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Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with renin-angiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection. Male and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8 weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment. Semaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice. Our results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade.

The costimulatory CD40-CD40L pathway plays a role in kidney inflammation. We have previously reported that renal CD40 upregulation precedes cellular interstitial infiltrate and fibrosis in the unilateral ureteral obstruction (UUO) model. Here we sought to evaluate whether the administration of siRNA-CD40 has a therapeutic effect in a reversible unilateral ureteral obstruction (D-UUO) mice model. Eight week-old C57BL6J male mice were divided into four groups: Vehicle (Phosphate-buffered saline) (n = 8); siRNA SC (non-specific siRNA) (n = 6); siRNA-CD40 (n = 8) and WT (wild type) (n = 6) mice. UUO was performed with a microvascular clamp. At day 3 after surgery, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Immediately, PBS, siRNA SC (50μg) or siRNA-CD40 (50μg) was administrated via the tail vein. Mice were killed 48h hours after the siRNA or saline administration. Wild type (WT) mice were used as controls. Blood samples were collected for measuring creatinine and blood urea nitrogen (BUN). Histology and kidney mRNA expression were performed. The administration of siRNA-CD40 reduced significantly the severity of acute renal failure associated with UUO. Pathologic analysis showed reduction of tubular dilation, interstitial fibrosis, F4/80 macrophage and CD3 (T cell) infiltration in animals treated with siRNA-CD40. Furthermore, kidney mRNA gene expression analysis showed significantly lower levels of macrophage markers (F4/80 and Mannose receptor), fibrosis matrix proteins (Fibronectin, MMP-9, Collagen IV and α-SMA), pro-inflammatory cytokines (iNOS and MCP-1) and the pro-fibrotic molecule TGF-β1 in siRNA-CD40. The administration of siRNA-CD40 therapy reduces the severity of the acute kidney injury induced by obstructive uropathy and promotes kidney repair. This strategy seems suitable to be tested in humans.

Short-term variability in dissolved methane (CH₄) is critical in coastal upwelling systems due to its highly variable dynamics, and limited temporal and spatial monitoring. Hourly dissolved CH₄ time series in an upwelling bay (Coliumo, 36.5°S, Chile) were registered using a buoy-based system during the upwelling season (September 2024–February 2025). Spectral and wavelet analyses revealed a multiscale structure with variance dominated by low-frequency fluctuations (>10 d) (52.1%), followed by synoptic (3–10 d; 40.3%) and a weak diurnal period (2.5%). Low-frequency (>10 d) variability provided the background over which synoptic events modulated CH₄ via alternating active upwelling and relaxation/downwelling events. During active upwelling, cold, saline, and CH₄-enriched waters upwelled, yielding higher CH₄ concentrations (mean 41.2±17.6 nM), whereas during relaxation, CH₄ decreased by almost half (mean 26.7±14.7 nM). The diurnal band (~24 h) was weak and negatively related to the land–sea breeze cycle and solar heating. High-frequency observations capture CH₄ dynamics previously missed, and their integration into coastal and regional CH4 models could significantly improve the representation of episodic emissions and reduce bias in the global CH₄ budget, particularly under future climate-driven coastal upwelling and wind.

Nitrous oxide (N2O) is a potent greenhouse gas emitted by oceanic and terrestrial sources, and its biogeochemical cycle is influenced by both natural processes and anthropogenic activities. Current atmospheric N2O monitoring networks, including tall-tower and flask measurements, often overlook major marine hotspots, such as the eastern tropical Pacific Ocean. We present the first 15 months of high-frequency continuous measurements of N2O and carbon monoxide from the newly established Galapagos Emissions Monitoring Station in the region. Over this period, N2O mole fractions vary by approximately 5 ppb, influenced by seasonal trade winds, local anthropogenic emissions, and air masses transported from marine N2O emission hotspots. Notably, between February and April 2024, we observe high variability linked to the southward shift of the intertropical convergence zone and weakened trade winds over the Galapagos Islands. Increased variability during this period is driven by stagnant local winds, which accumulate emissions, and the mixing of air masses with different N2O contents from the Northern Hemisphere and the Southern Hemisphere. The remaining variability is primarily due to differences in air mass transport and heterogeneity in surface fluxes from the eastern tropical Pacific. Air masses passing over the Peruvian and Chilean upwelling systems – key sources of oceanic N2O efflux – show markedly higher N2O mole fractions at the station.

