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Abstract Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.

Abstract Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes — a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Abstract Background To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. Methods This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015–2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. Results During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p

Este texto indaga la posibilidad de definir un nuevo paradigma arquitectónico a partir de la detección de una serie de características comunes a una arquitectura contemporánea aparentemente preocupada por la construcción de lo mínimo y de lo esencial. El análisis de determinados proyectos y posiciones críticas clave acontecidas en los últimos años permite construir una posible genealogía proyectual con la que aproximarse a la definición de la idea de “nueva esencialidad”: una manera de operar que recupera el interés por el suelo y la flexibilidad de los soportes, que persigue la adaptabilidad a diferentes contextos y programas, que refuerza el orden y la organización a través de la sencillez geométrica de la planta y que se manifiesta con una nítida honestidad constructiva.

Abstract Background Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. Methods 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. Results Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p

Abstract Background Dairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest. Methods We analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses’ Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty. Results During follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty. Conclusions The results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk.

Objectives To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD).Design Prospective population-based cohort study.Setting 10 primary healthcare centres in the north of the city of Madrid (Spain).Participants A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose

IntroductionThe COVID-19 pandemic lockdowns (people confined to home, with movement restrictions) presented an external shock to livelihoods and food systems worldwide, most severely affecting vulnerable households in low-income countries. While evidence is available regarding how COVID-19 generally affected low-income countries, the specific dynamics of local food-system responses and sustainably-certified coffee farm households has not been examined, despite them being usually deemed to be more resilient to shocks. This research examines how local food systems in Honduras changed during lockdowns, how certified coffee households coped with the shock, especially food insecurity, and the potential role of coffee cooperatives in increasing households’ resilience under future shocks and stressors.MethodsWe applied a mixed-methods approach that combined a structured household survey with semi-structured qualitative interviews with 91 households, 6 cooperative representatives, and 18 food-system representatives.ResultsWe found that coffee-income-dependent households experienced greater food insecurity during lockdown than coffee households with diversified incomes. Before lockdown the local food system was highly dependent on external fresh food from outside the state. Food suppliers changed altered fresh-food procurement strategies, mostly to maintain fresh-food availability at the beginning of the pandemic. However, more than half the interviewed households lacked confidence regarding food security, amid rising food prices and local shortages. Certified coffee cooperatives supported their members by providing food assistance, cash transfers, and credit.DiscussionSome of these strategies are difficult to maintain where crises are recurrent and that may render households more vulnerable to future extreme events. Rather, coffee cooperatives could diversify and support their members in growing and marketing additional food crops. This could be a key approach for boosting local food security and strengthening the local food system.

Background. Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson’s disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge. Methods. We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques. Results. Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88. Conclusion. We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson’s disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life.

The present study evaluated the mechanical behavior of five designs of Morse taper (MT) connections with and without the application of loads. For this, the detorque of the fixing screw and the traction force required to disconnect the abutment from the implant were assessed. A total of 100 sets of implants/abutments (IAs) with MT-type connections were used, comprising five groups (n = 20/group): (1) Group Imp 11.5: IA sets with a cone angulation of 11.5°; (2) Group SIN 11.5: with a cone angulation of 11.5°; (3) Group SIN 16: with a cone angulation of 16°; (4) Group Neo 16: with a cone angulation of 16°; and (5) Group Str 15: with a cone angulation of 15°. All sets received the torque recommended by the manufacturer. After applying the torque, the counter torque of the fixing screws was measured in ten IA sets of each group without the application of cyclic loads (frequencies ≤ 2 Hz, 360,000 cycles, and force at 150 Ncm). The other ten sets of each group were subjected to cyclic loads, after which the detorque was measured. Afterwards, the force for disconnection between the implant and the abutment was measured by traction on all the samples. The untwisting of the abutment fixation screws showed a decrease in relation to the initial torque applied in all groups. In the unloaded samples, it was found to be −25.7% in Group 1, −30.4% in Group 2, −36.8% in Group 3, −29.6% in Group 4, and −25.7% in Group 5. After the applied loads, it was found to be −44% in Group 1, −43.5% in Group 2, −48.5% in Group 3, −47.2% in Group 4, and −49.8% in Group 5. The values for the IA sets were zero for SIN 16 (Group 3) and Neo16 (Group 4), both without and with loads. In the other three groups, without loads, the disconnection value was 56.3 ± 2.21 N (Group 1), 30.7 ± 2.00 N (Group 2), and 26.0 ± 2.52 N (Group 5). After applying loads, the values were 63.5 ± 3.06 N for Group 1, 34.2 ± 2.45 N in Group 2, and 23.1 ± 1.29 N in Group 5. It was concluded that in terms of the mechanical behavior of the five designs of MT IA sets, with and without the application of loads, the Imp 11.5, SIN 11.5, and Srt 15 groups showed better results compared to the SIN 16 and Neo 16 groups, showing that lower values of cone angulation increase the friction between the parts (IA), thus avoiding the need to maintain the torque of the fixing screw to maintain the union of the sets.

