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We addressed construct validity and explored the relationship between self-compassion and compassion for others using the two main current operationalizations of compassion (Neff's and the Sussex-Oxford Compassion Scales, SOCSs). Relationships with psychological distress and wellbeing, and potential differences in the association between self-compassion and compassion for others by level of psychological distress and wellbeing were also explored. Participants ( n = 811) completed the Spanish adaptations of the Self-Compassion Scale (SCS), the Compassion Scale (CS), the SOCSs (for the self/others), the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS), and the Depression Anxiety Stress Scales-21 (DASS-21). We fitted bifactor models to estimate the general factor of each construct for the different operationalizations, and calculated correlations between them. Relationships between self-compassion and compassion for others from the same operationalization were intermediate, while those between the same constructs from different operationalizations were large. Both constructs showed positive associations with wellbeing, while only self-compassion was associated with decreased psychological distress. Participants with good mental health showed higher associations between self-compassion and compassion for others than those with poorer mental health. Self-compassion and compassion for others appear to be dimensional constructs that can converge or diverge. When they converge, it is associated with better mental health., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The tick Ixodes ricinus parasitizes a wide range of vertebrates. These hosts vary in the relative contribution to the feeding of the different tick life stages, and their interplay is pivotal in the transmission dynamics of tick-borne pathogens. We aimed to know if there is a phylogenetic signal in the feeding and propagation hosts of I. ricinus , independently of other traits, as well as in the amplification of Borrelia burgdorferi ( s.l. ) in feeding larvae. We used a compilation of 1127 published field surveys in Europe, providing data for 96,586 hosts, resulting in 265,124 larvae, 72,080 nymphs and 37,726 adults. The load of immature ticks on hosts showed a significant phylogenetic signal towards the genera Psammodromus , Podarcis, and Lacerta (nymphs only). We hypothesize that such signal is the background hallmark of the primitive hosts associations of I. ricinus , probably in the glaciation refugia. A secondary phylogenetic signal for tick immatures appeared for some genera of Rodentia and Eulipotyphla. Results suggest the notion that the tick gained these hosts after spread from glaciation refugia. Analyses support a phylogenetic signal in the tick adults, firmly linked to Cetartiodactyla, but not to Carnivora or Aves. This study provides the first demonstration of host preferences in the generalist tick I. ricinus . We further demonstrate that combinations of vertebrates contribute in different proportions supporting the tick life-cycle in biogeographical regions of the Western Palaearctic as each region has unique combinations of dominant hosts. Analysis of the amplification of B. burgdorferi ( s.l. ) demonstrated that each genospecies is better amplified by competent reservoirs with which a strong phylogenetic signal exists. These vertebrates are the same along the spatial range: environmental traits do not change the reservoirs along the large territory studied. The transmission of B. burgdorferi ( s.l. ) is amplified by a few species of vertebrates, that share biogeographical regions with the tick vector in variable proportions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Given their role as Co-Editor, Agustín Estrada-Peña had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Professor Aneta Kostadinova (Editor-in-Chief)., (© 2024 Published by Elsevier B.V.)

To explore the modulating role of unmet support needs on the relationship between age and the prevalence of cancer-related distress in colorectal cancer (CRC) survivors. Two hundred and forty four participants completed the questionnaires; linear regression and odd ratios were calculated. Both the prevalence of needs and their interaction with age were predictors of cancer-related distress. The risk of significant clinically distress associated with physical and socio/family needs was high in both age subgroups. Higher risk of clinical distress was associated with life perspective, sexual, occupational and health care needs in the younger subgroup and with needs for specific support resources in the older subgroup. In reducing cancer-related distress, two key issues arise: (i) the importance of managing the persistent negative symptoms following CRC treatment in survivors of any age and (ii) the need for a differentiated attention to other care needs based on the survivor's age., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Capacity building in migration and health in higher education is key to better, sustainable, and equitable health care provision. However, developments so far have been patchy, non-structural, and often unsustainable. While training programs have been evaluated and competency standards developed, perspectives from individual teachers are hardly accessible. We present expert perspectives from five European countries to illustrate good examples in higher education and identify gaps to further the advancement of capacity building in migration and health. Based on these perspectives, we have identified thematic areas at four levels: conceptual evolution, policy and implementation, organization at the academic level and teaching materials and pedagogies. Finally, we propose creating spaces to share concrete educational practices and experiences for adaptation and replication. We summarize key recommendations for the advancement of capacity building in migration and health., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Questions: The challenges faced by healthcare organizations require effective leaders. Leadership has been extensively studied in medicine and nursing, but it is limited in physiotherapy. The objective of this study is to know and analyze the published research on the characteristics of leadership in physiotherapy., Design: A scoping review was conducted following the PRISMA extension guidelines. MEDLINE, The Cochrane Library, PEDro, Embase, CINAHL, Web Of Science and Scopus databases were reviewed between 01/01/2000 and 30/06/2022.All quantitative studies addressing the characteristics of leadership in physiotherapy were selected. Data extraction was performed using a table including author, year of publication, country of origin, title, objective, measurement instrument, sample and main findings., Data Synthesis: The results obtained were framed within the framework for the study of leadership designed by Bolman and Deal., Results: Eight studies were selected. The characteristics most valued or used by physiotherapists are communication, desire for continuous learning and improvement, credibility and professionalism., Conclusion: Leadership is very important for physiotherapists, and for physiotherapy, as profession they consider it very important to have vision and to lead change. Communication skills are the most highly regarded characteristic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: High intake of ultraprocessed foods (UPFs) has been associated with higher cardiometabolic risk in adults; however, the evidence in children is limited., Objective: To investigate the association between UPF consumption and cardiometabolic risk factors in the Childhood Obesity Risk Assessment Longitudinal Study (CORALS)., Design, Setting, and Participants: This baseline cross-sectional analysis was conducted using the data of CORALS participants recruited between March 22, 2019, and June 30, 2022. Preschool children (aged 3-6 years) were recruited from schools and centers in 7 cities in Spain. Inclusion criteria included informed consent signed by parents or caregivers and having a completed a set of questionnaires about the child's prenatal history at home. Exclusion criteria included low command of Spanish or unstable residence., Exposure: Energy-adjusted UPF consumption (in grams per day) from food frequency questionnaires and based on the NOVA food classification system., Main Outcomes and Measures: Age- and sex-specific z scores of adiposity parameters (body mass index [BMI], fat mass index, waist-to-height ratio, and waist circumference) and cardiometabolic parameters (diastolic and systolic blood pressure, fasting plasma glucose, homeostasis model assessment for insulin resistance, high-density and low-density lipoprotein cholesterol, and triglycerides) were estimated using linear regression models., Results: Of 1509 enrolled CORALS participants, 1426 (mean [SD] age, 5.8 [1.1] years; 698 boys [49.0%]) were included in this study. Mothers of children with high UPF consumption were younger, had a higher BMI, were more likely to have overweight or obesity, and had lower education levels and employment rates. Compared with participants in the lowest tertile of energy-adjusted UPF consumption, those in the highest tertile showed higher z scores of BMI (β coefficient, 0.20; 95% CI, 0.05-0.35), waist circumference (β coefficient, 0.20; 95% CI, 0.05-0.35), fat mass index (β coefficient, 0.17; 95% CI, 0.00-0.32), and fasting plasma glucose (β coefficient, 0.22; 95% CI, 0.06-0.37) and lower z scores for HDL cholesterol (β coefficient, -0.19; 95% CI, -0.36 to -0.02). One-SD increments in energy-adjusted UPF consumption were associated with higher z scores for BMI (β coefficient, 0.11; 95% CI, 0.05-0.17), waist circumference (β coefficient, 0.09; 95% CI, 0.02-0.15), fat mass index (β coefficient, 0.11; 95% CI, 0.04-1.18), and fasting plasma glucose (β coefficient, 0.10; 95% CI, 0.03-0.17) and lower HDL cholesterol (β coefficient, -0.07; 95% CI, -0.15 to -0.00). Substituting 100 g of UPFs with 100 g of unprocessed or minimally processed foods was associated with lower z scores of BMI (β coefficient, -0.03; 95% CI, -0.06 to -0.01), fat mass index (β coefficient, -0.03; 95% CI, -0.06 to 0.00), and fasting plasma glucose (β coefficient, -0.04; 95% CI, -0.07 to -0.01)., Conclusions and Relevance: These findings suggest that high UPF consumption in young children is associated with adiposity and other cardiometabolic risk factors, highlighting the need for public health initiatives to promote the replacement of UPFs with unprocessed or minimally processed foods.

