Non-academic factors influencing the development of empathy in undergraduate nursing students: a cross-sectional study.

BACKGROUND: Empathy is described as a core competence of nursing. There is abundant research evidence supporting that empathy varies according to personal characteristics and targeted training. The aim of this study was to characterize non-academic factors (personal and environmental) influencing the development of empathy in undergraduate nursing studies who are not receiving a targeted training in empathetic abilities in their nursing schools. METHODS: A cross-sectional study was performed in the three nursing schools located in Cusco city, Peru (two private and one public). The Jefferson Scales of Empathy, Attitudes toward Physician-Nurse Collaboration, and Lifelong Learning, the Emotional Loneliness Scale for Adults, and the Scale of Life Satisfaction, were applied as the main measures. Also, information regarding gender, nursing school, and age, were collected. After psychometric properties were assessed, all measures were used in the development of a multivariate regression model to characterize factors of influence in empathy. RESULTS: In a sample composed by 700 undergraduate nursing students (72 males and 628 females), a multivariate linear regression model was created. This model explained the 53% of variance of empathy and fitted all conditions necessary for inference estimations. Teamwork abilities, loneliness, age, sex, subjective well-being, and nursing school, appeared as factors influencing the development of empathy in patients' care. CONCLUSIONS: Findings have indicated that, in absence of a targeted training, individual characteristics and characteristics associated with social and family environments play an important role of influence in the development of empathy in nursing students. These findings are also in consonance with others previously reported in different cultural settings including high-, middle- and low-income countries.

Single-incision versus four-port laparoscopic cholecystectomy in an ambulatory surgery setting: A prospective randomised double-blind controlled trial.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) can be done as a day-case procedure and may have advantages over conventional laparoscopic cholecystectomy (LC). We present the results of our study looking at post-operative pain and post-operative recovery time. METHODS: This was a single-institution randomised double-blind controlled trial. Seventy-three patients with symptomatic cholelithiasis were randomized to SILC (n = 37) or LC (n = 36). The primary endpoint was to compare post-operative pain. We also compared surgical time, procedural difficulty, adverse events, additional ports used and conversion rate, success of day surgery process, return to work, aesthetic satisfaction, quality of life and 4-year incisional hernia rate. RESULTS: In the SILC group, post-operative analgesic requirements were lower on day 7, there was an earlier return to work and cosmetic satisfaction was significantly higher. The SILC procedure presented a higher technical difficulty. Operative time, surgical complications, post-operative pain, success of the day-case process, return to normal activity, quality of life scores and incisional hernia rates were similar for both the procedures. CONCLUSIONS: SILC has advantages over LC in terms of late post-operative analgesic requirements and aesthetic results; however, it is technically harder to perform. There was no benefit in terms of day surgery outcomes.

Translational science in albuminuria: a new view of de novo albuminuria under chronic RAS suppression.

The development of de novo albuminuria during chronic renin-angiotensin system (RAS) suppression is a clinical entity that remains poorly recognized in the biomedical literature. It represents a clear increment in global cardiovascular (CV) and renal risk that cannot be counteracted by RAS suppression. Although not specifically considered, it is clear that this entity is present in most published and ongoing trials dealing with the different forms of CV and renal disease. In this review, we focus on the mechanisms promoting albuminuria, and the predictors and new markers of de novo albuminuria, as well as the potential treatment options to counteract the excretion of albumin. The increase in risk that accompanies de novo albuminuria supports the search for early markers and predictors that will allow practising physicians to assess and prevent the development of de novo albuminuria in their patients.

Recent advances and clinical insights into the use of proteomics in the study of atherosclerosis.

INTRODUCTION: The application of new proteomics methods may help to identify new diagnostic/predictive molecular markers in an attempt to improve the clinical management of atherosclerosis. Areas covered: Technological advances in proteomics have enhanced its sensitivity and multiplexing capacity, as well as the possibility of studying protein interactions and tissue structure. These advances will help us better understand the molecular mechanisms at play in atherosclerosis as a biological system. Moreover, this should help identify new predictive/diagnostic biomarkers and therapeutic targets that may facilitate effective risk stratification and early diagnosis, with the ensuing rapid implementation of treatment. This review provides a comprehensive overview of the novel methods in proteomics, including state-of-the-art techniques, novel biological samples and applications for the study of atherosclerosis. Expert commentary: Collaboration between clinicians and researchers is crucial to further validate and introduce new molecular markers to manage atherosclerosis that are identified using the most up to date proteomic approaches.