African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas.

Contemporary environmental awareness requires new architectural practices to reformulate the relationship between buildings and the ground. Among these, the way in which buildings land on the site emerges as a key architectural condition that must be reviewed, focusing on generating new systems of articulation, more sensitive and attentive to the specific conditions of the grounds. Drawing on the ecological perspectives put forth by authors like Bruno Latour in recent years, this article presents a critical analysis of the rooting systems developed by some of the most significant architectural practices today. This case study provides a catalogue of various sustainable topographical strategies that prioritize the conservation and nurturing of soil properties. The discussion of these strategies enables the synthesis of a series of design guidelines to foster new relationships of affinity with the land, positioning architecture not as an imposition on the territory but as a facilitator of its natural development.

Community colleges provide broad access to a college degree due to their less expensive tuition, greater course time offerings, and more open admission policies compared to four-year universities as reported (Juszkiewicz, 2015). These institutions have great potential to diversify who chooses STEM, such as engineering. Such diverse representation is important, because students from different backgrounds can contribute new perspectives that foster creative and innovative approaches to solving problems. However, approximately 40% of the students who enter community college in the U.S. leave before graduation (Xu & Jaggars, 2011). Harnessing the power of social media to reduce attrition, we tested a pilot intervention in which community college students in engineering courses completed a reflection exercise after watching YouTube videos of former engineering students from similar backgrounds who successfully transferred to a four-year college. Quasi-experimental analyses (N = 537) show that students in the intervention received higher engineering course grades and had greater odds of enrolling in an engineering course in the subsequent term compared to those who were not in the intervention. Additionally, we find support for the hypothesis that the intervention has larger benefits for women. Results suggest that hearing from other students about their engineering experience can be a useful tool for improving community college students' choices and performance.

Este trabajo se propone el estudio y la edición del romance «A una dama muy enemiga de gatos» del murciano Jacinto Polo de Medina. Se inserta el poema dentro del corpus de la literatura felina aurisecular. En el análisis, se abordan los dos tipos de lectura que sugiere la poesía del Siglo de Oro: una lectura retórica, que se enfoca en los tópicos y materiales empleados; y una lectura conceptista, que fija su atención en los recursos de agudeza verbal que se plasman en los versos. Por último, se presenta el poema editado según los criterios del GRISO, con modernización ortográfica y puntuación interpretativa.

Purpose: To summarize the results of Chile's 2022 Report Card (RC) on physical activity (PA) for Children and Adolescents. Methods: Chile's 2022 RC included ten core PA indicators common to the Global Matrix 4.0. Evidence from scientific articles, reports, and databases published between 2018 and January 2022 was included for each indicator. The data were collected and analyzed by a national scientific committee, which assigned letter grades (A to F) using a consensus based on benchmarks defined and revised by the Active Healthy Kids Global Alliance. Results: The committee assigned the following grades: Overall PA, D−; Organized Sports and Physical Activity Participation, C−; Active Play, Incomplete; Active Transportation, D; Sedentary Behavior, D−; Physical Fitness, Incomplete; Family and Peers, D; School, C; Community and Environment, D+; Government, A−. Conclusions: Chile's 2022 RC, like its previous versions, shows persistently low grades for most indicators. Overall PA remained nearly unchanged, while Community and Environment scored lower. Slight improvements were seen in Organized Sports, Family and Peers, and School Environment. While Chile has endeavored to increase children's activity levels, policies require implementation through a systemic, coherent framework to promote sustainable changes and reach a larger portion of children and youth.

