Biofabrication Directions in Recapitulating the Immune System-on-a-Chip.

Ever since the implementation of microfluidics in the biomedical field, in vitro models have experienced unprecedented progress that has led to a new generation of highly complex miniaturized cell culture platforms, known as Organs-on-a-Chip (OoC). These devices aim to emulate biologically relevant environments, encompassing perfusion and other mechanical and/or biochemical stimuli, to recapitulate key physiological events. While OoCs excel in simulating diverse organ functions, the integration of the immune organs and immune cells, though recent and challenging, is pivotal for a more comprehensive representation of human physiology. This comprehensive review covers the state of the art in the intricate landscape of immune OoC models, shedding light on the pivotal role of biofabrication technologies in bridging the gap between conceptual design and physiological relevance. The multifaceted aspects of immune cell behavior, crosstalk, and immune responses that are aimed to be replicated within microfluidic environments, emphasizing the need for precise biomimicry are explored. Furthermore, the latest breakthroughs and challenges of biofabrication technologies in immune OoC platforms are described, guiding researchers toward a deeper understanding of immune physiology and the development of more accurate and human predictive models for a.o., immune-related disorders, immune development, immune programming, and immune regulation.

Supervised physical activity in patients with symptomatic peripheral arterial disease: protocol for a randomized clinical trial (ARTPERfit Study).

INTRODUCTION: Peripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC). METHODS AND ANALYSIS: This study will be performed in Mataró Hospital's vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention. ETHICS AND DISSEMINATION: The study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations. TRIAL REGISTRATION NUMBER: NCT04578990.

Evaluation of Dietary Habits, Type A Behavior Pattern and Its Relationship with Oral Health Status in Dental Undergraduate Students: A Cross-Sectional Study.

Oral health status among dental students has been widely studied, and while the repercussions of certain factors, such as personality type, adherence to healthy lifestyle habits and certain eating patterns, have been considered in the past, this study aims to study the combination of such factors and to carry out, in addition, clinical examinations that could provide deeper knowledge of real oral health status. A sample of 195 dental students was gathered and basic sociodemographic data (gender, age, nationality, hygiene habits, body mass index (BMI)) were collected, and type A personality scale (ERCTA), emotional eating (EE) and healthy lifestyle scale (EVS) values were registered. Descriptive analysis, Pearson correlations, a hierarchical linear regression model and moderation analysis were performed. Results showed that higher EE values were associated with a higher BMI, an increase in the decayed, missing, and filled teeth (DMFT) index, a higher number of carious and filled teeth, a higher ERCTA and a lower adherence to the EVS. Likewise, a higher DMFT was associated with a higher BMI, higher bleeding on probing index (BOP) values, higher ERCTA values and lower adherence to EVS. Dental floss disuse, BMI, EE and EVS predicted 25.3% of DMFT. In addition, a type A personality has a moderating effect only in those with medium and high EE levels.

Organs-on-chip technology: a tool to tackle genetic kidney diseases.

Chronic kidney disease (CKD) is a major healthcare burden that takes a toll on the quality of life of many patients. Emerging evidence indicates that a substantial proportion of these patients carry a genetic defect that contributes to their disease. Any effort to reduce the percentage of patients with a diagnosis of nephropathy heading towards kidney replacement therapies should therefore be encouraged. Besides early genetic screenings and registries, in vitro systems that mimic the complexity and pathophysiological aspects of the disease could advance the screening for targeted and personalized therapies. In this regard, the use of patient-derived cell lines, as well as the generation of disease-specific cell lines via gene editing and stem cell technologies, have significantly improved our understanding of the molecular mechanisms underlying inherited kidney diseases. Furthermore, organs-on-chip technology holds great potential as it can emulate tissue and organ functions that are not found in other, more simple, in vitro models. The personalized nature of the chips, together with physiologically relevant read-outs, provide new opportunities for patient-specific assessment, as well as personalized strategies for treatment. In this review, we summarize the major kidney-on-chip (KOC) configurations and present the most recent studies on the in vitro representation of genetic kidney diseases using KOC-driven strategies.

Biomimetic models of the glomerulus.

The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes.

Long-Term Morbidity and Mortality after First and Recurrent Cardiovascular Events in the ARTPER Cohort.

