Miguel Hernández University of Elche

Our own experience of emotional events influences how we approach and react to others’ emotions. Here we observe that mice exhibit divergent interindividual responses to others in stress (that is, preference or avoidance) only if they have previously experienced the same aversive event. These responses are estrus dependent in females and dominance dependent in males. Notably, silencing the expression of the corticotropin-releasing factor (CRF) within the medial prefrontal cortex (mPFC) attenuates the impact of stress self-experience on the reaction to others’ stress. In vivo microendoscopic calcium imaging revealed that mPFC CRF neurons are activated more toward others’ stress only following the same negative self-experience. Optogenetic manipulations confirmed that higher activation of mPFC CRF neurons is responsible for the switch from preference to avoidance of others in stress, but only following stress self-experience. These results provide a neurobiological substrate underlying how an individual’s emotional experience influences their approach toward others in a negative emotional state.

Theta-band oscillations (3–8 Hz) in the mammalian hippocampus organize the temporal structure of cortical inputs, resulting in a phase code that enables rhythmic input sampling for episodic memory formation and spatial navigation. However, it remains unclear what evolutionary pressures might have driven the selection of theta over higher-frequency bands that could potentially provide increased input sampling resolution. Here, we address this question by introducing a theoretical framework that combines the efficient coding and neural oscillatory sampling hypotheses, focusing on the information rate (bits/s) of phase coding neurons. We demonstrate that physiologically realistic noise levels create a trade-off between the speed of input sampling, determined by oscillation frequency, and encoding precision in rodent hippocampal neurons. This speed-precision trade-off results in a maximum information rate of ∼1–2 bits/s within the theta frequency band, thus confining the optimal oscillation frequency to the low end of the spectrum. We also show that this framework accounts for key hippocampal features, such as the preservation of the theta band along the dorsoventral axis despite physiological gradients, and the modulation of theta frequency and amplitude by running speed. Extending the analysis beyond the hippocampus, we propose that theta oscillations could also support efficient stimulus encoding in the visual cortex and olfactory bulb. More broadly, our framework lays the foundation for studying how system features, such as noise, constrain the optimal sampling frequencies in both biological and artificial brains.

The dielectric slab rectangular waveguide (DSRW) has been widely studied and used for increasing the single-mode bandwidth (BW) of rectangular waveguides. This work presents a DSRW for equalizing the group velocity of the first two propagating modes in the structure. Suitably scaled, this DSRW design can be used in chip-to-chip communications to yield interconnects that avoid dispersion while enhancing the BW density of these systems. A theoretical analysis is introduced to show the equalization BW attained depending on the slab dimensions with regard to the rectangular waveguide width and the dielectric permittivity of the materials that fill the waveguide. A proof of concept slab rectangular waveguide is designed to meet a 45% equalization BW around a center frequency of 10.0 GHz. The design is scalable and can be adapted to fit the dielectric permittivity of available materials. Several waveguide sections were fabricated using additive manufacturing (AM) techniques and two dielectric materials with different permittivities. Simulations and measurements confirm the waveguide behavior at the design frequency range. TE $_{10}$ and TE $_{20}$ modes exhibit the same group velocity of 0.36 $\times$ $c_{0}$ at 7.95 GHz.

