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The development of novel drugs for Alzheimer’s disease has proven difficult, with a high failure rate in clinical trials. Typically, transgenic mice displaying amyloid-β peptide brain pathology are used to develop therapeutic options and to test their efficacy in preclinical studies. However, the properties of Aβ in such mice have not been systematically compared to Aβ from the patient brains. Here, we determined the structures of nineex vivoAβ fibrils from six different mouse models by cryo-EM. We found novel Aβ fibril structures in the APP/PS1, ARTE10, and tg-SwDI models, whereas the human familial type II fibril fold was found in the ARTE10, tg-APPSwe, and APP23 models. The tg-APPArcSwemice showed an Aβ fibril whose structure resembles the human sporadic type I fibril. These structural elucidations are key to the selection of adequate mouse models for the development of novel plaque-targeting therapeutics and PET imaging tracers.One Sentence SummaryCryo-EM structures of Aβ fibrils extracted from brains of mouse models used for Alzheimer’s disease preclinical research are presented.

Introduction: Vortioxetine is a multimodal antidepressant drug that has been reported to have a positive impact on cognition, social function, and fatigue. Nevertheless, it has not been widely studied. Our objective was to explore the effects of vortioxetine on these and other parameters in patients with multiple sclerosis (MS) and depression. background: Vortioxetine is a multimodal antidepressant drug which is able to relieve symptoms of depression. Although it has been reported to have a positive impact on cognition, social functions, and fatigue in genereal population, it has not been widely studied. Patients and methodology: This observational case series study included patients with MS and depression who received treatment with vortioxetine for at least 6 months. The patient history of depression and depressive symptoms was assessed. A neuropsychiatric evaluation was carried out using different scales, both before and after treatment. Results: Of the 25 patients who enrolled in the study, 17 completed the treatment. Significant improvements were observed in health status (EQ-5D; p = 0.002), mood (Beck’s Depression Inventory, BDI-II; p = 0.006), anxiety (State-Trait Anxiety Inventory, STAI-State; p = 0.021, and STAI-Trait; p = 0.011), and in the general health test (Short Form Health Survey, SF-36) for the vitality (p = 0.028) and mental health (p = 0.025) domains of the patients who completed the treatment. However, no statistically significant differences were observed in the cognitive tests related to attention, information processing speed, or fatigue. method: An observational study included patients with multiple sclerosis and depression, who received treatment with vortioxetine for at least 6 months. A history of depression and symptoms of depression were assessed. A neuropsychiatric evaluation was carried out, using different scales, both before and after the patients received the treatment Conclusion: In this population, vortioxetine treatment was effective in reducing the symptoms of depression and improving anxiety, vitality, and mental health. In contrast, it did not produce any improvement in cognition or fatigue but an increase in sample size would be necessary to confirm these results. conclusion: In this population, the treatment with vortioxetine was effective for reducing the symptoms of depression and improving anxiety, vitality and mental health. In contrast, the treatment did not produce any improvement in cognition or fatigue.

Objetivo: Caracterizar los riesgos ergon��micos y da��os presentes en el personal de enfermer��a del Hospital San Vicente de Pa��l, Ecuador. Materiales y m��todos: Se realiz�� un estudio descriptivo con un enfoque cuantitativo de corte transversal en mencionado hospital, durante el a��o 2020. Se incluyeron 87 enfermeros/as a los cuales se les aplic�� el cuestionario ERGOPAR. Resultados: De los sujetos evaluados, tuvieron un rango de edad entre 28 - 37 a��os, predominante mujeres (75,9%). Su distribuci��n en los diferentes servicios: 23,2% (n=20) Emergencia, 14,3% (n=13) Pediatr��a, 13,9% (n=12) Medicina Interna y Ginecolog��a. De acuerdo con el horario, el 96.4% (n=84) asiste en turno rotativo. De igual forma, se evidencia que el 62.2% del personal de enfermer��a est�� por m��s de 4 horas caminando, mientras que el 5.7% permanece de pie, 4.6% sube y baja diferentes niveles y el 2.3% sentado. En relaci��n a la presencia de dolor o molestia muscular, el 94,3% present�� s��ntomas cervicales, 87,4% dorso-lumbares, 59,7% en los pies y el 50,6% en las piernas cuyos dolores ocasionan impedimentos al momento de realizar el trabajo actual, lo que por ende ha presentado consecuencias en las tareas de su puesto de trabajo. Finalmente, el 71.4% mostraba un riesgo ergon��mico alto, mientras que el 26.6% mostraba un riesgo moderado. Conclusi��n: El personal de enfermer��a del Hospital San Vicente de Pa��l de Ecuador tiene una alta frecuencia de sintomatolog��a en los segmentos corporales de cuello, espalda, piernas y pies principales causantes de afectaciones cervicales, dorso-lumbares y piernas producto de actividades laborales.

