Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Alcohol effects on drivers' speed management: The influence of visual performance and road complexity.

OBJECTIVE: The aim of this work is to assess how drivers adapt their driving speed as a self-regulation mechanism when driving under the influence of alcohol (DUIA), and the influence of alcohol consumption, visual performance, road complexity, and personal traits. METHOD: Thirty one volunteers took part in the study. All of them underwent three experimental sessions: Baseline (no alcohol), Alcohol 1 (low-moderate dose), and Alcohol 2 (moderate-high dose). Vision was tested by means of contrast sensitivity and retinal straylight. Driving performance was assessed using a driving simulator. The difference between the driving speed and the speed limit was calculated in 10 road scenarios of different complexity. RESULTS: Drivers adapted their driving speed less (i.e., drove faster) in Alcohol 1 condition compared to Alcohol 2 (p = 0.007). This indicate that participants felt more confident under the influence of a low-moderate dose of alcohol. Participants with better contrast sensitivity drove faster (p = 0.021). The complexity of the road and other factors such as driving experience, gender, or DUIA frequency, also influenced speed choice. CONCLUSIONS: Drivers under the influence of a low-moderate dose of alcohol seem to be less aware of the risk. Contrast sensitivity is a good predictor of the speed choice when DUIA. A better understanding of drivers' behavior under the influence of substance use may be useful to adjust and improve the traffic laws and driving regulations.

Dynamic relationships among pathways producing hydrocarbons and fatty acids of maize silk cuticular waxes.

The hydrophobic cuticle is the first line of defense between aerial portions of plants and the external environment. On maize (Zea mays L.) silks, the cuticular cutin matrix is infused with cuticular waxes, consisting of a homologous series of very long-chain fatty acids (VLCFAs), aldehydes, and hydrocarbons. Together with VLC fatty-acyl-CoAs (VLCFA-CoAs), these metabolites serve as precursors, intermediates and end-products of the cuticular wax biosynthetic pathway. To deconvolute the potentially confounding impacts of the change in silk microenvironment and silk development on this pathway, we profiled cuticular waxes on the silks of the inbreds B73 and Mo17, and their reciprocal hybrids. Multivariate interrogation of these metabolite abundance data demonstrates that VLCFA-CoAs and total free VLCFAs are positively correlated with the cuticular wax metabolome, and this metabolome is primarily affected by changes in the silk microenvironment and plant genotype. Moreover, the genotype effect on the pathway explains the increased accumulation of cuticular hydrocarbons with a concomitant reduction in cuticular VLCFA accumulation on B73 silks, suggesting that the conversion of VLCFA-CoAs to hydrocarbons is more effective in B73 than Mo17. Statistical modeling of the ratios between cuticular hydrocarbons and cuticular VLCFAs reveals a significant role of precursor chain length in determining this ratio. This study establishes the complexity of the product-precursor relationships within the silk cuticular wax-producing network by dissecting both the impact of genotype and the allocation of VLCFA-CoA precursors to different biological processes, and demonstrates that longer chain VLCFA-CoAs are preferentially utilized for hydrocarbon biosynthesis.

High-Performance Aramids with Intrinsic Bactericide Activity.

Aramids, renowned for their high-performance attributes, find applications in critical fields such as protective equipment, aerospace components, and industrial filters. However, challenges arise in scenarios in which frequent washing is impractical, leading to bacterial proliferation, especially in textiles. This study outlines a straightforward and scalable method for preparing aramid-coated textiles and films endowed with inherent bactericidal activity, achieved by reacting parent aramids with vanillin. The functionalization of the aramids with bactericide moieties not only preserved the high-performance characteristics of commercial aramids but also improved their crucial mechanical properties. Tensile tests revealed an increase in Young's modulus, up to 50% compared to commercial m-aramid, accompanied by thermal performance comparable to commercial m-aramids. The evaluation of these coated textiles as bactericidal materials demonstrated robust effectiveness with A parameters (antibacterial activity) of 4.31 for S. aureus and 3.44 for K. pneumoniae. Reusability tests (washing the textiles in harsh conditions) underscored that the bactericide-coated textiles maintain their performance over at least 5 cycles. Regarding practical applications, tests performed with reconstructed human epidermis affirmed the nonirritating nature of these materials to the skin. The distinctive qualities of these metal-free intrinsic bactericidal aramids position them as ideal candidates for scenarios demanding a synergy of high performance and bactericidal properties. Applications such as first responders' textiles or filters stand to benefit significantly from these advanced materials.

Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

Wisconsin diversity panel phenotypes: spoken descriptions of plants and supporting data.

OBJECTIVES: Phenotyping plants in a field environment can involve a variety of methods including the use of automated instruments and labor-intensive manual measurement and scoring. Researchers also collect language-based phenotypic descriptions and use controlled vocabularies and structures such as ontologies to enable computation on descriptive phenotype data, including methods to determine phenotypic similarities. In this study, spoken descriptions of plants were collected and observers were instructed to use their own vocabulary to describe plant features that were present and visible. Further, these plants were measured and scored manually as part of a larger study to investigate whether spoken plant descriptions can be used to recover known biological phenomena. DATA DESCRIPTION: Data comprise phenotypic observations of 686 accessions of the maize Wisconsin Diversity panel, and 25 positive control accessions that carry visible, dramatic phenotypes. The data include the list of accessions planted, field layout, data collection procedures, student participants' (whose personal data are protected for ethical reasons) and volunteers' observation transcripts, volunteers' audio data files, terrestrial and aerial images of the plants, Amazon Web Services method selection experimental data, and manually collected phenotypes (e.g., plant height, ear and tassel features, etc.; measurements and scores). Data were collected during the summer of 2021 at Iowa State University's Agricultural Engineering and Agronomy Research Farms.

Effect of miR-21 in mesenchymal stem cells-derived extracellular vesicles behavior.

BACKGROUND: A challenging new branch of research related to aging-associated diseases is the identification of miRNAs capable of modulating the senescence-associated secretory phenotype (SASP) which characterizes senescent cells and contributes to driving inflammation. METHODS: Mesenchymal stem cells (MSC) from human umbilical cord stroma were stable modified using lentivirus transduction to inhibit miR-21-5p and shotgun proteomic analysis was performed in the MSC-derived extracellular vesicles (EV) to check the effect of miR-21 inhibition in their protein cargo. Besides, we studied the paracrine effect of those modified extracellular vesicles and also their effect on SASP. RESULTS: Syndecan-1 (SDC1) was the most decreased protein in MSC-miR21--derived EV, and it was involved in inflammation and EV production. MSC-miR21--derived EV were found to produce a statistically significant inhibitory effect on SASP and inflammaging markers expression in receptor cells, and in the opposite way, these receptor cells increased their SASP and inflammaging expression statistically significantly when treated with MSC-miR-21+-derived EV. CONCLUSION: This work demonstrates the importance of miR-21 in inflammaging and its role in SASP through SDC1.

Physiologic and Transcriptomic Effects Triggered by Overexpression of Wild Type and Mutant DNA Topoisomerase I in Streptococcus pneumoniae.

Topoisomerase I (TopoI) in Streptococcus pneumoniae, encoded by topA, is a suitable target for drug development. Seconeolitsine (SCN) is a new antibiotic that specifically blocks this enzyme. We obtained the topARA mutant, which encodes an enzyme less active than the wild type (topAWT) and more resistant to SCN inhibition. Likely due to the essentiality of TopoI, we were unable to replace the topAWT allele by the mutant topARA version. We compared the in vivo activity of TopoIRA and TopoIWT using regulated overexpression strains, whose genes were either under the control of a moderately (PZn) or a highly active promoter (PMal). Overproduction of TopoIRA impaired growth, increased SCN resistance and, in the presence of the gyrase inhibitor novobiocin (NOV), caused lower relaxation than TopoIWT. Differential transcriptomes were observed when the topAWT and topARA expression levels were increased about 5-fold. However, higher increases (10-15 times), produced a similar transcriptome, affecting about 52% of the genome, and correlating with a high DNA relaxation level with most responsive genes locating in topological domains. These results confirmed that TopoI is indeed the target of SCN in S. pneumoniae and show the important role of TopoI in global transcription, supporting its suitability as an antibiotic target.

