In the southeastern coast of Brazil, the bays of Ilha Grande and Sepetiba are linked by the Ilha Grande Channel, where remarkably vigorous currents have been consistently observed. The sheer intensity of these currents defies a simple explanation through tidal forcing alone, prompting researchers to delve into potential influences such as basin resonance and the baroclinic effect. This study aims to elucidate the role of remote meteorological effects within this complex hydrodynamic system. A numerical approach with a coastal model nested within an ocean model was employed, enabling an in-depth examination of the intricate interplay between meteorological and tidal forcings. The study revealed a significant finding: the lag in signal propagation plays a pivotal role in determining how these signals impact the dynamics of the bays. The astronomical signal exhibits a minimal lag along the coast (1 minute), and leads to water level differences between the sea and the coastline, resulting in the generation of tidal currents at the bay entrances. On the other hand, the remote meteorological signal, with a stronger signal lag along the coast (4.92 hours), leads to the creation of water level difference between the bay’s entrances, inducing significant fluxes along the narrow Ilha Grande Channel.

This research addresses the respiratory distress syndrome (RDS) in preterm newborns, caused by insufficient surfactant synthesis, which can lead to serious complications, including pneumothorax, pulmonary hypertension, and pulmonary hemorrhage, increasing the risk of a fatal outcome. By analyzing chest radiographs and blood gases, we specifically focus on the significant contributions of these parameters to the diagnosis and analysis of the recovery of patients with RDS. The study involved 32 preterm newborns, and the analysis of gas parameters before and after the administration of surfactants and inhalation corticosteroid therapy revealed statistically significant changes in values of parameters such as FiO2, pH, pCO2, HCO3 and BE (Sig.<0.05), ehile the pO2 parameter showed a potential change (Sig.=0.061). Parallel to this, the research emphasizes the development of a lung segmentation algorithm implemented in the MATLAB programming environment. The key steps of the algorithm include preprocessing, segmentation, and visualization for a more detailed understanding of the recovery dynamics after RDS. These algorithms have achieved promising results, with a global accuracy of 0.93±0.06, precision 0.81±0.16 and an F-score of 0.82±0.14. These results highlight the potential application of algorithms in the analysis and monitoring of recovery in newborns with RDS, also underscoring the need for further development of software solutions in medicine, particularly in neonatology, to enhance the diagnosis and treatment of preterm newborns with respiratory distress syndrome.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX, and of peptidase ClpP heptameric rings, are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype-phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of ClpXP with GFM1 and TUFM orthologs. ClpX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granule, and nucleoid; ClpB preferentially attaches to mitochondrial RNA granule and translation initiation components; ClpP is enriched with them all, and associates with release/recycling factors. Mutations in ClpP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that ClpB and ClpXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotide-phosphates. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth, and for the treatment of human infertility, deafness and neurodegeneration.

The acoustic environment in learning spaces significantly influences learning effectiveness and occupant well-being. Recent studies have shown that a series of architectural factors within physical learning environments can impact students' educational experiences. This research delves into the relationship between architectural characteristics and the perceived acoustic environment among 467 primary students in 19 learning spaces across 9 schools in Chile. The survey comprises a student questionnaire, a checklist evaluating space characteristics, and acoustic measurements of indoor noise levels during occupied conditions. Examined topics include Indoor Environmental Quality (IEQ) comfort perception, noise annoyance, hearing ability, and acoustic preference. Architectural characteristics considered encompass flexible and acoustic space design parameters. The results indicated that noise discomfort was a common issue, especially in traditional learning spaces without acoustic treatment. The type of learning space (traditional or flexible settings) has a greater impact on acoustic perception particularly concerning noise discomfort and acoustic preference. However, poorly acoustic spaces lacking absorbing materials or exhibiting lower spatial density (m2 per student) contribute to increased indoor noise levels affecting noise annoyance caused by children's talking inside. The study emphasizes the importance of considering both architectural design and acoustic conditioning for optimizing the acoustic experience in educational spaces.

Oral mucosa is a key player in the cancer patient and during cancer treatment. The increasing prevalence of cancer and cancer therapy associated side effects are behind the major role that oral mucosa plays in the oncological patient. Oral mucositis is a debilitating severe complication caused by early toxicity of chemo and/or radiotherapy that can restrict treatment outcome possibilities, even challenging patient’s survival. It has been referred to as the most feared cancer treatment complication. Predictive variables as to who and to what extent will be affected are still unclear. Additionally, oral mucositis is one of the sources of the increasing economic burden of cancer, not only for patients and their families but also for institutions and governments. All efforts should be implemented in the search for new approaches to minimize the apparently ineluctable outburst of oral mucositis along the cancer treatment. New perspectives derived from different approaches in explaining the interrelation between oral mucositis and oral microbiome or the similarities with genitourinary mucosa may help elucidate the biomolecular pathways and mechanisms behind oral mucosa cancer-therapy related toxicity and what is more important its management in order to minimize treatment side effects and to provide enhanced cancer support.

We ascertain the in vitro Benznidazole (BZN) and Nifurtimox (NFX) susceptibility pattern of epimastigotes, trypomastigotes, and amastigotes of 21 T. cruzi strains, from patients, reservoir and triatomine bugs of various geographic origin. Using this panel of isolates, we compute the Epidemiological cut off value (CO_wt). Then, the frequency of the susceptible phenotype (Wild type) towards BZN and nifurtimox (NFX) within this set of strains belonging to 3 discrete typing units (DTUs), TcI, TcII, and TcV was deduced. We have observed that the susceptibility status of individual T. cruzi isolates toward BZN and NFX is related to the genetic background and to underlying factors probably related to the individual life trait history of each strain. Analyzing drug susceptibility in this conceptual framework would offers the possibility to evidence a link between isolates expressing a low susceptibility level (not wild-type) as define by the CO_wt value and none-curative treatment. It will also permit to tract drug-resistant parasites in T. cruzi population.

Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration at weekdays and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19-64 years old, participating in the 2008-2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration at weekdays was categorised into tertiles to reflect short, normal and long sleep duration. Social jetlag was calculated as the difference between sleep duration at weekends and weekdays. The association between sleep duration/ social jetlag and dietary patterns, derived by principal components analysis, was assessed regressing diet on sleep whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average 0.45 (95% CI -0.78, -0.12) lower healthy dietary pattern score compared to middle tertile (p =0.007). There was an inverted u-shaped association between social jetlag and a healthy dietary pattern, such that when sleep at weekends exceeded weekday sleep by 1h 45min, scores for indicating a healthy dietary pattern declined (p =0.005). In conclusion, long sleep duration at weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.

Stunting in children is a serious problem of nutritional disorders and is strictly monitored by the Indonesian government, it is not only cause physical but also cognitive abnormalities in the form of less intelligence in children so that when they grow up, their productivity will decrease. The incidence of stunting in 2018 in Indonesia was 30.8 %, while in West Java was 29.92%, still at a moderate to high level, consequently, prevention and early detection efforts need to be carried out by various parties, including health professionals and health cadres. Therefore, the aim of this study was to examine the association between the socio demographic characteristics factors as well as the knowledge and motivation of health cadres in the stunting prevention in West Java. A correlational study with a cross-sectional approach was employed with the samples of health cadres from 8 districts/cities in West Java Province: Karawang, Tasikmalaya, Garut, Bandung, Subang, Sukabumi, Cianjur, and West Bandung. A total of 363 health cadres participated and the sampling technique used is the stratified method. The data were collected using a questionnaire developed specifically for this study and were analyzed using a correlation with Chi-Square test and presented in the form of a frequency distribution. The study findings found that majority of the health cadres have good knowledge of 81.27%, which was significantly influenced by education level and marital status with p <0.05. Meanwhile, approximately half of the respondents had moderate motivation with 47.66%, while one-third or 39.12% had high motivation. This motivation was significantly influenced by education level, marital status, and age with p <0.05. It was concluded that health cadres need to further enhance the roles and functions in the prevention and early detection of stunting in West Java by providing continuous guidance, stunting training prevention and award presentations.

Personal Information Management Systems (PIMS) are acquiring a prominent role in the data economy by promoting services that help individuals to have more control over the processing of their personal data, in line with the European data protection law. One of the highlighted solutions in this area is Solid, a new protocol that is decentralizing the storage of data, through the usage of interoperable Web standards and semantic vocabularies, to empower its users to have more control over the processing of data by agents and applications. However, to fulfill this vision and gather widespread adoption, Solid needs to be aligned with the law governing the processing of personal data in Europe, the main piece of legislation being the General Data Protection Regulation (GDPR). To assist with this process, we analyze the current efforts to introduce a policy layer in the Solid ecosystem, in particular, related to the challenge of obtaining consent for processing personal data, focusing on the GDPR. Furthermore, we investigate if, in the context of using personal data for biomedical research, consent can be expressed in advance, discuss the conditions for valid consent and how it can be obtained in this decentralized setting, namely through the matching of privacy preferences, set by the user, with requests for data and whether this can signify informed consent. Finally, we discuss the technical challenges of an implementation that caters to the previously-identified legal requirements.

Few-layer graphene oxide (GO) has shown none or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines such as glyoma cells and human skin HaCaT cells, in concentrations up to 100 µg/mL However, multi-layer GO has been hardly explored in the biomedical field. Thus, multi-layer GO was examined here in human keratinocyte HaCaT cells treated with different concentrations ranging from 0.01 to 150 µg/mL during different periods of times (3, 12 and 24 hours). The results of this study showed a time-concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 hours of GO exposure. Contrary to what has been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity compared to an epidermal growth factor (1.6-fold greater than the control group) after 96 hours. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN and VCAN) at the non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 hours. Thus, the lowest non-cytotoxic GO concentration was able to up-regulate the CAT, TGFB1, FN1 and CDH1 genes, which confirms the great potential of multi-layer GO in the biomedical field.