The Wyeth strain of vaccinia virus (VACV) produced by Wyeth Pharmaceuticals was supposedly used to manufacture the old freeze-dried American smallpox vaccine, Dryvax, until its discontinuation in 2008. Although the genomic sequences of numerous Dryvax clones have been reported, data on VACV-Wyeth genomes are still lacking. Genomic analysis of old VACV strains is relevant to understand the evolutionary relationships of smallpox vaccines, particularly with the recent resumption of smallpox vaccination in certain population groups as an attempt to control the worldwide monkeypox outbreak. Here we analyzed the complete genome sequences of three VACV-Wyeth clonal isolates obtained from a single seed vial donated to the Brazilian eradication program in the 1970s. Wyeth clones show >99.3% similarity to each other and >95.3% similarity with Dryvax clones, mapping together in clade I of the vaccinia group. Although the patterns of SNPs and INDELs comparing Dryvax and Wyeth clones are overall uniform, important differences were detected particularly at the ends of the genome. In addition, we detected recombinant events of clone Wyeth A111 and the Dryvax clone Acam2000, suggesting that other regions of the genomes may have similar patchy patterns of recombination. A small-scale serological survey using VACV-Wyeth as antigen in ELISA assays revealed that 63 of the 65 individuals born before the end of smallpox vaccination in Brazil still have anti-VACV IgG antibodies, demonstrating the usefulness of the VACV-Wyeth strain in future extended serological studies of the Brazilian population.

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important in segregating innocuous tactile input from pain-processing circuits, achieved through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions contributes to the development of mechanical hypersensitivity.

RESUMEN Las queratosis seborreicas son tumores benignos muy frecuentes en la práctica diaria y la mayoría de los pacientes desarrollarán alguna en el transcurso de la vida. La variante clonal es una forma histopatológica rara y su importancia radica en la necesidad de realizar diagnóstico diferencial con otras patologías de mayor relevancia como carcinoma basocelular e incluso melanoma. Se presenta el caso clínico de una paciente de 76 años con una lesión histológicamente compatible con la variante clonal de la queratosis seborreica. SUMMARY Seborrheic keratoses are benign tumors that are very common in daily dermatology practice and most patients will develop some over the course of their lives. The clonal variant is a rare histopathological form and its importance lies in the need to perform a differential diagnosis with other pathologies of greater relevance such as basal cell carcinoma and even malignant melanoma. We present the clinical case of a 76-year-old female patient with a diagnosis of clonal seborrheic keratosis.

Background Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications. Aims to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding. Methods Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding. Results Age was significantly lower (OR 0.48, 95% CI: 0.34–0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11–2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60–27.0) and diverticulitis (OR 4.23, 95% CI: 1.11–16.1). Conclusion This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.

Existe actualmente una miríada de soluciones cardiopléjicas con distintas composiciones, todas formuladas para evitar o “atenuar” las consecuencias deletéreas de la anoxia miocárdica en el período de clampeo aórtico; con el objetivo de preservar la reserva contráctil y evitar la necrosis durante el procedimiento. Presentamos una serie de pacientes consecutivos, operados en nuestro Servicio, durante el año 2016 a los que se le realizó protección miocárdica con solución cardiopléjica del Nido. Estudio retrospectivo sobre 150 pacientes adultos con patología tanto adquirida, inclusive las emergencias, como congénita. Concluimos que la utilización de la Solución Cardiopléjica del Nido en nuestro Servicio, se presenta como una opción viable por los buenos resultados obtenidos. No encontrándose diferencias significativas en complicaciones con parámetros observados frente a otra técnica de protección miocárdica, (Cardioplejía Cristaloide Saint Thomas); con alta tasa de latido espontáneo, conservación de la función sistólica y baja tasa de utilización de inotrópicos.