[Empathy, inter-professional collaboration, and lifelong medical learning in Spanish and Latin-American physicians-in-training who start their postgraduate training in hospitals in Spain. Preliminary outcomes]. / Empatía, habilidades de colaboración interprofesional y aprendizaje médico permanente en residentes españoles y latinoamericanos que inician los programas de formación médica especializada en España. Resultados preliminares.

OBJECTIVE: To identify similarities and differences in empathy, abilities toward inter-professional collaboration, and lifelong medical learning, between Spanish and Latin-American physicians-in-training who start their posgraduate training in teaching hospitals in Spain. DESIGN: Observational study using self-administered questionnaires. SETTINGS: Five teaching hospitals in the province of Barcelona, Spain. PARTICIPANTS: Spanish and Latin-American physicians-in-training who started their first year of post-graduate medical training. MAIN MEASUREMENTS: Empathy was measured using the Jefferson scale of empathy. Abilities for inter-professional collaboration were measured using the Jefferson scale attitudes towards nurse-physician collaboration. Learning was measured using the Jefferson scale of medical lifelong learning scale. RESULTS: From a sample of 156 physicians-in-training, 110 from Spain and 40 from Latin America, the Spanish group showed the highest empathy (p<.05). On the other hand, Latin-American physicians had the highest scores in lifelong learning abilities (p<.001). A positive relationship was found between empathy and inter-professional collaboration for the whole sample (r=+0.34; p<.05). CONCLUSIONS: These results confirm previous preliminary data and underline the positive influence of empathy in the development of inter-professional collaboration abilities. In Latin-American physicians who start posgraduate training programs, lifelong learning abilities have a positive influence on the development of other professional competencies.

Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression.

BACKGROUND: Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. METHODS: 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. RESULTS: CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CONCLUSIONS: CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome.

[Medical empathy of physicians-in-training who are enrolled in professional training programs. A comparative intercultural study in Spain]. / Empatía médica en médicos que realizan el programa de formación médica especializada. Estudio comparativo intercultural en España.

OBJECTIVE: To characterise some of the environmental factors that are sensitive to cultural influence, and are involved in the development of medical empathy in Spanish and Latin American physicians-in-training. DESIGN: Cross-sectional study using questionnaires. SETTING: Primary care and specialized medicine centres of the Healthcare System of La Rioja, Logroño, Spain. PARTICIPANTS: Physicians-in-training MAIN MEASUREMENTS: : Empathy was measured using the Jefferson Scale of Physician Empathy, version for healthcare professionals (JSE-HP). Socio-demographic, academic, and professional background information was collected. RESULTS: A total of 104 residents (67 from Spain and 32 from Latin America) answered and returned the questionnairess. The JSE-HP showed adequate psychometric properties. The empathy mean score of Spanish group was higher than that of the Latin American group (P=.01). Differences in the development of empathy were associated with: the development of professional models (P<.001), the positive encounter with other professionals (P=.001), and with a continuing medical education (P=.008). CONCLUSIONS: Some factors involved in the development of empathy that are sensitive to cultural influence have been characterised. The development of future research areas is suggested.

Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile.

Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period.

Uptake and factors that influence the use of 'sit less, move more' occupational intervention strategies in Spanish office employees.

