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Abstract Background Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. Methods We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0–47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 – 8.90) and age (OR 1.13, 95%CI 1.10 – 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques.

Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5–94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49–47.11); no chronic illness, aOR = 2.81 (95% CI 1.28–6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42–6.85); younger age, aOR = 0.97 (95% CI 0.94–0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97–0.99). To improve the surveillance of future epidemics, new approaches are recommended.

Abstract Global expansion in wind energy development is a notable achievement of the international community’s effort to reduce carbon emissions during energy production. However, the increasing number of wind turbines have unintended consequences for migratory birds and bats. Wind turbine curtailment and other mitigation strategies can reduce fatalities, but improved spatial and temporal data are needed to identify the most effective way for wind energy development and volant migratory species to coexist. Mexican free-tailed bats (Tadarida brasiliensis mexicana) account for a large proportion of known bat fatalities at wind facilities in the southwestern US. We examined the geographic concordance between existing wind energy generation facilities, areas of high wind potential amenable for future deployment of wind facilities, and seasonally suitable habitat for these bats. We used ecological niche modeling to determine species distribution during each of 4 seasons. We used a multi-criteria GIS-based approach to produce a wind turbine siting suitability map. We identified seasonal locations with highest and lowest potential for the species’ probability of occurrence, providing a potential explanation for the higher observed fatalities during fall migration. Thirty percent of 33,606 wind turbines within the southwestern US occurred in highly suitable areas for Mexican free-tailed bats, primarily in west Texas. There is also broad spatial overlap between areas of high wind potential and areas of suitable habitat for Mexican free-tailed bats. Because of this high degree of overlap, our results indicate that post-construction strategies, such as curtailing the timing of operations and deterrents, would be more effective for bat conservation than strategic siting of new wind energy installations.

Abstract Background Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3–5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. Methods We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. Results Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. Conclusion 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the ‘trough’ periods before the next dosing, even with this intensive regimen.

This article is based on two research studies conducted on the Uruguayan Juvenile Justice System (UJJS); the first study (2011) examined female adolescent incarceration contexts, and the second one (2016) focused on female adolescents in their passage through a program of non-custodial measures. This research is aimed at understanding gendered punishment practices performed on women who are subjected to judicial measures in the UJJS, in order to give visibility to an issue that is usually silenced, among other reasons because the number of women subjected to these measures is low and due to a hegemonic male model in adolescent offense construction. Following a qualitative methodology research, combined with an ethnographic approach, I discuss the singularities characterizing the passage of female adolescents through the UJJS, by applying two strategies: (re)constructing a lost domesticity and managing bodies and sexualities.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case–control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry–based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan–Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC’s pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

Abstract Background Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12‐week physical therapy programme in patients with stable HFpEF. Methods This study is a post‐hoc sub‐analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12‐week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin

Introduction Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause.Objective The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women.Methods A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration.Results Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking.Conclusions Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.

Introducción. La Colangitis Aguda Severa (CAS) o Colangitis III, se caracteriza por la obstrucción biliar total e infección de la bilis que puede evolucionar a una falla orgánica por infección sistémica, shock o muerte, su letalidad se incrementa en el retraso del tratamiento médico y su principal causa es por coledocolitiasis (1) Objetivo. Describir el efecto del Proceso de Atención de Enfermería (PAE) en un paciente en estado crítico con el diagnóstico médico de colangitis III. Materiales y métodos. Diseño cuantitativo, cuasi experimental, de corte transversal y se realizó una revisión bibliográfica en diversas plataformas como, Google Académico, PubMed y Elsevier así mismo, la organización de los datos se realizó con base a los patrones funcionales de salud, la redacción de diagnóstico se realizó con la taxonomía NANDA, los planes de cuidados con NOC y NIC. Resultados. El efecto de las intervenciones en los diagnósticos de mayor prioridad fue: limpieza ineficaz de las vías aéreas pre y postintervención 15-20, disminución del gasto cardiaco pre y postintervención 19-23 e hipertermia pre y postintervención 5-8. Conclusión. El efecto de las intervenciones de enfermería mediante la metodología del PAE asegura la calidad de la atención, y también nos permiten medir las respuestas humanas que indican una mejora del paciente, ayudando a identificar las áreas de oportunidad del cuidado.

