Inhibition of LTßR signalling activates WNT-induced regeneration in lung.

Lymphotoxin ß-receptor (LTßR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTßR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTßR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTßR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTßR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTßR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTßR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFß signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/ß-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTßR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.

TNF induced inhibition of Cirbp expression depends on RelB NF-κB signalling pathway.

The circadian clock is required for the rhythmic expression of a plethora of genes that orchestrate metabolism, sleep-wake behaviour and the immune response to pathogens. The cold-inducible RNA binding protein (CIRBP) is required for high amplitude expression of clock genes. Moreover, CIRBP protects the expression of clock genes from the inhibitory effects of tumour necrosis factor (TNF). However, since TNF represses Cirbp expression, the protective effect of CIRBP is lost. Here, we show that the TNF effect on Cirbp requires the non-canonical NF-κB signalling pathway. While a knock down of RelA does not alter the effects of TNF on Cirbp, a knock down of RelB represses this effect. In addition, the data indicate that p50 and p52 are required in the TNF induced inhibition of Cirbp. These results show that Cirbp expression in TNF treated cells is regulated via the non-canonical NF-κB pathway.

Turnos de 7 horas versus 12 horas en enfermería intensiva: vivir a contratiempo / Seven hour shifts versus 12 hours in intensive nursing care: Going against the tide

Los turnos de trabajo tienen repercusión sobre el bienestar de los profesionales sanitarios influyendo en su calidad de vida. El objetivo principal de este estudio es describir las consecuencias que tiene el turno de trabajo diurno de 12 h respecto al de 7 h en los profesionales de enfermería que trabajan en Unidades de Cuidados Intensivos. Se trata así de un estudio descriptivo transversal en 2 hospitales de tercer nivel de Barcelona: Hospital Clínico y Hospital Vall d'Hebron (turnos de 7 h y 12 h respectivamente). La recogida de datos se ha realizado mediante cuestionario ad hoc de 29 preguntas cerradas, anónimo y autoadministrado, basado en 2 escalas: Standard Shiftwork Index y Shiftwork locus of control. Dichos datos fueron procesados a través del programa SPSS V .18.0. De las 85 encuestas realizadas 52 fueron válidas: 22 en el Hospital Clínico de Barcelona y 30 en el Hospital Vall d'Hebron. Cabe destacar que los profesionales encuestados que trabajan en turno de 12 h expresan niveles superiores de conciliación laboral y personal, concretamente en tiempo de ocio a disfrutar (× 2: 10,635; p = 0,031) y tiempo de dedicación familia-amigos, así como niveles más bajos de percepción de fatiga. No se han encontrado diferencias entre el tipo de turno y facilidad de desarrollo del trabajo profesional, a pesar de que el turno de 12 h presenta niveles más altos

Working in shifts has an impact on the well being of health care professionals, affecting their quality of life. The main objective of this study is to describe the consequences of 12 hours work shifts versus 7 hours for nursing professionals working in intensive care units. A cost-sectional, descriptive study was conducted in two tertiary hospitals of Barcelona, these being the Hospital Clínico and Hospital Vall d'Hebron (of 7 hour and 12hour shifts, respectively). The data was collected through a questionnaire having 29 closed questions that was anonymous and self-administered. The questionnaire was based on two scales: Standard Shiftwork Index and Shiftwork. locus of control. Data was processed through SPSS V.18.0. The target population consisted of 85 people, for whom 52 surveys were valid: 22 in Hospital Clínico of Barcelona and 30 in Hospital Vall d'Hebron. Professionals working a 12-hour shift express higher levels of work and family conciliation, especially in the case of leisure time to enjoy (×2: 10.635 p = 0.031) and family-friends time dedication as well as lower levels of perceived fatigue. No differences were found between type of shift and ease of development of professional work, even though the 12-hour shift has higher level

[Seven hour shifts versus 12 hours in intensive nursing care: going against the tide]. / Turnos de 7 horas versus 12 horas en enfermería intensiva: vivir a contratiempo.

Working in shifts has an impact on the well being of health care professionals, affecting their quality of life. The main objective of this study is to describe the consequences of 12hours work shifts versus 7hours for nursing professionals working in intensive care units. A cost-sectional, descriptive study was conducted in two tertiary hospitals of Barcelona, these being the Hospital Clínico and Hospital Vall d'Hebron (of 7hour and 12hour shifts, respectively). The data was collected through a questionnaire having 29 closed questions that was anonymous and self-administered. The questionnaire was based on two scales: Standard Shiftwork Index and Shiftwork. locus of control. Data was processed through SPSS V.18.0. The target population consisted of 85 people, for whom 52 surveys were valid: 22 in Hospital Clínico of Barcelona and 30 in Hospital Vall d'Hebron. Professionals working a 12-hour shift express higher levels of work and family conciliation, especially in the case of leisure time to enjoy (×2: 10.635 p=0.031) and family-friends time dedication as well as lower levels of perceived fatigue. No differences were found between type of shift and ease of development of professional work, even though the 12-hour shift has higher levels.

Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors.

PURPOSE: Kahalalide F (KF) is a dehydroaminobutyric acid-containing peptide from marine origin with activity against several human malignant cell lines. This dose-escalating phase I clinical trial evaluated the maximum tolerated dose (MTD), and the recommended dose for further phase II studies (RD) of weekly KF given as a prolonged (3- to 24-h) intravenous (i.v.) infusion. METHODS: Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study. RESULTS: A total of 106 patients were treated with KF at four different weekly schedules: 3-h (n = 40), 24-h (n = 59), and two transitional schedules [6-h (n = 4) and 12-h (n = 3)]. For the 3-h weekly schedule, the MTD was 1,200 µg/m² and the RD was 1,000 µg/m². For the 24-h weekly schedule, the MTD was reached (6,650 µg/m²), but the RD could not be confirmed. Asymptomatic and reversible grade 3/4 transaminase increase was the most common dose-limiting toxicity in both schedules. Fatigue, paresthesia, pruritus, nausea, vomiting, and rash were the most common KF-related adverse events. No major deviations from linearity were detected in the pharmacokinetic (PK) profiles of both schedules, which showed a narrow distribution and short body residence. Prolonged disease stabilization (≥3 months) occurred in eight patients: two with the 3-h schedule and six with the 24-h schedule. CONCLUSIONS: Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.

Toxicidad pulmonar grave relacionada con la administración de gemcitabina / Fatal gemcitabine administration related pulmonary toxicity

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Transesophageal access to the cardiac cavities and descending thoracic aorta via echoendoscopy. An experimental study.

OBJECTIVE: The applications of endoscopic ultrasonography have diversified over recent years. The possibility of reaching cardiac territory has been successfully explored in experimental models, opening up a new field of possibilities for diagnostic and therapeutic interventions that were unthinkable until very recently. The aims set out in this study are to evaluate cardiac anatomy, its approach, the safety of the experimental procedure and the resulting morphological and histological changes after the procedure. MATERIAL AND METHODS: The study has been performed on two adult pigs. They have undergone different surgical approaches to the cardiac cavities and descending thoracic aorta with excellent results. RESULTS: Different cardiac structures have been identified and operated upon (right auricle, left auricle, left ventricle, cardiac valves), as well as major vessels. The use of contrast, both intracavitary and from a peripheral vein, enabled us to verify the anatomical spaces studied. During the procedures we monitored for arrhythmias, hemodynamic behavior, possibility of infection by obtaining sample hemocultures before and after procedures, and response to punctures. CONCLUSIONS: The present study has enabled us to evaluate access to the heart from the esophageal lumen using endoscopic ultrasonography, with results that are very similar to those described in the current bibliography. However, we offer two novelties: puncture of the right auricle through the interauricular partition and puncture of the descending thoracic aorta, both performed with ease and apparent safety.

Acceso transesofágico a cavidades cardiacas y aorta torácica descendente mediante ecoendoscopia. Estudio experimental / Transesophageal access to the cardiac cavities and descending thoracic aorta via echoendoscopy. An experimental study

Objetivo: las aplicaciones de la ultrasonografía endoscópicase han diversificado en los últimos tiempos. La posibilidad de accederal territorio cardiaco se ha explorado en modelos experimentalescon buenos resultados, abriendo un campo de nuevasposibilidades de intervencionismo diagnóstico y terapéutico hastahace poco impensables. Los objetivos planteados en este trabajopretenden evaluar la anatomía cardiaca, su abordaje, la seguridaddel procedimiento experimental y los cambios morfológicos e histológicosderivados.Material y métodos: se ha trabajado con dos animales adultosde la especie porcina a los que se han practicado diversosabordajes a cavidades cardiacas y aorta torácica descendente conexcelentes resultados.Resultados: se han identificado y abordado diversas estructurascardiacas (aurícula derecha, aurícula izquierda, ventrículo izquierdo,válvulas cardiacas) y grandes vasos. El uso de contrasteintracavitario y desde una vía venosa periférica ha permitido asegurarlos espacios anatómicos estudiados. Durante los procedimientosse ha monitorizado la aparición de arritmias, el comportamientohemodinámico, la posibilidad de infección mediante laobtención de hemocultivos antes y después de aquellos y la respuestaa las punciones.Conclusiones: el presente trabajo nos ha permitido evaluar elacceso al corazón desde la luz esofágica mediante ultrasonografíaendoscópica, con unos resultados muy similares a los observadosen la literatura, ofreciendo dos novedades como la punción de laaurícula derecha a través del tabique interauricular y de la aorta torácicadescendente, de forma fácil y aparentemente segura(AU)

