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Association of TCF7L2 mutation and atypical diabetes in a Uruguayan population

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World Journal of Diabetes 2018年第9期9卷 157-164页

作者： Carolina Beloso Jorge Souto Matias Fábregat gerardo Romanelli gerardo Javiel Adriana Mimbacas Biodiversity and Genetics Department Instituto de Investigaciones Biológicas Clemente Estable Cytogenetics Laboratory Hematology and Transplant Service of Hematopoietic Progenitors Maciel Hospital ASSE Department of Genetics Faculty of Medicine UDELAR Human Molecular Genetics Laboratory Institut Pasteur de Montevideo Cell Signaling and Nanobiology Laboratory Instituto de Investigaciones Biológicas Clemente Estable Unit of Diabetes Hospital Pasteur ASSE-Ministry of Public Health Diabetologyc Service of Private Health Center Centro de Asistencia del Sindicato Médico del Uruguay

AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan *** Healthy, nondiabetic controls(n = 133) and patients with type 2 diabetes(n = 177) were selected from among the presenting population at level-3 referral healthcare centers in Uruguay. Patients with type 2 diabetes were subgrouped according to "atypical diabetes"(n = 92) and "classical diabetes"(n = 85). Genotyping for the rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) in the TCFTL2 gene was carried out with Taq Man? probes. Random samples were sequenced by Macrogen Ltd.(South Korea). Statistical analysis of the SNP data was carried out with the SNPStats online tool(http://***/SNPstats). The best inheritance model was chosen according to the lowest values of Akaike's information criterion and Bayesian information criterion. Differences between groups were determined by unpaired t-tests after checking the normal distribution or were converted to normalize the data. The association of SNPs was tested for matched case-control samples by using χ2 analysis and calculation of odds ratios(ORs) with 95% confidence intervals(CIs). All statistical tests were performed using SPSS v10.0 and EpiI nfo7 statistical packages. Significant statistical differences were assumed in all cases showing adjusted P < *** We genotyped two TCF7 L2 SNPs(rs7903146 and rs12255372) in a population-based sample of 310 Uruguayan subjects, including 133 healthy control subjects and 177 clinical diagnosed with type 2 diabetes. For both SNPs analyzed, the best model was the dominant type: rs12255372 = G/G vs G/T+T/T, OR = 0.63, 95%CI: 0.40-0.98, P < 0.05 and rs7903146 = C/C vs C/T+T/T, OR = 0.79, 95%CI: 0.41-1.55, P = 0.3. The rs12255372 SNP showed high association with the type 2 diabetes cases(OR = 1.60, 95%CI: 1.20-2.51, P < 0.05). However, when the type 2 diabetics group was analyzed according to the atypical and classical subgroupings, t

关键词： TCF7L2 Atypical diabetes Type 2 diabetes Latin America TaqMan

Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

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Open Journal of Nephrology 2023年第2期13卷 126-149页

作者： Paula Xavier Dias-Pinto José gerardo G. Oliveira Portuguese Blood and Transplantation Institute Porto Portugal Faculty of Medicine University of Porto Porto Portugal CINTESIS FMUP Porto Portugal

Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.

关键词： Kidney Transplants Aspiration Biopsies Acute Rejection Chemokines Chemokine Receptors

Application of formal languages in polynomial transformations of instances between NP-complete problems

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Journal of Zhejiang University-Science C(Computers and Electronics) 2013年第8期14卷 623-633页

作者： Jorge A. ruiz-VANOYE Joaquín PREZ-ORTEGA Rodolfo A. PAZOS RANGEL Ocotlán DíAZ-PARRA Héctor J. FRAIRE-HUACUJA Juan FRAUSTO-SOLíS gerardo REYES-SALGADO Laura CRUZ-REYES DACI Universidad Autónoma del Carmen Computer Science Centro Nacional de Investigación y Desarrollo Tecnológico Systems and Computer Science Instituto Tecnológico de Ciudad Madero Informatics Universidad Politécnica del Estado de Morelos Computer Science Instituto Tecnológico de Cuautla

We propose the usage of formal languages for expressing instances of NP-complete problems for their application in polynomial transformations. The proposed approach, which consists of using formal language theory for polynomial transformations, is more robust, more practical, and faster to apply to real problems than the theory of polynomial transformations. In this paper we propose a methodology for transforming instances between NP-complete problems, which differs from Garey and Johnson's. Unlike most transformations which are used for proving that a problem is NP-complete based on the NP-completeness of another problem, the proposed approach is intended for extrapolating some known characteristics, phenomena, or behaviors from a problem A to another problem B. This extrapolation could be useful for predicting the performance of an algorithm for solving B based on its known performance for problem A, or for taking an algorithm that solves A and adapting it to solve B.