Low and high beta frequency rhythms were observed in the motor cortex, but their respective sources and behavioral correlates remain unknown. We studied local field potentials (LFPs) during pre-cued reaching behavior in macaques. They contained a low beta band (20 Hz) dominant in dorsal premotor cortex (PMd). Low beta correlated positively with reaction time (RT) from visual cue onset and negatively with uninstructed hand postural micro-movements throughout the trial. High beta reflected temporal task prediction, with selective modulations before and during cues, which were enhanced in moments of increased focal attention when the gaze was on the work area. This double-dissociation in sources and behavioral correlates of motor cortical low and high beta, with respect to both task-instructed and spontaneous behavior, reconciles the largely disparate roles proposed for the beta rhythm, by suggesting band-specific roles in both movement control and spatiotemporal attention.

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the unexpected remarkable promiscuity of some of these proteins when expressed in Escherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed, through in silico modelling, some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism and the in vivo implications for this human pathogen.

Although suggestions to shift towards plant-based diets have been proposed, and consumers have indicated their willingness to reduce meat consumption, there is a scarcity of research exploring consumers' attitudes and intentions regarding plant-based products. Therefore, this study analyses consumers’ hedonic sensory acceptance and its impact on the attitudes and predictors associated with purchasing intentions with regard to various plant-based products. Data were collected from 132 consumers using a validated questionnaire designed on the Qualtrics platform. Statistical package for the social sciences software was used to analyze the descriptive statistics relating to consumers' attitudes towards plant-based products, and partial least squares structural equation modeling was employed to identify the factors influencing their purchasing intentions. The results showed that consumers have tended to adopt moderate attitudes towards plant-based products. They rated their perceived behavioral control, subjective norms, and perceptions of the sensory characteristics of these products as high. However, they also reported only a moderate level of satisfaction after tasting the product. The results of the structural equation modelling analysis demonstrated that four factors significantly influenced consumers' intentions to purchase plant-based products: perceived behavioral control, sensory perceptions, attitude, and informed tasting. This study contributes to existing knowledge and provides empirical support for explaining the factors influencing Spanish consumers' decisions to purchase plant-based products. These findings have promising implications for the future sales of plant-based food products in Spain and other European countries.

Abstract RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1 sa15940 , a zebrafish mutant line with TL background. We found that rbfox1 sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1 del19 , and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1 del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1 sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.

Foundation: placental insufficiency is the most common cause of intrauterine growth retardation, which can cause cardiovascular alterations. Recently, erythropoietin therapies have been developed that protect hypoxic cardiac tissues.Objective: To evaluate the influence of human recombinant erythropoietin with low sialic acid content (NeuroEPO) on the fetal heart in a rat model of placental insufficiency.Methods: 14 Wistar rats gestated with unilateral ligation of the right uterine artery on day 16 of gestation were used. That same day, seven rats were administered NeuroEPO (0.5 mg/kg/day subcutaneously for three days) and the rest received placebo. On day 20 of gestation, the fetuses were divided into four groups: a control group, a group with intrauterine growth retardation, a NeuroEPO control group, and a group with intrauterine growth retardation and NeuroEPO. In the fetuses, placental weight, fetal weight and placental efficiency were obtained. In the histological study, the number of cardiomyocytes, number of blood vessels and quantity of collagen fibers were quantified.Results: the group with intrauterine growth retardation presented a decrease in fetal weight, the number of cardiomyocytes, the number of blood vessels and an increase in the amount of collagen fibers (pConclusions: the administration of this molecule improved fetal weight and allowed an adequate balance in the development of the fetal heart, perhaps due to the cytoprotective effects of this molecule.

Abstract Background Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. Results A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. Conclusions IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.

La situación generada por la Primera Guerra Mundial provocó la aparición de múltiples organizaciones destinadas a la población civil cuya acción humanitaria se desarrolló a nivel transnacional. Estas acciones se desarrollaron, también, como herramientas de influencia política apoyadas en los medios de comunicación de masas, en las que se involucraron intelectuales progresistas que facilitaron la movilización de amplias capas sociales. El Socorro Obrero Internacional estableció filiales en numerosos países con el doble objetivo de realizar acciones propagandísticas mientras desarrollaba acciones de apoyo a los obreros y sus familias, facilitando recursos en períodos de huelga, estableciendo comedores, hogares para niños o escuelas. La lucha contra el fascismo facilitó que se involucraran cineastas, fotógrafos, escritores, pintores, etc. en la elaboración y difusión de mensajes apoyados frecuentemente en imágenes que permitieron establecer los puentes emocionales adecuados para la creación de una red de intelectuales antifascistas, activa durante en el período de entreguerras y la Segunda Guerra Mundial. El objetivo del artículo es explorar las organizaciones y circunstancias que precedieron a esta red desde un enfoque transnacional y diacrónico que parte del concepto de solidaridad internacional y de sus implicaciones políticas. Para el estudio se han revisado publicaciones y archivos de las organizaciones cinematográficas vinculadas, así como los escritos realizados por Willy Münzemberg relacionados con la propaganda. Como resultado, los mensajes y las imágenes compartidas y difundidas en los medios de comunicación permitieron moldear la opinión, establecer emociones compartidas que facilitaron la movilización humanitaria y sirvieron de justificación ideológica y cultural.