Objective: the applications of endoscopic ultrasonographyhave diversified over recent years. The possibility of reachingcardiac territory has been successfully explored in experimentalmodels, opening up a new field of possibilities for diagnostic andtherapeutic interventions that were unthinkable until very recently.The aims set out in this study are to evaluate cardiacanatomy, its approach, the safety of the experimental procedureand the resulting morphological and histological changes afterthe procedure.Material and methods: the study has been performed ontwo adult pigs. They have undergone different surgical approachesto the cardiac cavities and descending thoracic aorta with excellentresults.Results: different cardiac structures have been identified andoperated upon (right auricle, left auricle, left ventricle, cardiacvalves), as well as major vessels. The use of contrast, both intracavitaryand from a peripheral vein, enabled us to verify theanatomical spaces studied. During the procedures we monitoredfor arrhythmias, hemodynamic behavior, possibility of infection byobtaining sample hemocultures before and after procedures, andresponse to punctures.Conclusions: the present study has enabled us to evaluate accessto the heart from the esophageal lumen using endoscopic ultrasonography,with results that are very similar to those describedin the current bibliography. However, we offer two novelties:puncture of the right auricle through the interauricular partitionand puncture of the descending thoracic aorta, both performedwith ease and apparent safety(AU)

A 1.2-V 140-nW 10-bit Sigma-Delta Modulator for Electroencephalogram Applications.

This paper presents a second-order Sigma-Delta modulator for electroencephalogram applications with 10 bits of resolution, 1.2 V of supply voltage, and only 140 nW of power consumption over a bandwidth of 25 Hz. Low-voltage operation has been achieved using quasi-floating-gate-based circuits. The use of a new class-AB operational amplifier in weak inversion allows very low power consumption. Experimental results show an energy efficiency of 1.6 pJ per quantization level, making it the most energy-efficient converter reported to date in the very low signal bandwidth range.

Double-balloon enteroscopy: a descriptive study of 50 explorations.

AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

Enteroscopia de doble balón: estudio descriptivo de 50 exploraciones / Double-balloon enteroscopy: a descriptive study of 50 explorations

Objetivo: valorar la utilidad de la enteroscopia de doble balón en enfermedades de intestino delgado. Diseño: estudio prospectivo descriptivo de 50 enteroscopias consecutivas (diciembre 2004 a julio 2005), analizando diagnóstico y terapéutica. Pacientes: cuarenta y cuatro pacientes (33 con cápsula endoscópica previa) con hemorragia digestiva oculta o lesiones detectadas mediante cápsula (angiodisplasias, pólipos, úlceras, enfermedad de Crohn, celiaca refractaria y tumores). Resultados: se realizó enteroscopia vía oral a 44 pacientes y vía oral más anal a 6. Por vía oral se progresó hasta íleon en todos los casos excepto uno (estenosis yeyunal), por vía anal en 4 de 7 (3 casos con dificultad de paso por Bahuin). La duración media fue 73 minutos. Se detectaron angiodisplasias (19 casos), úlceras en enteropatía por AINE, enfermedad de Crohn, enfermedad de Waldenström, y divertículos. Se realizaron biopsias en yeyuno-íleon en un tercio de los casos (adenocarcinoma, linfangiectasias secundarias a tumor sobre celíaca, enfermedad de Whipple). Se realizó terapéutica con argón a 19 pacientes con angiodisplasias (1 a 20 lesiones), polipectomía a 4 pacientes con pólipos esporádicos o Peutz Jeghers (1 a 15 pólipos) y se extrajo una cápsula endoscópica retenida en una estenosis. Conclusiones: la enteroscopia de doble balón es una técnica útil y eficaz en el diagnóstico y tratamiento de las lesiones del intestino delgado, complementando a la cápsula endoscópica. Hacen falta más estudios para analizar el impacto esperado en el cambio del manejo de estos pacientes

Aim: to evaluate the utility of double-balloon enteroscopy for small-bowel disease. Design: a prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. Patients: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn´s disease, tumors, and refractory celiac disease. Results: we carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn’s disease, diverticulosis, and Waldenström’s disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple’s disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. Conclusions: double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition

Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors.

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1-3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m(-2) day 1), and capecitabine (2000 mg m(-2) day 1-14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53-80%). Grade 3-4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand-foot syndrome, and constipation were the most frequent nonhaematologic events. Median progression-free and overall survival were 6.4 and 12.6 months. Cytoplasmic TP expression was more prevalent in patients with a laryngeal location vs other, and in patients with a recurrence vs primary disease. Microvessel density count was higher in patients with recurrent vs primary disease. The combination of cisplatin and capecitabine is effective in recurrent or unresectable HNSCC, and shows a manageable toxicity.

Masa pélvica hipervascularizada: una causa poco frecuente de hemorragia digestiva

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