Background: Despite the availability of treatment options, the percentage of individuals with gambling problems seeking help remains low. To reach a broader population of those affected by disordered gambling, online or self-guided interventions have been developed, with personalized normative feedback (PNF) being one of the most widely used strategies in preventing gambling issues among young adults. However, most studies on the efficacy of PNF focus only on its impact on the intensity and severity of gambling behavior, without exploring its potential effect on increasing intention to change and help-seeking behaviors. Furthermore, no studies have assessed the efficacy of PNF in addressing emerging online gambling-like behaviors, such as betting within video games or excessive financial trading of high-risk assets (e.g., cryptocurrencies), which have been linked to pathological gambling. Method/Design: This project has two main objectives: (1) to quantify intention to change and the prevalence of help-seeking behaviors in young adults in Spain with disordered gambling or trading behaviors, and (2) to assess the efficacy of online personalized normative feedback (PNF) in increasing these behaviors. A randomized controlled trial with a Solomon three-group design will be conducted, including a sample of at least 472 men and women aged 18-30 years. The study will include three assessments: a pre-test, an immediate post-test, and a 12-week follow-up assessment. The intervention will consist of online PNF, delivered to participants in two intervention groups. The impact of PNF on gambling and trading behavior (including intensity, frequency, and severity) and the longitudinal trajectory of these behaviors will be also evaluated. Additionally, individual, interpersonal, and contextual factors will be assessed to identify the profile of individuals most likely to benefit from this intervention. Discussion: This study is innovative in evaluating the efficacy of online PNF in promoting behavior change and help-seeking in young adults with gambling and trading disorders. The findings will offer valuable insights into the psychological and social impacts of these behaviors, informing future prevention and treatment strategies. Trial registration: ClinicalTrials.gov Identifier: NCT06681103; Date of Registration: November 7, 2024.

Hyperglucagonemia has been implicated in the pathogenesis of type 2 diabetes (T2D). In contrast to β-cells, studies on the function of the pancreatic α-cell in T2D are scarce. Consequently, the processes underlying hyperglucagonemia and α-cell dysfunction are largely unknown, limiting the appropriate design of specific pharmacological and therapeutic strategies. In the current study, we aimed to analyze the alterations of the pancreatic α-cell and its glucagon responses in diabetic db/db mice at early stages of the disease. In this context of glucose intolerance, hyperinsulinemia, and β-cell dysfunction, hyperglucagonemia was only present at fed conditions and was associated with insulin resistance. Yet, we found that the glucagon-to-insulin ratio in db/db mice did not change with fed or fasted states, further supporting that the metabolic regulation of glucagon release was impaired. Pancreatic β-cell dysfunction in db/db mice was manifested by increased basal secretion from isolated islets along with reduced insulin content. In contrast, α-cells from diabetic animals presented upregulated secretion and islet content of glucagon compared with controls. Electrophysiological analysis of dispersed α-cells revealed that altered secretion was not the result of impaired exocytosis. Instead, we found defective regulation of Ca²⁺ signaling by glucose. Besides these functional alterations, we also observed augmented α-cell mass in diabetic mice, which was accompanied by disrupted islet cytoarchitecture as well as increased α-cell size and number, without pieces of evidence of upregulated proliferation. Overall, these findings indicate that hyperglucagonemia in early T2D results from multifaceted α-cell deregulation in mice.

Pancreatic cancer is highly lethal and has limited treatment options available. Our team had previously developed ZZW-115, a promising drug candidate that targets the nuclear protein 1 (NUPR1), which is involved in pancreatic cancer development and progression. However, clinical translation of ZZW-115 was hindered due to potential cardiotoxicity caused by its interaction with the human Ether-à-go-go-Related Gene (hERG) potassium channel. To address this, we have performed a high-throughput screening of 10,000 compounds from the HitFinder Chemical Library, and identified AJO14 as a lead compound that binds to NUPR1, without having favorable affinity towards hERG. AJO14 induced cell death through apoptosis, necroptosis, and parthanatos (induced by the poly-ADP ribose polymerase (PARP) overactivation), driven by mitochondrial catastrophe and decreased ATP production. This process seemed to be mediated by the hyperPARylation (an excessive modification of proteins by PARP, leading to cellular dysfunction), as it could be reversed by Olaparib, a PARP inhibitor. In xenografted mice, AJO14 demonstrated a dose-dependent tumor reduction activity. Furthermore, we attempted to improve the anti-cancer properties of AJO14 by molecular modification of the lead compound. Among the 51 candidates obtained and tested, 8 compounds exhibited a significant increase in efficacy and have been retained for further studies, especially LZX-2-73. These AJO14-derived compounds offer potent NUPR1 inhibition for pancreatic cancer treatment, without cardiotoxicity concerns.