关键词： Formal languages Polynomial transformations NP-completeness

Is it growing exponentially fast? -Impact of assuming exponential growth for characterizing and forecasting epidemics with initial near-exponential growth dynamics

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Infectious Disease Modelling 2016年第1期1卷 71-78页

作者： gerardo Chowell Cecile Viboud School of Public Health Georgia State UniversityAtlantaGAUSA Division of International Epidemiology and Population Studies Fogarty International CenterNational Institutes of HealthBethesdaMDUSA

The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing models that capture the baseline transmission characteristics in order to generate reliable epidemic *** models for epidemic forecasting could be achieved by identifying signature features of epidemic growth,which could inform the design of models of disease spread and reveal important characteristics of the transmission *** particular,it is often taken for granted that the early growth phase of different growth processes in nature follow early exponential growth *** the context of infectious disease spread,this assumption is often convenient to describe a transmission process with mass action kinetics using differential equations and generate analytic expressions and estimates of the reproduction *** this article,we carry out a simulation study to illustrate the impact of incorrectly assuming an exponential-growth model to characterize the early phase(e.g.,3e5 disease generation intervals)of an infectious disease outbreak that follows near-exponential growth ***,we assess the impact on:1)goodness of fit,2)bias on the growth parameter,and 3)the impact on short-term epidemic *** findings indicate that devising transmission models and statistical approaches that more flexibly capture the profile of epidemic growth could lead to enhanced model fit,improved estimates of key transmission parameters,and more realistic epidemic forecasts.

关键词： dynamics. process. exponential

Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020

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Infectious Disease Modelling 2020年第1期5卷 264-270页

作者： Kenji Mizumoto gerardo Chowell Graduate School of Advanced Integrated Studies in Human Survivability Kyoto University Yoshida-Nakaadachi-choSakyo-kuKyotoJapan Hakubi Center for Advanced Research Kyoto UniversityYoshidahonmachiSakyo-kuKyotoJapan Department of Population Health Sciences School of Public HealthGeorgia State UniversityAtlantaGeorgiaUSA Division of International Epidemiology and Population Studies Fogarty International CenterNational Institutes of HealthBethesdaUSA

An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January eFebruary *** mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members,we characterize how the transmission potential varied over the course of the *** estimate of the mean reproduction number in the confined setting reached values as high as^11,which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore(approximate range:1.1e7).Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine *** recent estimates of Rt reached values largely below the epidemic threshold,indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

关键词： Corona Epidemic Confined settings Cruise Next generation matrix

A primer on stable parameter estimation and forecasting in epidemiology by a problem-oriented regularized least squares algorithm

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Infectious Disease Modelling 2017年第2期2卷 268-275页

作者： Alexandra Smirnova gerardo Chowell Department of Mathematics and Statistics Georgia State UniversityAtlantaUSA School of Public Health Georgia State UniversityAtlantaUSA Division of International Epidemiology and Population Studies Fogarty International CenterNational Institutes of HealthBethesdaMDUSA

Public health officials are increasingly recognizing the need to develop disease-forecasting systems to respond to epidemic and pandemic *** instance,simple epidemic models relying on a small number of parameters can play an important role in characterizing epidemic growth and generating short-term epidemic *** the absence of reliable information about transmission mechanisms of emerging infectious diseases,phenomenological models are useful to characterize epidemic growth patterns without the need to explicitly model transmission mechanisms and the natural history of the *** this article,our goal is to discuss and illustrate the role of regularization methods for estimating parameters and generating disease forecasts using the generalized Richards model in the context of the 2014e15 Ebola epidemic in West Africa.

关键词： Generalized Richards model Parameter estimation Regularization methods Epidemic forecasting Ebola

Positive frequency of autoantibodies in multiple sclerosis patients Are they associated with therapy?