Abstract Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer’s disease (AD), also known as “type 3 diabetes”. Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, β-amyloid oligomers, plaques, phosphorylated tau, and GSK3β expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.

Abstract Background The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. Aims To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. Methods We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p

Abstract Macrobrachium macrobrachion is an African native brackish river prawn with a high commercial value. Currently, there is little information on the post‐larval production of this species. Two experiments were conducted in the laboratory to develop production techniques for this species. The first experiment analyzed the duration of yolk resorption and the second described the larval stages. Yolk resorption was studied in 240 newly hatched larvae for 24 h based on the reduction in yolk area over time. For larval development stages, six breeding tanks containing 100 L with a density of 50 larvae/L were used. Larvae were fed a combination of Artemia nauplii, Brachionusplicatilis, and pelleted food (Larviva ProStart, Biomar Efico). The results have shown that the area of yolk reserves varied significantly in the hours after hatching. At 14 h after hatching, each larva resorbed approximately 85% of its yolk reserve, and at 18 h after hatching, each of them still had approximately 6.1%. Twelve larval stages were identified and described in three critical stages. M. macrobrachion larvae are lecithotrophic and need to start exogenous feeding at 14 h at the earliest and 18 h at the latest after hatching. These results are the first to highlight the potential for mass production of brackish river prawns.

Background: According to previous studies, a prolonged hospital stay, along with the patient’s clinical features, can lead to the onset of disability. Objectives: This study aimed to identify predictive factors of moderate-to-severe disability following hospital discharge in rib fracture patients. Methods: We conducted a retrospective study with hospitalized adult patients with rib fractures who received conservative treatment. Patients’ clinical profiles and characteristics were collected from their clinical histories and healthcare professional records. Results: Overall, patients exhibited a 44% rate of moderate-to-severe disability after a six-day hospital stay. The incidence of patients with a prolonged hospital stay who showed disabilities was associated with male sex (HR 0.73, p < 0.001), presence of first rib fracture (HR 1.78, p = 0.047), presence of flail chest (HR 1.29, p = 0.046), severity of lung injury (HR 1.65, p < 0.001), and functional status (HR 1.37, p < 0.001). Conclusions: Moderate-to-severe disability in patients with rib fractures may depend on factors such as sex, functionality, severity of lung injury, and presence of first rib fracture and flail chest during a prolonged hospital stay.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related to stress, Huntington's disease, and Alzheimer's disease. All these disorders are accompanied by different types of impairments in sociability, which has recently been linked to improper mitochondrial function. We hypothesize that Pyk2, which regulates mitochondria, could be associated with the regulation of mitochondrial dynamics and social skills. In the present manuscript, we report that a reduction of Pyk2 levels in mouse pyramidal neurons of the hippocampus decreased social dominance and aggressivity. Furthermore, social interactions induced robust Pyk2-dependent hippocampal changes in several oxidative phosphorylation complexes. We also observed that Pyk2 levels were increased in the CA1 pyramidal neurons of schizophrenic subjects, occurring alongside changes in different direct and indirect regulators of mitochondrial function including DISC1 and Grp75. Accordingly, overexpressing Pyk2 in hippocampal CA1 pyramidal cells mimicked some specific schizophrenia-like social behaviors in mice. In summary, our results indicate that Pyk2 might play a role in regulating specific social skills likely via mitochondrial dynamics and that there might be a link between Pyk2 levels in hippocampal neurons and social disturbances in schizophrenia.