BACKGROUND: Cardiovascular events are a major cause of mortality and morbidity worldwide. The risk of recurrence after a first cardiovascular event has been documented in the international literature, although not as extensively in a Mediterranean population-based cohort with low cardiovascular risk. There is also ample, albeit contradictory, research on the recurrence of stroke and myocardial infarctions (MI) after a first event and the factors associated with such recurrence, including the role of pathological Ankle-Brachial Index (ABI). METHODS: The Peripheral Arterial ARTPER study is aimed at deepening our knowledge of patient evolution after a first cardiovascular event in a Mediterranean population with low cardiovascular risk treated at a primary care centre. We study overall recurrence, cardiac and cerebral recurrence. We studied participants in the ARTPER prospective observational cohort, excluding patients without cardiovascular events or with unconfirmed events and patients who presented arterial calcification at baseline or who died. In total, we analyzed 520 people with at least one cardiovascular event, focusing on the presence and type of recurrence, the risk factors associated with recurrence and the behavior of the ankle-brachial index (ABI) as a predictor of risk. RESULTS: Between 2006 and 2017, 46% of patients with a first cardiovascular event experienced a recurrence of some type; most recurrences fell within the same category as the first event. The risk of recurrence after an MI was greater than after a stroke. In our study, recurrence increased with age, the presence of peripheral arterial disease (PAD), diabetes and the use of antiplatelets. Diabetes mellitus was associated with all types of recurrence. Additionally, patients with an ABI < 0.9 presented more recurrences than those with an ABI ≥ 0.9. CONCLUSIONS: In short, following a cardiac event, recurrence usually takes the form of another cardiac event. However, after having a stroke, the chance of having another stroke or having a cardiac event is similar. Lastly, ABI < 0.9 may be considered a predictor of recurrence risk.

Low, borderline and normal ankle-brachial index as a predictor of incidents outcomes in the Mediterranean based-population ARTPER cohort after 9 years follow-up.

BACKGROUND: Guidelines recommended adopting the same cardiovascular risk modification strategies used for coronary disease in case of low Ankle-brachial index (ABI), but here exist few studies on long-term cardiovascular outcomes in patients with borderline ABI and even fewer on the general population. AIM: The aim of the present study was to analyze the relationship between long-term cardiovascular events and low, borderline and normal ABI after a 9-year follow up of a Mediterranean population with low cardiovascular risk. DESIGN AND SETTING: A population-based prospective cohort study was performed in the province of Barcelona, Spain. METHOD: A total of 3,786 subjects >49 years were recruited from 2006-2008. Baseline ABI was 1.08 ± 0.16. Subjects were followed from the time of enrollment to the end of follow-up in 2016 via phone calls every 6 months, systematic reviews of primary-care and hospital medical records and analysis of the SIDIAP (Information System for Primary Care Research) database to confirm the possible appearance of cardiovascular events. RESULTS: 3146 individuals participated in the study. 2,420 (77%) subjects had normal ABI, 524 (17%) had borderline ABI, and 202 (6.4%) had low ABI. In comparison with normal and borderline subjects, patients with lower ABI had more comorbidities, such as hypertension, hypercholesterolemia and diabetes. Cumulative MACE incidence at 9 years was 20% in patients with low ABI, 6% in borderline ABI and 5% in normal ABI. The annual MACE incidence after 9 years follow-up was significantly higher in people with low ABI (26.9/1000py) (p<0.001) than in borderline (6.6/1000py) and in normal ABI (5.6/1000py). Subjects with borderline ABI are at significantly higher risk for coronary disease (HR: 1.58; 95% CI: 1.02-2, 43; p = 0,040) compared to subjects with normal ABI, after adjustment. CONCLUSION: The results of the present study support that low ABI was independently associated with higher incidence of MACE, ICE, cardiovascular and no cardiovascular mortality; while borderline ABI had significantly moderate risk for coronary disease than normal ABI.

Antibacterial efficacy of several intracanal medicaments for endodontic therapy.