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Frontal incomes play an important role in human behavioral regulation and can be a determinant of eating behavior. The aim of this study was to analyse the frontal incomes in obese patients with and without Binge Eating Disorder (BED), compared to normoweight (NW) subjects and to analyse the effect of sex and binge disorder on quality of life, with age and BMI as covariates. A total of 114 participants comprised three different groups (obese with BED, obese without BED and NW) completed the Frontal Assessment Battery (FAB) and Impact of Weight on Quality of Life (IWQOL-lite). The results showed that obese patients, with and without BED, have poorer frontal functioning than NW persons. Obese patients with BED have lower performance in frontal income than obese patients without BED. Male participants have a higher perception of quality of life in all dimensions, with women showing lower values in self-esteem and sex life. Obese with BED show greater weaknesses in physical function. These results suggest that low frontal incomes and worse quality of life characterize obese patients, more evident in obese patients with BED.

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

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

Human keratinocytes and melanoma can stick together to form clusters after eight days in co-culture. As in dynamic system concepts, one can consider cluster formation as the system attractor, cell seeding as the initial condition, and density change over time as a path within the basin of attraction. Herein, Cellular Automata, which is a class of Agent-Based Models, and Boolean Networks are discrete modeling methods used in population dynamics such that running the dynamics of cellular automata backward reveals an underlying network in terms of basin of attraction, also known as global dynamics. Thus, we hypothesize that one can estimate the local dynamic of an agent-based model from the basin of attraction of a boolean network. Here, we propose an approach to estimating these agent-based model rules, which consists of comparing the density states within each state transition and reaching a consensus among state transitions belonging to a basin of attraction of a boolean network. The objectives of this study are: (1) to infer a boolean network from the co-culture growth curve; (2) to estimate the rules of agent-based models; and (3) to implement spatial dynamics simulations. The binarization of the growth curve shows high population density after four days; the estimated agent-based model rules were compatible with cell proliferation and migration in agreement with literature, so we had to propose individual rules for survival and death. Spatial dynamics shows that (1) keratinocytes exhibit a higher density in neighborhoods where melanoma is present; (2) the chance of keratinocyte migration increases until the fourth day, then decreases, and the probability of survival increases substantially after four days; and (3) cells with low proliferation capacity die and free space for those with high ones. Our approach suggests that the attractor state of cell co-culture is induced mainly by an increase in keratinocyte migration and survival. Our approach has the potential to offer valuable clues about microenvironmental interactions or configurations that drive population dynamics.

Outdoor lighting design is a multidisciplinary topic that involves, among other aspects, design, energy savings, protection of nocturnal biodiversity and profitability, all of which are important functional and regulatory requirements. However, they do not necessarily consider user needs, which make perception and emotional response difficult parameters in the lighting design process. The studies carried out on lighting and its impact on emotions have mainly been done indoors. The objective of this work is to propose a methodology to evaluate emotional response to the illuminated nocturnal urban space with the purpose of providing knowledge to create emotionally efficient luminous spaces that improve people's perception and well-being. The instrument used was the survey (online questionnaires), based on Kansei engineering, created to incorporate the emotional variable in product design. The research was carried out with participants from Peru, Spain, and Germany. The results collected the reaction of the participants to different types of night-time luminous spaces presented, which contributes to a better understanding of user needs and activities regarding the space. This knowledge is intended to help designers meet their expectations.

Abstract: Arranged patterns obtained by ultrafast laser processing on the surface of Ti/Cu/Ti/Si and Ti/Zr/Ti/Si thin film systems are reported. Two differently designed multilayer thin films, Ti/Cu/Ti/Si and Ti/Zr/Ti/Si, were deposited on silicon by the ion sputtering method. The bioactive surfaces on these systems involve the formation of laser-induced periodic surface structures (LIPSS) in each of the laser-written lines of mesh patterns on 5x5 mm areas. The formation of nano- and micro-patterns with an ultra-thin oxide film on the surfaces was used to observe the effects of morphology and proliferation of the MRC-5 cell culture line. To determine whether Ti-based thin films have a toxic effect on living cells, an MTT assay was performed. The relative cytotoxic effect as a percentage of surviving cells showed that there was no difference in cell number between the Ti-based thin films and the control cells. There was also no difference in the viability of the MRC-5 cells, except for the Ti/Cu/Ti/Si system, where there was a slight 10% decrease in cell viability.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 is the second-best FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody–drug conjugate (ADC) has been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year’s harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs, after the withdrawal of peginesatide from the market in 2013. Following the trends of recent years, two bispecific drugs have been authorized in 2023. As in preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress i.e. lipid peroxidation induced by addition of hydrogen peroxide and/or Cu²⁺ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying combination of experimental techniques (AFM, force spectroscopy, ELS, DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.

Peri-implantitis continues to be one of the major reasons for implant failures. We propose a new approach for incorporating MTA into Zirconia implant surfaces with Nd:YAG laser and investigate the biological response of peri-implant cells as well as the microbiological response. Discs of Zirconia stabilized with Yttria and Titanium were produced according 4 tested groups: Nd:YAG laser textured Zirconia coated with MTA (Zr MTA); Nd:YAG laser textured Zirconia (Zr Textured); Zirconia and Titanium discs (Zr and Ti ). Contact profilometry was used to evaluate surface roughness. Human osteoblasts, gingival fibroblasts and S. oralis were cultured on samples. Cell adhesion and morphology, cell viability, cell differentiation markers and bacterial growth were assessed. Zr Textured roughness was significantly higher compared to all other groups. Cellular adhesion was observed at 1 day in all samples in both cell lines. Osteoblasts viability was lower in Zr MTA group, unlike fibroblasts viability was shown to be higher in Zr MTA group compared to Zr Textured group at 3 and 7 days. Osteocalcin and IL-8 release by osteoblasts were higher in Zr MTA. Zr Textured showed higher IL-8 values released by fibroblasts. No differences in S. oralis CFUs were observed between groups. The results suggest that Zirconia implant surfaces coated with MTA seems to promote fibroblasts proliferation and osteoblasts differentiation, however does not appear to have antibacterial properties.

Lifespan extension was recently achieved in Caenorhabditis elegans nematodes by mitochondrial stress and mitophagy, triggered via iron depletion. Conversely in man, deficient mitophagy due to Pink1/Parkin mutations triggers iron accumulation in patient brain and limits survival. We now aimed to identify murine fibroblast factors, which adapt their mRNA expression to acute iron manipulation, relate to mitochondrial dysfunction and may influence survival. After iron depletion, expression of the plasma membrane receptor Tfrc with its activator Ireb2, the mitochondrial membrane transporter Abcb10, the heme-release factor Pgrmc1, the heme-degradation enzyme Hmox1, the heme-binding cholesterol metabolizer Cyp46a1, as well as the mitophagy regulators Pink1 and Parkin showed a negative correlation to iron levels. After iron overload, these factors did not change expression. Conversely, a positive correlation of mRNA levels with both conditions of iron availability was observed for the endosomal factors Slc11a2 and Steap2, as well as for the iron-sulfur-cluster (ISC)-containing factors Ppat, Bdh2 and Nthl1. Positive correlation only after iron depletion was observed for the iron export factor Slc40a1, mitochondrial iron transporters Slc25a28, Abcb7 and Abcb8, mitochondrial ISC-containing factors Glrx5, Nfu1, Bola1 and Abce1, cytosolic Aco1 and Tyw5, as well as nuclear Dna2, Elp3, Pold1 and Prim2. The latter are regulators of nucleotide synthesis and DNA quality control, which have known importance for growth and lifespan. The only Pink1-/- triggered transcript modulation was the reduced expression of the ISC-containing ribosomal factor Abce1. These mammalian findings support previous fly data that Pink1 influences co-translational quality control via Abce1, as well as mitophagy. Our findings provide the first systematic survey how iron dosage triggers homeostatic transcriptional regulations and elucidate how iron deprivation results in mitophagy.

Oxidative stress has been implicated in cellular senescence and aging, as well as in the onset and progression of many diverse genetic and acquired diseases and conditions. The search for biomarkers of oxidative stress has become relevant to many biomedical fields using many different methods and approaches. Fluorescence methodology is advantageous because of its simplicity and high sensitivity. Fluorescent probes are frequently used to investigate the role of reactive oxygen species in oxidative stress in experimental or clinical settings, often involving the use of flow cytometry and related single-cell based technologies. To assess the specific role of reactive oxygen species in oxidative stress studies by cytometric methodologies, it is essential to detect and characterize these species accurately. However, the detection and quantitation of individual intracellular ROS is still a challenge, but different and complementary strategies may focus on other endpoints of oxidative stress. In this review we present and discuss briefly the limitations and perspectives of such approaches. Based on our results, we also provide recommendations for proper design of cytometric studies of oxidative stress in order to prevent or minimize experimental errors..

Tyrosinases (TYR) play an important role in oxidizing phenols and catechols, leading to the formation of catechols and ortho-quinones, respectively. In mammals, TYR catalyzes the conversion of L-Tyrosine to quinone, a pivotal step in melanogenesis, which generates melanin pigments responsible for protecting against UV radiation and oxidative stress. Given TYR's importance in melanin-related disorders and cosmetic applications, the inhibition of TYR has garnered attention for controlling melanin production. However, current inhibitors like hydroquinone, arbutin, and kojic acid (KA) have limitations in terms of side effects and effectiveness. A novel class of TYR inhibitors featuring arylpiperidine and arylpiperazine components has demonstrated potent inhibitory activity. This study presents a computational analysis of these inhibitors using molecular docking, molecular dynamics (MD) simulations, and the Linear Interaction Energy (LIE) method was used to estimate binding free energies. The arylpiperidine and arylpiperazine inhibitors exhibit remarkable stability within the TYR active site during simulations. The van der Waals interactions are notably sustained, indicating effective inhibition mechanisms. The results from LIE calculations closely align with experimental binding affinities. In summary, these results contribute to the understanding of TYR inhibition and underscore the potential of arylpiperidine and arylpiperazine derivatives as effective agents for modulating melanin production in both cosmetic and pharmaceutical applications. Overall, this study sheds light on the intricate interactions between inhibitors and TYR, opening avenues for the development of novel therapies and interventions.