Crafting and Analyzing Multi-Structured Aramid Materials and Their Pyrolytic Transformations: A Comprehensive Exploration.

Gradient porous materials, particularly carbon-based materials, hold immense potential in the fields of batteries, energy storage, electrocatalysis, and sensing, among others, by synergistically combining the attributes associated with each pore size within a unified structural framework. In this study, we developed a gradient porous aramid (GP-Aramid) by incorporating cellulose acetate as a porosity promoter in the polymer casting solution in different proportions. These GP-Aramids were subsequently transformed into their pyrolyzed counterparts (GP-Pyramids), retaining their original structures while displaying diverse cellular or dense microstructures inherited from the parent aramid, as confirmed via scanning electron microscopy. X-ray diffraction spectra provided evidence of the conversion of aramids into carbonaceous materials. The materials showed structural defects observed through the intensity ratio of the G and D bands (ID/IG = 1.05) in the Raman spectra, while X-ray photoelectron spectra (XPS) revealed that the carbonization process yielded pyrolyzed carbon materials unusually rich in nitrogen (6%), oxygen (20%), and carbon (72%), which is especially relevant for catalysis applications. The pyrolyzed materials showed bulk resistivities from 5.3 ± 0.3 to 34.2 ± 0.6 depending on the meta- or para-orientation of the aramid and the porous structure. This work contributes to understanding these gradient porous aromatic polyamides' broader significance and potential applications in various fields.

The Relationship between Anxiety, Visual Function, and Symptomatology in University Students.

Mental health concerns have emerged at the university level, with the psychological well-being of students being increasingly affected. This cross-sectional study investigated the proportion of university students having anxiety, and its effects on their visual function and symptomatology. We included 41 students (26.1 ± 4.8 years), and their visual function was assessed through several tests to produce a general visual performance index (VPI). The visual symptomatology was studied using the Conlon Visual Discomfort Survey and the Quality of Vision (QoV) questionnaire. The students were classified into two groups according to the Generalized Anxiety Disorder Screener (GAD-7) test ("no anxiety" and "anxiety" groups). The visual function evaluation indicated significantly worse VPI in the anxiety group (p = 0.047). These students also showed significantly higher scores in the Conlon survey (p = 0.004) and two subscales of the QoV questionnaire: symptom severity (p = 0.041) and symptom bothersomeness (p = 0.013). Moreover, the multiple linear regression model showed a significant association between visual discomfort according to the Conlon questionnaire and the level of anxiety (r = 0.405; R2 = 0.164; B = 0.405; p = 0.012). It is important to study the influence of psychological factors on vision, not only for refractive error, but also for binocular and accommodative disorders.

Effects of alcohol consumption on driving performance in the presence of interocular differences simulated by filters.

The role of interocular differences simulated by filters (fog filter and Bangerter foil) on visual and driving performance in alcohol users was assessed. We found that the binocular visual function deteriorates significantly in terms of contrast sensitivity (from 6 to 18 cpd). Additionally, driving performance is significantly impaired under these conditions as evidenced by increased mean speed, standard deviation of the lateral position, distance traveled outside the lane, reaction time and number of collisions. Furthermore, we found that interocular differences due to intraocular scattering and straylight are directly related to an overall reduction in visual and driving performance. This provided a comprehensive perspective from which to understand the relationship between binocular visual function, interocular differences, and driving performance. In practice, our findings contribute to the understanding of the importance of limiting interocular differences, which can be common among presbyopes corrected using the monovision technique, as well as in cases of cataract or other ocular pathology affecting only one eye, or even in cases of cataract surgery of the first eye. These interocular differences can have an adverse impact on road safety, especially when combined with moderate alcohol consumption.