The connection between physical activity and cognitive function has become a focus of attention in educational research in recent years. Regular exercise has been shown to have significant positive effects on physical health, but it also appears to have a significant impact on cognitive function and academic performance. Of all the exercise modalities, resistance training has drawn interest for its ability to improve cerebral abilities in addition to physical well-being. However, there is limited available knowledge exploring the relationship between resistance training regimens and academic performance. This narrative review aims to investigate the underlying mechanisms linking resistance training to academic performance. Firstly, we will examine the biological mechanisms and psychosocial links that potentially connect resistance training to academic performance to find and describe the different mechanisms by which resistance training improves academic performance. In the next part of the work, we delve into the existing observational and intervention studies that have explored the relationship between resistance training and academic performance. Lastly, we provide practical recommendations for including resistance training in institutional education settings, emphasizing the need of dispelling myths and addressing barriers to increase participation as well as the relevance of considering key training variables and adaptation of protocols to developmental stages, always guided by a properly trained professional. Overall, the available evidence supports that resistance training provides potential benefits to the academic performance of youth students with many biological and psychosocial factors that explain this relationship. However, most of the studies are observational, and broader interventional studies are needed to understand and maximize the benefits of this type of physical exercise.

The autopsy is recognized as a medical procedure of great usefulness and social benefit. To achieve these benefits and the proven importance of the autopsy, it is essential not only to perform it, but also to guarantee the highest possible quality in its execution. This work is aimed at exposing the main aspects and importance of the academic, healthcare, investigative and administrative achievements related to the autopsy, through the system of meetings, which allow charting the path to achieving this objective. In the methodology established for performing autopsies, fundamental guidelines are established to achieve optimal quality in their usefulness. If the results are only archived, the proposed objective is not achieved: Maximum use of the autopsy. In Cuba, 4 types of meetings are held: The so-called "fresh pieces", the review of the death certificate, the clinical-pathological meetings and those of the committee for the evaluation of deceased or mortality. Carrying out autopsies with optimal quality facilitates important academic, healthcare, investigative and even administrative achievements, through the system of meetings that enrich, in medical institutions, the results in the quality of the assistance provided, the contributions to teaching. undergraduate and postgraduate, and strengthen lines of research in order to reduce the morbidity and mortality of the population.

The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a “pacemaker” cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with contractile activity and c-Kit+ immunohistochemistry shared with ICCs. Among the locations where ICC-like cells have been observed, it is in the uterus where they have a significant functional and pathophysiological role. These cells are involved in obstetric phenomena of contractile action, such as ascending sperm transport, embryo implantation, pregnancy, delivery, and the expulsion of menstrual debris. Within the pathophysiology related to these cells, we find obstetric alterations such as recurrent miscarriages, premature deliveries, abolition of uterine contractions, and failures of embryo implantation, in addition to other common conditions in the fertile age, such as endometriosis and leiomyoma.

Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination. Despite a high objective response rate, responses are not durable and chemotherapy-induced toxicity may compromise treatment. Genetic variants in genes involved in the DNA-repair pathways and in etoposide metabolization could predict treatment efficacy and safety and help personalize platinum-based chemotherapy. Germline polymorphisms in XRCC1, ERCC1, ERCC2, ABCB1, ABCC3, UGT1A1 and GSTP1 genes were investigated in 145 patients with SCLC. The tumor expression of ERCC1 was determined using immunohistochemistry, and the tumor expression of ERCC1-XPF was determined via a proximity ligation assay. Survival analyses showed a statistically significant association between the ERCC1 rs11615 variant and median progression-free survival (PFS) in patients with limited-stage (LS) SCLC (multivariate: hazard ratio 3.25, [95% CI 1.38–7.70]; p = 0.007). Furthermore, we observed differences between the ERCC1-XPF complex and median PFS in LS-SCLC, although statistical significance was not reached (univariate: positive expression 10.8 [95% CI 4.09–17.55] months versus negative expression 13.3 [95% CI 7.32–19.31] months; p = 0.06). Safety analyses showed that the ERCC2 rs1799793 variant was significantly associated with the risk of grade ≥ 3 thrombocytopenia in the total cohort (multivariate: odds ratio 3.15, [95% CI 1.08–9.17]; p = 0.04). Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal tumor with increasing incidence, presenting numerous clinical challenges. The histopathological examination of novel, unexplored biomarkers offers a promising avenue for research, with significant translational potential for improving patient outcomes. In this study, we evaluated the prognostic significance of ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian clock regulators (CLOCK, BMAL1, PER1, PER2), and KLOTHO in a retrospective cohort of 41 patients deceased by PDAC. Immunohistochemical techniques (IHC) and multiple statistical analyses (Kaplan–Meier curves, correlograms, and multinomial linear regression models) were performed. Our findings reveal that ferroptosis markers are directly associated with PDAC mortality, while circadian regulators and KLOTHO are inversely associated. Notably, TFRC emerged as the strongest risk marker associated with mortality (HR = 35.905), whereas CLOCK was identified as the most significant protective marker (HR = 0.01832). Correlation analyses indicate that ferroptosis markers are positively correlated with each other, as are circadian regulators, which also positively correlate with KLOTHO expression. In contrast, KLOTHO and circadian regulators exhibit inverse correlations with ferroptosis markers. Among the clinical variables examined, only the presence of chronic pathologies showed an association with the expression patterns of several proteins studied. These findings underscore the complexity of PDAC pathogenesis and highlight the need for further research into the specific molecular mechanisms driving disease progression.