Background: The importance of knowing the workload of family nurses lies essentially in the possibility of improving health outcomes, care processes and the nurse’s professional life. There is a lack of studies that fully describe nursing workload in primary care, particularly, in the context of family health nursing, and the ideal metrics to be used remains unknown, making it impossible to characterize and therefor provide the necessary insight to acknowledge the different contributions of several aspects that embodies the global workload of family nurses. The objective of this scoping review was to map the known evidence and characterize the instruments used to assess the workload of family nurses. Methods: Scoping review, according the Joanna Briggs Institute proposed methodology for scoping reviews, consisting of 3 research stages: 1) initial research in Medline and CINHAL; 2) extended search, using keywords and search terms, in the following databases: JBI, CINAHL Complete, MEDLINE, Cochrane and Scopus; 3) Search the reference list of the selected articles. No time limit was defined. Results: Fourteen studies referring to ten as-sessment instruments were included. Nine of them analyze workload as a dimension of a broader instrument, and two studies refer to an instrument that focuses exclusively on workload. Con-clusions: The diversity of professional competencies and contexts, the conceptual complexity of workload and the absence of an theoretical framework, makes it difficult to identify consensual instruments to assess the workload of family nurses. This study was registered in Open Science Framework® with the following registration (https://osf.io/3k6vr).

The combined effects of the thermal processing (i.e., sterilisation treatment) and the prior frozen storage time (3 or 6 months at –18 ºC) on the quality loss in canned Atlantic horse mackerel (Trachurus trachurus) were determined. Thus, the sterilisation step led to a remarkable (p<0.05) formation in canned fish muscle of fluorescent compounds, free fatty acids (FFAs) and trimethylamine and to an increase of the L* and b* colour parameters; meantime, a decrease (p<0.05) of the total ω3 FA/total ω6 FA ratio and the a* colour value were detected. The prior frozen storage period led to an increased (p<0.05) lipid oxidation (peroxide, thiobarbituric acid reactive substance and fluorescent compound formation) and hydrolysis (FFA formation) development and to increased L* and b* colour values in the corresponding canned samples; additionally, a lower (p<0.05) polyene index and phospholipid content were observed in canned fish previously subjected to frozen storage. In most indices, physico-chemical changes related to quality loss were found higher if the previous storage period was increased. According to the marked effects of the sterilisation step and the prior frozen storage period, optimisation of such processing conditions is recommended to maximise the quality of canned horse mackerel.

Synthesis of nickel oxide nanoparticles (NiO NPs) is a low cost and ecofriendly route that brings great benefits over chemical and physical methods of synthesis. Our approach consisted of using aqueous extracts from treated waste of Manihot Esculenta (Cassava) as reducing, stabilizing and capping agents for the synthesis of NiO NPs. The results proved this approach might be a viable alternative. Extracts were mixed during 30 minutes with Ni(NO3)2.6H2O leading to NPs formation. NiO NPs were characterized through FTIR, XRD, TEM and Raman spectroscopy. NiO NPs showed different shapes and sizes around 5-10 nm in agreement with the particle size calculated by XRD Scherrer equation.

Esterases are hydrolases that catalyze the hydrolysis of esters into the corresponding acids and alcohols. The development of fluorescent probes for detecting esterases is of great importance due to their wide spectrum of biological and industrial applications. These probes can provide a rapid and sensitive method for detecting the presence and activity of esterases in various samples, including biological fluids, food products, and environmental samples. Fluorescent probes can also be used for monitoring the effects of drugs and environmental toxins on esterase activity, as well as to study the functions and mechanisms of these enzymes in several biological systems. Additionally, fluorescent probes can be designed to selectively target specific types of esterases, such as those found in pathogenic bacteria or cancer cells. In this review, we summarize the recent fluorescent probes described for the visualization of cell viability and some applications for in vivo imaging. On the other hand, Positron Emission Tomography (PET) is a nuclear-based molecular imaging modality of great value to study the activity of enzymes in vivo. We provide some examples of PET probes for imaging acetylcholinesterases and butyrylcholinesterases in brain, which are valuable tools for diagnosing dementia and monitoring the effects of anticholinergic drugs on the central nervous system.

Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was detected also for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86 and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light-chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429 and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in D. melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.

The COVID-19 outbreaks have caused universities all across the globe to close their campuses and forced them to initiate online teaching. This article reviews the pedagogical foundations for developing effective distance education practices, starting from the assumption that promoting autonomous thinking is an essential element to guarantee full citizenship in a democracy and for moral decision making in situations of rapid change, which has become a pressing need in the context of a pandemic. In addition, the main obstacles related to this new context are identified, and solutions are proposed according to the existing bibliography in learning sciences.

In recent years, advances in science, technology, and the way in which we view our world have led to anincreasingly broad use of the term “intelligence”. As we learn more about biological systems, we find more and more examples of complex and precise adaptive behavior in animals and plants. Similarly, as we build more complex computational systems, we recognize the emergence of highly sophisticated structures capable of solving increasingly complex problems. These behaviors show characteristics in common with the sort of complex behaviors and learning capabilities we find in humans, and therefore it is common to see them referred to as “intelligent”. These analogies are problematic as the term "intelligence" is inextricably associated with human-like capabilities. While these issues have been discussed by leading researchers of AI and renowned psychologists and biologists highlighting the commonalities and differences between AI and biological intelligence, there have been few rigorous attempts to create an interdisciplinary approach to the modern problem of intelligence. This article proposes a comparative framework to discuss what we call “purposeful behavior”, a characteristic shared by systems capable of gathering and processing information from their surroundings and modifying their actions in order to fulfill a series of implicit or explicit goals. Our aim is twofold: on the one hand, the term purposeful behavior allows us to describe the behavior of these systems without using the term "intelligence", avoiding the comparison with human capabilities. On the other hand, we hope that our framework encourages interdisciplinary discussion to help advance our understanding of the relationships among different systems and their capabilities.

The approach to the personal experience and previous ideas about Physical Education of future Primary Education teachers is a starting point of great interest for the teaching of the subject of Didactics of Physical Education. The study aims to investigate these prior beliefs and to verify to what extent this initial perception changes after taking the course on “Didactics of Physical Education”. A concurrent mixed-methods study was conducted, which included two data collection procedures: (1) a pre-experimental design with a single group featuring pre-test and post-test; (2) the analysis of students' autobiographical accounts of their school experience with physical education. The participants were students enrolled in the Bachelor’s degree program in Primary Education at the University of Santiago de Compostela (USC) who undertook the course last year. The results obtained reveal that after taking the subject of Didactics of Physical Education, students give greater value to more positive concepts of learning, socializing, participating, and playing, among others. Similarly, in the post-test, the assessment of concepts such as competitiveness and physical fatigue diminished. In their autobiographical memories, students associate good memories with relationships with classmates and the playful and socializing nature of the subject; and among the bad memories, they highlight the content related to physical performance, competitiveness, and lack of attention to the diversity of students and their individual characteristics.

Penicillium digitatum is the major postharvest pathogen of citrus fruit under Mediterranean climate conditions. In the present work, we have addressed the study of the role of P. digitatum’s proteases in virulence following two complementary approaches. In a first approach, we have undertaken the functional characterization of the P. digitatum prtT gene, which codes for a transcription factor previously shown to regulate extracellular proteases in other filamentous fungi. Deletion of prtT caused a significant loss in secreted protease activity during in vitro growth assays. However, there was no effect on virulence. Gene expression of the two major secreted acid proteases was barely affected in the ΔprtT deletant during infection of citrus fruit. Hence, no conclusion could be drawn on the role of these secreted acidic proteases on the virulence of P. digitatum. In a second approach, we have studied the effect of different protease inhibitors and chelators in virulence. Co-inoculation of citrus fruit with P. digitatum conidia and a cocktail of protease inhibitors resulted in almost a complete absence of disease development. Analysis of individual inhibitors revealed that the metalloprotease inhibitor 1,10-phenanthroline was responsible for the observed effect. The application of metal ions reverted the protective effect caused by the metallopeptidase inhibitor. These results may set the basis for the development of new alternative treatments to combat this important postharvest pathogen.

Objective: To carry out a bibliometric analysis study of systematic reviews and meta-analyses in dentistry, divided into different thematic areas. Material and method: A search was conducted in the Science Citation Index-Expanded on the core collection of Web of Science, they were selected from the area of Dentistry and Oral Surgery and Medicine categories, the data was downloaded on April 20, 2022 and The 100 most cited articles from each of the thematic areas were selected. Results: An increase in this type of articles was observed in the last decade in the areas of pediatric and medical dentistry and oral pathology. The thematic area that received the most citations was periodontics. The two authors with the most citations are Zwahlen, Marcel and Pjetursson, Bjarni Eluar. The countries that receive the most citations are European, along with the USA and China. The topics that are most published in this type of article deal with Cancer with 50 publications, caries treatment with 25 and fluoridation with 1. The entities that finance this type of articles the most are private companies (26.76%). Conclusions: Together with an exponential increase in the number of publications in dentistry, there has been an increase in the number of publications in systematic reviews. The areas publishing the most articles and having the most citations are Periodontics and Implantology, despite the fact that the most studied topic is cancer.

Gliomas are solid tumors of the Central Nervous System (CNS) that originated from different glial cells. The World Health Organization (WHO) classified these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as a grade IV. GBM are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.