BACKGROUND: Little is known about the types of 'sit less, move more' strategies that appeal to office employees, or what factors influence their use. This study assessed the uptake of strategies in Spanish university office employees engaged in an intervention, and those factors that enabled or limited strategy uptake. METHODS: The study used a mixed method design. Semi-structured interviews were conducted with academics and administrators (n = 12; 44 ± 12 mean SD age; 6 women) at three points across the five-month intervention, and data used to identify factors that influenced the uptake of strategies. Employees who finished the intervention then completed a survey rating (n = 88; 42 ± 8 mean SD age; 51 women) the extent to which strategies were used [never (1) to usually (4)]; additional survey items (generated from interviewee data) rated the impact of factors that enabled or limited strategy uptake [no influence (1) to very strong influence (4)]. Survey score distributions and averages were calculated and findings triangulated with interview data. RESULTS: Relative to baseline, 67% of the sample increased step counts post intervention (n = 59); 60% decreased occupational sitting (n = 53). 'Active work tasks' and 'increases in walking intensity' were the strategies most frequently used by employees (89% and 94% sometimes or usually utilised these strategies); 'walk-talk meetings' and 'lunchtime walking groups' were the least used (80% and 96% hardly ever or never utilised these strategies). 'Sitting time and step count logging' was the most important enabler of behaviour change (mean survey score of 3.1 ± 0.8); interviewees highlighted the motivational value of being able to view logged data through visual graphics in a dedicated website, and gain feedback on progress against set goals. 'Screen based work' (mean survey score of 3.2 ± 0.8) was the most significant barrier limiting the uptake of strategies. Inherent time pressures and cultural norms that dictated sedentary work practices limited the adoption of 'walk-talk meetings' and 'lunch time walking groups'. CONCLUSIONS: The findings provide practical insights into which strategies and influences practitioners need to target to maximise the impact of 'sit less, move more' occupational intervention strategies.

Medical Professionalism and Its Association with Dropout Intention in Peruvian Medical Students during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic introduced unprecedented challenges to medical education systems and medical students worldwide, making it necessary to adapt teaching to a remote methodology during the academic year 2020-2021. The aim of this study was to characterize the association between medical professionalism and dropout intention during the pandemic in Peruvian medical schools. METHODS: A cross-sectional online-survey-based study was performed in four Peruvian medical schools (two public) during the academic year 2020-2021. Medical students, attending classes from home, answered three scales measuring clinical empathy, teamwork, and lifelong learning abilities (three elements of medical professionalism) and four scales measuring loneliness, anxiety, depression, and subjective wellbeing. In addition, 15 demographic, epidemiological, and academic variables (including dropout intention) were collected. Variables were assessed using multiple logistic regression analysis. RESULTS: The study sample was composed of 1107 students (390 male). Eight variables were included in an explanatory model (Nagelkerke-R2 = 0.35). Anxiety, depression, intention to work in the private sector, and teamwork abilities showed positive associations with dropout intention while learning abilities, subjective wellbeing, studying in a public medical school, and acquiring a better perception of medicine during the pandemic showed a negative association with dropout intention. No association was observed for empathy. CONCLUSIONS: Each element measured showed a different role, providing new clues on the influence that medical professionalism had on dropout intention during the pandemic. This information can be useful for medical educators to have a better understanding of the influence that professionalism plays in dropout intention.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Impact of Prolonged Ischemia on the Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1).

Antibodies targeting programmed death receptor 1 or programmed death ligand 1 (PD-L1) have become a standard of care to treat different cancers; for some of these tumors, there is a correlation between tissue expression of PD-L1 and response rates in patients. Although most of the analytical challenges in the evaluation of PD-L1 expression have been standardized, preanalytical issues have been less explored. The objective of this study was to evaluate the impact of time of ischemia on the performance of 2 commonly used antibodies against PD-L1. Sixteen tonsillectomy samples were kept in ischemia for <30 minutes from sample obtention (control) and 1, 3, 6, 12, and 24 hours at room temperature before formalin fixation and paraffin embedding. Selected areas were inserted into TMA paraffin recipient blocks stained with SP142 and SP263 antibodies and evaluated by 2 blind observers. The proportion of suboptimally stained samples was significantly higher for samples with cold ischemia times 6 hours or over ( P <0.0001). False-negative results were 25% in samples exposed to 6 hours of ischemia and raised to 34% for samples remaining in ischemia for 12 or 24 hours. When all observations were pooled, SP142 provided suboptimal results in 24% of observations and SP263 in 12.5%; this is a statistically significant difference ( P =0.042). In conclusion, the quality of staining for PD-L1 in tonsil samples varies with the time of cold ischemia. The SP142 antibody presented a significantly lower tolerance to prolonged cold ischemia than SP263. These results reveal the relevance of controlled preanalytical processing of samples.