Abstract Background Adolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies. Methods Male and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus. Results The main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females. Conclusions This study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.

Abstract Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood. Here, we used single-molecule tracking (SMT) in combination with a WRN inhibitor to examine WRN dynamics within the nuclei of living cancer cells. WRN inhibition traps the helicase on chromatin, requiring p97/VCP for extraction and proteasomal degradation in a MSI-H dependent manner. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation. Finally, we show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells and confirm the in vivo activity of WRN inhibition using an MSI-H mouse xenograft model. This work elucidates a regulatory mechanism for WRN that may facilitate identification of new therapeutic modalities, and highlights the use of SMT as a tool for drug discovery and mechanism-of-action studies.

Abstract Background Abiotic factors play a significant role in the evolution of Leishmania infantum infection due to its vectorial nature. This study aims to assess the evolution in the detection of new L. infantum infection cases in Valdeorras (Ourense, Northwestern Spain) over a 20-year period and how different climatic variables and preventive measures may have affected it. Methods Indirect immunofluorescence antibody tests (IFAT) were performed on serum samples collected from dogs attending the ‘Servicios Veterinarios de Sil’ veterinary clinic (Valdeorras, Northwestern Spain) between May 2003 and April 2023 to detect L. infantum exposure. The percentage of new cases of L. infantum infection was calculated from May of one year to April of the following year. Climatic conditions in the region, global sales of ectoparasiticides and the number of vaccines against L. infantum delivered in the veterinary clinic from 2003 to 2022 were recorded. Statistical analyses were conducted to determine the associations between these factors and the percentage of new cases of L. infantum infection. Results A total of 2909 dogs were assessed, and 3785 IFAT tests were performed between May 2003 and April 2023. The mean percentage of new seropositive cases over the 20-year period studied was 21.65 ± 10.8%, with a decline from the beginning to the end of the period studied. The percentage was significantly higher between May 2003 and April 2008 compared with the other periods (May 2008 to April 2013, May 2013 to April 2018 and May 2018 to April 2023). There was a positive correlation between the percentage of new cases of L. infantum infection and the maximum relative humidity in winter. Conversely, there was a negative correlation between the percentage of new cases and sales of ectoparasiticides and vaccination against L. infantum. Conclusions This study is one of the longest evaluations of the evolution of L. infantum infection in a fixed location and its association with external factors including climatic conditions and preventive measures. The results confirm that Valdeorras is a high-risk area for L. infantum infection. The use of ectoparasiticides and vaccines against L. infantum has been shown to play a significant role in preventing L. infantum infection, highlighting the crucial role of veterinarians in the fight against this disease. Graphical Abstract

ObjectiveTo ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing–remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.MethodsMulticenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity.ResultsAfter a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients.ConclusionOcrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.

Objective: The aim was to examine the association between social frailty and diet quality in adults over 65 years of age, and whether results differed by sex. Design: Population-based cross-sectional study using data from the Spanish National Health Survey. Participants: 5,071 community-dwelling people ≥65 years from Spain. Measurements: Social frailty was deemed to exist when the person both lived alone and had low social support, measured with the Duke-UNC scale. Diet was assessed with the Spanish Healthy Eating Index (S-HEI), ranging from 0 to 100 points (highest diet quality). Means and 95% confidence intervals of the S-HEI score for each social frailty group were calculated using linear regressions, with socially robust people as reference. Analyses were adjusted for main confounders, including sociodemographic, lifestyle and morbidity variables. Results: There were no differences in the S-HEI adjusted mean of socially frail (74.3 points, 95%CI: 73.4−75.2) compared to socially robust older adults (75.4 points; 95%CI: 75.1−75.7). In sex-stratified analyses, the S-HEI adjusted mean of socially frail men (71.9 points; 95%CI: 70.6−73.2) was lower than robust men (74.8 points; 95%CI: 74.4−75.3). Specifically, social frailty was associated with lower consumption of vegetables, fruits, dairy and lower diet variety in men. Differences were not observed according to social frailty among older women. Conclusions: Social frailty was associated with poor diet quality in community-dwelling older men, but not in women in Spain. Gender differences in self-care could partly explain this association. Sex-specific interventions are required to minimize the impact of social frailty on diet quality.