Purpose: The aim of this report is to describe the resolution of refractory cystoid macular edema (CME) associated to retinitis pigmentosa (RP) with IV tocilizumab in three patients., Methods: Retrospective study of a series of consecutive cases of patients treated with off-label IV tocilizumab (anti IL6) for CME refractory to acetazolamide 250 mg for 3 months. Patients were diagnosed with RP by fundus appearance, electrophysiology, visual fields, and genetic testing. A complete ophthalmic examination including spectral-domain optical coherence tomography was performed., Results: Three patients with RP and CME refractory to acetazolamide 250 mg for 3 months were treated with monthly IV tocilizumab for at least six months.All patients resolved CME and improved visual acuity after the third month of IV tocilizumab, resolving systemic and ocular adverse events related to previous treatments for CME. Tocilizumab was well tolerated with no other adverse events., Discussion: CME causes visual impairment in RP, but current treatments are usually deficient. Tocilizumab has been successfully used as treatment for refractory CME in uveitis, retinal dystrophies, and autoimmune retinopathies. This article reports, for the first time, the long-term resolution of refractory CME in RP with IV tocilizumab.

Background and Aims: The present study aimed to synthesize existing quantitative evidence on the relationship between problematic smartphone use (PSU) and academic achievement with a focus on quantifying its magnitude and examining its potential moderators., Methods: Eligible studies were searched for up to February 10, 2023 in six different databases (i.e., MEDLINE, Current Contents Connect, PsycINFO, Web of Science, SciELO, and Dissertations & Theses Global). Studies were considered eligible if they provided information derived from self-report instruments that allowed statistical calculation of the relationship between PSU and academic achievement. Pooled effect sizes (r) were computed using a random-effects model. Meta-regressions were conducted to test the influence of study-level moderators on the relationship of interest. Influence analyses and a three-parameter selection model (3PSM) were conducted to examine the robustness of the results and publication bias, respectively., Results: A total of 33 effect sizes from 29 studies (n = 48,490) were retrieved. Results showed a small effect size (r = -0.110), which tended to be larger in samples consisting of students from elementary and middle schools., Discussion and Conclusions: Findings from the present study contribute to the understanding of a potential determinant of decreased academic achievement by providing evidence that PSU may be one of them.

As the number of Internet users grows, the increase in smart devices interconnected through the Internet of Things (IoT) have contributed to improvements in the functionality of everyday products and enhancement of user experience. Yet, they affect user privacy and render personal data more vulnerable. To foster a digital future fully aware of user privacy requirements, a line of design research emerges that focuses on balancing product innovation with user data protection. This matter relates to sociocultural, economic, and technological aspects, and its core is a human-centered design strategy. Still, there is a gap in academic research oriented towards guiding product developers on how to consider personal data privacy concerns when designing honest IoT devices. To define this gap and delve deeper into this relevant topic, this paper presents a systematic literature review of recent academic research using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. This review focuses on prevalent research topics such as data privacy, personal data, data surveillance, and user behaviour in IoT. The result is a state-of-the-art compilation of 45 scientific studies mapping the most relevant concepts and approaches for product development in the last ten years of research, aligned with some central research questions. The Discussion and Conclusion sections provide a deep understanding of the complexity of the fast-changing landscape of privacy and personal data management using IoT products. Finally, this study proposes future academic research directions devoted to providing product designer specific, specialised help from different (yet interconnected) scientific approaches., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

<b><br>Introduction:</b> Although PET/CT is effective for staging HNSCC, its impact on patient management is somewhat controversial. For this reason, we considered it necessary to carry out a study in order to verify whether PET/CT helps to improve the prognosis and treatment in patients. This study was designed to address the impact of PET-FDG imaging when used alongside CT in the staging and therapeutic management of patients with HNSCC.</br> <b><br>Material and methods:</b> Data was collected from 169 patients diagnosed with HNSCC with both CT and PET/CT (performed within a maximum of 30 days of each other). It was evaluated whether discrepancies in the diagnosis of the two imaging tests had impacted the treatment.</br> <b><br>Results:</b> The combined use of CT and PET/CT led to a change in the treatment of 67 patients, who represented 39.7% of the sample. In 27.2% of cases, it entailed a change in the type of treatment which the patient received. In 3.0% of the cases, using both diagnostic tests led to modifications of the therapeutic intention of our patients.</br> <b><br>Conclusions:</b> Using PET/CT in addition to the conventional imaging method in staging resulted in more successful staging and more appropriate therapeutic decision-making.</br&gt.