Prevalence of interpersonal violence against children in sport in six European countries.

BACKGROUND: Investigating prevalence of child abuse in sport is a relatively new field of research, born from the need for credible data on this phenomenon. OBJECTIVE: To establish prevalence rates of interpersonal violence against children in sport in six European countries. PARTICIPANTS AND SETTING: The sample (N = 10,302) consists of individuals aged 18-30 who had participated in organized sport prior to age 18 (49.3 % male, 50 % female). METHODS: A self-report questionnaire was developed (the Interpersonal Violence Against Children in Sport Questionnaire or IVACS-Q) to measure prevalence of five categories of interpersonal violence (neglect, psychological violence, physical violence, non-contact sexual violence, and contact sexual violence) against children who participate in sport. Validation testing (published separately) showed reasonable levels of convergent and divergent validity. Prevalence rates are calculated by national context, whether inside or outside sport, and by sex (male/female). RESULTS: Prevalence of IVACS inside sport differed by category: psychological violence (65 %, n = 6679), physical violence (44 %, n = 4514), neglect (37 %, n = 3796), non-contact sexual violence (35 %, n = 3565), and contact sexual violence (20 %, n = 2060). Relatively small geographical differences were found. Across all categories, males (79 %, n = 4018) reported significantly more experiences inside sport than females (71 %, n = 3653) (χ2(1) = 92.507, p < .000). Strong correlations were found between experiencing violence inside and outside sport. CONCLUSIONS: Interpersonal violence against children in sport is widespread. The sector's approach to prevention must recognize the risks to female and male children (and all children) and the additional vulnerabilities of abused children. Further comparative and longitudinal research within sport is required.

A cosmic stream of atomic carbon gas connected to a massive radio galaxy at redshift 3.8.

The growth of galaxies in the early Universe is driven by accretion of circum- and intergalactic gas. Simulations have predicted that steady streams of cold gas penetrate the dark matter halos of galaxies and provide the raw material necessary to sustain star formation. We report a filamentary stream of gas that extends for 100 kiloparsecs and connects to the massive radio galaxy 4C 41.17. We detected the stream using submillimeter observations of the 3P1 to 3P0 emission from the [C i] line of atomic carbon, a tracer of neutral atomic or molecular hydrogen gas. The galaxy contains a central gas reservoir that is fueling a vigorous starburst. Our results show that the raw material for star formation can be present in cosmic streams outside galaxies.

Role of Empathy and Lifelong Learning Abilities in Physicians and Nurses Who Work in Direct Contact with Patients in Adverse Working Conditions.

Empathy and lifelong learning are two professional competencies that depend on the four principles of professionalism: humanism, altruism, excellence, and accountability. In occupational health, there is evidence that empathy prevents work distress. However, in the case of lifelong learning, the evidence is still scarce. In addition, recent studies suggest that the development of lifelong learning varies in physicians and nurses and that it is sensitive to the influence of cultural stereotypes associated with professional roles. This study was performed with the purpose of determining the specific role that empathy and lifelong learning play in the reduction in occupational stress. This study included a sample composed by 40 physicians and 40 nurses with high dedication to clinical work in ambulatory consultations from a public healthcare institution in Paraguay. Somatization, exhaustion, and work alienation, described as indicators of occupational stress, were used as dependent variables, whereas empathy, lifelong learning, gender, discipline, professional experience, civil status, and family burden were used as potential predictors. Three multiple regression models explained 32% of the variability of somatization based on a linear relationship with empathy, lifelong learning, and civil status; 73% of the variability of exhaustion based on a linear relationship with empathy, somatization, work alienation, and discipline; and 62% of the variability of work alienation based on a linear relationship with lifelong learning, exhaustion, and discipline. These findings indicate that empathy and lifelong learning play important roles in the prevention of work distress in physicians and nurses. However, this role varies by discipline.