To determine the feasibility,tolerability, and safety of the ultrasound assessment of tubal patency using foam as contrast.This was a prospective multicenter study of 915 infertile nulliparous women scheduled for sonohysterosalpingography with foam instillation (HYFOSY) for tubal patency testing as a part of the fertility workup. Clinical and sonographic data were recorded into a web-shared database. Tubal patency, cervical catheterization, pain during the procedure and post-procedural complications were collected. Patients reported discomfort or pain experienced during the procedure with a visual analogue scale (VAS) score.Nine hundred fifteen women were included in the final analysis. Median age was 34 (range, 21-45) years and median body mass index was 23 (range, 16-41) kg/m2. Of 839 women, only 8(0.95 %) cases were abandoned due to impossibility of introducing the intracervical catheter. Most of the cervical os were easily cannulated with either paediatric nasogastric probes or special catheter for intrauterine insemination / sonohysterosalpingography 688/914(75.3 %). With a median instillation of 4 mL (range 1-16) of foam, both tubes were identified in 649/875 (70.9 %) patients, while unilateral patency was observed in 190/875 (20.8 %). Only 36/875 (3.9 %) of the women had bilateral tubal obstruction. The median VAS score for perception of pain during HyFoSy examination was 2 (range 0-10), and only 17 (1.9 %) of women reported severe pain (VAS ≥ 7). Pain was unrelated to tubal patency or tubal blockage. Unexpectedly, difficult cervical catheterizations that needed tenaculum, were more likely associated with mild pain during procedure [nasogastric probe group 176/289 (70.9 %) vs. insemination catheter group 166/399 (41.6 %) vs. tenaculum group 190/218(87.2 %) p0.001]. Finally, among 915 patients, we only noticed 3 (0.32 %) complications of the technique: two vasovagal episodes and a mild urinary infection.HYFOSY is a feasible, well-tolerated and safe technique for the evaluation of tubal patency in infertile women.

In this study we describe the important features of the process of steam injection through non-consolidated porous media made of sand. We have analyzed the resulting fluid flow patterns through normal and infrared visualization by varying the injection pressure into a horizontal cylindrical pipe and a circular cell on a vertical position. Such configurations mimic those occurring under the steam assisted gravity drainage (SAGD) in tertiary recovery from oilfields and geothermal reservoirs. We describe some characteristics of the ubiquitous condensation front in both experimental arrays. In the first case, a glass pipe filled with sand was subjected to steam injection at different pressures. In the second case, a circular cell on a vertical position brimful of sand cell was subjected to similar processes. For each case, the existence of several types of condensation fronts, depending on the injection pressure, has been evidenced by means of digital and infrared visualization which gives mutually complementary information.

Objective To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. Results Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Paneth cells. IL-9-positive mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimulation of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of α-defensin 5 and IL-23p19. Peripheral and synovial expansion of α4β7+ Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. Conclusion Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA.

Experiments reported here confirm experimentally the existence of the characteristic planar buoyant plumes that emerge as a consequence of the presence of a cylindrical heat source embedded in an homogeneous air-saturated and non-consolidated porous medium. The resultant buoyant plumes were visualized with IR thermography considering two important cases. First, under the action of natural convection and second, under the action of forced convection due to the passage of a constant air stream directed perpendicularly towards the horizontal cylindrical heat source buried in the porous medium. Such streams were induced at different tilt angles. For each case, the temperature distribution is shown and correspondence is found with the isotherms distribution predicted by the theoretical models reported in the literature. The use of infrared techniques appears as a helpful tool that allows us to witness all the process of rise and growth of the buoyant plumes until the phenomenon reaches steady state.