Background: HIV can infect bronchial epithelial cells rendering individuals susceptible to lung damage. Our objective was to determine the effects of human immunodeficiency virus (HIV) infection on pulmonary function tests., Methods: We performed a meta-analysis after conducting a literature search in PubMed, Embase, Cochrane Library and Virtual Health Library databases from inception to December 31st, 2022. We employed the inverse variance method with a random effects model to calculate the effect estimate as the mean difference (MD) and 95% confidence interval (CI). We calculated the heterogeneity with the I 2 statistic and performed a meta-regression analysis by age, sex, smoking, CD4 T-cells count and antiretroviral therapy. We also conducted a sensitivity analysis according to the studies' publication date, and excluding the study with the greatest weight in the effect. The PROSPERO registry number was CRD42023401105., Results: The meta-analysis included 20 studies, with 7621 living with HIV and 7410 control participants. The pooled MD (95%CI) for the predicted percentage of FEV 1 , FVC and DL CO were -3.12 (-5.17, -1.06); p=0.003, -1.51 (-3.04, 0.02); p=0.05, and -5.26 (-6.64, -3.87); p<0.001, respectively. The pooled MD for FEV 1 /FVC was -0.01 (-0.02, -0.01); p=0.002. In all cases, there was a considerable heterogeneity. The meta-regression analysis showed that among studies heterogeneity was not explained by patient age, smoking, CD4 T-cells count or antiretroviral therapy., Conclusion: Pulmonary function tests are impaired in people living with HIV, independently of age, smoking, CD4 T-cells count, and geographical region., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The aim of the present review was (1) to determine the effects of exercise based-interventions (EBIs) on pro-inflammatory and anti-inflammatory biomarkers in patients with fibromyalgia (FM), and (2) to determine the most effective type (acute or maintained) and modality (aerobic, resistance, etc.)., Methods: A systematic search was conducted in various electronic databases to identify all the relevant studies: Medline (PubMed), PEDro, EBSCO and Google Scholar. Clinical trials assessing the effects of EBIs in patients with FM were selected. Methodological quality was evaluated by two independent investigators using the Cochrane Risk of Bias Tool. Qualitative analysis was based on the classification of the results into levels of evidence according to GRADE., Results: Eleven studies were included. The meta-analysis showed a statistically significant decrease in proinflammatory biomarkers by EBIs with a large clinical effect in 19 comparisons (SMD: 1.74; 95 % CI: 0.85-2.62; p < 0.05), especially for IL8. The certainty of the evidence was low. The meta-analysis showed no statistically significant increase in anti-inflammatory biomarkers (IL10) by EBIs in 6 comparisons and very low certainty of evidence. Evidence was found for acute and maintained effects of exercise, with aerobic and aquatic exercise modalities showing better improvements than resistance exercise., Conclusions: EBIs are effective in inducing an immunomodulatory response in FM, characterized by decreased pro-inflammatory signaling. However, there was no evidence of an increase in anti-inflammatory biomarkers. These results should be interpreted with caution due to low certainty of evidence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction and Objective: Physicians find it difficult to take on the role of the patient and they show unusual behaviors when ill. One of these behaviors is presenteeism, which is working while sick. The objective of this research is to analyze the factors that contribute to the phenomenon of presenteeism in Spanish physicians., Material and Methods: Mixed methodology study: one national survey through the General Council of Medical Associations website (quantitative part), 22 semistructured interviews with sick residents and practicing physicians, and three focus groups involving professionals from the occupational health services (qualitative). A bivariate analysis using parametric and non-parametric tests. The significance level was p<0.05 (95% confidence interval). Qualitative analysis using the comparative-constant method until saturation of information., Results: Presenteeism is reported by 89.4% of doctors who responded to the survey, and it is more common among women. Contributing factors include fear of overburdening colleagues (the main reason and more common among women 58.14% vs 48.35%), self-perception of doing one's duty (the second reason and more common among men, 44.63% vs 33.14%) and economic impact and difficulty in accepting the role of a sick person. This behavior has an impact on patient safety, and is part of the hidden curriculum that also affects the training of medical professionals., Conclusions: Presenteeism is a widespread and accepted practice among medical professionals. Although normalized, and even appreciated as a way to avoid overburdening colleagues, presenteeism has important implications for clinical ethics and patient safety., (Copyright © 2024 FECA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Text comprehension is a major obstacle for many Primary school students with special education needs (SEN). Reading episodes bring students opportunities to be exposed to new vocabulary and knowledge, potentially boosting their development of text comprehension skills., Aims: Our study seeks to understand how reading frequency (leisure and academic) and reading medium (print and digital) contribute to the development of text comprehension during Primary school in students with and without SEN., Methods and Procedures: We tested 2289 Spanish students from fourth to sixth grade, from which 212 had an official decision of SEN. Students self-reported their reading frequency (as a measure of their reading habits) and completed a standardized text comprehension test. We employed multiple regression models with a robust maximum likelihood estimator to test associations between reading frequency and comprehension., Outcomes and Results: Students' comprehension was positively associated with their leisure print reading habits, and negatively associated with their frequency of academic digital reading. Those associations were independent of SEN status., Conclusions and Implications: Results highlight the importance of promoting leisure reading in print to all students, regardless of SEN status. In addition, caution is advised when encouraging Primary school children to use digital texts when the emphasis is on comprehending texts for acquiring knowledge., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The present study analyzes factors of adolescents' ecological-relational contexts in relation to suicidal behavior. In particular, it examined the role of peer bullying and cyberbullying, classroom climate, violence and partner victimization, parental socialization styles, and child-to-parent violence., Method: The participants are 2,977 Spanish adolescents attending seven secondary schools. They were aged 11-17 (M = 14.0, SD = 1.40; 51.5% girls). Multivariate logistic regression analyses and a two-step cluster analysis were applied to analyze the data., Results: Findings showed a prevalence of suicidal thoughts in 43.3% of the sample, with 7.7% reporting suicide attempts. Adolescents experiencing high/low victimization (ORa = 3.10, p < .001) and high cybervictimization (ORa = 1.67, p < .001) were at risk. However, high cyberbullying involvement (ORa = 0.55, p < .001) and not having a partner (ORa = 0.61, p < .001) emerged as protective factors. Sex-specific analyses underscored distinct interaction effects, with suicidal behavior in girls being significantly related to maternal negative socialization (ORa = 1.57, p = .05)., Conclusions: An ecological-relational and sex approach is needed to understand and prevent suicidal behavior in adolescents.