Burnout in International Medical Students: Characterization of Professionalism and Loneliness as Predictive Factors of Burnout.

BACKGROUND: Burnout is a common mental problem in medical students. For those who are following medical studies abroad there is a higher risk of suffering this syndrome, due to the combination of academic stress and the stress derived from their new living situation. This study was performed with the purpose of testing the following hypothesis: in medical students enrolled in medical programs abroad, abilities associated with professionalism and family support play a protective role in the prevention of suffering burnout. METHODS: A cross-sectional study was performed in the Faculty of Medicine of the University of Zagreb, where a fully English medical program is offered. The general version of the Maslach Burnout Inventory (MBI-GS) was used as a dependent variable, while Jefferson Scales of empathy, teamwork, and physician lifelong learning and the Social and Emotional Loneliness Scale for Adults were used as predictive variables. In addition, information related to sex, country of birth, native language, age, academic achievement, and living situation were collected in a socio-demographic form. Linear regression models were applied to identify predictors of burnout. RESULTS: In a sample composed of 188 medical students (38 Croatians and 144 foreigners from 28 countries), 18% of the global score in the MBI-GS was explained by lifelong learning and family loneliness. A separate analysis for each domain of the MBI-GS allowed the creation of three models: the first model explained 19% of the variance of the "exhaustion" domain by "country of birth", "living with parents", "academic year", and "cynicism"; a second model explained 24% of the variance of the "cynicism" domain by "academic year", "empathy", "lifelong learning", and "exhaustion"; and finally, a third model explained 24% of the variance of the "professional efficacy" domain by "lifelong learning", "family loneliness", and "cynicism". All obtained models presented an effect size between medium and large, as well as matching the required conditions for statistical inference. CONCLUSIONS: These findings confirm the important role that family plays as a source of support for medical students. Empathy and lifelong learning, two specific elements of medical professionalism, appear as protective factors in the prevention of burnout in international students.

Characterization of Factors Predicting a Favorable Opinion of Research Applications Submitted for an Ethical Review Process.

Introduction: In Spain, biomedical research applications must receive a positive ethical opinion from Research Ethics Committees (RECs) before being executed. There is limited information on how to optimize the ethical review process to reduce delays. This study was performed to characterize variables predicting favorable opinions at the first ethical review performed by a REC. Material and Methods: The study assessed all research applications revised by a REC in 2019-2020. Data was extracted from REC's database of La Rioja, Spain. Variables collected covered three areas: (i) principal investigator's profile; (ii) study design; and (iii) ethical review process. A model based on multiple logistic regression analysis was created to identify variables explaining favorable opinions in first rounds of ethical review processes. Results: The sample included 125 applications (41 submitted in 2019, and 84 in 2020). At the first review, nine (7%) applications were rejected, 56 (45%) were approved, and the remaining 60 (48%) required at least two reviews prior to approval. When comparing both years, a 2-fold increase in the number of applications submitted, and a difference in the ratio of applications with a favorable vs. non-favorable opinion were observed. Furthermore, a model predicted 71% of probability of obtaining a favorable opinion in the first ethical review. Three variables appeared as being explanatory: if the principal investigator is either the group leader or the department's head (OR = 17.39; p < 0.001), and if the informed consent (OR = 11.79; p = 0.01), and methods and procedures (OR = 34.15; p < 0.001) are well done. Conclusions: These findings confirm an increase in the number of submissions and a difference in the ratio of applications approved by year. Findings observed also confirm deficiencies in "informed consent" and in "methods and procedures" are the two main causes of delay for favorable ethical opinions. Additionally, findings highlight the need that group leaders and heads of departments should be more involved in guiding and supervising their research teams, especially when research applications are led by less experienced researchers. Based on these findings, it is suggested that an adequate mentoring and targeted training in research could derive in more robust research applications and in smoother ethical review processes.

Differential Effects of Anti-TNFα and Anti-α4ß7 Drugs on Circulating Dendritic Cells Migratory Capacity in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4ß7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin ß7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.

Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters.

AIMS: The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH). METHODS AND RESULTS: Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway. CONCLUSION: We propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH.