In vitro characterisation of low-cost synthetic meshes intended for hernia repair in the UK.

PURPOSE: Low-cost meshes (LCM) were repurposed for the repair of hernias in the developing world. In vivo studies have shown LCM to have comparable results to commercial meshes (CM) at a fraction of the cost. However, little has been done to characterise the mechanical and biocompatible properties of LCM, preventing its clinical use in the UK. The objectives of the research are to assess mechanical and ultrastructural properties of two UK-sourced low-cost meshes (LCM) and the characterisation of the LCMs in vitro biocompatibility. METHODS: Mechanical properties of the two LCM were measured through uniaxial tensile test and ultrastructure was evaluated with Scanning Electron Microscopy. LIVE/DEAD® Viability/Cytotoxicity Assay kit and alamarBlue were used to assess cellular viability and proliferation, respectively. Images were acquired with a fluorescence microscope and analysed using ImageJ (NIH, USA). RESULTS: LCM1 and LCM2 were both multifilament meshes, with the first having smaller pores than the latter. LCM1 exhibited significantly higher tensile strength (p < 0.05) than LCM2 but significantly lower extensibility (p < 0.0001), while Young's Modulus of the two samples was not significantly different. No significant difference was found in the cellular viability and morphology cultured in LCM1 and LCM2 conditioned media. Metabolic assay and fluorescence imaging showed cellular attachment and proliferation on both LCMs over 14 days. CONCLUSION: The characterisation of the two UK-sourced LCMs showed in vitro biocompatibility and mechanical and ultrastructural properties comparable to the equivalent CM. This in vitro data represents a step forward for the feasibility of adopting LCM for surgical repair of hernias in the UK.

Guía de práctica clínica para el tratamiento de la enfermedad de Crohn en población adulta / Clinical practice guidelines for the treatment of Crohn's disease in the adult population

Resumen Objetivo: La enfermedad de Crohn es un trastorno inflamatorio idiopático de etiología desconocida con características genéticas, inmunológicas e influencias del medio ambiente. La incidencia y la prevalencia de la enfermedad de Crohn han aumentado en Colombia. El tratamiento de estos pacientes no es fácil y ha evolucionado en los últimos años; por lo tanto, es necesario desarrollar una guía de práctica clínica en Colombia, orientada al tratamiento de esta compleja enfermedad, para unificar criterios. Materiales y métodos: Esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes a la entidad y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: Se realizó una guía de práctica clínica basada en la evidencia, para el tratamiento tanto médico como quirúrgico de la enfermedad de Crohn en población adulta en Colombia. Se diseñaron algoritmos de manejo teniendo en cuenta la actividad, el comportamiento y la localización de la enfermedad. Conclusiones: Se estableció que una adecuada evaluación clínica, endoscópica e imagenológica, así como una estratificación de riesgo individual son importantes para el manejo, y se especificaron las indicaciones para el adecuado tratamiento tanto médico como quirúrgico de estos pacientes.

Abstract Objective: Crohn's disease is an idiopathic inflammatory disorder of unknown origin, influenced by genetic, immunological, and environmental factors. The incidence and prevalence of Crohn's disease have increased in Colombia. The treatment of these patients is not easy and has improved in recent years. Therefore, it is necessary to develop the Colombian Clinical Practice Guideline to guide the treatment of this complex disease and unify criteria. Materials and methods: The present guideline was carried out by a multidisciplinary team with support from the Asociación Colombiana de Gastroenterología, the Cochrane ITS Team, and the Clinical Research Institute of the Universidad Nacional de Colombia. Clinical questions regarding this disease were developed, and national and international guidelines were searched in specialized databases. The existing guidelines were evaluated in terms of quality and applicability. The Cochrane Group conducted a systematic search of the existing literature. Evidence tables were elaborated, and recommendations were made using the GRADE methodology. Results: An evidence-based clinical practice guideline was developed for the medical and surgical treatment of Crohn's disease in the adult population in Colombia. Treatment algorithms were designed, taking into account the activity, behavior, and location of the disease. Conclusions: It was established that proper clinical, endoscopic, and imaging assessment, as well as individual risk stratification, are important for treatment. Also, the indications for adequate medical and surgical treatment of these patients were specified.

Controlled local release of PPARγ agonists from biomaterials to treat peripheral nerve injury.