1) Background: It has been more than a decade since the concern about addictive use of the Internet and mobile phones was first expressed and its possible inclusion into the lists of mental disorders has been a popular topic of discussion recently, thus it seems to be a fitting moment to investigate the evolution of this issue over time. The aim of the present study was to analyze the evolution of the perception of problematic Internet and smartphone use in young people over the period 2006–2017; 2) Methods: To this end, a questionnaire on Internet use habits and the CERI and CERM questionnaires on negative consequences of Internet and smartphone use were administered to a sample of 792 university students and compared with data from former studies over the period 2006–2017; 3) Results: The perception of problematic Internet and mobile phone use has increased over the last decade, social networks are considered responsible for this increase, and females are the ones perceived to be more affected than males. The degree to which participants agree with the statement “I am addicted to the Internet” can be used as a screening item for problematic use.

The deterioration and destruction of the environment is becoming more and more considerable and greater efforts are needed to stop it. To accomplish this feat, all members of society must identify with environmental problems, with collective environmental action being one of the most relevant means of doing so. From this perspective, the analysis of the psychosocial factors that lead to participation in environmental collective action emerges as a priority objective in the research agenda. Thus, the aim of this study is to examine the role of "environmental identity" as conceptualized by Clayton, as a central axis for explaining environmental collective action. The inclusion of the latter in the theoretical framework of the SIMCA model gives rise to the model that we have called EIMECA. Two studies were conducted, and the results reveal that environmental identity, a variety of negative affects, as well as group efficacy accompanied by hope for a simultaneous additive effect, are critical when it comes to predicting environmental collective action.

This paper has two objectives: the first, to analyze the mediating effect of teacher empowerment between innovation culture and innovation capacity, and between inclusive leadership and innovation capacity; the second, to analyze the moderating effects of the school context on the innovation capacity. Data were collected in a representative sample of secondary schools in Valencia, Spain. The research model adopted is structural equation modeling, using the partial least squares (PLS) technique. The model has confirmed that teacher empowerment mediates between innovation culture and innovation capacity and between inclusive leadership and the innovation capacity. It is found that the educational context does not moderate the relationships in the proposed analysis model. This paper emphasizes the role of teacher empowerment in educational innovation and extends the knowledge of culture and leadership in the school organization.

Obesity is a worldwide epidemic; hence it is crucial to understand how it can be effectively prevented/treated. Thus, obesity should be tackled considering that it is a multifactorial condition. This work examines a wide range of factors and attempts to understand which contribute most to variability in overweight/obesity. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analyzing three 24-hour recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity through accelerometry, cardiometabolic parameters were determined in blood samples and body composition by anthropometry and bioimpedance. Factor analysis of principal components (PCA) was carried out (SPSS v22.0). Large interindividual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥30%), but body composition was homogeneous. Volunteers had an unbalanced diet and low physical activity. PCA reduced the 26 analyzed variables into 7 factors, accounting for 81,5% of total data variability. The main factor was the ‘‘caloric and lipid factor’’ related to diet, responsible for 25.9% of total variability, followed by ‘‘adiposity factor’’ (16,9%) and ‘‘cardiometabolic risk factor’’ (13,2%). Diet seems to be the factor that contributes the most to data variability in people with overweight/obesity, especially the intake of lipids, energy and proteins.

Epidemiological data show that the use of alcohol and other psychoactive substances is higher among university students when compared with the general population and high school students. The use of psychotropic drugs by students in health courses deserve special attention due to because they will be responsible for the health education and care of the population. The present study aims to describe, through a cross-sectional study, the risks and the profile of consumption of psychoactive substances by students of the Biological and Health Sciences courses at the Federal University of Bahia (UFBA). An online and anonymous questionnaire was applied from September 20, 2019 to June 15, 2021. 514 responses were obtained, of which 502 were considered according to the inclusion criteria. For recreational use of psychoactive substances, both for lifetime use and for use in the last 3 months, the prevalence of alcohol, cannabis and tobacco were the highest ones in that order. Only alcohol, cannabis and inhalants showed a percentage of individuals at high risk of developing problems. These results indicate the need for local intervention, in order to prevent risky behavior, damage to mental health and major consequences for society and university performance.

Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.

In the present study the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers, around 20nm. Characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by a replacement of citrate by the MTX carboxyl group. The drug release profiles showed faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Also, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNPs-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a lighter dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 on the contrary than line A-549, supporting the specific uptake of folate-conjugated AuNPs-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Anexin V-PI test sustain as cell death mechanism apoptosis, which is normally disabled in cancer cells.

The most relevant fungal disease of the olive tree in Portugal is anthracnose, which has negative effects on fruit destruction and consequently on the yield and quality of the olive oil. Moreover, the loss of quality caused by olive fruit fly is associated with the presence of fungi in the galleries made by the larvae. The present study focuses on the effect of olive anthracnose and olive fly on the content of bioactive compounds, namely on hydroxytyrosol (HYT) and its derivatives (health claim) in olive oils extracted from 'Galega Vulgar' and 'Cobrançosa' cultivars. The olives, with different damage levels (olive fly and anthracnose disease), were harvested in Castelo Branco (Center of Portugal) in organic rainfed orchards, at four harvest times during 2019, 2020 and 2021 harvest years. The fruits were immediately submitted to olive oil extraction. The results of the quality criteria show that Galega olive oils extracted from olives with a higher anthracnose incidence show no conformity for the Extra Virgin Olive Oil (EVOO) and Virgin Olive Oil (VOO) categories, with high acidity values and negative sensory notes accompanied by the disappearance of oleacein (the main phenolic compound of both monovarietal olive oils). Conversely, no sensory defects were observed in Cobrançosa olive oils extracted from fruit with high anthracnose and olive fly incidence. Moreover, despite a decrease in all the positive attributes associated with the cultivar, namely in oleacein and oleocanthal contents, quality criteria were still in accordance with the EVOO category. The total HYT and tyrosol (TYR) content (> 5 mg/20g) allows the use of the health claim on the label of all the analysed Cobrançosa olive oils.

Modeling the reaction time required for the removal of chemical oxygen demand (COD) from wastewater is important because can be an indicator of harmful pollutants that may pose risks to human health.. Here, we evaluate the use of an inverse artificial neural network (ANNi) to optimize the removal of COD from aqueous herbicide solutions using sonophotocatalysis as the treatment process.. This algorithm takes the operating conditions as input and estimates the optimal reaction time to reach the required effluent COD. This model was validated by comparison with both experimental measurements and simulated analysis, resulting in low error (0.5%), high Pearson correlation (R2 = 0.9956), and short computing time (less than one minute). The results for the proposed methodology (ANNi-GAs) were efficient and attractive in a reasonable way providing a satisfactory picture of the relationships between the optimal input parameters. Such parameters control the degradation process of herbicides online and can be used to predict the behavior of COD removal, thus taking actions to reduce the impact of aqueous treatment with alazine and gesaprim herbicides on aquatic, soil biota, and human health. Therefore, this technique constitutes a promising framework for predicting the environmental impact of herbicides within a tolerable degree of error.

Batteries are called to be part of the electricity grid by providing ancillary services. Area regulation services seem to provide substantial revenues and profit. But Li-ion batteries are still too expensive to enter widely into this market. On the other hand, electric vehicle batteries are considered inappropriate for traction purposes when they reached a state of health of 80%. The reuse of these batteries offers affordable batteries for second life stationary applications. This study analyzes how batteries may provide services to a gas turbine cogeneration power plant and how long these batteries may last under different loads.

Increased norepinephrine (NE) release from the sympathetic nerves during pregnancy in women or animal models, as occurs during stress, modifies the fetal environment and increases flow of NE to the fetus, programing the progeny and affecting its cardiovascular and metabolic function in adulthood. In the present work, gestating rats were exposed to stress during gestation and the female progeny was analyzed for heart and metabolic function. Pregnant Sprague–Dawley rats were exposed to cold stress (4 °C/3 h/day); rats’ female progeny were euthanized at 4, 20 and 60 days old and their hearts evaluated to determine the β-adrenergic receptor (βAR) mRNA, abundance and affinity to agonists and NE concentration. The in vivo response to glucose overload and the arterial pressure response to isoproterenol (ISO, 125 µg/kg weight/day/10 days) were monitored. Results: At 20 and 60 days old, stressed female progeny presented an increase in ventricular weight and no changes in the cardiac NE as compared with their age-matched controls. The β1AR mRNA in control rats decreased between 4 and 20 days of age, but stressed rats maintained 50% higher levels of mRNA as compared with their age-matched controls. This difference was also found in the protein abundance of β1AR. No differences were found at 60 days old. The β2AR mRNA levels were higher than in controls at both 4 and 20 days old, but not expressed in the amount of protein. An increase in the ratio of β1/β2 receptors was found at 20 days old but not at 60 days old. The displacement of 3H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist) showed decreased affinity (at 60 days old) but no changes in the βAR number. In vivo exposure to ISO induced a β-adrenergic overload and provoked death in 40% of stressed females by day 3 of ISO treatment. Regarding metabolic function, we found that stressed rats presented insulin resistance when adults. These data suggest permanent changes to the heart’s adrenergic response and metabolic function after rat progeny were stressed in the uterus.