Background Empathy is considered a key factor in patient satisfaction, treatment adherence, clinical outcomes, and professional fulfillment. Consequently, training health sciences students in empathy has become a priority in universities worldwide. However, empathy-focused interventions have not achieved the desired success due to the complex nature of empathy. Both internal and external factors shape and influence empathy. Resilience has been proposed as one such factor, but the association between these two concepts is poorly understood. This study aims to evaluate the association between different dimensions of resilience and empathy in health science students. Methods A Cross-sectional analysis evaluated the levels of empathy and resilience in 993 Medical, Nursing, and Dentistry students at Universidad del Norte using the Jefferson Scale of Empathy-Health Professions Students (JSE-HPS) and the Ecological, Engineering, Adaptation (EEA) Resilience Scale. Data were examined through univariate and multivariate normality analyses and descriptive statistics. To evaluate the theoretical structure of empathy and resilience, a confirmatory factor analysis (CFA) was performed on the three-dimensional models of each construct. Reliability was established using the Omega coefficient. Finally, structural equation modeling (SEM) with a robust maximum likelihood estimator was applied to analyze the association between resilience and empathy. Results The normal distribution assumptions were largely met for empathy scale data, its respective dimensions, and individual items. The theoretical model was well-supported for both constructs, and the data suggested acceptable reliability. SEM analysis revealed that the association between empathy and resilience dimensions vary. Ecological resilience was positively correlated with all empathy dimensions while engineering and adaptative resilience were negatively correlated with all three dimensions of empathy. Conclusions There is no universal effect of resilience on empathy. Designers of empathy-focused educational interventions and researchers should consider the potential differential effects of different dimensions of resilience on different aspects of empathy. In particular, focusing on ecological resilience may create the conditions for achieved empathy to be expressed, while strategies to mitigate the potential negative impact of adaptive resilience on empathy should be further explored.

Background Teachers are considered potential empathetic mentors who can serve as positive role models in the development of empathy skills among students in health sciences disciplines, positively influencing their relationships with healthy or ill individuals. Objective: To estimate and classify the levels of empathy among health sciences professors in Latin America and compare their distribution by gender. Methods: This was a descriptive- analytical cross-sectional study design, involving 1,128 health sciences professors from six Latin American countries. The Jefferson Scale of Empathy – Health Professions version (JSE-HP) was administered. Descriptive statistics were applied, along with confirmatory factor analysis (using the WLSMV estimator) and analysis of variance by gender. Empathy levels were calculated based on established cut-off points. Results More that half of the professors showed empathy levels in the medium to very low range. Measurement invariance by gender was supported. Statistically significant but small differences were observed, with women scoring slightly higher in Perspective Taking dimension and overall empathy. Conclusion Health sciences faculty in Latin America showed predominantly moderate empathy levels with small gender differences. These findings emphasize the need to strengthen empathy support in academic settings.

Background The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort. Methods All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology [SER], cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations. Results In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%). In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02–1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00–1.07), the presence of Raynaud’s phenomenon (OR 1.41, 95% CI 1.09–1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63–2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12–1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11–2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90–4.15), vasculitis (OR 1.81, 95% CI 1.25–2.62), hematological manifestations (OR 1.31, 95% CI 1.00–1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14–3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00–1.75; P = 0.054). The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality. Conclusion Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.

To investigate the prevalence of suicidal thoughts and behaviours (STB; i.e. suicidal ideation, plans or attempts) in the Spanish adult general population during the first wave of the Spain coronavirus disease 2019 (COVID-19) pandemic (March-July, 2020), and to investigate the individual- and population-level impact of relevant distal and proximal STB risk factor domains. Cross-sectional study design using data from the baseline assessment of an observational cohort study (MIND/COVID project). A nationally representative sample of 3500 non-institutionalised Spanish adults (51.5% female; mean age = 49.6 [s.d. = 17.0]) was taken using dual-frame random digit dialing, stratified for age, sex and geographical area. Professional interviewers carried out computer-assisted telephone interviews (1-30 June 2020). Thirty-day STB was assessed using modified items from the Columbia Suicide Severity Rating Scale. Distal (i.e. pre-pandemic) risk factors included sociodemographic variables, number of physical health conditions and pre-pandemic lifetime mental disorders; proximal (i.e. pandemic) risk factors included current mental disorders and a range of adverse events-experiences related to the pandemic. Logistic regression was used to investigate individual-level associations (odds ratios [OR]) and population-level associations (population attributable risk proportions [PARP]) between risk factors and 30-day STB. All data were weighted using post-stratification survey weights. Estimated prevalence of 30-day STB was 4.5% (1.8% active suicidal ideation; n = 5 [0.1%] suicide attempts). STB was 9.7% among the 34.3% of respondents with pre-pandemic lifetime mental disorders, and 1.8% among the 65.7% without any pre-pandemic lifetime mental disorder. Factors significantly associated with STB were pre-pandemic lifetime mental disorders (total PARP = 49.1%) and current mental disorders (total PARP = 58.4%), i.e. major depressive disorder (OR = 6.0; PARP = 39.2%), generalised anxiety disorder (OR = 5.6; PARP = 36.3%), post-traumatic stress disorder (OR = 4.6; PARP = 26.6%), panic attacks (OR = 6.7; PARP = 36.6%) and alcohol/substance use disorder (OR = 3.3; PARP = 5.9%). Pandemic-related adverse events-experiences associated with STB were lack of social support, interpersonal stress, stress about personal health and about the health of loved ones (PARPs 32.7-42.6%%), and having loved ones infected with COVID-19 (OR = 1.7; PARP = 18.8%). Up to 74.1% of STB is potentially attributable to the joint effects of mental disorders and adverse events-experiences related to the pandemic. STB at the end of the first wave of the Spain COVID-19 pandemic was high, and large proportions of STB are potentially attributable to mental disorders and adverse events-experiences related to the pandemic, including health-related stress, lack of social support and interpersonal stress. There is an urgent need to allocate resources to increase access to adequate mental healthcare, even in times of healthcare system overload. NCT04556565.

The COVID-19 outbreak, which was followed by home confinement, is expected to have had profound negative impact on the mental health of people. Associated factors, such as losing jobs and income, can be expected to lead to an increased risk of suffering from psychopathological problems. Therefore, this study was aimed at researching the associations of job and income loss with mental health, as well as the possible mediating role of perceived financial stress during the COVID-19 outbreak. The sample included 2381 Spanish workers who were interviewed right after the first COVID-19 lockdown. Measures were taken for generalized anxiety disorder, panic attacks, depression, post-traumatic stress disorder, substance abuse, suicidal thoughts and behaviors, working conditions, sociodemographic variables, and perceived financial stress. Logistic regression models were calculated with psychological variables as outcomes, and with job loss and income loss as predictors. Mediation analyses were performed by adding the financial threat as a mediator. Nineteen point six percent and 33.9% of participants reported having lost their jobs and incomes due to the pandemic, respectively. Only income loss was related to a higher risk of suffering from depression and panic attacks. When adding financial stress as a mediator, the indirect effects of job and income loss on the mental health measures were found to be significant, therefore indicating mediation. These findings pinpoint the vulnerability of this population, and highlight the need for interventional and preventive programs targeting mental health in economic crisis scenarios, such as the current one. They also highlight the importance of implementing social and income policies during the COVID-19 pandemic to prevent mental health problems.