OBJECTIVE: Poor clinical outcomes following peripheral nerve injury (PNI) are partly attributable to the limited rate of neuronal regeneration. Despite numerous potential drug candidates demonstrating positive effects on nerve regeneration rate in preclinical models, no drugs are routinely used to improve restoration of function in clinical practice. A key challenge associated with clinical adoption of drug treatments in nerve injured patients is the requirement for sustained administration of doses associated with undesirable systemic sideeffects. Local controlled-release drug delivery systems could potentially address this challenge, particularly through the use of biomaterials that can be implanted at the repair site during the microsurgical repair procedure. APPROACH: In order to test this concept, this study used various biomaterials to deliver ibuprofen sodium or sulindac sulfide locally in a controlled manner in a rat sciatic nerve injury model. Following characterisation of release parameters in vitro, ethylene vinyl acetate tubes or polylactic-co-glycolic acid wraps, loaded with ibuprofen sodium or sulindac sulfide, were placed around directly-repaired nerve transection or nerve crush injuries in rats. MAIN RESULTS: Ibuprofen sodium, but not sulindac sulfide caused an increase in neurites in distal nerve segments and improvements in functional recovery in comparison to controls with no drug treatment. SIGNIFICANCE: This study showed for the first time that local delivery of ibuprofen sodium using biomaterials improves neurite growth and functional recovery following PNI and provides the basis for future development of drug-loaded biomaterials suitable for clinical translation.

Electron irradiation of multilayer [Formula: see text] field effect transistors.

Palladium diselenide ([Formula: see text]) is a recently isolated layered material that has attracted a lot of interest for its pentagonal structure, air stability and electrical properties that are largely tunable by the number of layers. In this work, multilayer [Formula: see text] is used as the channel of back-gate field-effect transistors, which are studied under repeated electron irradiations. Source-drain [Formula: see text] electrodes enable contacts with resistance below [Formula: see text]. The transistors exhibit a prevailing n-type conduction in high vacuum, which reversibly turns into ambipolar electric transport at atmospheric pressure. Irradiation by [Formula: see text] electrons suppresses the channel conductance and promptly transforms the device from n-type to p-type. An electron fluence as low as [Formula: see text] dramatically changes the transistor behavior, demonstrating a high sensitivity of [Formula: see text] to electron irradiation. The sensitivity is lost after a few exposures, with a saturation condition being reached for fluence higher than [Formula: see text]. The damage induced by high electron fluence is irreversible as the device persists in the radiation-modified state for several hours, if kept in vacuum and at room temperature. With the support of numerical simulation, we explain such a behavior by electron-induced Se atom vacancy formation and charge trapping in slow trap states at the [Formula: see text] interface.

Associations between disordered eating and intimate partner violence mediated by depression and posttraumatic stress disorder symptoms in a female veteran sample.

OBJECTIVE: This study established a link between intimate partner violence (IPV) and eating disorders (EDs) via mediators of depression and posttraumatic stress disorder (PTSD) symptoms in female veterans. METHOD: A nationally representative sample of female veterans (N = 190, Mean age = 48.41 years) completed online surveys assessing IPV and symptoms of depression, PTSD, and EDs, at three time points from 2014 to 2017. RESULTS: Approximately 14.11% of participants met criteria for any ED (7.83% Bulimia Nervosa; 6.28% Binge Eating Disorder), and 49.42% reported lifetime histories of IPV. Eating disorder symptoms were significantly associated with lifetime IPV, PTSD and depression symptoms at the bivariate level. Mediation model results revealed that lifetime IPV was indirectly associated with EDDS scores, via PTSD symptoms and depression symptoms. CONCLUSION: Findings confirmed elevated rates of probable EDs and lifetime IPV among female veterans; significant associations between EDs, lifetime IPV, depression, and PTSD; and mediation of the association between IPV and EDs by PTSD and depression symptoms. Implications for screening, treatment and research are discussed.

Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk. PURPOSE: The aim of our study was to investigate the ambulatory blood pressure monitoring-derived short-term blood pressure variability in patients with primary hyperparathyroidism, in comparison with patients with essential hypertension and normotensive controls. METHODS: Twenty-five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive) underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of them were re-evaluated after parathyroidectomy. Short-term-blood pressure variability was derived from ambulatory blood pressure monitoring and calculated as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2) the average of day-time and night-time-Standard Deviation, weighted for the duration of the day and night periods (24-h "weighted" Standard Deviation of BP); 3) average real variability, i.e., the average of the absolute differences between all consecutive BP measurements. RESULTS: Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively. Normotensive-primary hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01) and average real variability (P < 0.05) of systolic blood pressure higher than that of 12 normotensive controls. 24-h average real variability of systolic BP, as well as serum calcium and parathyroid hormone levels, were reduced in operated patients (P < 0.001). A positive correlation of serum calcium and parathyroid hormone with 24-h-average real variability of systolic BP was observed in the entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02; respectively). CONCLUSION: Systolic blood pressure variability is increased in normotensive patients with primary hyperparathyroidism and is reduced by parathyroidectomy, and may potentially represent an additional cardiovascular risk factor in this disease.