Primary health care (PHC) systems are a crucial instrument for achieving equitable population health, but there is little evidence of how PHC reforms impact equities in population health. In 2010, Sweden implemented a reform that promoted marketization and privatization of PHC. The present study uses a novel integration of intersectionality-informed and evaluative epidemiological analytical frameworks to disentangle the impact of the 2010 Swedish PHC reform on intersectional inequities in avoidable hospitalizations. The study population comprised the total Swedish population aged 18-85 years across 2001-2017, in total 129 million annual observations, for whom register data on sociodemographics and hospitalizations due to ambulatory care sensitive conditions were retrieved. Multilevel Analysis of Individual Heterogeneity and Discriminatory Analyses (MAIHDA) were run for the pre-reform (2001-2009) and post-reform (2010-2017) periods to provide a mapping of inequities. In addition, random effects estimates reflecting the discriminatory accuracy of intersectional strata were extracted from a series MAIHDAs run per year 2001-2017. The estimates were re-analyzed by Interrupted Time Series Analysis (ITSA), in order to identify the impact of the reform on measures of intersectional inequity in avoidable hospitalizations. The results point to a complex reconfiguration of social inequities following the reform. While the post-reform period showed a reduction in overall rates of avoidable hospitalizations and in age disparities, socioeconomic inequities in avoidable hospitalizations, as well as the importance of interactions between complex social positions, both increased. Socioeconomically disadvantaged groups born in the Nordic countries seem to have benefited the least from the reform. The study supports a greater attention to the potentially complex consequences that health reforms can have on inequities in health and health care, which may not be immediate apparent in conventional evaluations of either population-average outcomes, or by simple evaluations of equity impacts. Methodological approaches for evaluation of complex inequity impacts need further development., Competing Interests: Declarations of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mitochondrial carrier homologs 1 (MTCH1) and 2 (MTCH2) are orphan members of the mitochondrial transporter family SLC25. Human MTCH1 is also known as presenilin 1-associated protein, PSAP. MTCH2 is a receptor for tBid and is related to lipid metabolism. Both proteins have been recently described as protein insertases of the outer mitochondrial membrane. We have depleted Mtch in Drosophila and show here that mutant flies are unable to complete development, showing an excess of apoptosis during pupation; this observation was confirmed by RNAi in Schneider cells. These findings are contrary to what has been described in humans. We discuss the implications in view of recent reports concerning the function of these proteins., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Filgotinib is an oral small molecule that selectively inhibits JAK1. It is already approved for the treatment of moderately to severely active ulcerative colitis (UC). Ongoing studies are evaluating the efficacy and safety of filgotinib in Crohn's disease (CD). The purpose of this review is to summarize the available data regarding filgotinib in the management of UC and CD. We used Pubmed, Embase and clinicaltrials.gov websites to search all available data and currently ongoing studies regarding the efficacy and safety of filgotinib in inflammatory bowel diseases. Filgotinib is an effective and safe drug for the management of biologic-naive and biologic-experienced patients with moderate-to-severe UC. The same efficacy results have not been achieved in CD.

The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long-Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration., (Copyright © 2023. Published by Elsevier Ltd.)

Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Elena Garcia-Martin reports financial support was provided by 10.13039/501100004587Carlos III Health Institute. Maria J Rodrigo reports financial support was provided by 10.13039/501100004587Carlos III Health Institute. Luis E Pablo reports financial support was provided by Spain 10.13039/501100004837Ministry of Science and Innovation. Maria J Rodrigo reports was provided by Spain Ministry of Science and Innovation. Maria J Cardiel reports financial support was provided by Spain 10.13039/501100004837Ministry of Science and Innovation. Elena Garcia-Martin has patent #No. 20 382 021.2 pending to Pending European patent application (No. 20 382 021.2) related to this technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality., Methods: A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy., Results: Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1-5 exercise PVCs, P <0.001) and HR, 1.3 (1-5 recovery PVCs, P <0.001). Risks were higher with increasing PVC count: HR, 1.8 (>20 exercise PVCs, P <0.001) and HR, 1.6 (>5 recovery PVCs, P <0.001). A similar trend was observed for all-cause mortality, although associations were only significant for high PVC burdens: HRs, 1.6 (>20 exercise PVCs, P <0.001) and 1.5 (>5 recovery PVCs, P <0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs., Conclusions: In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy., Competing Interests: Disclosures Dr Petersen provides Consultancy to Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. The remaining authors report no conflict.

A better understanding of multiple myeloma (MM) biology has led to the development of novel therapies. However, MM is still an incurable disease and new pharmacological strategies are needed. Dinaciclib, a multiple cyclin-dependent kinase (CDK) inhibitor, which inhibits CDK1, 2, 5 and 9, displays significant antimyeloma activity as found in phase II clinical trials. In this study, we have explored the mechanism of dinaciclib-induced death and evaluated its enhancement by different BH3 mimetics in MM cell lines as well as in plasma cells from MM patients. Our results indicate a synergistic effect of dinaciclib-based combinations with B-cell lymphoma 2 or B-cell lymphoma extra-large inhibitors, especially in MM cell lines with partial dependence on myeloid cell leukemia sequence 1 (MCL-1). Simultaneous treatment with dinaciclib and BH3 mimetics ABT-199 or A-1155463 additionally showed a synergistic effect in plasma cells from MM patients, ex vivo. Altered MM cytogenetics did not affect dinaciclib response ex vivo, alone or in combined treatment, suggesting that these combinations could be a suitable therapeutic option for patients bearing cytogenetic alterations and poor prognosis. This work also opens the possibility to explore cyclin-dependent kinase 9 inhibition as a targeted therapy in MM patients overexpressing or with high dependence on MCL-1., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Cognitive stimulation (CS) is a popular and cost-effective intervention, which applies different types of techniques focused on cognitive skills and can be administered by different professionals. CS can be defined as activities that involve cognitive processing usually conducted in a social context and often in a group. Therefore, CS can improve psychosocial functioning and quality of life (QoL), depression, anxiety and activities of daily living (ADLs) independent of the pharmacological treatment such as acetylcholinesterase inhibitors. The objective of this systematic review and meta-analysis was to evaluate the effects of CS on psychosocial outcomes in older adults (aged 65 years or over), with healthy cognitive ageing, mild cognitive impairment (MCI), and dementia., Methods: PubMed, Scopus and Web of Science databases were examined from inception to October 2021. A total of 1,997 studies were initially identified in these databases. After discarding studies that did not meet the inclusion criteria, 30 studies were finally included in the systematic review and the meta-analysis performed with robust variance estimator (RVE) due the inclusion of studies with repeated measurements. The quality assessment tools from the National Institutes of Health were used to evaluate the quality of the studies., Results: CS was significantly associated with a higher QoL in participants who received personalized/adapted CS (RVE = 0.11±0.19 [-0.76, 0.99], t(1.86) = 0.6, p = 0.61). ., Conclusion: Personalized/adapted CS seems to improve QoL in older adults., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Globally, depression is the most common psychiatric disorder and is frequently associated with somatic symptom disorders, including pain as a physical symptom. There is a current need to improve the detection and management of the individuals in which depression and pain coexist. Hence, the aim of this document is to provide recommendations in the diagnosis and management of patients with major depressive disorder (MDD) who have pain as a physical symptom (PPS), in order to reduce the variability of clinical practice., Material and Methods: The methodology used is based on the internationally recognized RAND/UCLA consensus method. The scientific committee, consisted of a group of eight multidisciplinary experts, defined 12 clinically relevant questions. After the systematic review of the literature, the scientific committee assessed the evidence and developed recommendations. The panel group with 15 participants validated these recommendations using a single Delphi round. To conclude, there was a final consensus meeting held to redefine with minor modifications the final recommendations., Results: The scientific committee developed a total of 19 recommendations on the diagnosis and detection, impact of PPS in MDD, treatment of MDD with associated PPS, use of healthcare resources, additional recommendations, and care coordination of these patients. Globally, a substantial level of agreement (≥80%) was reached on all items during the Delphi round. All the 19 achieved consensus, seven of them (37%) were agreed with unanimity during the Delphi round. The recommendations with higher consensus were in relation to diagnosis, impact of PPS in MDD, treatment and use of healthcare resources., Conclusions: Currently, the evidence base for patients with MDD and PPS is still being developed and this consensus statement aims to bridge that gap by providing practical recommendations., (Published by Elsevier España S.L.U.)

