Terapia con luz en el tratamiento de la hidradenitis supurativa.

Resumen Antecedentes: la terapia con luz es una alternativa en el tratamiento de las lesiones causadas por la hidradenitis supurativa, ya sea utilizando fotosensibilizador o no, aplicándola intralesional o tópica. Objetivos: evaluar la eficacia, efectividad y seguridad de las distintas modalidades de terapia con luz en el tratamiento de la hidradenitis supurativa, mediante una revisión sistemática. Material y métodos: se han considerado los trabajos realizados en pacientes con hidradenitis supurativa, mayoritariamente series de casos y revisiones sistemáticas. Se han identificado los estudios mediante una búsqueda electrónica en las siguientes bases de datos: MEDLINE, EMBASE, Universidad de York, Cochrane Database of Systematic Reviews, Cochrane Skin Group, Centre of Evidence based dermatology de la Universidad de Nottingham, TESEO. Adicionalmente, se han buscado los trabajos registrados en webs electrónicas: ClinicalTrials.gov, Registro Español de Ensayos Clínicos, Clinicaltrialsregister.eu. Resultados: se incluyeron 6 series de casos y 1 revisión sistemática; 1 estudio utilizaba láser nd:YAG, 1 estudio luz intensa pulsada, y 6 TFD, con un total de 133 pacientes tratados. Los resultados estadísticamente significativos de la terapia con luz, se observan en la medición del índice de calidad de vida dermatológica (DQLI), con una reducción de su puntuación comparando antes y después de cada tratamiento; observándose así: disminución de 21 puntos en 4 sesiones de TFD tópica con ALA (Andino R(1)); 89,3% de mejora en dicha puntuación con TFD intralesional con AM (Agut-Busquet E(2)) y disminución de 19.3 puntos después de la cirugía más TFD con ALA (Bu W(3)). En cuanto a la efectividad medida mediante la escala de Sartorius se objetiva: mejoría de las lesiones de hidradenitis del 77,3% con TFD tópica con AM (Fadel M.A(4)); respuesta completa entre el 37% y 76,3% de los pacientes tratados con TFD intralesional con ALA al 5% (Suárez MJ(5)) y de los pacientes tratados con TFD intralesional con ALA al 1% (Valladares LM(6)); reducción del 12% inmediatamente después de la terapia, 10% a los 3 y 6 meses y 3% a los 12, en el tratamiento con luz intensa pulsada (Highton L(7)); después de 3 meses de tratamiento con láser nd:YAG (Tierney E(8)) reducción del 65.3% sobre todas las regiones anatómicas, 73.4% inguinal, 62.0% axilar y 53.1% inframamaria. En general, el riesgo de sesgos fue elevado y la calidad de las publicaciones baja. Conclusión: se necesitan ensayos clínicos controlados y aleatorizados que confirmen la eficacia de cada uno de estos tratamientos, ya se TFD, láser o luz intensa pulsada y estandaricen el protocolo más adecuado para poder garantizar un adecuado nivel de evidencia en términos de eficacia y seguridad

DISCAPACIDAD Y RELACIONES LABORALES EN ESPAÑA

El objetivo de este trabajo es conocer la situación en la que se encuentran las personas con discapacidad en el mercadolaboral, tanto actualmente como la evolución que ha habido a lo largo del tiempo. Por supuesto, queremos tambiénconcienciarnos y poder ayudar o contribuir de alguna manera a la mejora de empleo de estas personas, bien sea demanera indirecta o en un futuro, en nuestra trayectoria profesional, en un departamento de relaciones laborales orecursos humanos, poder implantar las medidas que sean necesarias para esta mejora. <br /

Service Learning in the Nursing Bachelor Thesis: A Mixed-Methods Study

The Final Degree Project (FDP) is a module that, although intended for the completion of a bachelor thesis (BT), consists of theoretical and clinical teaching. Therefore, introducing service learning (SL) can support student adjustments to the real-world professional role. This study plans to evaluate a teaching innovation project that combines BT and SL through Kirkpatrick’s four-level model (reaction, learning, behaviour and results). It takes the form of a convergent parallel mixedmethods design study. The participants were 15 final-year students obtaining a Bachelor of Nursing degree, 4 BT supervising mentors and 4 nurses. At the request of a hospital institution, in their BT, students completed a review of evidence-based nursing protocols. For data collection, the researchers used: an SL questionnaire, student narratives, mentor field diaries and nurse interviews. According to student opinion, the results showed high satisfaction rates (4.44 out of 5), the most developed skills were IndependentWork and Information Management, but they signal the need to reinforce the research methodology skills. Finally, positive feedback from all participants is that using SL promotes both the opinion that the BT is useful and also promotes a collaboration between academic and clinical settings

Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential : a molecular and clinicopathological study

Background: The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. Methods: We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Results: Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Conclusions: Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions

Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction

Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. Histopathological characterization is commonly used to detect the location, size and shape of MI sites. However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. In infarcted myocardium, the spectrum of these main absorptions was deeply altered. FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI

Nuevas estrategias terapéuticas basadas en el papel pro-aterogénico del LRP1

Trabajo presentado en el XXXIV Congreso de la Sociedad Española de Arteriosclerosis, celebrado en Madrid (España), del 8 al 10 de junio de 2022Background: The LRP1 (CR9) domain and, in particular, the sequence Gly1127-Cys1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis. Methods: Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hM¿) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells. Results: P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hM¿ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hM¿ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUVmean) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group. Conclusions: P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature

Immunization with the Gly 1127 -Cys 1140 amino acid sequence of the LRP1 receptor reduces atherosclerosis in rabbits. Molecular, immunohistochemical and nuclear imaging studies

Altres ajuts: The main support to develop this project was received from Fundació MARATÓ TV3 Project 201521-10 (to VLl-C) and co-financed with ERDFs. Support was received from Fundació Marató TV3 (Project 201521-10) for post-doctoral funding to OB. DdG-C, VL-C and JCE-G are members of the Group of Vascular Biology of the Spanish Society of Atherosclerosis (SEA).Background : The LRP1 (CR9) domain and, in particular, the sequence Gly 1127 -Cys 1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis. Methods : Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hMΦ) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells. Results : P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hMΦ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hMΦ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUV) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group. Conclusions : P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature

Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) plays a key role in fatty acid metabolism and glucose homeostasis. In the context of dyslipemia, LRP1 is upregulated in the heart. Our aim was to evaluate the impact of cardiomyocyte LRP1 deficiency on high fat diet (HFD)-induced cardiac and metabolic alterations, and to explore the potential mechanisms involved. Methods: We used TnT-iCre transgenic mice with thoroughly tested suitability to delete genes exclusively in cardiomyocytes to generate an experimental mouse model with conditional Lrp1 deficiency in cardiomyocytes (TNT-iCre+-LRP1flox/flox). Findings: Mice with Lrp1-deficient cardiomyocytes (cm-Lrp1-/-) have a normal cardiac function combined with a favorable metabolic phenotype against HFD-induced glucose intolerance and obesity. Glucose intolerance protection was linked to higher hepatic fatty acid oxidation (FAO), lower liver steatosis and increased whole-body energy expenditure. Proteomic studies of the heart revealed decreased levels of cardiac pro-atrial natriuretic peptide (pro-ANP), which was parallel to higher ANP circulating levels. cm-Lrp1-/- mice showed ANP signaling activation that was linked to increased fatty acid (FA) uptake and increased AMPK/ ACC phosphorylation in the liver. Natriuretic peptide receptor A (NPR-A) antagonist completely abolished ANP signaling and metabolic protection in cm-Lrp1-/- mice. Conclusions: These results indicate that an ANP-dependent axis controlled by cardiac LRP1 levels modulates AMPK activity in the liver, energy homeostasis and whole-body metabolism

Lipid Loading of Human Vascular Smooth Muscle Cells Induces Changes in Tropoelastin Protein Levels and Physical Structure

Aggregated low-density lipoprotein (agLDL), one of the main LDL modifications in the arterial intima, contributes to massive intracellular cholesteryl ester (CE) accumulation in human vascular smooth muscle cells (VSMC), which are major producers of elastin in the vascular wall. Our aim was to analyze the levels, physical structure, and molecular mobility of tropoelastin produced by agLDL-loaded human VSMC (agLDL-VSMC) versus that produced by control VSMC. Western blot analysis demonstrated that agLDL reduced VSMC-tropoelastin protein levels by increasing its degradation rate. Moreover, our results demonstrated increased levels of precursor and mature forms of cathepsin S in agLDL-VSMC. Fourier transform infrared analysis revealed modifications in the secondary structures of tropoelastin produced by lipid-loaded VSMCs. Thermal and dielectric analyses showed that agLDL-VSMC tropoelastin has decreased glass transition temperatures and distinct chain dynamics that, in addition to a loss of thermal stability, lead to strong changes in its mechanical properties. In conclusion, agLDL lipid loading of human vascular cells leads to an increase in cathepsin S production concomitantly with a decrease in cellular tropoelastin protein levels and dramatic changes in secreted tropoelastin physical structure. Therefore, VSMC-lipid loading likely determines alterations in the mechanical properties of the vascular wall and plays a crucial role in elastin loss during atherosclerosis