Background The presence of CMV in blood is quite common in patients with severe flares of ulcerative colitis (UC) and Crohn’s disease (CD) and seems to predict an adverse outcome. The impact of antiviral treatment on CMV in this setting (indications and drug options) is an unresolved issue. Our aim was to reassess the CMV role in patients with IBD hospitalised for severe exacerbations, analysing the relationship between CMV positivity, clinical characteristics, antiviral therapy and disease outcomes. Methods We evaluated a homogeneous cohort of 97 consecutive patients with IBD hospitalised from 2012 to 2018. Data regarding age, gender, smoke, familial predisposition, type of IBD, extent, according to Montreal classification, disease activity (clinical and endoscopic), therapy at the time of relapse were registered in a dedicated database. CMV was tested by PCR in whole blood. The relationship between antiviral therapy and disease outcomes (rate of colectomy, mortality) was analysed. Results Among the 97 patients, 51 were females. In the UC group (67 patients, 69.1%), mean age was 48,8, SD ± 17,7 whereas in the CD group (30 patients, 31%), mean age was 39,9 years (SD ± 15,2). Fifteen per cent of patients had a family predisposition for IBD. There were no differences at baseline between UC and CD, except disease duration (longer in UC) and therapy at the time of relapse (high dose steroids more common in UC). Thirty-one patients (32 %) tested positive for CMV on PCR. Smoking habit, shorter disease duration, therapy on admission (high dose steroid and/or immunomodulators) and endoscopic activity assessed by Mayo endoscopic sub-score were the variables significantly related to CMV positivity. Antiviral therapy was adopted in 22% of patients and the decision to treat was based on clinical judgement and viral load. Treated patients had higher endoscopic activity than untreated (Mayo sub-score 3 vs. 2,6, p < 0,004). The mean hospital duration was longer in treated patients 22.3 ( ± 11.1) days, vs. 14,8(+/−8,6) days. 3 patients underwent surgery within 90 days, 2 patients died; all of them were positive for CMV DNA. No significant differences were observed on either colectomy or mortality rate in relation to the use of antiviral therapy. Conclusion This single-centre study confirms that the CMV reactivation during disease flares of IBD is common and related to disease duration, severe endoscopic lesions, and immunosuppression (high dose steroids and/or immunomodulators).Antiviral drugs do not seem to modify surgical outcomes or mortality but increase the hospitalisation length. However, the retrospective design and the limited sample size of the study do not allow to draw definitive conclusions: the real impact on outcome and the role of antiviral therapy will require adequately powered prospective studies.

