Chronic pancreatitis in children: treat like an adult?

A 15-year-old boy with a medical background of obesity, familial hyperlipidemia and acute recurrent pancreatitis, presented to emergency department reporting a 3-day course of periumbilical abdominal pain and nausea. Pain was noticed on epigastric palpation. Laboratory evaluation revealed leucocytosis, neutrophilia and pancreatic enzymes elevation more than three times the upper limit of normal. An acute recurrence of pancreatitis was diagnosed, was admitted to the hospital, being discharged after 5 days. Four days after, he was readmitted because of symptoms recurrence. Elevation of transaminases, gamma-glutamyltransferase (GGT) and direct bilirubin were noticed. Pancreatic enzymes still elevated but lower than in the previous episode. An endoscopic ultrasound revealed a Wirsung with a cephalic stricture and diffuse structural abnormalities suggestive of chronic pancreatitis. The patients was submitted to endotherapy with several sessions of endoscopic retrograde cholangiopancreatography including stenting and pancreatoscopy with marked clinical and imaging improvement. A genetic variant was identified.info:eu-repo/semantics/publishedVersio

Quantitative Proteomic Profiling of Small Molecule Treated Mesenchymal Stem Cells Using Chemical Probes.

The differentiation of human adipose derived stem cells toward a neural phenotype by small molecules has been a vogue topic in the last decade. The characterization of the produced cells has been explored on a broad scale, examining morphological and specific surface protein markers; however, the lack of insight into the expression of functional proteins and their interactive partners is required to further understand the extent of the process. The phenotypic characterization by proteomic profiling allows for a substantial in-depth analysis of the molecular machinery induced and directing the cellular changes through the process. Herein we describe the temporal analysis and quantitative profiling of neural differentiating human adipose-derived stem cells after sub-proteome enrichment using a bisindolylmaleimide chemical probe. The results show that proteins enriched by the Bis-probe were identified reproducibly with 133, 118, 126 and 89 proteins identified at timepoints 0, 1, 6 and 12, respectively. Each temporal timepoint presented several shared and unique proteins relative to neural differentiation and their interactivity. The major protein classes enriched and quantified were enzymes, structural and ribosomal proteins that are integral to differentiation pathways. There were 42 uniquely identified enzymes identified in the cells, many acting as hubs in the networks with several interactions across the network modulating key biological pathways. From the cohort, it was found by gene ontology analysis that 18 enzymes had direct involvement with neurogenic differentiation

Urban Green Spaces, Greenness Exposure and Species Richness in Residential Environments and Relations with Physical Activity and BMI in Portuguese Adolescents

Environmental factors play an important role in obesity-related behaviors. Evidence indicates significant associations between weight and urban green spaces in adults, but it is not clear whether this relationship applies to adolescents. Therefore, our aim was to determine the associations between urban green spaces, greenness exposure and species richness in residential environments with physical activity and body mass index. Sixty-two adolescents between 12 and 18 years of age answered a self-administered questionnaire, providing information on height, weight, age, sex and home address. Data on socioeconomic deprivation were obtained from the European Index of Deprivation for Small Portuguese Areas. Physical activity levels were assessed using accelerometers. Urban green space counts and the normalized difference vegetation index values were measured using buffers along the roads with distances of 300, 500, 1000 and 1500 m from each participant’s residence. To quantify the species richness, the species richness index was used. Linear regression models were fitted to analyze whether urban green spaces, exposure to green spaces and species richness counts for each distance were associated with physical activity and self-reported body mass index. We did not find significant associations between the independent variables and the probability of overweight or obesity. The relationship between environmental variables, adolescents’ physical activity and body weight seems to be complex and further studies may contribute to better understanding of the topic.This research was funded by FEDER through the Operational Program for Competitiveness and Internationalization and received national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Research Center in Physical Activity, Health and Leisure (CIAFEL) (UIDB/00617/2020) and also under the Epidemiology Research Unit (EPIUnit)—Institute of Public Health of the University of Porto (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). Ana Isabel Ribeiro was supported by national funds through FCT, under the ‘Stimulus of Scientific Employment—Individual Support’ program within the contract info:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND/02386/2018/CP1538/CT0001/PT

A comprehensive guide for performing sample preparation and top-down protein analysis