The broad bean plant contains L-DOPA, a compound that is essential for patients with Parkin-son’s disease. However, little has been reported on other broad bean compounds that have bene-ficial effects on health. The objective was to evaluate plants of four Mexican broad bean varieties to determine the content and yield of total phenolic compounds (TPC), total flavonoids (TF), and L-DOPA, as well as to analyze the flavonoid profile and antioxidant (AA) and anti-inflammatory (AANTI) activity in vitro. Broad bean seeds were sown in the field and plants were harvested 20 days after emergence. The analyses were performed with visible UV spectrophotometry and HPLC. The variety José María produced the highest yield of TPC (9.30 g m-2), TF (8.08 g m-2) and L-DOPA (5.64 g m-2) per unit of area. The highest yields per plant were obtained with the Rojita variety: TPC (0.25 g plant-1), TF (0.21 g plant-1) and L-DOPA (0.17 g plant-1). This variety also had the highest antioxidant (CI50= 87.68 µg mL-¹) and anti-inflammatory (CI50= 74.40 mg mL-1) activi-ty, which was attributed to the L-DOPA compounds and to rutin and isoorientins, respectively. The flavonoid profile revealed the presence of rutin and isoorientins, which had not been previ-ously detected in the broad bean plant.

This study aimed to establish a predictive model for neoadjuvant chemoradiotherapy (nCRT) response in patients with locally advanced rectal carcinoma (LARC) using clinicopathological (CP) features along with radiomics from pretreatment Magnetic Resonance Imaging (MRI) 3D T2W contrast sequence scans. The study also assessed the impact of radiomic dimensionality on predictive performance. Seventy-five patients were prospectively enrolled with clinicopathologically confirmed LARC who underwent nCRT before surgery. Tumor properties were assessed by calculating 2142 shape, first-order, and second-order radiomics features. Least absolute shrinkage and selection operator (LASSO) and multivariate regression were used for feature selection. Two predictive models were constructed, one using 72 CP and 107 radiomics features, and the other using 72 CP and 1862 radiomics features. The models revealed moderately advantageous impact of increased dimensionality, while their predictive performance was in the range generally considered excellent, with respective AUCs of 0.86 and 0.90. A CP-only model (AUC=0.80) served as the benchmark for predictive performance without radiomics. The predictive models developed in this study using pretreatment MRI data, radiomics features, and clinicopathological parameters could potentially be used to routinely predict chemoradiotherapy responders, enabling clinicians to personalize treatment strategies for rectal carcinoma.

Serine peptidase CLPP is conserved among bacteria, chloroplasts, and mitochondria. In humans and mice, its loss causes Perrault syndrome with growth deficit, infertility, deafness, and ataxia. In the filamentous fungus Podospora anserina, CLPP-loss leads to longevity. CLPP substrates are selected by CLPX, an AAA+ unfoldase. CLPX is known to target delta-amino-levulinic-acid synthase (ALAS) to promote pyridoxal-phosphate (PLP) binding. CLPX may influence cofactor association with other enzymes. Here, the evaluation of P. anserina metabolomics highlighted arginine/histidine reduction. In Mus musculus cerebellum, reductions of Arginine/Histidine and Citrulline occurred with concomitant accumulation of heme-precursor protoporphyrin-IX. This suggests that increased biosynthesis of 5-carbon (C5) chain deltaALA consumes not only C4 succinyl-CoA with C1 glycine but also specific C5 delta amino-acids. As responsible enzymes for these converse effects, elevated abundance of CLPX and ALAS is paralleled by elevation of OAT (PLP-dependent, ornithine-delta-aminotransferase). Possibly as consequence of altered C1 metabolism, CLPP-null cells in P. anserina proteome profiles showed strong accumulation of a methyltransferase and two mitoribosomal large subunit factors. Reduced Histidine levels may explain previously observed metal interaction problems. As main nitrogen-storing metabolite, deficient Arginine would affect the urea cycle and polyamine synthesis. Supplementation of Arginine and Histidine might rescue growth deficits of CLPP-mutant patients.

Petroselinum crispum (Mill.) Fuss (Apiaceae), popularly known as parsley, is a ubiquitous aromatic herb used for culinary and medicinal purposes worldwide. Besides the richness in nutrients, sev-eral bioactive secondary metabolites, especially the flavone apigenin and its glycosides, have been described in the species. Parsley has already been shown to have several health-promoting activi-ties, such as antithrombotic, antihypertensive, and hypolipidemic. The multiple studies conducted in animal models so far suggest the species is a potential source of cardioprotective agents. This review provides up to date information and perspectives on the potential of parsley and its bioac-tive compounds for the development of nutraceutical products and drugs for the promotion of cardiovascular health. It includes not only a discussion on reported bioactivities, but also the knowledge of supplements and food additives developed as innovative parsley-based products.

This work describes practical immunization of European sea bass (Dicentrarchus labrax) juveniles against viral nervous necrosis virus (VNNV), a betanodavirus causing worldwide mortalities in many fish species. Protection was obtained with the so called spinycterin vehicles consisting in irreversibly DNA-damaged DNA-repair-less E.coli displaying at their surface a downsized antigen. In this work we, i) maximized bacterial expression levels by downsizing the C protein to a fragment (frgC91-220) containing most of its antigenicity, ii) developed an scalable autoinduction bacterial media based in soy-bean increasing membrane display and reproducibility, iii) enriched surface expression by screening different anchors from several prokaryotic origins (anchor+frgC91-220), iv) preserved frgC91-220 antigenicity by inactivating bacteria by irreversible DNA-damage by means of Ciprofloxacin, and v) increased safety using a repair-less E.coli strain as spinycterin chassis. These second generation of spinycterins protected fish against VNNV challenge with partial (Nmistic+frgC91-220) or 100 % (YBEL+frgC91-220 ) protection, in contrast to those fish immunized with frgC91-220 spinycterins. The proposed spinycterin platform has high levels of environmental safety and cost effectiveness, thus providing potential for small fish vaccines for sustainable aquaculture.

The genome of the Bacillus thuringiensis BM311.1 strain was sequenced and assembled in 359 contigs containing a total of 6,390,221 bp. The plasmidic ORF of a putative cry gene from this strain was identified as a potential novel Cry protein of 1138 amino acid residues with a 98% identity respect to Cry7Aa1 protein and a predicted molecular mass of 129.4 kDa. The primary structure of this Cry7Aa2 protein, which revealed the presence of eight conserved blocks and the classical structure of three domains, differed in 28 amino acid residues from that of Cry7Aa1. The cry7Aa2 gene was amplified by PCR and then expressed in the acrystalliferous strain BMB171. SDS-PAGE analysis confirmed the predicted molecular mass for the Cry7Aa2 protein and revealed that, after in vitro trypsin incubation, it was degraded to a toxin of 62 kDa. However, when treated with digestive fluids from Leptinotarsa decemlineata larvae two proteinase-resistant fragments of 60 and 65 kDa were produced. Spore and crystal mixture produced by the wild-type BM311.1 strain against L. decemlineata neonate larvae resulted in a LC₅₀ (18.8 μg/ml), which was statistically equal to the estimated LC₅₀ (20.8 μg/mL) for the recombinant BMB17-Cry7Aa2 strain. In addition, when this novel toxin was activated in vitro with commercial trypsin, the LC₅₀ value was reduced 4 times approximately (LC₅₀ = 4.9 μg/mL). The advantages of Cry7Aa2 protoxin compared to Cry7Aa1 protoxin when used in the control of insect pests are discussed.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

To date, the impact of COVID-19 vaccination on formerly menstruating women remains unknown. For this reason, a retrospective observational cross-sectional study was conducted (N= 548) using an online survey. General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5% vs. dose 2: 44.8%; McNemar=9.15; mid P-value=0.002), as well as the simultaneous occurrence of two or more of these symptoms (dose 1: 11.2% vs. dose 2: 15.3%; McNemar=13.53; mid P-value=0.044) after receiving the second one. Among them, those related with the length and flow stand out, being of long-term nature in about 17-20% of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight (AOR 1.02, CI 95% 1.01–1.03, P&lt;.001), perimenopause (AOR 2.28, CI 95% 1.37–3.77, P=.001), pre-existing diagnoses of non-autoimmune rheumatic/articular conditions (AOR 0.31, CI 95% 0.10–1.00, P=0.05), hormonal contraceptive use (AOR 0.25, CI 95% 0.07-0.82, P=0.02), suffering from other vaccine side effects − such as arm pain (AOR 0.61, CI 95% 0.39–0.95, P=0.03), headache (AOR 0.53, CI 95% 0.35 – 0.80, P=.003), swollen glands (AOR 0.29, CI 95% 0.15 – 0.60, P=.001) and nauseas (AOR 0.35, CI 95% 0.14 – 0.86, P=0.02) – and the number of previous pregnancies (AOR 2.70, CI 95% 1.54 – 4.76, P=.001). Formerly menstruating women may experience long-term menstrual-related disturbances following COVID-19 vaccination.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

The disruption in healthcare attention to people with alcohol dependence, along with psychological decompensation consequence of lockdown derived from COVID-19 pandemic, could have a negative impact on people who suffers from alcohol abuse disorder. Retrospective observational study of 9,966 men aged ˃16 years registered as having diagnosis of alcohol abuse disorder in the electronic medical records (EMR) of the Aragon Regional Health Service (Spain). Of those who were not infected during the study period (9,576), clinical (Glutamate-oxaloacetate -GOT-, Glutamate pyruvate -GPT-, creatinine, glomerular filtration, systolic blood pressure -SBP-, diastolic blood pressure -DBP-, total cholesterol, LDL, HDL, triglycerides, and body mass index -BMI-), pharmacological (dose per inhabitant per day -DHD- of drugs used in addictive disorders, benzodiazepines and antidepressants) and health resource use variables (primary and specialized care) were considered. Student´s T-test for matched samples was performed. After carrying out the Levene´s test, the Student´s T-test was used to analyze the changes in clinical variables between alcohol abuse disorder patients with and without COVID-19. Only creatinine and LDL show a significant but clinically irrelevant changes just after and 6 months after the end of strict lockdown. The total number of DHDs for all drugs included in the study (except for Benzodiazepines), decreased. In the same way, the use of health services by these patients also decreased. The impact of COVID-19 among this group of patients has been moderate. The reorganization of health and social services after the declaration of the state of alarm in our country, made possible the maintenance of care for this vulnerable patients.