The antibacterial efficacy of intracanal medicaments for 2 and 7 days, in open apex root canals contaminated with Enterococcus faecalis biofilms was compared. One hundred and thirty-eight standardized uniradicular human roots were inoculated with E. faecalis. Colony forming units (CFU) were recorded before and after medication. Samples were divided in two (2/7 days), and subdivided (n=8/group): triple antibiotic paste (TAP); double antibiotic paste (DAP); dental base paste (DBP), consisting of calcium hydroxide, propylene glycol and calcium carbonate; DBP+0.2% chlorhexidine (CHX); DBP+0.2% cetrimide (CTR); DBP+0.2% CHX+0.2% CTR; 2.5% sodium hypochlorite (NaOCl); and distilled water. At both periods TAP, DAP, DBP+0.2% CHX, DBP+0.2% CTR and DBP+0.2% CHX+0.2% CTR exhibited no growth (NG) of E. faecalis. Distilled water and 2.5% NaOCl obtained the lowest CFU reduction. No growth with DBP was reached only at 7 days. CHX and/or CTR pastes were as effective as DAP and TAP. A 2-day period provided an effective disinfection.

Evolución y grado de control de los factores de riesgo cardiovascular tras 5 años de seguimiento y su relación con la incidencia de arteriopatía periférica: cohorte poblacional ARTPER / Evolution and degree of control of cardiovascular risk factors after 5 years of follow-up and their relationship with the incidence of peripheral arterial disease: ARTPER cohort

Fundamento y objetivo: Los factores de riesgo cardiovascular (FRCV) son bien conocidos, pero su grado de control no es óptimo. Este trabajo pretende valorar la evolución y el control de los FRCV clásicos tras 5 años de seguimiento de una cohorte poblacional y su relación con la incidencia de arteriopatía periférica (AP). Material y método: Estudio de cohortes prospectivo. Selección de pacientes 2006-2008; segunda visita entre 2011-2012. En ambas fases se realizó un índice tobillo-brazo en condiciones estandarizadas. Se registraron variables demográficas, antecedentes y FRCV, presión arterial, perfil lipídico, glucosa y hemoglobina glucosilada en pacientes diabéticos y cálculo del riesgo cardiovascular mediante REGICOR. Resultados: Fueron analizados 2.125 individuos. Se incrementó la prevalencia de hipertensión arterial (HTA) en un 15,4%, en un 8,2% la diabetes (DM) y en un 20,4% la hipercolesterolemia, manteniéndose estables la obesidad y el tabaquismo. REGICOR se mantuvo alrededor de 5,5%. Se incrementó el control de los FRCV durante el seguimiento, excepto para la DM y la obesidad. En el análisis multivariante la HTA no controlada presentó un riesgo de más del doble para AP incidente (odds ratio [OR] 2,3; intervalo de confianza al 95% [IC 95%] 1,3-4,1), y el tabaquismo, de 5 veces (OR 5,0; IC 95% 2,5-10,2). Conclusiones: Tabaquismo y HTA mal controlados incrementan el riesgo para AP en esta población. A pesar del aumento del tratamiento farmacológico persiste un control subóptimo de los FRCV (AU)

Background and objective: Although cardiovascular risk factors (CVRF) are well known, their degree of control is not optimal. The aim of this study is to assess the evolution and control of CVRFs after 5 years of monitoring a population-based cohort and their association with the incidence of peripheral arterial disease (PAD). Material and method: Prospective cohort study recruited between 2006-2008. Second phase between 2011-2012. An ankle brachial index was determined for all participants in both phases. Demographic variables, CVRF and previous cardiovascular events, blood pressure, total cholesterol and its fractions (HDL, LDL), triglycerides, glucose and glycosylated hemoglobin levels in diabetic patients and the cardiovascular risk score according to the REGICOR table were recorded. Results: A total of 2,125 individuals were analyzed. We observed an increase in the prevalence of hypertension (HT) (15.4%), diabetes (DM) (8.2%) and hypercholesterolemia (20.4%), with no changes in obesity and smoking. The cardiovascular risk determined on the basis of the REGICOR table remained at around 5.5%. We observed an increased control of CVRF throughout the follow-up period, except in the case of DM and obesity. In the multivariate analysis, uncontrolled HT 2-folded the risk of onset of PAD (odds ratio [OR] 2.3; 95% confidence interval [95% CI] 1.3-4.1), whereas smoking 5-folded this risk (OR 5.0; 95% CI 2.5-10.2). Conclusions: Smoking and uncontrolled HT increase the risk of onset of PAD in this population. Despite the increase in drug treatments, the control of CVRFs continues to be suboptimal (AU)

Evolution and degree of control of cardiovascular risk factors after 5 years of follow-up and their relationship with the incidence of peripheral arterial disease: ARTPER cohort. / Evolución y grado de control de los factores de riesgo cardiovascular tras 5 años de seguimiento y su relación con la incidencia de arteriopatía periférica: cohorte poblacional ARTPER.

