A linear rainfall-runoff relation was observed at annual scale with higher scatter in pervious than impervious catchments. Larger scattering was observed at event scale, although pervious lithology and agricultural land use promoted significant rainfall-runoff linear relations in winter and spring. These relationships were particularly analysed during five hydrological years in Es Fangar catchment (3.35 km2; Mallorca, Spain) as a temporal downscaling to assess intra-annual variability in which antecedent wetness conditions played a significant role in runoff generation.

The Dual-Frequency Precipitation Radar (DPR) on the Core GPM satellite provides spaceborne 3-dimensional observations of the precipitation field and surface rainfall rate with quasi global coverage. The present study evaluates the behavior of liquid precipitation intensity, radar reflectivity factor (ZKu and ZKa) and Drop Size Distribution (DSD) parameters (weighted mean diameter Dm and intercept parameter Nw) of the GPM DPR derived products version 07 from 2014 to 2023. Observations from seven Parsivel disdrometers located in different topographic zones in the Western Mediterranean are taken as ground reference. Four matching techniques between satellite estimates and ground level observations were tested, and best results were found for the so-called optimal comparison approach. Overall, GPM DPR products capture well the variability of the observed DSD at different rainfall intensities. However, overestimation of the mean Dm and underestimation of the mean Nw are observed, being much more sensitive to errors in drop diameters larger than 1.5 mm. Moreover, lowest errors were found for radar reflectivity factor and Dm, and highest for Nw and rainfall rate. In addition, the GPM DPR convective and stratiform classification was tested and it was found a substantial overestimation of stratiform cases compared to disdrometer observations.

This study investigates the impact of inoculating Torulaspora delbrueckii (Td) strains during the initial phase of Carbonic Maceration (CM) vinification, aiming to enhance the fermentative process and unique characteristics of CM wines. CM is a winemaking technique where whole bunches (without destemming and crushing) are enclosed in tanks filled with carbon dioxide, inducing intracellular fermentation. The study compares the effects of two Td strains on the MLF performance and sensory characteristics of CM wines, using both inoculated and spontaneous MLF strategies. Although general physicochemical parameters remained consistent across conditions, organoleptic attributes showed significant differences due to T. delbrueckii presence. T. delbrueckii introduction during CM resulted in wines with increased anthocyanin content and a particular volatile profile. Isoamyl acetate, a key aroma in CM wines, was notably elevated, especially in the TdP strain. Sensory evaluations also revealed distinctions, with TdV wines displaying more pronounced aromas of red fruit, banana, and grass. Regarding MLF, T. delbrueckii presence notably enhanced performance, particularly in spontaneous MLF cases, accelerating fermentation completion. Inoculating the Oenococcus oeni strain OoVP41 also shortened MLF duration. These findings highlight the potential of Td strains to improve MLF efficiency and sensory attributes in CM wines. Employing T. delbrueckii strains strategically enables winemakers to optimize MLF and improve sensory profiles, offering an opportunity to produce higher-quality CM wines.

Ctenophores are marine organisms attracting significant attention from evolutionary, molecular biology and ecological research. Here we describe an easy and affordable set-up to maintain a stable culture of the ctenophore Mnemiopsis leidyi. The challenging delicacy of the lobate ctenophores can be met by monitoring the water quality, providing the right nutrition, and adapting the handling and tank set-up to their fragile gelatinous body plan. Following this protocol allows stable laboratory lines, a continuous supply of embryos for molecular biological studies, and independence from population responses to environmental fluctuations.

Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 65 million cases and one point five million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date. We created a novel computational pipeline aimed to speed up the process of repurposable candidate drug identification. Compared with current drug repurposing methodologies, our strategy is centered on filtering the best candidate among all selected targets focused on the introduction of a mathematical formalism motivated by recent advances in the fields of algebraic topology and topological data analysis (TDA). This formalism allows us to compare three-dimensional protein structures. Its use in conjunction with two in silico validation strategies (molecular docking and transcriptomic analyses) allowed us to identify a set of potential drug repurposing candidates targeting three viral proteins (3CL viral protease, NSP15 endoribonuclease, and NSP12 RNA-dependent RNA polymerase), which included rutin, dexamethasone, and vemurafenib among others. To our knowledge, it is the first time that a TDA based strategy has been used to compare a massive amount of protein structures with the final objective of performing drug repurposing

Coronavirus disease 19 (COVID-19) continues to spread worldwide as a severe pandemic. The Omicron BA.2 became the predominant variant and the protagonist of the ongoing surge. As the virus continues to mutate, using of approved drugs or developing new therapeutic or prophylactic therapies against COVID-19 could be more complex. Sotrovimab is a monoclonal antibody (mAb) targeting the conserved epitope on the spike protein receptor; the most recent studies observed that it has substantially decreased in vitro activity against the Omicron BA.2 subvariant, but real-life data are still scarce. We describe the outcome of a case series of outpatients with BA.1 or BA.2 infection treated with sotrovimab. We conducted a retrospective observational study including all non-hospitalized adult patients treated with sotrovimab, for which a Sanger sequencing of SARS-CoV-2 was performed within a regional genomic surveillance program. Eleven (50%) patients with BA.1 infection and eleven (50%) with BA.2 infection were considered. Most patients were immunocompromised. During the follow-up period, no patient died and only one with BA.1 infection was hospitalized for severe COVID-19 pneumonia onset. One month after treatment, 90.9% of patients were completely asymptomatic in each group. We demonstrated that patients carrying the BA.2 variant treated with sotrovimab did not evolve to severe COVID-19, showing a similar outcome to BA.1 infected patients. Further studies are needed to prove that vaccination or the presumably high doses of mAbs used can protect this group of patients at high risk of progression.

There are scarce data regarding flu vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects’ adherence over the last 3 seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to vaccinate. The population was divided into two groups: fully adherent (all 3 campaigns, 117 patients) and non-fully adherent (1 or 2 campaigns, 102 patients). Adherence increased in non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbelieves emerged: influenza vaccine was considered protective SARS-CoV-2 (22.8% of total population); almost half of all patients thought influenza vaccine could improve their CD4+ cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p<0.05). A quarter of the non-fully adherent group would not have vaccinated in a location other than our clinic (24.5% vs 11.9% in fully adherent group, p<0.05). Conclusively, offering a secure and private space for vaccination seems to encourage vaccination; healthcare professionals should improve counselling to increase adherence and correct misbeliefs.

Patients with COPD have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from January 1st to May 10th, 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2,51%; CI95% 2,33 – 2,68) was significantly higher than in the general population aged > 40 years (1,16%; 95%CI 1,14 – 1,18); P < .001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31,1 % vs 39,8%: OR 1,57; 95%CI 1,14 – 1,18) and mortality (3,4% vs 9,3%: OR 2,93; 95%CI 2,27 – 3,79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (P<0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.

Objective To measure, exposure to PM2.5 particles in outdoor smoking areas and changes in breathing rates in patients with asthma or chronic obstructive pulmonary disease (COPD). Setting Sixty venues in Czechia, Ireland and Spain, in an open, non-randomised, clinical trial. Participants We studied 60 patients-30 asthma patients (Female 63.3%), with a mean age (+/-standard deviation [SD]) of 47.4 (19.0 SD), and 30 COPD patients (Female 51.6%), mean age 63.5 (10.1 SD), smokers, non-smokers or ex-smokers, recruited through medical clinics. Intervention Patients wore a PM2.5 particle monitor (AirSpeck), and a breath monitor (RESpeck) for 24 hours to determine changes in breathing rates (Br) at rest and during a visit to an outside smoking area. Spirometry and breath CO were measured before and the day after visiting an outdoor smoking area. Results PM2.5 levels in the 60 venues were highly variable, in 1 premises levels of PM2.5 were sustained for at least 15 minutes at ≥ 2,000 µg/m3, in 4 premises, ≥ 500 (range 1,933-539) µg/m3, in 8 premises, ≥ 200(range 480-203) µg/m3, in 9 premises, ≥ 100 (range 170-108) µg/m3, in 8 premises, ≥ 40 (range 80.5- 40.1) µg/m3, in 9 premises, ≥ 25 µg/m3, in 10 premises, ≥ 10 µg/m3, in 8 premises, and ≤10 µg/m3 in only 3 premises, with a single wall. The overall breathing rates/minute (Br)did not change significantly but in 28 patients mean Br increased from 21.47 (1.74 SD) to 22.8 (2.29 SD), change of -1.35 (-1.80-0.91 C.I), p value 0.00 and mean in 29 patients Br decreased from 21.95(2.43 SD) to 20.38(2.79 SD), 1.57(1.03-2.12 C.I), p value 0.00. Conclusion Exposure to high levels of PM2.5, and associated alteration of patients’ breathing rates occurred in outdoor smoking areas despite national comprehensive smokefree laws. These exposure levels support the abolition of such areas. (Words 295) ClinicalTrials.gov ID: NCT03074734 Ethics: Approval Number: Ref: 15-103

Ecuador is an important center of biodiversity of the plant family Amaryllidaceae, specially the subfamily Amaryllidoideae, known as a source of important bioactive molecules. The aim of this study was to assess the chemical and biological potential of four different species of Amaryllidoideae collected in Ecuador: Urceolina formosa, Urceolina ruthiana, Clinanthus incarnatus, and Stenomesson aurantiacum. Sixteen alkaloids were identified in the bulb extract of these species by GC-MS, which the extract of S. aurantiacum exhibiting the greatest structural diversity. The potential of these three genera against Alzheimer’s disease was evaluated by measuring their AChE and BuChE inhibitory activity, revealing that C. incarnatus and U. formosa (from Sucumbíos province) showed the best results with IC50 values of 1.73 ± 0.25 and 30.56 ± 1.56 g·ml-1, respectively. Molecular dynamic assays were conducted to elucidate the possible interactions that occurs among 2-hydroxyanhydrolycorine and AChE enzyme, suggesting some similarity with those observed for galanthamine. This study enhances our understanding of the biodiversity of Amaryllidoideae species from Ecuador, highlighting their potential as a source of chemical compounds with pharmaceutical potential.

High-quality and large-size single crystals of lead-free Na0.5Bi0.5TiO3 were grown using the Czo-chralski technique. The crystals had pure perovskite structure with rhombohedral symmetry and were translucent in the visible and near infrared spectral ranges recorded in the interval 350-1050 nm. The energy gaps determined from the X-ray photoelectron spectroscopy (XPS) and optical measurements were approximately 2.92 eV. The current-voltage characteristics, depolarization current, dc (σdc) and ac (σac) electrical conductivity, and Seebeck coefficient of the crystals were investigated. The frequency/temperature-dependent electrical properties were also measured and analyzed through complex impedance spectroscopy. An overlapping reversible insulator-metal transition (resistive switching) on nanoscales, caused by the electric field, was detected. This was the first time that most of these investigations were performed for this material. The following conductivity mechanisms of NBT single crystals were identified: (i) quasi-free electron and hole conduction and hopping-charges mechanism at low temperatures, (ii) small polaron conductivity in the middle temperature range, and (iii) a significant contribution of the oxygen vacancies to conductivity in the high temperature range. The activation energy values determined from the conductivity data, the imaginary part of the electric impedance and the modulus indicate that the relaxation process in the high-temperature range is attributable to both single and double ionized oxygen vacancies, in combination with the hopping of electrons between Ti4+ and Ti3+. P-type electrical conductivity was also found. These discoveries create new possibilities of reducing the electrical conductivity of NBT and improving the process of effectively poling this material. The density of the electronic states was investigated using an ab initio method. The energy gap cal-culated for NBT (R3c) was 2.8 eV, and is well comparable to those determined from XPS and optical measurements. Our results indicate the possibility of tuning material properties by inten-tionally creating non-stoichiometry/structural defects (oxygen vacancies, cation excess and cation deficiency).

Objective: Several authors have analyzed the impact of the pandemic on the incidence rates of different conditions. Our aim was to analyze the impact of the COVID-19 pandemic on primary care new diagnoses of respiratory diseases. Methods: This was an observational retrospective study performed to describe the impact of COVID-19 pandemic on primary care new diagnosis of respiratory diseases other than lung cancer. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found an decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications. Instead, we found increases in new diagnoses of flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic. The real clinical impact of this situation is still unknown. Large-scale real-life studies will make it possible to evaluate the long-term true impact of COVID-19 pandemic on the respiratory diseases management.

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given daily a placebo (controls) or BC during suckling. The liver miRNAome was analyzed in recently weaned animals by microarray hybridization. BC impacted the liver miRNAome differently in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.

1) Background: Traditionally, complex biological products such as vaccines presented unique challenges to implementation of even rudimentary characterization packages; thus, the product was defined almost exclusively by its manufacturing process. The advances in technology and analytical tools allowed the application of more comprehensive characterization packages for products such as adsorbed combination vaccines, which contain several antigens in a single formulation to protect against more than one disease, and may contain adjuvants and excipients. Aluminum phosphate (AlPO4) is a well-established adjuvant for enhancing the uptake of vaccines and to induce robust immunity against pathogens. During manufacturing, adjuvant is mixed with protein antigens which may in turn impact their higher order structure and stability. 2) Methods: To study the structural changes of protein antigens after adsorption several analytical tools including DLS, FTIR, Fluorescence, LD, and SEM were used. 3) Results: the AlPO4 adjuvant suspension consists of small submicron particles that form a continuous porous surface. Secondary structure alpha-helix and beta-sheet content of DT and TT increased after adsorption to AlPO4 adjuvant, whereas no significant changes were noted for other protein antigens. Interactions were noted between AlPO4 adjuvant and DT, TT, and FHA. 4) Conclusions: here we report for the first time the use of SEM for the visualization of adsorbed multivalent vaccine components. A unique signature profile detected for each multivalent vaccine by FTIR can be used as a lean in-process test to verify vaccine product composition and identity prior to filling.

Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. Conclusion: Despite the prevalence of cefotaxime non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.