Objectives: This study aimed to evaluate all known risk factors, from perinatal to adolescence and identify those predominantly related with prospective BMI deterioration., Methods: Prospective data analysis from the European Feel4Diabetes-study involving 12,211 children from six countries. Details on perinatal and sociodemographic characteristics were collected by parental self-reported questionnaires. Children's anthropometric data were measured by research personnel. Associations between risk factors and children's BMI deterioration (i.e increase) from baseline (mean age 8.2 ± 0.98 years) to the 2-year follow-up (10.3 ± 1.0 years) were explored by applying logistic regression analyses., Results: Univariate analysis revealed that all known risk factors for early overweight/obesity development, remained dominant in prospective BMI deterioration. When multivariate analysis was applied including additional variables such as parents' current BMI status, family socio-demographic characteristics and country economic classification based on Gross National Income, most perinatal risk factors were no longer significant. Multivariate analysis revealed that pre-pregnancy maternal overweight/obesity (OR, 95%CI: 2.71, 1.67-4.38), early introduction of solid foods (2.54, 1.21-5.31), parental current BMI status (3.53, 2.17-5.72) and country economic classification (low income: 4.67, 2.20-9.93; under austerity measures: 6.78, 3.18-14.48) were the only parameters associated with higher odds for children's BMI deterioration from the study baseline to 2-year follow-up after adjusting for children's gender., Conclusions: The most predominant risk factors influencing children's prospective BMI deterioration were parental BMI and country economic classification as compared to perinatal. These findings should guide public health initiatives aiming to tackle the childhood obesity epidemic and social inequalities on a European level., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

FLAD1, along with its FAD synthase (FADS, EC 2.7.7.2) product, is crucial for flavin homeostasis and, due to its role in the mitochondrial respiratory chain and nuclear epigenetics, is closely related to cellular metabolism. Therefore, it is not surprising that it could be correlated with cancer. To our knowledge, no previous study has investigated FLAD1 prognostic significance in pancreatic ductal adenocarcinoma (PDAC). Thus, in the present work, the FAD synthesis process was evaluated in two PDAC cell lines: (a) PANC-1- and PANC-1-derived cancer stem cells (CSCs), presenting the R273H mutation in the oncosuppressor p53, and (b) MiaPaca2 and MiaPaca2-derived CSCs, presenting the R248W mutation in p53. As a control, HPDE cells expressing wt-p53 were used. FADS expression/activity increase was found with malignancy and even more with stemness. An increased FAD synthesis rate in cancer cell lines is presumably demanded by the increase in the FAD-dependent lysine demethylase 1 protein amount as well as by the increased expression levels of the flavoprotein subunit of complex II of the mitochondrial respiratory chain, namely succinate dehydrogenase. With the aim of proposing FADS as a novel target for cancer therapy, the inhibitory effect of Chicago Sky Blue on FADS enzymatic activity was tested on the recombinant 6His-hFADS2 (IC 50  = 1.2 μm) and PANC-1-derived CSCs' lysate (IC 50  = 2-10 μm). This molecule was found effective in inhibiting the growth of PANC-1 and even more of its derived CSC line, thus assessing its role as a potential chemotherapeutic drug., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Globalization and the configuration of production processes around Global Value Chains (GVCs) have become key factors for explaining the recent evolution of environmental and economic indicators. Indeed, previous research found evidence on the significant impact of GVCs indicators (participation and position) on CO 2 emissions. Additionally, results obtained in previous literature vary depending on the time period and geographical areas considered. In this context, the main aims of this paper are to analyze the role the GVCs in explaining the evolution of CO 2 emissions, and to identify possible structural breaks. This study uses the Multiregional Input-Output framework to calculate a position indicator and two different measures of participation in GVCs (interpreted either as trade openness or international competitiveness). The analysis useS Inter-Country Input-Output tables (ICIO) as main database, which includes 66 countries and 45 industries and covers the period 1995-2018. It is first concluded that upstream positions in GVCs are associated to lower global emissions. Additionally, the effect of participation depends on the measure used: trade openness is linked to lower emissions, while a higher competitiveness in international trade leads to higher emissions. Finally, two structural breaks are identified in 2002 and 2008, revealing that position is significant in the two first subperiods, while participation becomes significant from 2002 onwards. Thus, policies to mitigate CO 2 emissions might to be different before and after 2008: currently, reductions in emissions can be achieved by increasing value-added embodied in trade while decreasing the volume of transactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Catalytic conversion of glucose represents an interesting field of research with multiple applications. From the biotechnology point of view, glucose conversion leads to the fabrication of different added-value by-products. In the field of nanocatalytic medicine, the reduction of glucose levels within the tumor microenvironment (TME) represents an appealing approach based on the starvation of cancer cells. Glucose typically achieves high conversion rates with the aid of glucose oxidase (GOx) enzymes or by fermentation. GOx is subjected to degradation, possesses poor recyclability and operates under very specific reaction conditions. Gold-based materials have been typically explored as inorganic catalytic alternatives to GOx in order to convert glucose into building block chemicals of interest. Still, the lack of sufficient selectivity towards certain products such as gluconolactone, the requirement of high fluxes of oxygen or the critical size dependency hinder their full potential, especially in liquid phase reactions. The present work describes the synthesis of platinum-based nanodendrites as novel enzyme-mimicking inorganic surrogates able to convert glucose into gluconolactone with outstanding selectivity values above 85%. We have also studied the enzymatic behavior of these Pt-based nanozymes using the Michaelis-Menten and Lineweaver-Burk models and used the main calculation approaches available in the literature to determine highly competitive glucose turnover rates for Pt or Pt-Au nanodendrites.