Instant Cascara (IC) is a sustainable beverage made from dried coffee cherry pulp, a by-product of coffee processing. It is rich in nutrients and bioactive compounds and has a high concentration of antioxidants. This study explored the impact of regular IC consumption on colonic motor function and innervation. Over a period of 4 weeks, male and female healthy rats were given drinking water containing 10 mg/mL of IC. Thereafter, colon samples were obtained to evaluate the longitudinal (LM) and circular (CM) smooth muscle contractile response to acetylcholine (ACh) and electrical field stimulation (EFS) in an organ bath, before and after atropine administration (10−6 M). Histological and immunohistochemical analyses assessed colon damage, muscle thickness, and immunoreactivity to substance P (SP) and neuronal nitric oxide synthase (nNOS). ACh and EFS induced similar responses across groups, but the CM response to EFS was greater in females compared with males, despite their lower body weight. Atropine completely blocked the response to ACh but only partially antagonized the neural response to EFS, particularly that of CM in females treated with IC, which had a greater liquid intake than those exposed to water. However, in the myenteric ganglia, no statistically significant differences were observed in SP or nNOS. Our results suggest that regular IC exposure may enhance specific neural pathway functions, particularly in females, possibly due to their increased IC consumption.

Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.

It is known that lung cancer survivors experience sequelae due to the evolution of the disease and oncological treatment. However, there is no consensus about their sequelae after radiotherapy treatment. The aim of this study was to analyze the clinical–functional profile of lung cancer survivors who receive radiotherapy treatment. This prospective observational study evaluated lung cancer patients who were candidates for radiotherapy treatment in the oncological radiotherapy unit of San Cecilio University Hospital in Granada. Symptoms (i.e., fatigue, cough, and dyspnea), functionality (i.e., physical activity levels and muscle mass), and quality of life were evaluated pre- and post-radiotherapy treatment. Sixty-five participants were included, and sixty-one completed both evaluations. Patients showed a significant increase in symptoms (p < 0.05) and a decline in functionality (p < 0.001) after completing radiotherapy. Quality of life was significantly lower after completing radiotherapy treatment (p < 0.05). Lung cancer survivors showed an increase in symptoms, a decline in physical activity levels, and a decline in perceived quality of life after receiving radiotherapy treatment. These results provide more accurate knowledge about the functional impairment experienced by lung cancer patients and can facilitate the future management of impairment in lung cancer patients, thus improving their quality of life.

The aim of this study is to evaluate the relationship between clinical severity and functionality, occupational performance, and health-related quality of life in patients hospitalized with pulmonary embolism. Pulmonary embolism patients were grouped by clinical severity using the Pulmonary Embolism Severity Index. Those scoring ≥160 were in the high-severity group (HSG); those scoring < 160 in the low–moderate group (LMSG). The main variables were functionality assessed by the World Health Organization Disability Assessment Schedule (WHODAS), self-perception of occupational performance assessed by the Canadian Occupational Performance Measure (COPM), pain and fatigue assessed by a Visual Analogue Scale (VAS), and health-related quality of life assessed by the EuroQol-5Dimensions (EQ-5D). Patients were evaluated at hospital admission and at 1-month and 3-month follow-up. At admission, there were significant differences between groups in the WHODAS and health-related quality of life in favor of the LMSG. At 1-month and at 3-month follow-up, there were significant differences between the LMSG and HSG in WHODAS, COMP, NRS pain, fatigue and EQ-5D scores in favor of the LMSG. An association exists between clinical severity and mid-term functionality, self-perception of occupational performance, pain, fatigue, and health-related quality of life in PE patients.