Keratitis in association with herpes zoster and varicella vaccines.

The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination.

Oblique wrinkles.

We prove theoretically that when a soft solid is subjected to an extreme deformation, wrinkles can form on its surface at an angle that is oblique to a principal direction of stretch. These oblique wrinkles occur for a strain that is smaller than the one required to obtain wrinkles normal to the direction of greatest compression. We go on to explain why they will probably never be observed in real-world experiments.This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'

Guía de práctica clínica para el tratamiento de la enfermedad de Crohn en población adulta / Clinical practice guideline for treatment of Crohn's Disease in adult population

Generar recomendaciones informadas en la evidencia para el tratamiento de los pacientes con enfermedad de Crohn. Apoyar al tratamiento oportuno y seguro de los pacientes de enfermedad de Crohn considerando las minimización de secuelas y la hospitalización. Apoyar a los tomadores de decisiones a formular políticas para el manejo adecuado de la enfermedad de Crohn. Grupos que se consideran: Pacientes mayores de 16 años con diagnóstico de Enfermedad de Crohn independiente del tiempo de evolución y estado clínico de la enfermedad sin importar régimen de aseguramiento.

Guía de práctica clínica para el diagnóstico y tratamiento de la colitis ulcerativa en población adulta / Clinical practice guideline for the diagnosis and management of adult patients with Ulcerative Colitis

Objetivo: desarrollar una guía de práctica clínica que permita orientar el diagnóstico de los pacientes con colitis ulcerativa mediante el uso adecuado de criterios clínicos y direccionar la conducta terapéutica en las diferentes etapas de la enfermedad y en los diferentes niveles de atención. Materiales y métodos: esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes a la entidad y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad; una de las guías cumplió con los criterios de adaptación y el grupo decidió actualizar la búsqueda, desarrollando de novo las preguntas adicionales contempladas. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: se desarrolló una guía de práctica clínica, basada en la evidencia, para el diagnóstico y tratamiento de la colitis ulcerativa en adultos en Colombia. Conclusiones: se estableció la importancia para el diagnóstico de la evaluación clínica, endoscópica e histológica y se especificaron las indicaciones para el adecuado tratamiento de los pacientes con colitis ulcerativa, de acuerdo con su severidad y estado de remisión.

Objective: To provide an evidence-based clinical practice guideline for the diagnostic and treatment of ulcerative colitis for patients, caregivers, administrative, and government bodies at all levels of care in Colombia. Materials and Methods: This guide was developed by a multidisciplinary team with the support of the Colombian Association of Gastroenterology, Cochrane STI Group and Clinical Research Institute of the Universidad Nacional de Colombia. Relevant clinical questions were developed and the search for national and international guidelines in databases was performed. Existing guidelines were evaluated for quality and applicability. One of the guidelines met the criteria for adaptation, so the group decided to update the search and develop de novo the additional questions. Systematic literature searches were conducted. The tables of evidence and recommendations were made based on the GRADE methodology. Results: An evidence-based Clinical Practice Guidelines for the management of ulcerative colitis was developed for the Colombian context. Conclusions: The opportune management of ulcerative colitis would have an impact of the disease in Colombia.

Guía de práctica clínica para el diagnóstico y tratamiento del síndrome de intestino irritable en población adulta / Clinical Practice Guideline for the Diagnosis and Management of Adult Patients with Irritable Bowel Syndrome

Objetivo: diseñar una guía de práctica clínica para disminuir la variabilidad injustificada en el diagnóstico y tratamiento de los pacientes mayores de 18 años con síndrome de intestino irritable en Colombia mediante un diagnóstico orientado y unas pautas terapéuticas establecidas. Materiales y métodos: el equipo multidisciplinario que conformó el presente Grupo Desarrollador contó con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad; ninguna de ellas cumplió el criterio de adaptación, por lo que se decidió desarrollar una guía de novo. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: se desarrolló una guía de práctica clínica basada en la evidencia para el diagnóstico y tratamiento farmacológico de los pacientes mayores de 18 años con síndrome de intestino irritable en Colombia. Conclusiones: se establecieron los criterios clínicos y signos de alarma, las pruebas diagnósticas y las aproximaciones terapéuticas de acuerdo con el síntoma predominante en los pacientes con síndrome de intestino irritable en Colombia.