BACKGROUND AND OBJECTIVE: Although cardiovascular risk factors (CVRF) are well known, their degree of control is not optimal. The aim of this study is to assess the evolution and control of CVRFs after 5 years of monitoring a population-based cohort and their association with the incidence of peripheral arterial disease (PAD). MATERIAL AND METHOD: Prospective cohort study recruited between 2006-2008. Second phase between 2011-2012. An ankle brachial index was determined for all participants in both phases. Demographic variables, CVRF and previous cardiovascular events, blood pressure, total cholesterol and its fractions (HDL, LDL), triglycerides, glucose and glycosylated hemoglobin levels in diabetic patients and the cardiovascular risk score according to the REGICOR table were recorded. RESULTS: A total of 2,125 individuals were analyzed. We observed an increase in the prevalence of hypertension (HT) (15.4%), diabetes (DM) (8.2%) and hypercholesterolemia (20.4%), with no changes in obesity and smoking. The cardiovascular risk determined on the basis of the REGICOR table remained at around 5.5%. We observed an increased control of CVRF throughout the follow-up period, except in the case of DM and obesity. In the multivariate analysis, uncontrolled HT 2-folded the risk of onset of PAD (odds ratio [OR] 2.3; 95% confidence interval [95% CI] 1.3-4.1), whereas smoking 5-folded this risk (OR 5.0; 95% CI 2.5-10.2). CONCLUSIONS: Smoking and uncontrolled HT increase the risk of onset of PAD in this population. Despite the increase in drug treatments, the control of CVRFs continues to be suboptimal.

Incidence of peripheral arterial disease in the ARTPER population cohort after 5 years of follow-up.

BACKGROUND: To know the epidemiology (prevalence, incidence, progression and morbidity and mortality associated) of peripheral artery disease in general population and the factors associated with this progression is essential to know the evolution of atherosclerosis and develop preventive strategies. The aim of the study was to determine the incidence of PAD after 5 years of follow-up population-based cohort ARTPER, and the evolution of Ankle brachial Index (ABI) in this period. METHODS: Peripheral artery disease incidence analysis after 5 years of follow-up of 3786 subjects > 50 years old. Peripheral artery disease incident when the second cross section Ankle brachial Index was <0.9 in any of the lower limbs, with normal baseline (0.9 to 1.4). RESULTS: Between 2012 and 2013 2762 individuals (77% participation) were re-examined . Finally analyzed 2256 subjects (after excluding pathological Ankle brachial Index) followed for 4.9 years (range 3.8 to 5.8 years), totalling 11,106 person-years. Peripheral artery disease 95 new cases were detected, representing an incidence of 4.3% at 5 years and 8.6 per 1000 person-years (95% CI 6.9 to 10.5) being higher in men (10.2, 95% CI 7.4 to 13.5) than in women (7.5, 95% CI 5.5 to 9.9). Linear correlation between the baseline Ankle brachial Index and the second cross section was low (r = 0.23). CONCLUSIONS: The incidence of peripheral artery disease in ARTPER cohort was 8.6 cases per 1000 person-years, being higher in men, especially <65 years. The correlation between two measures Ankle brachial Index after 5 years of follow-up was low. One might consider whether Ankle brachial Index repeated measures could improve the correlation.