The sustainable design of product systems has been addressed in numerous research works. However, studies regarding the sustainability of services are fewer and they are focused mostly on the study of environmental aspects during the service provision stage. Regarding cultural services, the application of sustainability principles in their design process is increasingly required due to reasons such as environmental awareness, social responsibility, visitors' preferences and innovation strategies. Although up to date a limited number of initiatives have been promoted. The objectives of this work are the description of a specific sustainable design method based on the development of systematic tasks and supported on three complementary approaches, and the application of this method to the design of two different types of cultural exhibitions. The design of an itinerary exhibition, which is developed in a sheltered indoor space, and an exhibition, which is developed in the streets of a big city, are, respectively, carried out. The sustainability performance of different design alternatives are valued in each case by analyzing the incidence of those systems, activities, and stakeholders involved along the entire service development and using not only environmental but also socio-economic indicators. Thus, this research work aims at providing the appropriate methodological support to designers of cultural services and managers of cultural institutions, to carry out more sustainable projects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The mechanical properties of the crystalline lens are crucial in determining the changes in lens shape that occur during the accommodation process and are also a major factor in the development of the two most prevalent age-related diseases of the lens, presbyopia and cataracts. However, a comprehensive understanding of these properties is currently lacking. Previous methods for characterizing the mechanical properties of the lens have been limited by the amount of data that could be collected during each test and the lack of complex material modeling. These limitations were mainly caused by the lack of imaging techniques that can provide data for the entire crystalline lens and the need for more complex models to describe the non-linear behavior of the lens. To address these issues, we characterized the mechanical properties of 13 porcine lenses during an ex vivo micro-controlled-displacement compression experiment using optical coherence elastography (OCE) and inverse finite element analysis (iFEA). OCE allowed us to quantify the internal strain distribution of the lens and differentiate between the different parts of the lens, while iFEA enabled us to implement an advanced material model to characterize the viscoelasticity of the lens nucleus and the relative stiffness gradient in the lens. Our findings revealed a pronounced and rapid viscoelastic behavior in the lens nucleus (g 1  = 0.39 ± 0.13, τ 1  = 5.01 ± 2.31 s) and identified the lens nucleus as the stiffest region, with a stiffness 4.42 ± 1.20 times greater than the anterior cortex and 3.47 ± 0.82 times greater than the posterior cortex. However, due to the complex nature of lens properties, it may be necessary to employ multiple tests simultaneously for a more comprehensive understanding of the crystalline lens., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation., Methods: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed., Results: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories., Conclusions: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.

Purpose: This study presents a treatment planning system for intraoperative low-energy photon radiotherapy based on photogrammetry from real images of the surgical site taken in the operating room., Material and Methods: The study population comprised 15 patients with soft-tissue sarcoma. The system obtains the images of the area to be irradiated with a smartphone or tablet, so that the absorbed doses in the tissue can be calculated from the reconstruction without the need for computed tomography. The system was commissioned using 3D printing of the reconstructions of the tumor beds. The absorbed doses at various points were verified using radiochromic films that were suitably calibrated for the corresponding energy and beam quality., Results: The average reconstruction time of the 3D model from the video sequence in the 15 patients was 229,6±7,0 s. The entire procedure, including video capture, reconstruction, planning, and dose calculation was 520,6±39,9 s. Absorbed doses were measured on the 3D printed model with radiochromic film, the differences between these measurements and those calculated by the treatment planning system were 1.4% at the applicator surface, 2.6% at 1 cm, 3.9% at 2 cm and 6.2% at 3 cm., Conclusions: The study shows a photogrammetry-based low-energy photon IORT planning system, capable of obtaining real-time images inside the operating room, immediately after removal of the tumor and immediately before irradiation. The system was commissioned with radiochromic films measurements in 3D-printed model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Depression and Alzheimer's disease (AD) are frequent interacting diseases in the elderly with a negative impact on the quality of life of patients and caregivers. Late-life depression may be regarded either as an early symptom of AD or a risk factor for AD, depending on the context. This review was focused on the latest developments in the fields of the neurobiological basis and treatment of depression in AD. We found that some plausible hypotheses are emerging to correlate with depression in AD, such as neuroinflammation and dysimmune regulation. It seems that depression is not related to amyloid deposition, but this issue is not completely resolved. The response to antidepressants is controversial according to the evidence from 10 small double-blind randomized placebo-controlled clinical trials with antidepressants in AD patients with depression: four with sertraline, one with three arms (sertraline, mirtazapine, placebo), one with fluoxetine, one with imipramine, one with clomipramine, one with escitalopram, and one with vortioxetine. The total number of treated patients completing the trials was 638. The main criterion of a positive response was a reduction in the scores of clinical scales for depression of at least 50%. The weighted OR (odds ratio) was calculated with the method of Mantel-Haenszel: 1.29; 95% CI: 0.77-2.16. No significant differences were found compared with placebo. Antidepressants did not have a meaningful negative influence on cognition, which was measured with the mini-mental state examination (MMSE) in 18 clinical trials. Alternatives other than drugs are also discussed. Although there have been important advances in this field, pathophysiology and treatment deserve further research., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii , an intracellular parasite that presents a worldwide risk. Humans can become infected by ingesting meat infected with T. gondii , and the consumption of infected sheep and goat meat is a significant public health issue. Antibodies against T. gondii have been found in sheep in Spain, indicating the presence of the parasite in the country. However, no previous studies have assessed the presence of T. gondii in sheep meat in Spain. In view of the significance of the transmission of T. gondii through meat consumption and given the lack of previous studies in Spain, we carried out an investigation to evaluate the presence of T. gondii in adult sheep meat (mutton). A total of 216 muscle samples were analyzed by digestion, and a real-time PCR assay was used to determine the presence of T. gondii DNA. A total of 24.5% of the samples were found to be parasitized, indicating that the consumption of sheep meat can present an important risk for human health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Renal vascularization is classically described as a renal artery and vein. However, this vascular pattern presents numerous anatomical variations in terms of their number, origin and course due to ontogenetic alterations. The aim was to carry out a descriptive study of the renal vascular pattern observed during the dissection of cadavers intended for teaching purposes. A descriptive and observational study of renal vascular anatomy was carried out by dissecting 16 renal blocks from 8 cadavers donated to science and used for teaching at the Faculty of Medicine of the University of Zaragoza. The prevalence of arterial variations was 75% (56.3% for polar renal arteries, 12.5% for pre-hilar branching and 6.25% for double communicating arterial arch) and venous was 62.5% (12.5% for polar renal veins, 25% for late venous confluence, 6.25% for triple renal vein and 18.75% for double circumaortic renal vein). We conclude that the renal vascular anomalies occur with high frequency; for this reason, knowledge of these anomalies is extremely important for the correct planning of numerous medical-surgical activities.