No previous study has evaluated the effectiveness of routine physical therapy with and without neural mobilization for patients with chronic musculoskeletal neck disorders and cervical radiculopathy. The objective is to evaluate the effectiveness of routine physical therapy with and without neural mobilization on pain and mobility in patients with chronic musculoskeletal neck disorders and cervical radiculopathy. A systematic review with meta-analysis of randomized clinical trials involving the use of neural mobilization techniques for the treatment of chronic musculoskeletal neck disorders and cervical radiculopathy was conducted. Methodological quality was assessed by the Cochrane Risk of Bias Tool and PEDro scale. Data were pooled and a meta-analysis was performed using a random effects model with Review Manager 5 software. Seven articles were included in our review. Significant differences were found in mobility but not in pain in favor of using routine physical therapy with neural mobilization for the treatment of chronic musculoskeletal neck disorders and cervical radiculopathy. Our results show that routine physical therapy accompanied by neural mobilization is superior for improving mobility in comparison with routine physical therapy alone in patients with musculoskeletal neck disorders and cervical radiculopathy.

El objetivo de este artículo se centra en reflexionar sobre los procesos de aprendizaje de los alumnos con Trastorno del Espectro del Autismo (TEA) en la etapa de educación primaria (de 6 a 11 años). La metodología que se lleva a cabo se basa en la revisión teórica donde se detalla la impor-tancia de proporcionar una respuesta pedagógica satisfactoria propia a las necesidades educativas particulares. El trastorno del Espectro del Autismo repercute de un modo global al desarrollo cogni-tivo-social-emocional desde la primera infancia, y su sintomatología repercute individualmente en las distintas etapas evolutivas. La multiplicidad de aspectos cognitivos y conductuales del autismo determina una mente multidimensional. En conclusión, se detalla la necesidad del conocimiento de la individualidad del alumnado con TEA para poder establecer la intervención educativa más adecua-da y eficaz, que promueva la calidad de vida del discente con autismo y, por consiguiente, la de sus familias. Desde esta perspectiva, el ámbito escolar se considera un espacio de desarrollo individual y social. Para ello, se precisa que la intervención pedagógica se centra en proporcionar respuestas a las necesidades particulares tanto a nivel académico como a escala cognitivo-social-emocional.

La papa es un alimento que permite comprender el proceso de poblamiento y desarrollo de sociedades complejas en América. Las evidencias arqueológicas, etnohistóricas y etnobotánicas compiladas para este artículo dan cuenta de la presencia y manipulación de solanum sp. Desde hace 13000 años. Para ello, se presentan los hallazgos arqueológicos que relacionan la papa en investigaciones de microrestos, macrorestos y representaciones que hacen parte de las colecciones de museos, se ilustra el proceso de descripción, producción y usos en dos centros productivos de papa en América del sur en época colonial: el altiplano cundiboyacense en los andes del norte y Huarochiri en los andes centrales. Finalmente, se retoman los usos, significados y formas productivas de las papas nativas desde la cosmovisión andina. Como resultado, encontramos una gran diversidad de papas que da cuenta de cambios culturales en los usos, concepciones, prácticas y manejos desde épocas prehispánicas, generando un consumo y producción de papa en el mundo.

El objetivo de este estudio es identificar las variables que influyen en la repetición de curso en Educación Obligatoria en España según la literatura científica. Se realizó una revisión sistemática en las bases de datos Web of Science, Scopus y Dialnet, y mediante análisis de contenido se identificaron 67 variables que fueron incorporadas a un modelo estructurado en seis factores correspondientes a dos grupos: no académicos (individuales y familiares) y académicos (estudiante, compañeros de clase, profesorado y centro educativo). Se concluye que el diagnóstico de estas variables puede contribuir al diseño de medidas de actuación (prevención e intervención) ajustadas a las necesidades de cada estudiante. Además, el elevado peso de las variables familiares, tanto en el estudiante como en el contexto del centro educativo, refuerza la necesidad de buscar sinergias entre la política educativa y la social para apoyar a las familias más desfavorecidas.