Characterization of integration sites and transfer DNA structures in Agrobacterium-mediated transgenic events of maize inbred B104.

In maize, the community-standard transformant line B104 is a useful model for dissecting features of transfer DNA (T-DNA) integration due to its compatibility with Agrobacterium-mediated transformation and the availability of its genome sequence. Knowledge of transgene integration sites permits the analysis of the genomic environment that governs the strength of gene expression and phenotypic effects due to the disruption of an endogenous gene or regulatory element. In this study, we optimized a fusion primer and nested integrated PCR (FPNI-PCR) technique for T-DNA detection in maize to characterize the integration sites of 89 T-DNA insertions in 81 transformant lines. T-DNA insertions preferentially occurred in gene-rich regions and regions distant from centromeres. Integration junctions with and without microhomologous sequences as well as junctions with de novo sequences were detected. Sequence analysis of integration junctions indicated that T-DNA was incorporated via the error-prone repair pathways of nonhomologous (predominantly) and microhomology-mediated (minor) end-joining. This report provides a quantitative assessment of Agrobacterium-mediated T-DNA integration in maize with respect to insertion site features, the genomic distribution of T-DNA incorporation, and the mechanisms of integration. It also demonstrates the utility of the FPNI-PCR technique, which can be adapted to any species of interest.

Pain Catastrophizing in Dance Students in Relation to Resilient Behavior and Self-Reported Injuries.

AIMS: Pain catastrophizing is characterized by a set of negative emotional and cognitive processes in response to pain, with a tendency to focus inordinately on the painful sensation, exaggerate the damage, and perceive feelings of helplessness. It is a psychological factor that can be treated to help people more effectively cope with pain. In this cross-sectional study, we explored the relationship between self-reported injuries, resilient behavior, and pain catastrophizing in dance students, with more than 3 years of study in public conservatories or private academies. METHODS: A sample of 147 dance students participated, 75.5% of whom were female with a mean age of 28.34 yrs (SD 11.42). Pain catastrophizing was assessed using the Pain Catastrophizing Scale, and resilience was assessed using the Resilience Scale. RESULTS: Students in the high resilience category reported lower scores on rumination and magnification, with a marginal difference in total catastrophizing and no difference in helplessness. Those who reported having suffered injuries during the last 3 years showed higher scores in total catastrophizing, rumination, and magnification, but not in helplessness. Those who reported mild injuries showed differences in pain catastrophizing, rumination, and magnification, while those with moderate and severe/very severe injuries only showed differences in magnification. CONCLUSION: The individual nature of pain perception and coping strategies suggests that pain catastrophizing may be considered before dance performance and in those dancers who do not recover as expected after injury.

A systematic review on the impact of gastrointestinal microbiota composition and function on cognition in healthy infants and children.

Evidence from animal models or children with neurodevelopmental disorders has implicated the gut microbiome (GM) in neurocognitive development. However, even subclinical impairement of cognition can have negative consequences, as cognition serves as the foundation for skills necessary to succeed in school, vocation and socially. The present study aims to identify gut microbiome characteristics or changes in gut microbiome characteristics that consistently associate with cognitive outcomes in healthy, neurotypical infants and children. Of the 1,520 articles identified in the search, 23 were included in qualitative synthesis after applying exclusion criteria. Most studies were cross-sectional and focused on behavior or motor and language skills. Bifidobacterium, Bacteroides, Clostridia, Prevotella, and Roseburia were related to these aspects of cognition across several studies. While these results support the role of GM in cognitive development, higher quality studies focused on more complex cognition are needed to understand the extent to which the GM contributes to cognitive development.

Medication Adherence and Contraceptive Counseling.