Objective: To design a clinical practice guideline to reduce unwarranted variation in the diagnosis and treatment of patients over 18 years old with irritable bowel syndrome in Colombia through targeted diagnosis and a treatment guidelines established. Materials and Methods: This guide was developed by a multidisciplinary team with the support of the Colombian Association of Gastroenterology, Cochrane STI Group and Clinical Research Institute of the Universidad Nacional de Colombia. Relevant clinical questions were developed and the search for national and international guidelines in databases was performed. Existing guidelines were evaluated quality and applicability. No guideline met the criteria for adaptation, so the group decided to develop the guideline de novo. Systematic literature searches were conducted by the Cochrane Group. The tables of evidence and recommendations were made based on the GRADE methodology. Results: An evidence-based Clinical Practice Guidelines for the diagnosis and treatment of irritable bowel syndrome in patients over 18 years old was developed for the Colombian context. Conclusions: the clinical criteria and warning signs, diagnostic tests and therapeutic approaches were established in accordance with the predominant symptom in patients with irritable bowel syndrome in Colombia.

Guía de práctica clínica para el diagnóstico y tratamiento del estreñimiento crónico funcional en población adulta / Clinical Practice Guideline for the Diagnosis and Management of Adult Patients with Functional Chronic Constipation

Objetivo: diseñar una guía de práctica clínica para orientar el diagnóstico, y establecer la clasificación y el tratamiento farmacológico y no farmacológico en los pacientes adultos con estreñimiento crónico funcional en Colombia. Materiales y métodos: el grupo desarrollador de la presente guía estuvo conformado por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad; ninguna de ellas cumplió criterios de adaptación, por lo que se decidió desarrollar una guía de novo. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: se desarrolló una guía de práctica clínica basada en la evidencia para el diagnóstico, clasificación y tratamiento farmacológico y no farmacológico de los pacientes con estreñimiento crónico funcional en Colombia. Conclusiones: se establecieron los criterios clínicos y signos de alarma, las pruebas diagnósticas y los esquemas terapéuticos que se recomiendan en la atención de los pacientes con estreñimiento crónico funcional en Colombia.

Objective: Design a clinical practice guideline to orient the diagnosis and establishing the classification and pharmacological and non-pharmacological treatment in adult patients with chronic functional constipation in Colombia. Materials and Methods: This guide was developed by a multidisciplinary team with the support of the Colombian Association of Gastroenterology, Cochrane STI Group and Clinical Research Institute of the Universidad Nacional de Colombia. Relevant clinical questions were developed and the search for national and international guidelines in databases was performed. Existing guidelines were evaluated for quality and applicability. None of the guidelines met the criteria for adaptation, so the group decided to develop a de novo guideline. Systematic literature searches were conducted by the Cochrane Group. The tables of evidence and recommendations were made based on the GRADE methodology. Results: A clinical practice based on evidence was developed for the diagnosis, classification and pharmacological and non-pharmacological treatment of patients with chronic functional constipation in Colombia. Conclusions: The clinical criteria and warning signs, diagnostic tests and therapeutic regimens that are recommended in the care of patients with chronic functional constipation were established in Colombia.

Influence of nucleus deformability on cell entry into cylindrical structures.

The mechanical properties of cell nuclei have been demonstrated to play a fundamental role in cell movement across extracellular networks and micro-channels. In this work, we focus on a mathematical description of a cell entering a cylindrical channel composed of extracellular matrix. An energetic approach is derived in order to obtain a necessary condition for which cells enter cylindrical structures. The nucleus of the cell is treated either (i) as an elastic membrane surrounding a liquid droplet or (ii) as an incompressible elastic material with Neo-Hookean constitutive equation. The results obtained highlight the importance of the interplay between mechanical deformability of the nucleus and the capability of the cell to establish adhesive bonds and generate active forces in the cytoskeleton due to myosin action.

Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has been found to be strongly related to an increased arterial stiffness in patients with essential hypertension, suggesting a pathophysiologic link between major cardiovascular and metabolic abnormalities associated with liver steatosis and the functional and structural alterations of the arterial wall. The aim of our study was to investigate, in a group of essential hypertensive patients without additional cardiovascular risk factors, the relationship between NAFLD and arterial stiffness. METHODS AND RESULTS: Sixty-eight consecutive patients with essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and were separated according to the presence (n = 40) or absence (n = 28) of NAFLD at liver ultrasonography. The Ambulatory Arterial Stiffness Index (AASI) and Symmetric AASI (Sym-AASI) were derived from ABPM tracings. Patients with diabetes, obesity, hyperlipidaemia or other risk factors for cardiovascular or liver disease were excluded. Hypertensive patients were compared with a normotensive control group.The two hypertensive groups had comparable age, sex distribution and clinic/ABPM blood pressure levels. In hypertensive patients with NAFLD, body mass index, fasting glucose, insulin, homeostasis model of assessment of insulin resistance index and triglyceride levels were higher, whereas plasma adiponectin was lower than in patients without NAFLD. In hypertensive patients, AASI and Sym-AASI were higher (P < 0.001) than in normotensive subjects, but both indices of vascular stiffness were comparable in patients with and without NAFLD. CONCLUSIONS: In essential hypertensive patients without additional cardiovascular risk factors, NAFLD is associated with insulin resistance but not with increased arterial stiffness.