Background:Giant cell arteritis (GCA) is the most common vasculitis in North America and Western Europe. GCA is more likely to occur in women [1,2]. However, there are scarce data on the epidemiology, clinical presentation, comorbidities, treatment and outcomes between men and women.Objectives:Our aim was to assess the previous differential features between gender found in ARTESER registryMethods:ARTESER is a large Spanish multicenter epidemiological registry of GCA promoted by the Spanish Society of Rheumatology in which 26 national hospitals participated. Patients were included according to whether they met the 1990 ACR criteria, had a positive diagnostic test (biopsy or imaging test) or by the clinical judgement of the investigator. The recruitment period was between 2013 and 2019 and standardized data were included for all patients diagnosed with GCA in these centers. Differences between sexes were compared in a bivariate analysis.Results:A total of 1675 patients with GCA were included, 1178 women and 497 men. The annual incidence of GCA was higher in the female group (10.07; 95%CI: 8.7-11.5) than in the male group (4.83; 95%CI: 3.8-5.9) with a similar mean age at diagnosis and symptom onset between the two groups of 76.9 and 76.7 years, respectively.Among the comorbidities presented at diagnosis, male had a higher presentation of diabetes mellitus (27.2% vs 18.6%), tobacco use (46.0% vs 7.7%), alcohol consumption (18.9% vs 2.2%), cardiovascular disease (33.1% vs 17.4%) and neoplasms (19.3% vs 9.3%). In female only osteoporosis was more frequent (22.3% vs 4.5%).Clinical manifestations were divided into cranial, extracranial and general. Among the cranial manifestations, headache (79.9%), temporal (49.2%) and visual (36.1%) disturbances were the most frequent. Polymyalgia rheumatica was the predominant extracranial manifestation (41.8%) and asthenia the most general symptom reported (52.2%). Main data are shown in Table 1.We analyzed the distribution according to sex and observed a higher frequency of headache (p=0.028), polymyalgia rheumatica (p=0.003) and asthenia (p=0.035) in the female group. In contrast, we found a higher frequency of dysphasia in the male group (p=0.013) and visual symptoms, with no statistically significant differences in the latter.In terms of laboratory findings, elevated glomerular sedimentation rate (ESR) (p=0.039) and platelet count (p< 0.001) were higher in female.Treatment and outcome data are shown in Table 2. Regarding the use of glucocorticoids and related adverse effects no differences between the two groups were detected. The use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was more frequent in males (p=0.005), but no differences were found regarding tocilizumab administration.There were no differences in the number of relapses or disease remission. However, the proportion of deaths during follow-up was higher in women (13.8% vs. 6.6%, p< 0.001).Conclusion:GCA was more frequent in females, with more than twice as many cases as males. Some of the classic manifestations, such as headache, polymyalgia rheumatica and asthenia, were more common in women. In addition, women had higher ESR and platelet levels than men. The use of csDMARDs was higher in the male group but mortality was increased in females.REFERENCES:[1] Sharma A, Mohammad AJ, Turesson C. Incidence and prevalence of giant cell arteritis and polymyalgia rheumatica: A systematic literature review. Semin Arthritis Rheum. 2020 Oct;50(5):1040-8. DOI: 10.1016/j.semarthrit.2020.07.005.[2] Watts RA, Hatemi G, Burns JC et al. Global epidemiology of vasculitis. Nat Rev Rheumatol. 2022 Jan;18(1):22-34. DOI: 10.1038/s41584-021-00718-8.Table 1. Differences in clinical manifestations and laboratory abnormalities at diagnosis and during follow-up according to sex in ARTESER Registry.Table 2. Differences in treatment and outcomes during follow-up according to sex in ARTESER Registry.Acknowledgements:NIL.Disclosure of Interests:None declared.