Background Assessing self-efficacy in evidence-based practice (EBP) is crucial for identifying training needs, evaluating the effectiveness of educational programs, and assessing the overall application confidence of EBP in healthcare professions, including occupational therapy (OT). Thus, the objectives of this study were to cross-culturally adapt the Evidence-Based Practice Confidence Scale (EPIC) for Spanish-speaking OT students and professionals and to evaluate its internal consistency, test–retest reliability, and construct validity. Methods A professional translation and cross-cultural adaptation of the EPIC was developed, including a pilot study that resulted in the EPIC Spanish version. A total of 260 OT students and 202 professionals completed the Spanish EPIC at baseline, with 177 (68.1%) students and 129 (63.9%) professionals participating in the test–retest reliability assessment two weeks later. The EPIC’s internal consistency was evaluated using Cronbach’s alpha. Test–retest reliability was assessed using Spearman’s correlations and intra-class correlations (ICC). Known-groups validity hypothesis based on participants' roles (students, diploma/bachelor’s, master’s, and doctorate) was explored using ANOVA. Finally, an exploratory factor analysis with oblique Promax rotation was conducted to examine the EPIC factor structure. Results Cronbach’s alpha for the total EPIC score was excellent in both OT professionals (α = 0.91) and students (α = 0.90). For OT students, Spearman’s correlation was 0.67 (p < 0.001) for the total score, and the ICC was 0.66 (95%CI 0.57–0.73). Conversely, for OT professionals, test–retest reliability showed a Spearman’s correlation of 0.87 (p < 0.001) for the total score, and the ICC was 0.87 (95%CI 0.81–0.90). The highest scores were observed in professionals with a doctorate followed by those with a master’s degree (p < 0.001). The exploratory factor analysis yielded a 3-factor solution that explained 71% of the observed variance, with item-level loadings ≥ 0.35. Conclusions The EPIC scale showed excellent internal consistency, strong test–retest reliability, and adequate construct validity for evaluating EBP self-efficacy among Spanish-speaking OT professionals using the total score. However, test–retest reliability was moderate among Spanish-speaking OT students, indicating that changes in EBP confidence assessed with the EPIC scale in this group should be interpreted with caution.

This work proposes the use of multilayer scaffolds as a strategy for developing biomimetic structures for bone tissue regeneration. The scaffolds consist of a glass–ceramic core composed of CaSiO3/Ca2P6O17, which provides mechanical properties of 2.3 MPa and a total porosity of ∼74%. To modify the surface morphology a double bioactive coating consisting of Ca3(PO4)2/CaSiO3 doped with Na⁺ and K⁺, along with varying amounts of Mg²⁺ (0–0.75 g MgCO3) was carried out giving a total porosity of 89.8%. The resulting scaffolds were assessed for in vitro bioactivity according to ISO 23317. After immersion in SBF, the W‐05 scaffolds displayed diverse surface morphologies: square HA structure (W‐05‐3D), hollow HA spheres (W‐05‐7D) and smooth HA layer (W‐05‐21D). Cell viability of 3T3 fibroblasts exposed to W‐05 scaffolds in direct and indirect assays at concentrations of 15 and 30 mg/mL was assessed according to ISO 10993–5. Initially, cell proliferation decreased compared to controls, but differences became non‐statistically significant after 72 h. Hollow spheres (W‐05‐7D) enhanced cell viability compared to other morphologies and plastic controls. Additionally, degradation products of W‐05 stimulated cell division, underscoring scaffold biocompatibility.

Introduction Overuse of medical services is a challenge worldwide, posing a threat to the quality of care, patient safety and the sustainability of healthcare systems. Some data suggest that females receive more low-value practices (LVPs)—defined as medical interventions that provide little or no benefit to patients and can even cause harm—than males. This study aims to evaluate and compare the occurrence of LVPs in primary care among both males and females. Design A retrospective study was conducted. Setting Primary care in the Alicante province (Spain) during 2022. Participants Data were extracted from the digital medical records of 978 936 patients attended by 1125 family physicians across 262 primary healthcare centres in the Alicante province. Outcome measures Data on age, sex, diagnosis and treatment were extracted. The primary outcome measure was the frequency of 12 selected LVPs prescribed to male and female patients. These LVPs were expected to be relatively frequent occurrences with the potential to cause harm. Results A total of 45 955 LVPs were identified, of which 28 148 (5.27% of 534 603, CI95% 5.20–5.32) were prescribed to female patients and 17 807 (4.00% of 444 333, CI95% 3.95–4.06) to male patients (x², p value <0.0001). The most common LVPs were prescribing treatment for overactive bladder without excluding other pathologies that may cause similar symptoms (30.87%), using hypnotics without having a previous aetiological diagnosis in patients with difficulty maintaining sleep (14%) and recommending analgesics (NSAIDs, paracetamol and others) for more than 15 days per month in primary headaches that do not respond to treatment (13.33%). Conclusions Future clinical training, management and research must consider biological differences or those based on gender factors when analysing the frequency and causes of LVP. Trial registration number NCT05233852 .