Anthropogenic noise in marine and freshwater environments has increased dramatically, with a range of negative impacts and detrimental consequences on many aquatic animals across taxa. Benthic organisms, including many invertebrates, can sense underwater sounds, yet the responses they trigger in these organisms have received little attention. We conducted two laboratory-based experiments to investigate the effect of underwater sound playback on the movement behavior and feeding performance of the red cherry shrimp Neocaridina davidi as a model of freshwater decapod. Movement speed decreased significantly upon opening the divider in both the sound and control treatments. However, there were no significant sound-dependent changes overall between the control and sound treatments. The spatial distribution of shrimp in response to the sound treatment showed significant changes; shrimp spent more time at the farthest one-third position from the sound source. Feeding latency (latency to find food) also increased in the sound treatment compared to the control. Moreover, in terms of the number of successes and failures in finding the food source in the control treatment, significantly more shrimp succeeded in finding the food source. The number of revisits to the food source decreased in the sound treatment compared to control and more shrimp were significantly distracted in the sound treatment. Our study highlights the potential for human-made sound to impact on crustacean activity. Thus, they are prone to the impacts of anthropogenic noise, causing negative impacts on their movement-swimming activities, and feeding behavior. Behavioral changes observed, namely altered feeding and locomotory behavior may have wider-reaching negative effects, including detrimental impacts on animal fitness.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, and fasciculations—and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients’ prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut.

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe3+) was observed in placenta samples stained with Perls’ Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

Conduct problems (CP) in childhood and adolescence have a significant impact on the individual, family, and community. To improve treatment for CP, there is a need to improve the understanding of the developmental pathways leading to CP in boys and girls. Prior research has linked the child’s fearlessness and callous–unemotional (CU) traits, as well as experiences of parental warmth and punitive parenting, to CP. However, few studies have tested the interplay of these factors in contributing to future CP development. The present study aimed to test the InterFear model, which suggests that fearlessness in early childhood leads to CP through an indirect pathway involving low positive parenting, high negative/punitive parenting, and callous–unemotional (CU) traits. The sample included 2467 Spanish children (48.1% girls; Mage = 4.25; SD = 0.91), followed up across a five-year period. Besides a direct association between fearlessness in early childhood and future CP, the results found an indirect pathway whereby fearlessness reduces positive parenting and increases punitive parenting, which contributes to the development of CU traits and sets the stage for CP in later childhood. The specific indirect effect from fearlessness to CP via CU traits accounted for most of the variance, suggesting the existence of a temperamental pathway independent of parental variables. Further, two additional indirect pathways, exclusive of fearlessness, were identified, which started with low parental warmth and positive parenting, leading to CP via CU traits. These findings support the InterFear model, demonstrating multiple pathways to CP with the involvement of fearlessness, parenting practices, and CU traits. This model might play a pivotal role in the development of targeted prevention and intervention strategies for CP.

Doctrinal texts on architectural heritage conservation emphasize the importance of fully understanding the structural and material characteristics and utilizing information systems. Photogrammetry allows for the generation of detailed, geo-referenced Digital Elevation Models of architectural elements at a low cost, while GIS software enables the addition of layers of material characteristic data to these models, creating different property maps that can be combined through map algebra. This paper presents the results of the mechanical characterization of materials and salt-related decay forms of the polygonal apse of the 13th-century monastery of Santa María de Bonaval (Guadalajara, Spain), which is primarily affected by salt crystallization. Rock strength is estimated using on-site nondestructive testing (ultrasound pulse velocity and Leeb hardness). They are mapped and combined through map algebra to derive a single mechanical soundness index (MSI) to determine whether the decay of the walls could be dependent on the orientation. The presented results show that salt decay in the building is anisotropic, with the south-facing side of the apse displaying an overall lower MSI than the others. The relative overheating of the south-facing side of the apse enhances the effect of salt crystallization, thereby promoting phase transitions between epsomite and hexahydrite.