Organic solar cells (OSCs), especially those employing bulk heterojunction architecture, present a promising avenue in renewable energy technology. These devices utilize organic materials and can be doped by solvents such as dimethylformamide (DMF), tetrahydrofuran (THF), and dimethyl sulfoxide (DMSO). Solvent doping (DMF, THF, and DMSO) is observed to augment the efficiency of OSCs. However, a trade‐off exists between the volume of solvent used and the device's efficiency. The judicious selection of solvents is crucial as it directly impacts the environmental footprint of the fabrication process and the power conversion efficiency. Notably, the use of solvents in OSC fabrication contributes to reducing the environmental impact across various categories, in particular Abiotic Depletion, Global Warming, and Human Toxicity. Among the solvents studied, THF demonstrates the most significant reduction in environmental impact. Therefore, optimizing the choice and volume of solvents in OSC fabrication is paramount for achieving both enhanced device performance and minimal environmental footprint.

Abstract Multiple stakeholders in the microfinance sector seek to foster financial, social, and environmental development in a sustainable way by providing a wide range of products and services for financial inclusion. This heterogeneity is also reflected in the multiple methods to evaluate the performance of financial service providers. For this reason, it can be challenging for stakeholders to identify and understand the evaluation approaches that may be required to meet their needs and help them improve their performance. This study presents a comprehensive review of the existing approaches for the evaluation of the financial and social performance of microfinance. This research provides a systematic and comprehensive classification of microfinance performance evaluation methods, an explanation of evaluation methods and techniques, and a theoretical framework suitable to explain the applicability every method to assess different dimensions of microfinance. These results of this research are useful to help policymakers, donors, and practitioners understand and compare existing evaluation methods. Also, this framework enables the identification of the appropriate evaluation method according to the type of performance being examined and considering how to communicate this information effectively to the market.

Abstract Background Dysregulated T lymphocyte response is thought to play a key role in chronic intestinal inflammation (CIE). Objectives To evaluate the presence of changes in peripheral and intestinal T lymphocyte subsets and to describe potential immune and inflammatory biomarkers in dogs with CIE. Animals Sixteen healthy dogs and 26 dogs were diagnosed with CIE. Methods Prospective case‐control study evaluating peripheral and intestinal T lymphocytes using flow cytometry and inflammatory markers obtained from complete blood cell counts. Results Dogs with CIE had higher peripheral activated T helper (Th) lymphocytes (87/μL [18‐273] CIE, 44/μL [16‐162] healthy control (HC, P = .013) and regulatory T cells (Treg; 108/μL [2‐257] CIE, 34/μL [1‐114] HC, P = .004). In the intestinal epithelium, CIE dogs presented lower percentages of Th (4.55% [1.75‐18.67] CIE, 8.77% [3.79‐25.03] HC, P = .002), activated Th cells (0.16% [0.02‐0.83] CIE, 0.33% [0.05‐0.57] HC, P = .03) and CD4/CD8 ratio (0.08 [0.02‐0.39] CIE, 0.21 [0.07‐0.85] HC, P = .003). Conversely, higher percentage of activated T cytotoxic cells (20.24% [3.12‐77.12] CIE, 12.32% [1.21‐39.22] HC, P = .04) and interferon‐gamma (IFN‐γ) producing T lymphocytes (7.36% [0.63‐55.83] CIE, 1.44% [0.00‐10.56] HC, P = .01) within the epithelium was observed. In the lamina propria the percentage of Treg lymphocytes was higher (6.02% [1.00‐21.48] CIE, 3.52% [0.18‐10.52] HC, P = .02). Conclusions and Clinical Importance Systemic and intestinal immune alterations occur in dogs with CIE suggesting that blood IFN‐γ producing T lymphocytes and the systemic immune‐inflamation index (SII) could potentially serve as biomarkers for the disease.