Background A growing body of evidences indicate that the aberrant activation of innate immune systems, occurring in genetically predisposed patients, drives inflammatory processes in Ankylosing Spondylitis (AS).1 Objectives Aim of this study was to evaluate the activation and the functional relevance of inflammasome pathways in patients with AS. Methods Intestinal, synovial and bone marrow expression of inflammasome pathways, pyroptosis and IL-1b and IL-18 was evaluated in AS patients. Organic acid extraction was performed on ileal samples as previously described on.2 The expression of the metabolite-sensing receptors GPR43 and GPR109A involved in the regulation of the intestinal inflammasome was also assessed. The role of intestinal dysbiosis in modulating inflammasome activation was also studied in AS patients and HLA-B27 transgenic rats. Inflammasome activation was evaluated in isolated peripheral AS monocytes. The role of LPS, PGE2 and nicotine in inducing monocyte inflammasome activation and the role of inflammasome in modulating IL-23 production was also evaluated. Results Activation of inflammasomes was observed in the inflamed gut, synovial and bone marrow samples of AS patients and associated with an increased expression of caspase-1, IL-1b and IL-18. In AS, AIM2 expression was observed in the context of tuft cells and of adherent ileal bacteria. Inflammasome activation in AS gut, was associated with the occurrence of dysbiosis and increased pyroptosis as demonstrated by the membrane localization of Gasdermin D. Isolated intestinal bacteria from AS ileal samples, significantly modulated inflammasome activation in isolated monocytes. Reduced Short-chain fatty acids concentrations and increased expression of GPR43 and GPR109 were demonstrated in the AS ileal samples. Inflammasome activation was also observed in the inflamed gut of HLA-B27 TG rats and suppressed by antibiotics treatment. Increased expression of NLRP3, NLRC4 and AIM2 was confirmed in AS isolated peripheral monocytes. Serum levels of IL-1b and IL-18 were increased in AS patients, especially in smoker patients, and directly correlated with the ASDAS-CRP. In in vitro studies, LPS and nicotine strongly activated NLRP3, NLRC4 and AIM2 pathways in AS monocytes. The CC genotype of PTGER4 SNP rs6896969 was associated with a significantly increased activation of inflammasome in AS. Finally, inflammasome activation in AS monocytes was required for the induction of IL-23p19 expression in an IL-1b-dependent way. Conclusions Inflammasome activation occurs in AS patients being modulated by a plethora of different stimuli. Inflammasome drives IL-23 production in an IL-1b-dependent mechanism in AS patients supporting the auto-inflammatory nature of the disease and possibly representing a future therapeutic target in AS. References [1] Ciccia F, et al. Intestinal dysbiosis and innate immune responses in axial spondyloarthritis. Curr Opin Rheumatol2016. [2] Fuller M, et al. The short chain fatty acid receptor, FFA2, contributes to gestional glucose homeostasis. American Journal of Physiology – Endocrinology and Metabolism2015. [3] Macia L, et al. Metabolite-sensing receptors GPR43 and GPR109 facilitate dietary fibre-induced gut homeostasis through the regulation of the inflammasome. Nat Commun2015. Disclosure of Interest None declared

Gastroesophageal reflux disease (GERD) is a very common disease, as about a quarter of the Western population has GERD symptoms at least weekly and GERD is the most frequent reason for outpatient gastroenterology consultation. GERD treatment is based on proton pump inhibitor (PPI) use, but PPI may be ineffective in some patients and potentially unsafe if administered for very long time. A new medical compound (Marial®) has been introduced on the Italian market. This product contains magnesium alginate and a phytopolymer: it may be able to repair ulcer/erosion, protect mucosal tissue, and contrast acid contents. The current survey was conducted on a large group of GERD patients visited at 56 Italian gastroenterological offices. Patients were treated with PPI alone, PPI plus add-on, or Marial® for 4 weeks: the choice was decided by each gastroenterologist on the basis of the best practice criterion. A reflux symptoms index (RSI) questionnaire was used to weekly assess the clinical features. Marial® and PPI plus add-on significantly reduced RSI scores, from the second week. Noteworthy, Marial® was more effective than PPI plus add-on. In conclusion, the current survey demonstrated that patients with GERD perceived a significant improvement of GERD symptoms measured by the RSI questionnaire. Marial® was as effective as PPI plus add-on.

Gastroesophageal reflux disease (GERD) is a very common disorder. As there is no gold standard diagnostic tool, patient-based strategy is adopted in clinical practice. In this regard, there are questionnaires able to easily and rapidly assess symptom severity directly by the patient. The GERD Impact Scale (GIS) and the Reflux Symptom Index (RSI) have been validated as diagnostic tools in routine clinical care. The present study aimed to correlate RIS values with GIS scores in a large cohort of GERD patients visited at gastroenterological clinics. Globally, 785 subjects (51.2% males, 48.8% females, mean age: 49.59 years) were visited in 56 Italian gastroenterological offices. The current study demonstrates that a GIS value19 may be a reliable cut-off to define the positivity of the test, and GIS and RSI were significantly correlated. Therefore, both tests may be recommended for GERD patients in clinical practice.