Small diverse antioxidant functionalities for oxidative stress disease drug discovery.

There is an up-surge of interest in antioxidants because of their potential use in mitigating a wide array of oxidative stress mediated diseases. In the course of our literature search for diverse functional groups, with utility in the design of potential drugs for preventing oxidative stress related cell injury, we have collected a small literature library of core structures or moieties possessing antioxidant activities. These functional groups can be re-configured into robust antioxidants drug molecules, in their own right, or incorporated into drug structures where the antioxidant capability is required. The lack of single papers presenting a collection of diverse small molecule antioxidant moieties as potential design leads prompted us to write this short review of twenty five such functionalities.

[Employment of disabled people regarding Italian Law "68/99": Florence's ASL N. 10 experience]. / Inserimento lavorativo dei soggetti disabili ai sensi della legge 68/99: l'esperienza della ASL10 di Firenze.

The reform of mandatory employment in Italy, performed by the national Law 68/99, represented a crucial step for the assertion of the right to work for disabled people. The aim of our experience is to obtain information about health and safety conditions of disabled people employed in targeted workplaces and about the issues for that workers keep or lose their job, possibly in order to take actions on workplaces and to improve job conditions for all other workers also. In this paper we used data regarding targeted employments of disabled people, collected during the year 2008 in the Province of Florence.

Usefulness of a second endoscopic arm to improve therapeutic endoscopy in the lower gastrointestinal tract. Preliminary experience - a case series.

Endoscopic submucosal dissection is a difficult procedure with frequent complications. Our aim was to test the feasibility of utilizing a second endoscopic arm to improve the dissection. An Olympus prototype blind probe, with an external diameter of 6 mm and a 2.8-mm working channel, was used as a second endoscopic arm. Its purpose was to lift the lesion during dissection. The main endoscope served both to perform the dissection and to visualize the second endoscopic arm in the monitor. Eight patients with polypoid lesions in the rectum or distal sigmoid were treated successfully. The procedure was feasible, and submucosal exposure was ameliorated allowing easier dissection. The resection was curative in all cases. No recurrences have been detected during up to 18-months of follow-up. A small perforation and two cases of delayed bleeding were managed nonsurgically. Applying counter-traction with a second endoscopic arm can facilitate submucosal dissection of distal colorectal lesions.

The influence of endoscopic biliary stents on the accuracy of endoscopic ultrasound for pancreatic head cancer staging.

BACKGROUND AND STUDY AIMS: Biliary stents have been found to interfere with endoscopic ultrasound (EUS) tumor (T) and nodal (N) staging in patients with periampullary cancer. Our aim was to determine whether this also occurs in patients with pancreatic head cancer. PATIENTS AND METHODS: We studied a consecutive series of patients who were undergoing preoperative EUS for diagnosis and staging of suspected pancreatic cancer, some of whom had biliary stents in situ and some of whom did not. The main end point was the uni- and multivariate association of biliary stenting with T and N mis-staging by EUS. The surgical T and N stages were used as gold standards. RESULTS: A total of 65 patients were identified (19 with biliary stents in situ and 46 without). Surgical stage T4 was found more frequently in patients with stents (53% vs. 22%, P = 0.014). The T stage by EUS was correct in 85% of the patients without biliary stents and in 47% of the patients with stents. The frequency of mis-staging by EUS was significant only among patients with a biliary stent. The distribution by EUS N stage did not differ significantly from the surgical N-stage distribution in the two groups of patients. According to the multivariate analysis, patients with stents were 6.55 times more likely to be incorrectly T staged (95% confidence interval [CI] 1.69-25.49) and 3.71 times more likely to be incorrectly N staged (95% CI 1.11-12.45) than patients without stents. CONCLUSIONS: The results add support to the recommendation that EUS staging of pancreatic head neoplasms should be performed prior to stent placement.

The mechanical behaviour of chondrocytes predicted with a micro-structural model of articular cartilage.

The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.

Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in patients with renal diseases.

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.