Providing user-friendly software for groups with special needs is crucial. However, there is a lack of specific evaluation methods and techniques adapted to the characteristics and needs of some users, such as those with autism spectrum disorder (ASD). The main objective of this work is to validate a UX evaluation methodology that focuses specifically on the use of systems, products, and services by adults with ASD through a specific use case. This methodology was developed by taking into account the perspectives of UX experts and ASD professionals on the one hand and potential users on the other. It comprises a three-stage validated process based on the UX/ASD model. It focuses on assessing the user experience of systems used by adults with ASD by considering specific tools and techniques for effective evaluation, in contrast to the existing UX methodologies for evaluating software applications for users with ASD that are limited to the use of generic usability analysis tools. The choice of the PlanTEA application is motivated by the fact that it is designed specifically for users with ASD to assist them in their visits to medical centers by planning and anticipating those situations. However, it has not been evaluated from the ASD user experience point of view. Applying this specific methodology for users with ASD has provided significant feedback for improving their satisfaction and perception of PlanTEA before making it available to society. Moreover, the methodology has been proven to be a powerful tool in the whole process of the UX evaluation of PlanTEA, allowing for more comprehensive UX assessments and reporting.

Every minute, the world produces an astonishing 3825 tons of municipal solid waste, resulting in an annual accumulation totaling 2.02 billion tons. The projections for the year 2050 suggest that this figure could surpass 3.4 billion tons. In this regard, social awareness and responsibility are deemed of utmost importance when it comes to sustainable communities and cities as the everyday environmental endeavors are not just a responsibility of governments or nations. Hence, volunteering activities concerning waste accumulation around the world can be a great indicator of social interaction and environmental resilience between communities. This research aims to explore volunteerism activities in the context of waste accumulation within the countries affiliated with the ‘Let’s do it World’ global organization, Through the utilization of Key Performance Indicators (KPIs), this study seeks to meticulously examine various facets of volunteer involvement and engagement, serving as metrics to gauge the effectiveness and success of organizational or project endeavors. Additionally, the research endeavors to explore both the tangible and potential outcomes of volunteerism within cleanup activities, encompassing assessments of environmental impacts such as waste removal quantities, rehabilitated areas, and preserved or restored ecosystems. Furthermore, it aims to uncover broader social and economic implications, including community empowerment, heightened public awareness, and potential cost savings for local governments. By illuminating the significance of volunteerism in waste management, this research contributes to a deeper comprehension and enhancement of efforts towards environmental protection and sustainability.

The aim of the present study is to highlight the effect of two commonly used plastics, polyethylene (PE) and polyethylene terephthalate (PET), on the quality and health indices of soil. To this end, a pot experiment was carried out using two soils, one acidic and one alkaline. The soil samples were collected from rural areas of central and Northern Greece and had similar particle size composition and almost equal copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb) concentrations. PE and PET microplastics (MPs) were added into the soil samples in two ratios (2% and 4% v/v) and remained in the soils for 20, 60 and 120 days. Then, the changes in the properties, nutrients, potentially toxic elements and health indicators of the soil samples were measured. PE addition at 4% v/v caused the maximum increase in trace element availability when it remained in the soil sample for 120 days. In contrast, PET addition caused a maximum decrease in the DTPA-extractable concentration of toxic elements (Cd and Pb), after 120 days of incubation in acid and alkaline soil. The present work provides a fresh perspective evaluating MPs from unwanted waste to materials with potential positive benefits, enhancing the circular economy approach to soil systems. Knowledge of the MPs present in soils, along with physicochemical soil properties, including their nutrient and toxic element content, are critical aspects that need to be addressed to ensure that soil quality and health are not adversely affected.