© 2017 by the authors. Methodologies for the global analysis of proteins in a sample, or proteome analysis, have been available since 1975 when Patrick O'Farrell published the first paper describing two-dimensional gel electrophoresis (2D-PAGE). This technique allowed the resolution of single protein isoforms, or proteoforms, into single 'spots' in a polyacrylamide gel, allowing the quantitation of changes in a proteoform0s abundance to ascertain changes in an organism's phenotype when conditions change. In pursuit of the comprehensive profiling of the proteome, significant advances in technology have made the identification and quantitation of intact proteoforms from complex mixtures of proteins more routine, allowing analysis of the proteome from the 'Top-Down'. However, the number of proteoforms detected by Top-Down methodologies such as 2D-PAGE or mass spectrometry has not significantly increased since O'Farrell's paper when compared to Bottom-Up, peptide-centric techniques. This article explores and explains the numerous methodologies and technologies available to analyse the proteome from the Top-Down with a strong emphasis on the necessity to analyse intact proteoforms as a better indicator of changes in biology and phenotype. We arrive at the conclusion that the complete and comprehensive profiling of an organism0s proteome is still, at present, beyond our reach but the continuing evolution of protein fractionation techniques and mass spectrometry brings comprehensive Top-Down proteome profiling closer

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.This work did not receive any funding either from public, commercial, or nonprofit agencies

A therapeutic potential for marine skeletal proteins in bone regeneration

A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-β) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use. © 2013 by the authors; licensee MDPI

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30-14.53) and disseminated disease (OR 4.52 95%CI 1.44-14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.info:eu-repo/semantics/publishedVersio

MHJ-0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae

© 2015 The Authors. Published. Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ-0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ-0461 (rMHJ-0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ-0461 resides on the surface of M. hyopneumoniae. rMHJ-0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ-0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ-0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae

Pain Intensity and Time to Death of Cancer Patients Referred to Palliative Care

Introdução: A dor é uma experiência frequente nos doentes com cancro, especialmente naqueles em fase final de vida. Com este estudo, pretendemos estudar a intensidade de dor nos doentes com cancro avançado, referenciados aos cuidados paliativos, analisar os factores associados à ocorrência de dor moderada ou intensa e avaliar a sua relação com o tempo até à morte destes doentes. Material e Métodos: Estudo prospectivo observacional que incluiu consecutivamente todos os doentes referenciados aos cuidados paliativos com tumores sólidos metastizados e sem tratamento oncológico específico. Foi considerada a intensidade de dor da escala de Edmonton, de acordo com a graduação zero a 10, onde 0 = ausência de dor e 10 = máxima dor possível. Resultados: Entre outubro de 2012 e junho de 2015, foram incluídos 301 doentes, com idade mediana de 69 anos (37 - 94), 57% homens e 64,8% dos doentes com performance status 3/4. Aproximadamente 42% dos doentes apresentaram dor ≥ 4 e cerca de 74,4% estavam medicados com analgesia opióide. A intensidade de dor esteve associada ao performance status dos doentes, de acordo com a análise multivariável (OR: 1,7; IC 95%: 1,0 - 2,7; p = 0,045). A mediana do tempo de sobrevivência foi de 37 dias (IC 95%: 28 - 46), tendo os doentes com dor moderada ou intensa (intensidade de dor ≥ 4) uma mediana de sobrevivência de 29 dias (IC 95%: 21 - 37), comparada com os 49 dias (IC 95%: 35 - 63) para os doentes sem dor ou dor ligeira (p = 0,022). Discussão: O performance status, para além de ter estado associado a uma maior intensidade de dor, esteve associado a um menor tempo até à morte dos doentes com cancro avançado referenciados aos cuidados paliativos. Também o internamento, a presença de metastização intra-abdominal e a analgesia opióide estiveram associados de forma negativa ao tempo até à morte destes doentes. Conclusão: A dor oncológica continua a ser um problema clinicamente relevante nos doentes com cancro avançado

Physiological response and performance of tambaqui fed with diets supplemented with Amazonian nut

The present study evaluated the effectiveness of Amazonian nut (Bertholletia excelsa) as an alternative source of vegetal protein in tambaqui (Colossoma macropomum) diet. Performance and physiological status of fish fed for 60 days were evaluated. Four experimental isonitrogenous diets with 36% crude protein were formulated with increasing levels of nut meal (0, 10, 20 and 30%). Results showed the same growth performance for fish fed with diet with different levels of Amazonian nut than that without this ingredient (control). Analysis of physiological parameters (hematocrit, erythrocyte number, hemoglobin concentration, hematimetric indexes, total plasma protein and plasma glucose) corroborate these results, with no significant differences among treatments. Therefore, adding up to 30% of Amazonian nut in tambaqui diet there is no negative effect on physiological homeostasis and growth performance, indicating that the Amazonian nut is a promising alternative dietary protein source ingredient for tambaqui