Imagen corporal y autoestima en mujeres mastectomizadas / Body image and self-esteem in women subjected to radical mastectomy

Objetivo: Estudiar la imagen corporal que construyen las pacientes diagnosticadas de cáncer de mama tras someterse a intervención quirúrgica, mastectomía radical y cirugía conservadora, tanto en lo referente a aspectos corporales relacionados directamente con la lesión como a zonas corporales no relacionadas, e investigar cómo esa imagen afecta a la autoestima centrada en lo corporal. Método: Contamos con una muestra de 23 pacientes (12 mujeres mastectomizadas y 11 con cirugía conservadora) y 24 mujeres sanas que sirvieron como grupo control. El instrumento de evaluación utilizado es la Técnica de la Rejilla Corporal. Se analizaron las diferencias entre los grupos mediante ANOVA de un factor y las pruebas no paramétricas H de Kruskal Wallis y U de Mann-Whitney. Resultados y conclusiones: Los resultados del estudio han permitido identificar qué aspectos son los más dañados en la autoestima y autoimagen de las pacientes, estableciendo que no existen diferencias significativas en la imagen corporal global y la autoestima centrada en lo corporal entre mujeres mastectomizadas y mujeres sometidas a cirugía conservadora, aunque sí en la imagen que se tiene de las zonas corporales específicamente implicadas en la cirugía. Sí se han encontrado diferencias entre estos dos grupos y el grupo de mujeres sanas en imagen corporal global y autoestima. Los resultados obtenidos permitirán identificar los aspectos de la imagen corporal más afectados en las pacientes y por tanto orientar posibles intervenciones psicológicas futuras hacia la reconstrucción adaptativa y sana de los mismos

Aim: To study the body image built by patients with breast cancer after surgery, radical mastectomy and partial mastectomy, related to body parts directly involved in surgery and not directly related to it, and to investigate how this image affects bodily self-esteem. Method: Our sample comprised 23 patients (12 had been subjected to radical mastectomy and 11 to partial mastectomy) and 24 healthy women (they served as control group). Participants were assessed with the Body Grid technique. We analyzed the differences between groups using one way ANOVA and non-parametric tests (namely, H de Kruskal Wallis and U de Mann-Whitney). Results: Our findings allowed us to identify which were the most damaged aspects about self-esteem and body image in these patients, showing that there were no significant differences in body image and bodily self-esteem between patients subjected to radical and partial mastectomy. However, we found significant differences between body parts directly involved in surgery and those not directly related to it. Finally, we found significant differences between both groups of patients and the control group regarding body image and self-esteem.Conclusions: Our results show that the Body Grid Technique is helpful to identify the most affected aspects of body image in patients subjected to mastectomy and tailor psychological treatments aimed at improving body image in these patients

Sepsis fulminante por Capnocytophaga canimorsus: diagnóstico por espectrometría de masas con analizador de tiempo de vuelo y desorción/ionización láser / Fulminant sepsis due to Capnocytophaga canimorsus: Diagnosis by matrix-assisted laser desorption/ionization-time of flight mass spectrometry

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Diagnostic and management of spontaneous rectus sheath hematoma.

BACKGROUND: Spontaneous rectus sheath hematoma is an uncommon and often misdiagnosed cause of abdominal pain. The aim of this study is to describe our experience in their management. METHODS: Retrospective analysis of the characteristics and outcomes of the spontaneous rectus sheath hematomas diagnosed over the last 12years was conducted. RESULTS: 24 patients were included (66% women; mean age: 74years; range: 54-87). All cases presented predisposing factors mainly anticoagulant therapy in 21 (87.5%) patients, hypertension in 19 (79.1%) and abdominal surgery in 12 (50%) cases. Eighteen (75%) referred triggering factors like coughing being the most common one, present in 17 (70.8%) patients. The main clinical findings were abdominal pain in 21 (87.5%) cases and the existence of an abdominal mass in 20 (83.3%). The diagnosis was confirmed by abdominal ultrasonography and/or computerized tomography in 23 (95.8%) patients. Nineteen cases (79.1%) responded to conservative management while 5 (20.8%) required interventional treatment, which consisted in an arteriography with selective embolization of the epigastric arteries in all cases. Four (80%) of the patients needing interventional treatment were receiving low molecular weight heparin. Nine (37.5%) patients developed hypovolemic shock and 1 (4%) died. CONCLUSIONS: Spontaneous rectus sheath hematomas should be considered in the differential diagnosis of abdominal pain, particularly in elderly women under anticoagulant therapy with onset of symptoms after a bout of cough. Most cases respond to conservative management, although those related to low molecular weight heparin might require interventional treatment; arteriography with selective embolization of the epigastric arteries is the first therapeutic option.