Ruminal microorganisms play a pivotal role in cattle nutrition. The discovery of the main microbes responsible for enhancing the gain of weight in beef cattle might be used in therapeutic approaches to increase animal performance and cause less environmental damages. Here, we examined differences in bacterial and fungal composition of rumen samples of Braford heifers raised in a natural grassland from Pampa Biome in Brazil. We aimed to detect microbial patterns in the rumen that could be correlated with the gain of weight. 16S and ITS1 genes were amplified from ruminal samples and sequenced to identify the closest microbial relatives within the microbial communities. A predictive model based on microbes responsible for the gain of weight was build and further tested using the entire dataset. The model detected a set of microorganisms associated with animals in the high gain of weight group, including the bacterial taxa RFN20, Prevotella, Anaeroplasma and RF16 and the fungal taxa Aureobasidium, Cryptococcus, Sarocladium, Pleosporales and Tremellales. Most of these organisms have been correlated to the production of substances that improve the ruminal digestion process. These findings provide new insights about cattle nutrition and suggest the use of these microbes to improve beef cattle breeding.

Iron deprivation activates mitophagy and extends lifespan in nematodes. In patients suffering from Parkinson’s disease (PD), PINK1-PRKN mutations via deficient mitophagy trigger iron accumulation and reduce lifespan. To evaluate molecular effects of iron chelator drugs as a potential PD therapy, we assessed fibroblasts by global proteome profiles and targeted transcript analyses. In mouse cells, iron shortage decreased protein abundance for iron-binding nucleotide metabolism enzymes (prominently XDH and ferritin homolog RRM2). It also decreased the expression of factors with a role for nucleotide surveillance, which associate with iron-sulfur-clusters (ISC), and are important for growth and survival. This widespread effect included prominently Nthl1-Ppat-Bdh2, but also mitochondrial Glrx5-Nfu1-Bola1, cytosolic Aco1-Abce1-Tyw5, and nuclear Dna2-Elp3-Pold1-Prim2. Incidentally, upregulated Pink1-Prkn levels explained mitophagy induction, the downregulated expression of Slc25a28 suggested it to function in iron export. The impact of PINK1 mutations in mouse and patient cells was pronounced only after iron overload, causing hyperreactive expression of ribosomal surveillance factor Abce1 and of ferritin, despite ferritin translation being repressed by IRP1. This misregulation might be explained by the deficiency of the ISC-biogenesis factor GLRX5. Our systematic survey suggests mitochondrial ISC-biogenesis and post-transcriptional iron regulation to be important in the decision, whether organisms undergo PD pathogenesis or healthy aging.

Many buildings built before the energy performance regulations are in a situation of thermal discomfort and energy inefficiency. The creation of intelligent environments advances towards new opportunities, based on real-time monitoring and on the development of sensors and technologies. Furthermore, the standards for building automation and electronic systems enable interoperability and interconnection between control devices and systems. The application of soft computing has significantly improved the energy efficiency, however, requires prior assessment to design the automation functions. Temperature, humidity, air quality, occupancy and energy consumption are the most common measured parameters, but the relationship with other operational variables such as occupancy or some building states remains as a research challenge. This article presents a methodology to develop the automatization of an existing large public building. The methodology consists of three stages: 1. Assessment and diagnosis to set appropriate actions using EN ISO 52120-1. 2. EN 50090 for open communication networks, and EN ISO 52120-1 to assign the technical building management. 3. System control deploying of low-cost and low-consumption input and output devices. It has been proved that it is possible to effectively automate an obsolete building with a low cost, open source system that can be easily applied in other buildings.

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

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

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

Human pigmentation has been largely associated with different disease prevalence among populations, but most of these studies are observational and inconclusive. Known to be genetically determined, pigmentary traits have been largely studied by GWAS, mostly in Caucasian ancestry cohorts from North Europe, identifying robustly, several loci involved in many of the pigmentary traits. Here, we conduct a detailed analysis of 13 pigmentary-related traits in a South European cohort of Caucasian ancestry (n=20,000). We observed fair phototype strongly associated with non-melanoma skin cancer and other dermatoses and confirmed by PRS-approach the shared genetic basis with skin and eye diseases, such as melanoma (OR=0.95), non-melanoma skin cancer (OR=0.93), basal cell carcinoma (OR=0.97) and darker phototype with vitiligo (OR=1.02), and cataracts (OR=1.04). Detailed genetic analyses revealed 37 risk loci associated with 10 out of 13 analyzed traits, and 16 fine-mapped genes significantly associated with at least two pigmentary traits. Some of them widely reported, such as MC1R, HERC2, OCA2, TYR, TYRP1, SLC45A2, and unveiling three new candidates RP11-1084J3.4, C1QTNF3 and C17orf112, not reported in GWAS Catalog. These results highlight the importance of phototype assessment as a genetic proxy of skin functionality when evaluating disease screening in mixed populations.

Sustainability is pivotal in the urban transformation strategy in order to reach more resource-efficient, resilient and smarter cities. The goal of being a sustainable city should drive the decisions for city interventions. Nonetheless, impacts need to be quantified, lacking of standard and/or common methodologies that could be replicable across multiple cities. There exist many initiatives aiming at defining indicators and assessment procedures, but without convergence in the definition of terms and application methodologies, making complex its real implementation. Within mySMARTLife project (GA#731297), a KPI-driven evaluation framework is defined with the aim of covering the multiple pillars of a city (i.e. energy, mobility, citizens, economy) in a holistic way. This methodology also defines the concepts and terms to guide urban planners and/or experts at time of implementing the framework in a specific city. The evaluation framework has been deployed in the three cities of Nantes, Hamburg and Helsinki and some lessons learnt have been extracted, such as the necessity of providing a definition of measurement boundary to avoid interpretations. Thanks to a co-creation strategy, the main difficulties and issues from the cities have been taken into consideration for increasing the replicability.

This study utilizes data from the fourth National Health Survey conducted in 2019. in the Republic of Serbia, aiming to contribute to a deeper understanding of the factors influencing the mobility of the elderly population. It examines the sociodemographic and psychosocial factors associated with functional limitations in older adults. By analyzing variables such as age, gender, marital status, education, income, social support, and mental health, the study seeks to explain their impact on the prevalence of walking limitations.Questionnaires were employed as a research instrument in line with the methodology of the European Health Survey (EHIS). The analysis is based on a sample of 3,705 participants aged 65 and above. Statistical significance between variables was assessed using the Chi-square test. Post-hoc comparisons were performed using pairwise z-tests. Univariate logistic regression was employed to identify predictors of walking difficulties. Additionally, multivariable logistic regression was conducted to further explore predictors while adjusting for potential confounding variables, with odds ratios and corresponding 95% confidence intervals estimated.Women exhibit significantly higher prevalence of walking difficulties compared to men (p < 0.001). There is a significant variation in the prevalence of walking difficulties among different age groups. Individuals aged 75-84 show the highest prevalence in all categories of walking difficulties, with particular significance in the categories of "no difficulty," "some difficulty," and "unable to walk at all" (p < 0.001). Higher levels of education generally correlate with lower prevalence of walking difficulties. Married or partnered individuals have 0.522 times lower odds of reporting difficulties in walking compared to singles (p < 0.05). Individuals with lower wealth index (1-Least affluent) have significantly higher prevalence of walking difficulties.This knowledge can inform targeted interventions to enhance mobility and improve the overall well-being of older individuals.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. In this study, we report a new species of Talaromyces, isolated from cocoa soil from San Vicente de Chucurí-Colombia. The characterization of the culture was performed on six different standardized media and was distinguished by characteristic colony morphology: biverticillate and monoverticillate penicilli, acerose phialides, and slightly globose smooth-walled conidia. Culture was featured by bright yellow mycelium in young culture on CYA and CYAS medium. Colonies grew faster on Malt and Oat agar, attaining 36 and 32 mm diameter after seven days at 20 ºC. High acid production on CREA medium at 20-30 ºC was observed. Phylogenetic analysis was based on the ITS region and the RPB2, Calmodulin (CaM) and β-Tubulin genes that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus and related to T. soli, T. tumuli and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0-400 ppm Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-days incubation period and In vitro cadmium tolerance tests showed a high tolerance index = 0,81 when the mycelium was exposed to 300 ppm of Cd. Results suggest T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils.

Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

Trend patterns of melanoma skin in Serbia from 1999 to 2020 *Rancic K. Natasa 1,2, Tiodorovic B. Danica 1,4, Ilic V. Mirko 2, Biljana N. Kocic 1,2, Maksimovic S. Natasa 3, Ilija D. Kocic 4, Dusan P. Miljkovic 4, Otasevic A. Suzana 1,2 Introduction. Melanoma of the skin represents about 1% of all skin cancers and it causes nearly 80% of skin cancer deaths. Due to its increasing incidence, particularly in the most developed countries it represents a great challenge for primary prevention. Objective. To explore patterns and analyze incidence trends of melanoma in Central Serbia from 1999 to 2020. Materials and Methods. Descriptive study was done and data were obtained from the Population-based Cancer Registry of Serbia. The joinpoint regression analysis was done to assess the incidence trend of the melanoma skin: the annual percent change (APC) along with its 95% confidence interval (95% CI) was calculated. Results. A total number of 9952 new melanoma cases were registered melanoma (5204 in males and 4748 in females) during the observed period. Males represented 52.3% of all patients, with male to female ratio of incidence 2.09:1. A non significant increasing trend of incidence in males from 1999 to 2013 with APC of 2.53% (95%CI: from -18.2 to 21.9, p=1) and significantly increasing trend from 2013 to 2020 with the APC of 11.29 % (95%CI: from 1.4 to 5.8, p<0.001) was established. An incidence trend in females has stabilized in the whole studied period, with APC of 0.42% (95%CI: from -3.3 to 6.8, p=0.1). Melanoma of the skin was not common before the age of 30. Out of all cases and about of 76% new cases were diagnosed in persons ≥ 50 years of age. Conclusion. The incidence trend of new melanoma cases significantly increase in the whole population from 1999 to 2020. The significant increasing of incidence trend in males and stabilization of incidence trend in females was established. Males had significantlly higher incidence rates than femalesand over of 76% new melanoma cases were diagnosed in persons above 50 years of age.