Relativistic field theory for a vector field on a curved space-time is considered assuming that the Lagrangian field density is quadratic and contains field derivatives of first order at most. By applying standard variational calculus, the general Euler–Lagrange equations for the field are derived and the existence of a conserved current is achieved. The field equations are also analysed from an eikonal-like point of view. The Hilbert energy-momentum tensor of the field is also derived and the influence of each one of the irreducible pieces appearing in the Lagrangian is studied. Particular values of the free parameters allow to retrieve known results.

Background Long-term care hospitals have been considered an efficient response to the health care needs of an increasingly aging population. These centers are expected to contribute to better hospital bed management and more personalized care for patients needing continuous care. The evaluation of their outcomes is necessary after a sufficient period to assess their impact. Hospitals for Acute and Chronic Long-Term Extended Stay (HACLES) emerged in Spain in the late 20th century as a response to the aging population and the increase in chronic diseases. Objective This study aimed to analyze the profile of patients treated in a HACLES, particularly analyzing gender differences, and evaluate the cost savings associated with using these centers. Methods A retrospective study was conducted based on data from patients 65 years old or older admitted to a HACLES between 2022 and 2023. Gender, age, household cohabitation data, diagnosis and comorbidity, daily medication intake, and degree of dependency were obtained to describe the profile of patients who attended the HACLES. Data coded in SIA-Abucasis (version 37.00.03; Consellería Sanitat, Generalitat Valenciana; a digital medical record system used in the Valencian region) were reviewed, and descriptive statistics and comparison tests were used. The direct cost savings of HACLES admissions were calculated by comparing the daily cost of a general hospital bed with that of a HACLES bed. Results Data from 123 patients with a mean age of 77 years were analyzed. Most (n=81, 65.9%) had a cohabiting family member as their primary caregiver. Palliative care was the most frequent reason for admission (n=75, 61%). The mortality rate (odds ratio [OR] 61.8, 95% CI 53.2-70.5) was similar between men and women (OR 54.1, 95% CI 47.8-71.5 vs OR 59.7, 95% CI 42.2-66.0; P=.23). The cognitive assessment, using the Pfeiffer scale, improved at discharge (mean 3.2, SD 3.2 vs mean 2.5, SD 3.1; P=.003). The length of stay was significantly larger for patients who returned home compared with patients discharged to other facilities (mean 89.8, SD 58.2 versus mean 33.1, SD 43.1 days; P<.001). The direct cost savings were estimated at US $42,614,846 per 1000 admissions. Conclusions Patients typically treated in HACLES are older, with a high level of cognitive impairment and physical dependency, and a significant proportion are in palliative care, highlighting the importance of adapting care to the individual needs of the admitted patients. The HACLES model contributes to the sustainability of the public health system.

Background/Objectives: Acute appendicitis (AA) is one of the most common causes of emergency department visits due to acute abdominal pain, with a lifetime risk of 7–8%. Managing AA presents significant challenges, particularly among vulnerable patient groups, due to its association with substantial morbidity and mortality. Methods: The EUPEMEN (European PErioperative MEdical Networking) project aims to optimize perioperative care for AA by developing multidisciplinary guidelines that integrate theoretical knowledge and clinical expertise from five European countries. This study presents the key elements of the EUPEMEN protocol, which focuses on reducing surgical stress, optimizing perioperative care, and enhancing postoperative recovery. Results: Through this standardized approach, the protocol aims to lower postoperative morbidity and mortality, shorten hospital stays, and improve overall patient outcomes. The recommendations are tailored to address the variability in clinical practice across Europe and are designed to be widely implementable in diverse healthcare settings. Conclusions: The conclusions drawn from this study highlight the potential for the EUPEMEN protocol to significantly improve perioperative care standards for AA, demonstrating its value as a practical, adaptable tool for clinicians.