Combined oral contraceptives (COC) are a very popular form of birth control. Incorrect use and lack of adherence to treatment reduce the effectiveness of this method. Having a standard tool to identify poor-adherence profiles quickly and objectively can be helpful for midwives and potentially for COC users. The MMAS-4 adherence scale has been used in various medical fields, but there is little evidence of its potential in contraceptive consultation. This paper presents a piece of multicenter observational research based on a sample of 327 women who had attended contraceptive counselling in Spain and were COC users or had informed the midwife that they want to start to use this method. Two interviews were conducted: at the time of consultation and after one year. In our research, the MMAS-4 identified high-risk behaviors: during the 1-year follow-up period, COC users classified as poorly adherent had a significantly higher risk of missed contraceptive pills, more incidents and problems related to the method of contraception, as well as a lower degree of satisfaction with the contraceptive method. One case of unplanned pregnancy and two cases of emergency contraception were identified, all of them corresponding to poorly adherent women. The use of MMAS-4 in consultation can improve midwives' contraceptive counselling.

Demographic history and genetic structure in pre-Hispanic Central Mexico.

Aridoamerica and Mesoamerica are two distinct cultural areas in northern and central Mexico, respectively, that hosted numerous pre-Hispanic civilizations between 2500 BCE and 1521 CE. The division between these regions shifted southward because of severe droughts ~1100 years ago, which allegedly drove a population replacement in central Mexico by Aridoamerican peoples. In this study, we present shotgun genome-wide data from 12 individuals and 27 mitochondrial genomes from eight pre-Hispanic archaeological sites across Mexico, including two at the shifting border of Aridoamerica and Mesoamerica. We find population continuity that spans the climate change episode and a broad preservation of the genetic structure across present-day Mexico for the past 2300 years. Lastly, we identify a contribution to pre-Hispanic populations of northern and central Mexico from two ancient unsampled "ghost" populations.

Alta capacidad: competencias sociales y cyberbullying / High capacity: social competences and cyberbullying

Resumen La Alta Capacidad intelectual (ACI) es una manifestación diferencial de la inteligencia humana, de base neurobiológica, pero que debe expresar su alto potencial a lo largo del desarrollo de la per sona que la posee, mediante la covariación de factores moduladores endógenos (como la competencia social) y exógenos. El objetivo del trabajo es doble: 1) conocer, comparativamente la competencia social de menores con y sin ACI, 2) diferenciar aquellas competencias sociales que podrían ser factores protectores o de riesgo frente al mal uso de las tecnologías digitales. Se administra la Social Skills Improvement System-Rating Scales a una muestra de n = 70 aprendices (n = 35 con ACI, n = 35 con inteligencia promedio) de 11 a 16 años, analizando si existen diferencias estadísticamente significativas en habilidades sociales y en dificultades de conducta. Los resultados muestran diferencias estadísticamente significativas, a favor de los participantes con ACI en habilidades sociales (especialmente en: Responsabilidad, Cooperación y Autocontrol) y mejor ajuste personal, con baja inci dencia de dificultades internalizantes y externalizantes. Se concluye y discute el rol protector de las habilidades sociales para afrontar contextos interactivos complejos como el derivado de la era digital y agresiones como el cyberbullying.

Abstract High Intellectual Ability (HIA) is a differential manifestation of human intelligence with a neurobiologi cal basis but which must express its high potential along the developmental trajectory through the covariation of endogenous (such as social competence) and exogenous modulating factors. The aim of the study is twofold: 1) to know, comparatively, the social competence of children with and without HIA, 2) to differentiate those social competences that could be protective or risk factors against the misuse of digital technologies. The Social Skills Improvement System-Rating Scales were administered to a sample of n = 70 learners (n = 35 with ICA, n = 35 with average intelligence) aged 11 to 16, analysing whether there are statistically significant differences in social skills and behavioural difficulties. Results show statistically significant differences in favour of participants with ICA in social skills (especially in: Responsibility, Co-operation and Self-Control) and better personal adjustment, with low incidence of internalising and externalising difficulties. We conclude and discuss the protective role of social skills in coping with complex interactive contexts such as the digital age and aggressions such as cyberbullying.