Background: Current procedures for diagnosing multiple sclerosis (MS) present a series of limitations, making it critically important to identify new biomarkers. The aim of the study was to identify new biomarkers for the early diagnosis of MS using spectral-domain optical coherence tomography (OCT) and artificial intelligence., Methods: Spectral domain OCT was performed on 79 patients with relapsing-remitting multiple sclerosis (RRMS) (disease duration ≤ 2 years, no history of optic neuritis) and on 69 age-matched healthy controls using the posterior pole protocol that incorporates the anatomic Positioning System. Median retinal thickness values in both eyes and inter-eye difference in healthy controls and patients were evaluated by area under the receiver operating characteristic (AUROC) curve analysis in the foveal, parafoveal and perifoveal areas and in the overall area spanned by the three rings. The structures with the greatest discriminant capacity - retinal thickness and inter-eye difference - were used as inputs to a convolutional neural network to assess the diagnostic capability., Results: Analysis of retinal thickness and inter-eye difference in RRMS patients revealed that greatest alteration occurred in the ganglion cell (GCL), inner plexiform (IPL), and inner retinal (IRL) layers. By using the average thickness of the GCL (AUROC = 0.82) and the inter-eye difference in the IPL (AUROC = 0.71) as inputs to a two-layer convolutional neural network, automatic diagnosis attained accuracy = 0.87, sensitivity = 0.82, and specificity = 0.92., Conclusion: This study adds weight to the argument that neuroretinal structure analysis could be incorporated into the diagnostic criteria for MS., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Spheroids are in vitro quasi-spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. The main objective of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics., Method: We propose a continuum mechanobiological model which accounts for the most relevant phenomena that take place in tumor spheroid evolution under in vitro suspension, namely, nutrient diffusion in the spheroid, kinetics of cellular growth and death, and mechanical interactions among the cells. The model is qualitatively validated, after calibration of the model parameters, versus in vitro experiments of spheroids of different glioblastoma cell lines., Results: Our model is able to explain in a novel way quite different setups, such as spheroid growth (up to six times the initial configuration for U-87 MG cell line) or shrinking (almost half of the initial configuration for U-251 MG cell line); as the result of the mechanical interplay of cells driven by cellular evolution., Conclusions: Glioblastoma tumor spheroid evolution is driven by mechanical interactions of the cell aggregate and the dynamical evolution of the cell population. All this information can be used to further investigate mechanistic effects in the evolution of tumors and their role in cancer disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The mechanics of accommodation is a complex process that involves multiple intraocular ocular structures. Recent studies suggest that there is deformation of the sclera during accommodation that may also play a role in accommodation, influencing ciliary muscle contraction and contributing to the accommodative response. However, the type and magnitude of the deformations measured varies significantly across studies. We present high-resolution synchronous OCT measurements of the anterior sclera contour and thickness and lens thickness acquired in real-time during accommodative responses to 4D step stimuli. The lens thickness was used as an assessment of objective accommodation. No changes in nasal and temporal anterior scleral contour and scleral thickness were found during accommodation within the precision of our measurements. Our results demonstrate that there are no significant scleral deformations during accommodation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Although strength exercise is often prescribed for people with haemophilia (PWH), it remains unknown how exercise variables and pain thresholds are used to prescribe strength training in PWH., Aim: To analyse how strength exercise variables and pain thresholds have been used to prescribe strength training in PWH., Methods: A systematic search was conducted in PubMed, Embase, Web of Science, CENTRAL and CINAHL databases from inception to 7 September 2022. Studies whose intervention included strengthening training in adults with haemophilia were included. Two independent reviewers were involved in study selection, data extraction and risk of bias assessment., Results: Eighteen studies were included. The least reported variables among the studies were: prophylactic factor coverage (11.1%), pain threshold/tolerability (5.6%), intensity (50%), total or partial range of motion (27.8%), time under tension (27.8%), attentional focus modality (0%), therapist experience in haemophilia (33.3%) and adherence assessment (50%). In contrast, weekly frequency (94.4%), duration (weeks) (100%), number of sets/repetitions (88.9%), repetitions to failure/not to failure (77.8%), types of contraction (77.8%), rest duration (55.6%), progression (55.6%), supervision (77.8%), exercise equipment (72.2%) and adverse event record (77.8%) had a higher percentage of reported (>50% of studies)., Conclusion: Future research on strength training for PWH should improve information on pain threshold and other important variables such as prophylactic factor coverage, intensity, range of motion, time under tension, attentional focus modality, therapist experience in haemophilia and adherence assessment. This could improve clinical practice and comparison of different protocols., (© 2023 John Wiley & Sons Ltd.)

Hyperactivity of the parasympathetic nervous system has been linked to the development of paroxysmal atrial fibrillation (AF). The parasympathetic neurotransmitter acetylcholine (ACh) causes a reduction in action potential (AP) duration (APD) and an increase in resting membrane potential (RMP), both of which contribute to enhance the risk for reentry. Research suggests that small-conductance calcium activated potassium (SK) channels may be an effective target for treating AF. Therapies targeting the autonomic nervous system, either alone or in combination with other drugs, have been explored and have been shown to decrease the incidence of atrial arrhythmias. This study uses computational modeling and simulation to examine the impact of SK channel block (SKb) and β-adrenergic stimulation through Isoproterenol (Iso) on countering the negative effects of cholinergic activity in human atrial cell and 2D tissue models. The steady-state effects of Iso and/or SKb on AP shape, APD at 90% repolarization (APD 90 ) and RMP were evaluated. The ability to terminate stable rotational activity in cholinergically-stimulated 2D tissue models of AF was also investigated. A range of SKb and Iso application kinetics, which reflect varying drug binding rates, were taken into consideration. The results showed that SKb alone prolonged APD 90 and was able to stop sustained rotors in the presence of ACh concentrations up to 0.01 μM. Iso terminated rotors under all tested ACh concentrations, but resulted in highly-variable steady-state outcomes depending on baseline AP morphology. Importantly, the combination of SKb and Iso resulted in greater APD 90 prolongation and showed promising anti-arrhythmic potential by stopping stable rotors and preventing re-inducibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The pathophysiology of heart failure with reduced ejection fraction (HFrEF) is a complex process in which a number of neurohormonal systems are involved. Targeting only some of these systems, but not all, translates into a partial benefit of HF treatment. The nitric oxide-soluble guanylate cyclase (sGC)-cGMP pathway is impaired in HF, leading to cardiac, vascular and renal disturbances. Vericiguat is a once-daily oral stimulator of sGC that restores this system. No other disease-modifying HF drugs act on this system. Despite guidelines recommendations, a substantial proportion of patients are not taking all recommended drugs or when taking them, they do so at low doses, limiting their potential benefits. In this context, treatment should be optimized considering different parameters, such as blood pressure, heart rate, renal function, or potassium, as they may interfere with their implementation at the recommended doses. The VICTORIA trial showed that adding vericiguat to standard therapy in patients with HFrEF significantly reduced the risk of cardiovascular death or HF hospitalization by 10% (NNT 24). Furthermore, vericiguat does not interfere with heart rate, renal function or potassium, making it particularly useful for improving the prognosis of patients with HFrEF in specific settings and clinical profiles.