Background and objective: Research shows that 60–90% of school children have caries, representing a serious public health issue. Here, we present a model of oral health promotion that has been conducted in the Primorje-Gorski Kotar County (PGC), Croatia, from 2008 to 2019. We assessed the oral status of first and fifth grade elementary students and determined the sustainability and influence of our model on the status and behavior regarding the children’s oral status. Additionally, during the observed period, promotional and preventative activities aiming to improve oral health were conducted. Since 2014, the Program has begun to be continuously, comprehensively, and systematically introduced into preschools as well. Material and methods: We assessed the number of children with caries by analyzing the changes in the decayed, missing, and filled teeth for primary teeth (dmft)/decayed, missing, and filled teeth for permanent teeth (DMFT) index mean during the observed period. Results: From 2008 to 2019 we assessed 44422 children in the PGC (21714 first grade and 22708 fifth grade students). The average response rate throughout the Program has been 83%. We have noted a dmft/DMFT index decrease from 4,66 to 3,73 (first graders) and from 2,50 to 1,00 (fifth graders). Conclusions: The Program has improved the behavior and oral health of children; stakeholders from various professions have been included, such as health visitors, school medicine teams, and pediatricians, avoiding additional financial expenses, increasing the number of children in care, and proving the sustainability of our oral health improvement model.

The required processes and steps for making bread include technological and innovative concepts. The current trend is the use of less toxic compounds and green processes. Besides lactic acid bacteria and yeast, other microorganisms with special properties, such as enzymes, new aroma and flavor, exopolysaccharides, and vitamins, among other compounds with beneficial properties, could be added to bread manufacture, improving bread quality and health effects for the consumers. Freeze drying, new encapsulation methods, cryoprotectants, spray drying, fluidized bed drying, and vacuum drying are used for probiotics and microorganism cultures that will be used as starters or biological additives in the fermentation. The same development is observed in the preservation methods, and studies with plant extracts and essential oils have been proposed and introduced, replacing chemical agents, such as propionate, within the clean-label bread formulations concept. Baking science is a growing research line incorporating innovative methods and biological additives.

Pet ownership is common in modern society. In Portugal, 38% and 31% of all households own, at least, one dog or cat, respectively. Few studies have ascertained the knowledge of pet owners about pet ownership and zoonoses, and none of them was carried out in Portugal. The aim of the present study was to assess household knowledge and practices related to pet ownership and zoonoses in the North of Portugal. A questionnaire was completed by 424 pet owners, during November 2019 to February 2020. Most respondents (97.2%) considered pets as an important part of the family, especially women (p = 0.036); 73.1% allowed their pets free access to indoors; 41.3% denied sharing the bed with their pets and 29% assumed they did it daily; 20.3% reported never kissing their pets/pets licking their faces; 73.6% considered animals as potential sources of diseases to humans, but only 25.9% reported knowing the definition of zoonoses; 96.9% considered important the role of veterinarians in protecting public health. The low level of knowledge of pet owners and the occurrence of high-risk behaviors indicate a need to strengthen communication between veterinarians, physicians, pet owners and the general public to reduce the risk of acquisition and transmission of zoonoses.

This study focuses on the synthesis, characterization and study of a new perovskite-type materials as cathode in SOFC. The synthesized doped perovskites have been successfully synthesized with high purity. The electrochemical performance of these materials was extensively examined through the characterization of I-V-P and EIS curves at the three temperatures: 750, 800 and 850 °C. Where it is revealing a substantial reduction of total resistances by approximately 50% and 70%, accom-panied by an impressive increase in power densities by around 200% and 300%, respectively. The cell featuring Sm0.01Sr0.99Fe0.5Co0.5O3 exhibited the most commendable electrochemical properties at each temperature, following closely were Pr0.01Sr0.99Fe0.5Co0.5O3 and La0.01Sr0.99Fe0.5Co0.5O3.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

The rapid increasing rate of soil and water bodies pollution is the main anthropogenic effect caused by the mismanagement of post-consumer plastics. This research evaluated the effectiveness of cattail (Typha Latifolia) fibers (CFs) as bio-adsorbents of microplastic particles (MPPs) from wastewater. The effect of the adsorption environment composition on the adsorption rate was investigated. Batch tests were conducted to evaluate the “spontaneous” adsorption of MPs onto CFs. Five MPPs materials (PVC, PP, LDPE, HDPE, and Nylon 6) were evaluated. An industrial wastewater (PW) and Type II Distilled Water (DW) were employed as adsorption environments. The batch tests results show that CFs are effective in removing MPPs from DW and PW. However, higher removal percentage of MPPs were obtained in PW, ranging from 89% to 100% for PVC, PP, LDPE, and HDPE; while the adsorption of Nylon 6 increased to 29.9%, a removal increased of 50%. These observations indicate that hydrophobic interactions drive the “spontaneous and instantaneous” adsorption process and that adjusting the adsorption environment effectively enhances the MPPs removal rate. This research demonstrates the important role that bio-substrates can play in reducing the environmental pollution as efficient, sustainable, low cost, and reliable adsorbents for the removal of MPPs from wastewaters.

The social vulnerability approach (SV) has set up that social inequalities and disadvantages have gone beyond monetary poverty in the last years, since the process is built at different scales. In its objectives, the SV multidimensional measurement is contemplated as a priority tool to monitor the compliance of the first goal – eliminate poverty in all its forms. Therefore, the objective of this research is to calculate the SV of the fishing communities of the Gulf of Ulloa (GU), Mexico by macro-markers to subsequently contrast them with field micro-data, and finally perform a behavior scenario, considering the current public policies restrictive to fishing in such areas. The results showed significant differences depending on the type of information used, obtaining a contingency coefficient of 83.42%, which indicates that the calculus depends strongly on the data used and suggesting that macro-data may be masking the true SV values in the area, in such a way they could be severely underestimated. Even though the context at micro-scale is not the only one, SV should be calculated to analyze the fishing communities since coastal fishery represents almost the total livelihood of the inhabitants. Nevertheless, these communities confront numerous local and global threats, and these pressures on SV put their livelihoods, well-being, food security and traditional lifestyle at risk. Therefore, the role of researching human dimensions and governance is not only basic but also urgent to turn to sustainable socioeconomic management.

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

Addressing the growing need for effective and environmentally friendly fungicides in agricul-ture, this study explored the potential of alginate microparticles loaded with metal ions as a novel approach to combat fungal pathogens. Novel alginate microparticles (microspheres and microcapsules) loaded with zinc or simultaneously with zinc and silver ions were prepared and physicochemically characterized (microparticle size, morphology, topography, encapsulation efficiency, loading capacity, and swelling behavior). Investigation of molecular interactions in microparticles using FTIR-ATR spectroscopy exhibited complex interactions between all con-stituents. Fitting to the simple Korsmeyer-Peppas empirical model revealed the rate-controlling mechanism of zinc and silver ions release from microparticles is Fickian diffusion. Lower values of the release constant k imply a slower release rate of Zn or Ag ions from microcapsules com-pared to that of microspheres. The antimicrobial potential of the new formulations against the fungus Botrytis cinerea was evaluated. When subjected to tests against the fungus, microspheres and microparticles loaded with both zinc and silver ions effectively reduced its growth and al-tered the fungal hyphal structures well as exhibited superior antifungal activity. The results showed the potential of these novel microparticles as potent fungicides in agriculture.

Immersive Unit Visualization is an emergent form of visualization that arose from Immersive Analytics where, unlike traditional visualizations, each data point is represented by an individual visual mark in an immersive virtual environment. This practice has focused almost exclusively on virtual reality, excluding augmented reality (AR). This article develops and tests a prototype of an immersive Unit Visualization (Floating Companies II) with two AR devices: head-mounted display (HMD) and hand-held display (HHD). Results from the testing sessions with 20 users were analyzed through qualitative research analysis and thematic coding indicating that, while the HHD enabled a first contact with AR visualization on a familiar device, HMD improved the perception of hybrid space by supporting greater stability of virtual content; wider field of view; improved spatial perception; increased sense of immersion; and more realistic simulation, which impacted on information reading and sense-making. The materialization of abstract quantitative values into concrete reality through its simulation in the real environment and the ludic dimension stand out as important opportunities of this type of visualization. This paper investigates the aspects distinguishing two experiences regarding data visualization in hybrid space; and characterizes ways of seeing information with AR, identifying opportunities to advance information design research.

Background: Silent MRA has shown promising results in evaluating the stents used for intracranial aneurysm treatment. A deep learning-based algorithm was recently introduced by GE. The purpose of this study was to compare the performance of several MRA techniques in lumen visibility in silicone models with flow diverter stents. Methods: Two Surpass Evolve stents of different sizes were implanted in two silicone tubes. The tubes were placed in separate boxes in straight position and in two different curve configurations and connected to a pulsatile pump to construct a flow loop. Using a GE 3.0T scanner, TOF and silent MRA images were acquired, and deep learning reconstruction was applied to the silent MRA dataset. Intra-luminal signal intensity in the stent (SIin-stent), in the tube outside the stent (SIvessel) and of the background (SIbg) were measured for each scan. Results: The SIin-stent/SIbg and SIin-stent/SIv ratio were higher on silent scans and DL-based reconstructions than on TOF images. The stent tips created severe artefacts on TOF images, which could not be observed on silent scans. Conclusions: Our study demonstrated that the DL algorithm improved the quality of the silent technique in evaluating the flow diverter stent patency.