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Neural Regeneration Research 2010年第4期5卷 257-260页

作者： gerardo Iuliano Luigi Cinquanta Anna Maria Ferruzzi Rosa Napoletano Azienda Ospedaliera Ospedali Riuniti di SalernoU.O.NeurologiaCentro Provinciale Sclerosi Multipla Azienda Ospedaliera Ospedali Riuniti di SalernoU.O.Laboratorio Patologia Clinica Azienda Ospedaliera Ospedali Riuniti di Salerno

BACKGROUND： Humoral autoimmunity in patients with multiple sclerosis is often asymptomatic and transient during interferon therapy. OBJECTIVE： To analyze the frequency of positivity to autoantibodies in multiple sclerosis patients and to clarify whether it is modified by immunomodulating therapy. DESIGN： A retrospective *** AND SE＇rrlNG： The study was performed at the Multiple Sclerosis Center, Department of Neurosciences, Salerno Hospital, Italy, between 2005 and 2007. PARTICIPANTS： A total of 169 multiple sclerosis patients were included, 57 males and 112 females Individuals were mainly outpatients and were usually tested yearly for autoantibodies. Patients with previous immunological diseases were excluded from statistical evaluation. METHODS： The frequency of positivity was calculated in patients grouped for gender, multiple sclerosis clinical parameters, magnetic resonance imaging features and disease modifying therapy. A total of 113 patients were treated with beta interferons. MAIN OUTCOME MEASURES： Frequency of positivity to any autoantibody. Prevalences and incidences were ***： The overall prevalence of autoantibodies within 3 years was 47.3%. In multiple sclerosis patients who were untreated or treated with drugs other than interferons, the prevalence was higher, and greater positivity to autoantibodies was seen in patients treated with interferons [odds ratio （95% confidence interval）, 2.87 （1.5 - 5.2）, P 〈 0.05 - 0.01]. Multiple regression analysis showed a significant association of the positivity to autoantibodies with interferon therapy, rather than gender, relapse or magnetic resonance imaging. CONCLUSION： Interferon therapy is associated with significantly higher frequency of autoantibodies in patients with multiple sclerosis. The differences among the therapies are not influenced by other variables such as gender or clinical pattern.

关键词： multiple sclerosis autoimmunity autoantibodies immunomodulation interferon

Focus on acute diarrhoeal disease

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World Journal of Gastroenterology 2009年第27期15卷 3341-3348页

作者： Fabio Baldi Maria Antonia Bianco gerardo Nardone Alberto Pilotto Emanuela Zamparo Gastroenterology Unit S. Orsola-Malpighi HospitalVia Massarenti 9 40138 Bologna Italy

Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classif ied according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and loperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as loperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, def ined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are poor. At least 75% of those travelling for short periods mention health problems, and in particular traveller's diarrhoea.

关键词：急性腹泻病治疗方法临床分析发病率

Influence of steel jacket thickness on the RC bridges' seismic vulnerability

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Journal of Traffic and Transportation Engineering(English Edition) 2019年第1期6卷 15-34页

作者： Bertha Olmos José Manuel Jara gerardo Gómez Guillermo Martínez Department of Civil Engineering Universidad Michoacana de San Nicolas de Hidalgo

The seismic demands of bridges subjected to strong earthquakes are mostly concentrated on piers. The main objective of this study is to assess the seismic vulnerability of retrofitted bridges with steel jackets. It analyzes the influence of the steel jacket thickness on the seismic capacity and demand of bridges. The bridges in study have two simple supported spans with superstructure composed by AASHTO type girders and a substructure formed with one circular pier over a stiff foundation. They are located on the Pacific coast of Mexico that is a zone of high seismicity. The bridges seismic capacity are evaluated through nonlinear static analyses and the shear force and displacement demands were determined using capacity spectra with a group of 10 real accelerograms from a subduction source. The response spectra were scaled to several peak ground accelerations(PGA) with the aim to estimate four damage scenarios linked each one to a probability of exceedance in a specific period, for return periods in the range of 72-3500 years that represent service level and maximum considered earthquake. Results show that the confining effect provided by the steel jackets substantially improves the seismic performance of the bridges piers. The increase of jacket thickness guides to important increments on columns base shear capacity, and the influence of the steel jacket thickness depends on the limit state and bridge slenderness ratio.

关键词： Steel jacket Piers’retrofit Subduction earthquakes RC piers’vulnerability