There are discrepancies in the different studies that attempt to correlate the risk factors of developing amyotrophic lateral sclerosis (ALS) and the impact on their prognosis. Some of these factors are intrinsic to the rural livelihood. Therefore, we propose to study if any of these influence the onset and/or prognosis of the disease in the health region of Lleida, a predominantly rural area.Variables related to general factors, clinical, environmental and laboratory were collected and analyzed at the time of diagnosis of ALS in 38 patients and were retrospectively related to the onset of the disease and its survival.The family history of ALS (p0.02) and elevated CK (p0.0001) were associated with increased survival. Smoking (p0.04), physical work (p0.03), low creatinine (p0.03), elevated CK (p = 0.0005) were associated with an early onset of the disease. The bulbar onset form was significantly related to a late onset of the disease (p0,01). Total cholesterol and PCR did not influence the onset or course of ALS. There is a non-significant trend at statistical level in favor of moderate physical exercise being associated with a later onset, while intense exercise at an early onset of ALS.The results suggest that there are a number of factors that influence the development and prognosis of ALS, some of which are more prevalent in rural areas, such as physical work.Influencia de los factores ambientales-analiticos sobre el fenotipo de esclerosis lateral amiotrofica en un medio rural.Introduccion. Existen discrepancias en los diversos estudios que intentan correlacionar los factores de riesgo de desarrollar esclerosis lateral amiotrofica (ELA) y el impacto en su pronostico. Algunos de dichos factores son intrinsecos al medio de vida rural. Por ello, proponemos estudiar si alguno de estos influye sobre el inicio o el pronostico de la enfermedad en la region sanitaria de Lleida, un ambito predominantemente rural. Pacientes y metodos. Se recogieron y analizaron variables relacionadas con factores generales, clinicos, ambientales y de laboratorio en el momento del diagnostico de ELA en 38 pacientes, y se relacionaron retrospectivamente con el inicio de la enfermedad y su supervivencia. Resultados. Los antecedentes familiares de ELA (p0,02) y la creatincinasa elevada (p0,0001) se asociaron a mayor supervivencia. El tabaquismo (p0,04), el trabajo fisico (p0,03), la creatinina baja (p0,03) y la creatincinasa elevada (p = 0,0005) se asociaron a un inicio precoz de la enfermedad de modo estadisticamente significativo. La forma de inicio bulbar se relaciono significativamente con un inicio tardio de la enfermedad (p0,01). El colesterol total y la proteina C reactiva no influyeron en el inicio ni en el curso de la ELA en nuestra muestra. Existe una tendencia estadisticamente no significativa a favor de que el ejercicio fisico moderado se asocia con un inicio mas tardio, mientras que el ejercicio intenso se asocia con un inicio precoz de la ELA. Conclusiones. Los resultados apuntan a que existe una serie de factores que influye en el desarrollo y pronostico de la ELA, y alguno de estos es mas prevalente en el ambito rural, como el trabajo fisico.

In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care. Digestive diseases were the first or second cause of hospitalizations in Italy in 1999–2009, with more than 1,500,000 admissions/year; however only 5–9% of these admissions was in specialized Gastroenterology units. Reported data show a better outcome in Gastroenterology Units than in non-specialized units: shorter average length of stay, in particular for admissions with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days); better case mix (higher average diagnosis-related groups weight in Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery units); lower inappropriateness of admissions (16–25% versus 29–87%); lower in-hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was 2.3% in Gastroenterology units versus 4.0% in others. The present document summarizes the scientific societies’ official report, which constitutes the “White paper of Italian Gastroenterology”

Sao Paulo State Univ UNESP, Ctr Human Reprod Prof Franco Jr, Paulista Ctr Diag Res & Training, Dept Gynecol & Obstet,Botucatu Med Sch, Ribeirao Preto, Brazil

Background: Surrogate markers of colorectal inflammation are increasingly being recognized as important in differentiating organic from functional intestinal disorders. Fecal calprotectin (FC) can be easily measured in the stool, being released by leukocytes in inflammatory conditions. Aim: We evaluated FC as an index of inflammation in consecutive outpatients referred for colonoscopy for chronic, nonbloody diarrhea. Methods: Stool specimens of 346 outpatients with chronic, nonbloody diarrhea, referred for colonoscopy, were measured for FC levels. The proportion of patients correctly diagnosed with the test and the relationship with endoscopic and histologic findings were measured. Results: Abnormal endoscopic findings were detected in 104 patients (30.1%). Histologic findings included 142 patients (41.0%) with inflammation and 204 (59.0%) without inflammation. Fecal excretion of calprotectin significantly correlated with the finding of inflammation at endoscopy and histology (P