One of the IRDiRC goals for 2017-2027 is to achieve definitive diagnosis for rare undiagnosed diseases within one year, as diagnosis delay remains one of the pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was created in response to this challenging scenario to cover patients’ needs and after seeing the success of the UDP in USA. SpainUDP offers a multidisciplinary approach to those patients who have long sought a diagnosis without any success. During a first phase of the protocol, undiagnosed cases are sent to SpainUDP by individual patients, patient organizations or hospitals. After a carefully analysis of phenotype, data from sequencing experiments (WES) is processed with a standard pipeline and a detailed standardized phenotypic information (mapped to HPO) is connected to genetic data. In addition, the participation of SpainUDP in international initiatives such as the European projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International (UDNI), and the MatchMaker Exchange platform, allows the establishment of a global data sharing strategy across multiple projects submitting data to these international initiatives. From the official beginning of the program (at the end of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time, 37 cases (25 %) dropped out the program due to several reasons. The remaining 110 cases are distributed as follows: phenotypic and genotypic (WES) characterization was finished in 30 cases, of which 20 (67 %) were diagnosed; 21 cases are pending on variants validation by Sanger; in 25 cases, WES is ongoing and 34 cases are in a deep phenotypic characterization. As a conclusion, SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC: the patients’ diagnosis in a period of time as short as possible and the promotion of data sharing (especially genomic) at the international level.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

Mitochondrial dysfunctions, e.g. abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy, activate innate immunity. Recent reports also showed that deletion of mitochondrial matrix peptidase ClpP in mice transcriptionally upregulates inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, immunoblots, and reverse transcriptase polymerase chain reaction. Anomalies in the mitochondrial unfolded protein responses pathway were prominent for the co-chaperone DNAJA3, and for its known interactor STAT1. Their mitochondrial dysregulation affected also their extra-mitochondrial abundance, as possible innate immune modulators. Increased expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). They can be explained by the accumulation of mitoribosomes and mitochondrial nucleoids in ClpP-null cells, which may act as damage-associated molecular patterns. The consistent dysregulation of these factors from early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity.Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C).Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C.Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

Background. Rectal Magnetic Resonance Imaging (MRI) is a key test in advanced rectal cancer and in the preoperative staging of a lesion suitable for transanal endoscopic surgery (TES). MRI is not operator-dependent, but its results when determining anatomical landmarks are variable. Method. Observational study of inter-observer concordance regarding four diagnostic tests used to establish the anatomical characteristics of rectal lesions: colonoscopy, rectal ultrasound (EUS), rectal MRI, and intraoperative rigid rectoscopy (IRR) in patients scheduled for transanal endoscopic surgery (TES) with curative intent. This inter-observational study assessed the concordance between four expert radiologists regarding the topographic evaluation by means of rectal MRI of lesions under consideration for TES. Results. Fifty-five consecutive rectal tumors were studied. For most of the items, the correlation between IRR and colonoscopy or EUS was generally very good (intraclass correlation coefficient -ICC-)>0.75), although the correlation between MRI and IRR in relation to size by quadrants (ICC=0.092) and location by quadrants (ICC=0.292) was weak. The ICC for the other items obtained excellent correlations: Kappa index >0.80 for all items except for the distance from the peritoneal reflection to the anal verge, where it was merely good (IK=0.606). Conclusions. The anatomical description of rectal lesions that are candidates for TES provided by means of IRR, EUS, colonoscopy and MRI is reliable. The MRI is less reliable, but in the hands of expert radiologists, the anatomical study of rectal lesions is accurate and reproducible.

Dengue virus an arbovirus is endemic in an area that comprise almost half of the world's population, contrary to past beliefs that dengue virus differentiate from other neuroinvasive arbovirus due to its lack of neurological invasion and disease related neurological complications excluding hemorrhagic and thromboembolic , the body of evidence have grown to demonstrate a series of neurological manifestations linked to dengue virus with possible mechanisms involving direct virus invasion of the nervous system or immune mediated complications. In this review we provide a wide approach to this neglect but not so rare manifestations of a very common disease.

Patients with chronic (CM) and high frequency episodic migraine (HFEM) report cognitive complaints that contribute to migraine burden. Although, there is little evidence about the ef-fects of migraine treatments on these symptoms. Objective: To evaluate the effect of preventive treatment on the impact of cognitive symptoms, specifically the ability to concentrate, in individuals with CM and HFEM. Methods: Prospective cohort study in patients with CM and HFEM initiating treatment with botulinum toxin (BT) or anti-CGRP/R monoclonal antibodies (mAbs). Patients were evaluated at baseline and after 3 months of treatment, using a headache diary and a question about the im-pact of migraine attacks on concentration (never, rarely, sometimes, often, and always). Results: 108 patients (105 females, 44.3 years of age on average), 75% with CM and 27% with HFEM were included, 55 received a first session of BT and 53 received 3 injections of a monthly mAb. In both groups, there was a significant decline on the impact of migraine in concentration (related samples Wilcoxon signed rank test <0.001) compared to baseline. Reduction in monthly headache days was the main predictor of any concentration improvement, while treatment group, age, ongoing medication with topiramate or baseline medication overuse were not sig-nificant. Conclusion: Preventive treatment of HFEM or CM with drugs not acting on central nervous sys-tem is associated with a decrease of the impact of migraine attacks on concentration, predicted by the decline in headache days. These results indicate that migraine preventive treatment also improves non-pain symptoms, which is relevant given the contribution of cognitive complaints to the impact of headache attacks

Socks with the same three-dimensional plantar design, but with different compositions in the separation of their weaves could have different thermoregulatory effects. The objective of this study was therefore to evaluate the temperatures on the sole of the foot after a 10-km run, using two models of socks with different weave separations. In a sample of 20 individuals (14 men and 6 women), plantar temperatures were analysed using a Flir E60bx® (Flir Systems) thermographic camera before and after a run of 10 km wearing two models of socks that had different separations between the fabric weaves (5 mm versus 3 mm). After the post-exercise thermographic analysis, the participants responded to a Likert type survey to evaluate the physiological characteristics of the two models of socks. There was a significant increase in temperature in the areas of interest (p&lt;0.001) after the 10-km run with both models of sock. The temperature under the 1st metatarsal head was higher with the AWC 2.1 model than with the AWC 1 (33.6±2.0°C vs 33.2±2.1°C) (p = 0.014). No significant differences were found in the scores on the physiological characteristics comfort survey (p&gt;0.05 in all cases. The two models presented similar thermoregulatory effects on the soles of the feet, although the model with the narrowest weave separation generated greater temperatures (+0.4°C) under the first metatarsal head.

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions > 2.5 Å and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, π-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

Humans can recombine thousands of different facial expressions. This variability is due to the ability to voluntarily or involuntarily modulate emotional expressions, which, in turn, depends on the existence of two anatomically separate pathways. The Voluntary (VP) and Involuntary (IP) pathways mediate the production of posed and spontaneous facial expressions, respectively, and might also affect the left and right sides of the face differently. This is a neglected aspect in the emotion literature, where posed expressions instead of genuine expressions are often used as stimuli. Two experiments with different induction methods were specifically designed to inves-tigate the unfolding of spontaneous and posed facial expressions of happiness along the facial vertical axis (left, right) with a high-definition 3D optoelectronic system. The results showed that spontaneous expressions were distinguished from posed facial movements as revealed by relia-ble spatial and speed key kinematic patterns in both experiments. Moreover, VP activation pro-duced a lateralization effect: compared with the felt smile, the posed smile involved an initial acceleration of the left corner of the mouth, while an early deceleration of the right corner oc-curred in the second phase of the movement, after the velocity peak.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

Hydrotherapy, including the use of therapeutic showers and bathtubs, has been studied for its potential benefits in labor pain management. Previous research has indicated that hydrotherapy can alleviate pain, but comparative studies between therapeutic showers and bathtubs are scarce. Objective: This study aims to compare the effects of therapeutic showers and bathtubs on pain perception, labor duration, use of epi-dural analgesia, and maternal and neonatal outcomes during labor. Methods: A total of 124 pregnant women were included in this study. Participants were divided into two groups: those who used a thera-peutic shower and those who used a bathtub during labor. Pain levels were measured using a visual analog scale (VAS). Labor duration, use of epidural analgesia, types of delivery, maternal outcomes (postpartum hemorrhage, perineal status, maternal hypotension, fever, and breastfeeding), and neonatal outcomes (APGAR scores, fetal heart rate, complications, and neonatal unit admissions) were recorded and analyzed. Results: Both the therapeutic shower and the bathtub effectively reduced pain perception, with the bathtub showing a greater reduction in VAS scores. The therapeutic shower group experienced a signifi-cantly shorter labor duration compared to the bathtub group. The majority of participants in both groups did not require epidural analgesia, with no significant differences between the groups. There were no sig-nificant differences in the types of delivery. Maternal outcomes indicated a lower incidence of perineal tears and episiotomies in the therapeutic shower group. Neonatal outcomes, including APGAR scores and fetal heart rate, were similar between the groups, with no significant differences in complications or neo-natal unit admissions. Conclusions: Both therapeutic showers and bathtubs are effective for pain relief during labor, with the bathtub showing a higher reduction in pain intensity. The therapeutic shower is as-sociated with a shorter labor duration and a lower incidence of perineal tears and episiotomies. Both meth-ods are safe for neonatal well-being, making hydrotherapy a viable non-pharmacological option for pain management in labor. However, the therapeutic shower may offer additional benefits in terms of labor du-ration and maternal outcomes.