Deregulation of small non-coding RNAs (sncRNAs) has been associated with the onset of metastasis. We evaluated the expression of sncRNAs in patients with early-stage breast cancer, performing RNA sequencing in 60 patients for whom tumor and sentinel lymph node (SLN) samples were available, and conducting differential expression, gene ontology, enrichment and survival analyses. Sequencing annotation classified most of the sncRNAs into small nucleolar RNA (snoRNAs, 70%) and small nuclear RNA (snRNA, 13%). Our results showed no significant differences in sncRNA expression between tumor or SLNs obtained from the same patient. Differential expression analysis showed down-regulation (n = 21) sncRNAs and up-regulation (n = 2) sncRNAs in patients with locoregional metastasis. The expression of SNHG5, SNORD90, SCARNA2 and SNORD78 differentiated luminal A from luminal B tumors, whereas SNORD124 up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (SNORD93, SNORA16A, SNORD113-6, SNORA7A, SNORA57 and SNORA18A) that distinguished patients with locoregional metastasis and predicted patient outcome. Gene ontology and Reactome pathway analysis showed an enrichment of biological processes associated with translation initiation, protein targeting to specific cell locations, and positive regulation of Wnt and NOTCH signaling pathways, commonly involved in the promotion of metastases. Our results point to the potential of several sncRNAs as surrogate markers of lymph node metastases and patient outcome in early-stage breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant sncRNAs and to validate our results in a larger cohort of patients.

This study aims to determine whether post-hospitalization psychological distress is associated with exercise capacity, physical function and health status in COVID-19 survivors. In this observational study, hospitalized COVID patients were included and divided into two groups according to the mental component summary subscale of the 12-item Short-Form Health Survey. Patients with a score ≤ 45 were included in the psychological distress group, and patients with a score > 45 were included in the non-psychological distress group. The main variables were exercise capacity, physical function, and health status. Patients were evaluated at discharge, 3 months, and at 6 months follow-up. Finally, a total of 60 patients were included in the study. Significant differences were found in exercise capacity, physical function, and health status (p < 0.05), with worse results in the group with psychological distress at discharge and 3 months follow-up. At 6 months after discharge, COVID patients with psychological distress exhibited worse results in exercise capacity, physical function, and health status, being significant exercise capacity and physical function (p < 0.05). It can be concluded that COVID patients with psychological distress at hospital discharge reported worse exercise capacity, physical function and health status at hospital discharge, 3 months and 6 months follow-up.

La digitalización de las comunicaciones sociales y personales desarrollada en las últimas décadas nos han situado ante un terreno desconocido que progresa con una rapidez inédita hasta el momento. La serie de televisión Black Mirror permite reflexionar sobre las repercusiones que esta transformación tecnológica tiene para la sociedad y las relaciones personales. Mediante el análisis textual y de contenido de las 5 temporadas emitidas hasta el momento, podemos establecer los patrones más comunes que han sido representados en la serie, reflejando la transformación de una sociedad agrupada en torno a la pantalla televisiva a una sociedad que utiliza pantallas individuales como herramienta de control y acceso a relaciones personales y sociales.

Abstract While organic photovoltaics are accessing specific application sectors taking advantage of their unique properties, it is important to identify as many differentiators as possible to expand the market penetration and consolidation of this technology. In this work, for the first time, the large‐scale fabrication of organic photovoltaic modules embedded into structural plastic parts through industrial injection molding is demonstrated. Thermoplastic polyurethane is chosen as the injected material to show that this additional processing step can yield flexible, lightweight photovoltaic modules with enhanced device robustness and virtually unchanged performance. The critical optomechanical and physico‐chemical material properties, as well as the plastic processing parameters to enable in‐mold plastic solar cells with improved performance and stability, are discussed and provided with perspective.

La menstruación sostenible se impone poderosamente en el área de la salud y la higiene por su importancia a futuro y su valor como herramienta activa de conciencia social, visibilización y responsabilidad. Mediante este estudio se pretende evaluar el grado de aceptación, uso y conocimiento de productos como las compresas reutilizables o las copas y bragas menstruales, todos ellos artículos sustentables para la gestión de los periodos. Para este fin se ha llevado a cabo una encuesta en línea en España a una muestra representativa de personas menstruantes desde la menarquía hasta la menopausia, recopilando información sobre los hábitos y rutinas de higiene menstrual, incluyendo la correspondiente disposición de los individuos a hacer uso de los mencionados artículos sostenibles para su gestión y abordaje. Se observó un conocimiento generalizado de estos productos, de sus beneficios y ventajas, con una tendencia favorable a su implementación en el futuro. Se dibuja la necesidad de continuar desarrollando soluciones innovadoras que promuevan la salud, la sostenibilidad y la igualdad en la gestión menstrual. Tras un análisis exhaustivo de los resultados, se han plasmado las posibles líneas futuras de investigación en este campo, abriendo una puerta a un tratamiento más amplio, integrativo, transversal y multidisciplinar de esta temática.