Tourism sustainability is a long-term exploration process of human beings seeking to coexist harmoniously with the ecological environment. The core of sustainable tourism development is to achieve the harmonious development of the economy, society, and environment. Aragon's rich tourism resources attract many tourists, and the local government has formulated a sustainable development strategy to develop tourism vigorously. This paper constructs a tool to assess the sustainable development of tourism in Aragon based on the theory of sustainable tourism development and related methods. It proposes the construction of synthetic indicators based on the environmental-social-economic triad model, identifies individual indicators suitable for the study of the region based on indicators that appear more frequently in related studies, and defines and evaluates these indicators. We construct the matrices by questionnaire and expert consultation method and find that environmental and social factors significantly impact sustainable development. The indicators are then standardized and weighted using hierarchical analysis to determine the level of sustainable development of the local tourism industry based on the standard for assessing sustainable tourism development. The steps and methods of constructing synthetic indicators proposed in this paper can guide future analysis of the strengths and weaknesses of tourism development in Aragon and similar areas under different conditions, as well as for the study of factors affecting tourism development, and provide targeted suggestions for improving the competitiveness of local tourism, taking into account regional tourism characteristics and actual conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: Prior research has solely focused on the association between handgrip strength and risk of depression in single countries or general populations, but more knowledge is required from wider-spread cohorts and target populations., Aims: This study aimed to investigate the association between handgrip strength and risk of depression using repeated measures in adults aged 50 years and over., Method: Data on handgrip strength and risk of depression were retrieved from the Survey of Health, Ageing and Retirement in Europe (SHARE) waves 1, 2, 4, 5, 6 and 7, using a hand dynamometer (Smedley, S Dynamometer, TTM) and the EURO-D 12-item scale, respectively. Time-varying exposure and covariates were modelled using both Cox regression and restricted cubic splines., Results: A total of 115 601 participants (mean age 64.3 years (s.d. = 9.9), 54.3% women) were followed-up for a median of 7.3 years (interquartile range: 3.9-11.8) and 792 459 person-years. During this period, 30 208 (26.1%) participants experienced a risk of depression. When modelled as a continuous variable, we observed an inverse significant association for each kg increase of handgrip strength and depression up to 40 kg in men and up to 27 kg in women., Conclusions: Being physically strong may serve as a preventive factor for depression in older adults, but this is limited up to a maximum specific threshold for men and women.

Objective: This systematic review aimed to summarise and update existing knowledge about ageism among nursing students through the following research question: what is the perception and attitudes of ageism among student nurses?, Design: A systematic review of longitudinal and cross-sectional studies of ageism in nursing students was carried out., Data Sources: The literature search was conducted in the scientific databases Pubmed and Scopus in February 2021., Review Methods: After the screening process, 22 studies meeting the selection criteria were selected; 8 more were identified after manually searching the selected paper' reference lists. A total of 30 studies were included in the review. The JBI Critical Appraisal Checklists for Analytical Cross-Sectional studies and for Cohort Studies were used to appraise the articles' quality., Results: There was large variability in the manifestation of ageism among student nurses, as well as in the instruments used for assessment. Most of the articles analysed attitudes towards old age, the majority of which were positive. Being a female student, being on the final year of study and having regular contact or cohabitation with an older adult were three of the main determinants in the expression of positive attitudes towards the elderly., Conclusions: Our findings suggest that student nurses generally have positive attitudes towards old age, although ageist beliefs and discriminatory behaviours were identified and should be studied in greater depth. Training programs for future care professionals have a responsibility to educate from a non-stereotypical perspective based on current societal needs., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In silico models of biological systems are usually very complex and rely on a large number of parameters describing physical and biological properties that require validation. As such, parameter space exploration is an essential component of computational model development to fully characterize and validate simulation results. Experimental data may also be used to constrain parameter space (or enable model calibration) to enhance the biological relevance of model parameters. One widely used computational platform in the mathematical biology community is PhysiCell,  which provides a standardized approach to agent-based models of biological phenomena at different time and spatial scales. Nonetheless, one limitation of PhysiCell is the lack of a generalized approach for parameter space exploration and calibration that can be run without high-performance computing access. Here, we present PhysiCOOL , an open-source Python library tailored to create standardized calibration and optimization routines for PhysiCell models., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023.)

As the body's immunity declines with age, elderly-hospitalized patients due to COVID-19 might be at higher mortality risk. Therefore, the aim of this prospective study was to examine the possible risk factors (demographic, social or comorbidities) most associated with mortality one-year after diagnosis of COVID-19. Routine data were collected from a cohort of hospitalized adults with severe COVID-19. The primary endpoint was mortality at one-year after diagnosis of COVID-19. We used a Cox proportional hazard model to estimate the hazard ratios (HRs) for both all-cause and specific cardiorespiratory mortality. A fully adjusted model included sex, socioeconomic status, institutionalization status, disability, smoking habit, and comorbidities as confounders. A total of 368 severe cases hospitalized on average 67.3 ± 15.9 years old were included. Participants aged ≥ 71 years had significantly higher HRs for all-cause mortality (adjusted HRs = 2.86, 95%CI: 2.01-4.07) and cardiorespiratory mortality (adjusted HRs = 2.86, 95%CI: 1.99-4.12). The association between age and mortality after diagnosis of COVID-19 due to both all-causes and cardiorespiratory mortality showed a consistent dose-response fashion. Institutionalization, disability, and socioeconomic status also showed a significant association with mortality. In conclusion, aging itself was the most important risk factor associated with mortality one year after diagnosis of COVID-19. People with disabilities, institutionalized or low socioeconomic status are significantly more likely to die after COVID-19., (copyright: © 2022 Nunez-Cortes et al.)

Background: Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP)., Aims: To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age., Methods: Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered., Results: We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes., Conclusions: The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.

Introduction: Motor imagery and mental practice can be defined as a continuous mechanism in which the subject tries to emulate a movement using cognitive processes, without actually performing the motor action. The objective of this review was to analyse and check the efficacy of motor imagery and/or mental practice as a method of rehabilitating motor function in patients that have suffered a stroke, in both subacute and chronic phases. Material and Methods . We performed a bibliographic search from 2009 to 2021 in the following databases, Medline (PubMed), Scopus, WOS, Cochrane, and OTSeeker. The search focused on randomized clinical trials in which the main subject was rehabilitating motor function of the upper limb in individuals that had suffered a stroke in subacute or chronic phases., Results: We analysed a total of 11 randomized clinical trials, with moderate and high methodological quality according to the PEDro scale. Most of the studies on subacute and chronic stages obtained statistically significant short-term results, between pre- and postintervention, in recovering function of the upper limb., Conclusions: Motor imagery and/or mental practice, combined with conventional therapy and/or with other techniques, can be effective in the short term in recovering upper limb motor function in patients that have suffered a stroke. More studies are needed to analyse the efficacy of this intervention during medium- and long-term follow-up., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Enrique Villa-Berges et al.)