Abstract Background The role of diet quality on malnutrition in older adults is uncertain, due the paucity of the research conducted and the use of use of screening tools that did not consider phenotypic criteria of malnutrition. Objective To evaluate the association of two indices of diet quality, namely the Mediterranean Diet Adherence Screener (MEDAS) and the Alternative Healthy Eating Index (AHEI-2010), with malnutrition among community-dwelling older adults in Spain. Methods Cross-sectional analysis of data from 1921 adults aged ≥ 60 years from the Seniors-ENRICA-1 (SE-1) study, and 2652 adults aged ≥ 65 years from the Seniors-ENRICA-2 (SE-2) study. Habitual food consumption was assessed through a validated diet history. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) phenotypic criteria. Statistical analyses were performed with logistic regression with adjustment for socioeconomic and lifestyle variables as well as for total energy and protein intake. Results The prevalence of malnutrition in the SE-1 study was 9.5% (95% confidence interval: 8.2 to 10.9) and 11.7% (10.5 to 13.9) in the SE-2. Adherence to the MEDAS score was associated with lower prevalence of malnutrition [pooled odds ratio for high (≥ 9 points) vs. low adherence (

Abstract Background Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. Methods Plasma, hypothalamus, pituitary gland and liver of Pappa2 ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. Results Reduced body and femur length of Pappa2 ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3β, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2 ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2 ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2 ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2 ko/ko females. Conclusions Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

ObjectiveTo evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage.MethodsSingle-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded.ResultsFifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77–0.98, p=0.022). Larger studies are needed to validate these results.ConclusionCOVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.

IntroductionAlemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS).AimTo evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years.MethodsThis prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison.ResultsThe study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7–42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56–10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1–3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7–52.7] pg/ml and 158.9 [IQR, 126.9–255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03–8.54] pg/ml and 91.0 [72.6–109] pg/ml, respectively) (p

Substance use disorders (SUD), also named addiction when it is severe, is a chronic brain disorder with serious impact on individual who suffer, the public health and with high burden of disease. They are multitude of mechanisms/factors involved in addiction: from individual characteristics of the person (from genetic to impacts of stress, sex, and age) to social and environmental situation (availability and accessibility of substances, cultural and legal aspects, socio-economical situation) and type of substance of use (pharmacological characteristics) Then, research on Addiction must include different, complementary, and translational perspectives. In this review, we explore the neurobiological, psychosocial, and epidemiological knowledge of substance addiction, and the main role played by pharmacology in the research in this field. In Spain, since 2002, collaborative networks have emerged for comprehensive research on addictions, with the creation of the Addictive Disorders Network (RTA), currently redefined as the Research Network for Primary Care in Addictions (RIAPAd) with the support of the Carlos III Health Institute (Instituto de Salud Carlos III). Basic (including neuropharmacology and behavioral pharmacology), clinical and epidemiological research groups stand out, combining efforts to address prevention, early detection and treatment through interdisciplinary cooperation and the subsequent dissemination of results.

Abstract Optical fiber with YPO4:Pr3+ nanocrystals (NCs) is presented for the first time using the glass powder—NCs doping method. The method’s advantage is separate preparation of NCs and glass to preserve luminescent and optical properties of NCs once they are incorporated into optical fiber. The YPO4:Pr3+ nanocrystals were synthesized by the co-precipitation and hydrothermal methods, optimized for size (

Abstract Background Traffic exposure has been associated with biomarkers of increased biological ageing, age-related chronic morbidities, and increased respiratory, cardiovascular, and all-cause mortality. Whether it is associated with functional impairments and unhealthy ageing trajectories is unknown. Methods Nationally representative population-based cohort with 3,126 community-dwelling individuals aged ≥60 years who contributed 8,291 biannual visits over a 10 year period. Unhealthy ageing was estimated with a deficit accumulation index (DAI) based on the number and severity of 52 health deficits, including 22 objectively-measured impairments in physical and cognitive functioning. Differences in DAI at each follow-up across quintiles of residential traffic density (RTD) at 50 and 100 meters, and closest distance to a petrol station, were estimated using flexible marginal structural models with inverse probability of censoring weights. Models were adjusted for sociodemographic and time-varying lifestyle factors, social deprivation index at the census tract and residential exposure to natural spaces. Results At baseline, the mean (SD) age and DAI score of the participants were 69.0 (6.6) years and 17.02 (11.0) %, and 54.0% were women. The median (IQR) RTD at 50 and 100 meters were 77 (31-467) and 509 (182-1802) vehicles/day, and the mean (SD) distance to the nearest petrol station of 962 (1317) meters. The average increase in DAI (95%CI) for participants in quintiles Q2-Q5 (vs Q1) of RTD at 50 meters was of 1.51 (0.50, 2.53), 0.98 (-0.05, 2.01), 2.20 (1.18, 3.21) and 1.98 (0.90, 3.05), respectively. Consistent findings were observed at 100 meters. By domains, most of the deficits accumulated with increased RTD were of a functional nature, although RTD at 50 meters was also associated with worse self-reported health, increased vitality problems and higher incidence of chronic morbidities. Living closer to a petrol station was associated with a higher incidence of functional impairments and chronic morbidities. Conclusions Exposure to nearby residential traffic is associated with accelerated trajectories of unhealthy ageing. Diminishing traffic pollution should become a priority intervention for adding healthy years to life in the old age.