Objective The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin-23 (IL-23). IL-23 is known to regulate IL-22 production through lamina propria NKp44+ natural killer (NK) cells, which are thought to be involved in protective mucosal mechanisms. This study was undertaken to evaluate the frequency of NKp44+ NK cells and the expression of IL-22 in the ileum of AS patients. Methods Tissue NKp44+ NK cells, NKp46+ NK cells, and IL-22–producing cells were analyzed by flow cytometry. Quantitative gene expression analysis of IL-22, IL-23, IL-17, STAT-3, and mucin 1 (MUC-1) was performed by reverse transcriptase–polymerase chain reaction on ileal samples from 15 patients with AS, 15 patients with Crohn's disease (CD), and 15 healthy controls. NKp44, pSTAT-3, and IL-22 expression was analyzed by immunohistochemistry. Results The frequency of NKp44+ but not NKp46+ NK cells was increased in the inflamed ileum of AS patients compared to CD patients and controls. The frequency of NKp46+ NK cells was significantly increased only in CD patients. Among CD4+ lymphocytes and NKp44+ NK cell subsets, the latter were the major source of IL-22 on lamina propria mononuclear cells from AS patients. Significant up-regulation of IL-22, IL-23p19, MUC-1, and STAT-3 transcripts in the terminal ileum of patients with AS was observed. Immunohistochemical analysis confirmed the increased IL-22 and pSTAT-3 expression in inflamed mucosa from AS and CD patients. Conclusion Our findings indicate that overexpression of IL-22, together with an increased number of IL-22–producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.

The motion of the upper free surface of a liquid column released from the rest in a vertical conical container is analyzed theoretically and experimentally. An inviscid one dimensional model for a weakly increasing cross section in vertical tubes describes how the recently reported super free fall of liquids occurs in liquids of very low viscosity. Experiments show that the inviscid one dimensional model developed here agrees with theoretical results.

Background: Oesophagogastroduodenoscopy is currently recommended for the screening of varices in cirrhosis. In addition to the assessment of varices, oesophagogastroduodenoscopy can detect conditions that, while unrelated to portal hypertension, may require treatment. Aims: We evaluated in a large cohort of cirrhotic patients the prevalence of upper digestive findings other than oesophagogastric varices, the associations between upper gastrointestinal findings, portal hypertension and features of cirrhosis, and the incidence of new lesions in the course of a surveillance program. Methods: Analysis of the records of 611 consecutive cirrhotic patients undergoing oesophagogastroduodenoscopy for screening and surveillance. Results: 232 patients (38%) presented endoscopic lesions not related to portal hypertension: peptic diseases (n =193), proliferative diseases (n =27) and vascular diseases (n =12). In the screening group, 127 patients (39.4%) had pathologic lesions. At multivariate analysis, an association was found between peptic diseases and the absence of portal hypertensive gastropathy (RR 3.3; 95% Cl 2.2-4.8); vascular diseases were associated with endoscopic signs of portal hypertension (p = 0.01). During surveillance, 9/55 patients (16.3%) in the group without previous pathologic findings developed new lesions. Conclusions: Oesophagogastroduodenoscopy in patients with cirrhosis undergoing endoscopy for screening diagnosed pathologic lesions unrelated to portal hypertension requiring a change in management in 39.4% of asymptomatic subjects. (C) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Objective Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin-2 [IL-2], transforming growth factor β [TGFβ], and IL-10) and transcription factors (FoxP3 and STAT-5) in the ileum of patients with AS. Methods Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg-related cytokines (IL-2, TGFβ, and IL-10) and transcription factors (STAT-5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry. Results A significant up-regulation of IL-2, TGFβ, FoxP3, STAT-5, and IL-10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5-fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL-10. In vitro studies showed that blocking IL-10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients. Conclusion Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL-10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.