Lithium silicate-based glass-ceramics are widely employed dental materials, showing superior aesthetics (determined by translucency) but poorer wear resistance under severe contact conditions than alternative, artificial crown materials. This work investigates possible correlations between the level of translucency and resistance to wear (in vitro) under sliding contact against hard zirconia antagonists in commercial lithium disilicate and zirconia-reinforced lithium silicate dental glass-ceramics. Wear rates are quantified, and mechanisms responsible for material removal are analyzed. Results are discussed in terms of the materials’ microstructure and mechanical properties within the framework of a fracture mechanics model. Finally, implications for materials selection in dentistry are briefly discussed. Resumen: Los vitrocerámicos a base de silicato de litio son ampliamente utilizados como materiales dentales, debido a que presentan una mejor estética (determinada por su traslucidez), aunque peor resistencia a desgaste bajo condiciones de contacto severo, que los materiales artificiales alternativos para coronas protésicas. Este trabajo investiga posibles correlaciones entre el grado de traslucidez y la resistencia a desgaste (in vitro) bajo contacto deslizante contra un antagonista duro de zirconia en vitrocerámicos dentales comerciales de disilicato de litio y silicato de litio reforzado con zirconia. Se cuantifican las tasas de desgaste y se analizan los mecanismos responsables de la eliminación de material. Los resultados se discuten con base en la microestructura y propiedades mecánicas de los materiales en el marco de un modelo de mecánica de la fractura. Finalmente, se discuten brevemente algunas implicaciones relativas a la selección de materiales en odontología.

This paper was developed to analyze the level of implementation of intellectual property management processes in Higher Education Institutions (HEI). Intellectual Property management processes in the public sector have been reduced, at least in understanding the concept, to the processes of protecting and maintaining intellectual property titles; however, it is a more extensive process than conceptualized. In this sense, Martinez et al. (2018) generated a methodology involving 19 indicators (processes) of intellectual property management implemented during the R&D&I process. These indicators were used to measure their implementation in Mexican public sector HEIs with information from the transparency portal. The research shows the importance of generating multidisciplinary groups in R&D&I processes, enhancing the financial redundancy of research investment.

In recent years, the teaching and learning of history have been transformed by the incorporation of active methodologies and digital tools. Virtual reality (VR) is one such tool that is being increasingly used in classrooms. It allows students to visit and experience spaces from other historical periods, even those that have been lost. However, due to its relatively slow adoption in formal educational settings, there is still a paucity of scientific references where this type of experience has been empirically tested to prove its potential benefits. Further research on this issue is therefore needed. This study presents a comparative analysis of the didactic use of historical heritage from the Roman period using two different methodological strategies: an educational visit to a museum and a virtual tour via electronic devices. The main objective is to compare the effectiveness of these two methods in terms of usability, learning outcomes, and emotional responses. The study was conducted with 51 primary school teachers in training. Data were collected using two ad hoc questionnaires, which were based on a previous one. A hybrid analysis methodology was adopted, with SPSS used for interpreting the quantitative data and Atlas Ti for the qualitative information. The results indicate that the two methodologies were perceived by future teachers as valuable resources for learning and teaching history. The emotions they evoked were primarily curiosity, joy, and motivation, with only minor occurrences of frustration, nervousness, or fear. The experience gained from this first application will make it possible to extend the study to other educational levels, to enrich the conclusions obtained and to evaluate the potential scope of using this combination of methods to develop historical competences and improve heritage education.