Prevalencia e incidencia de cáncer en habitantes de Sibaté, y georeferenciación de casos 2010-2014

Introducción: El Cáncer es prevenible en algunos casos, si se evita la exposición a sustancias cancerígenas en el medio ambiente. En Colombia, Cundinamarca es uno de los departamentos con mayores incrementos en la tasa de mortalidad y en el municipio de Sibaté, habitantes han manifestado preocupación por el incremento de la enfermedad. En el campo de la salud ambiental mundial, la georreferenciación aplicada al estudio de fenómenos en salud, ha tenido éxito con resultados válidos. El estudio propuso usar herramientas de información geográfica, para generar análisis de tiempo y espacio que hicieran visible el comportamiento del cáncer en Sibaté y sustentaran hipótesis de influencias ambientales sobre concentraciones de casos. Objetivo: Obtener incidencia y prevalencia de casos de cáncer en habitantes de Sibaté y georreferenciar los casos en un periodo de 5 años, con base en indagación de registros. Metodología: Estudio exploratorio descriptivo de corte transversal,sobre todos los diagnósticos de cáncer entre los años 2010 a 2014, encontrados en los archivos de la Secretaria de Salud municipal. Se incluyeron unicamente quienes tuvieron residencia permanente en el municipio y fueron diagnosticados con cáncer entre los años de 2010 a 2104. Sobre cada caso se obtuvo género, edad, estrato socioeconómico, nivel académico, ocupación y estado civil. Para el análisis de tiempo se usó la fecha de diagnóstico y para el análisis de espacio, la dirección de residencia, tipo de cáncer y coordenada geográfica. Se generaron coordenadas geográficas con un equipo GPS Garmin y se crearon mapas con los puntos de la ubicación de las viviendas de los pacientes. Se proceso la información, con Epi Info 7 Resultados: Se encontraron 107 casos de cáncer registrados en la Secretaria de Salud de Sibaté, 66 mujeres, 41 hombres. Sin división de género, el 30.93% de la población presento cáncer del sistema reproductor, el 18,56% digestivo y el 17,53% tegumentario. Se presentaron 2 grandes casos de agrupaciones espaciales en el territorio estudiado, una en el Barrio Pablo Neruda con 12 (21,05%) casos y en el casco Urbano de Sibaté con 38 (66,67%) casos. Conclusión: Se corroboro que el análisis geográfico con variables espacio temporales y de exposición, puede ser la herramienta para generar hipótesis sobre asociaciones de casos de cáncer con factores ambientales.

Wheat proteins evolution and environmental triggers of Wheat-related diseases

Cereals, and in particular wheat, have always been recognized as a fundamental food worldwide. In particular, the success of wheat is linked with unique properties of the gluten protein fraction used in bread making process to obtain products that are widely used in traditional and modern diets. The rapid increase in the world population let to a parallel increases in food production, particularly of wheat. Increasing yield potential and selection of cultivars much more resistant to plant disease and to environmental factors could have negatively affected the quality of the grain. Moreover, the “green revolution” was characterized by a widespread use of agricultural chemicals and by industrialization of food production that led to a huge rise in the consumption of refined products. Modern baking practices have shortened bread leavening, increased the use of chemical/yeast leavening agents and there is well-documented scientific evidence of the negative effects of ultra-processed food in human healthy. All this changes profoundly modified the human diet and, as a result, may have affected Gluten-related disease (GRDs) that has arisen in the whole word populations. Gluten-related diseases (GRDs) are multifactorial pathologies in which environmental factors and genetic background contribute to a low-grade chronic inflammation of the gastrointestinal tract. Here, I investigated the potential pro-inflammatory effect of different wheat varieties and whether bread making processing are involved in the onset or worsening of gut inflammation. In vitro, ex vivo and in vivo studies conducted throughout my Phd period have shown a pro-inflammatory effect of wheat especially marked in modern varieties and a higher inflammatory response linked to the use of common raising agent as Saccharomyces Cerevisiae and to the addiction of chemical bakery improver substances.

Comprehensive characterization of SDH-deficient GIST using NGS data and iPSC models

Gastrointestinal stromal tumors (GIST) are the most common di tumors of the gastrointestinal tract, arising from the interstitial cells of Cajal (ICCs) or their precursors. The vast majority of GISTs (75–85% of GIST) harbor KIT or PDGFRA mutations. A small percentage of GIST (about 10‐15%) do not harbor any of these driver mutations and have historically been called wild-type (WT). Among them, from 20% to 40% show loss of function of the succinate dehydrogenase complex (SDH), also defined as SDH‐deficient GIST. SDH-deficient GISTs display distinctive clinical and pathological features, and can be sporadic or associated with Carney triad or Carney-Stratakis syndrome. These tumors arise most frequently in the stomach with predilection to distal stomach and antrum, have a multi-nodular growth, display a histological epithelioid phenotype, and present frequent lympho-vascular invasion. Occurrence of lymph node metastases and indolent course are representative features of SDH-deficient GISTs. This subset of GIST is known for the immunohistochemical loss of succinate dehydrogenase subunit B (SDHB), which signals the loss of function of the entire SDH-complex. The overall aim of my PhD project consists of the comprehensive characterization of SDH deficient GIST. Throughout the project, clinical, molecular and cellular characterizations were performed using next-generation sequencing technologies (NGS), that has the potential to allow the identification of molecular patterns useful for the diagnosis and development of novel treatments. Moreover, while there are many different cell lines and preclinical models of KIT/PDGFRA mutant GIST, no reliable cell model of SDH-deficient GIST has currently been developed, which could be used for studies on tumor evolution and in vitro assessments of drug response. Therefore, another aim of this project was to develop a pre-clinical model of SDH deficient GIST using the novel technology of induced pluripotent stem cells (iPSC).

Development of a porcine lactation model for the evaluation of mammary transfer of exogenous molecules - A contribution from the conception project

Around 5 million women give birth each year in Europe and, while breastfeeding, the majority of them may need to take medications, either occasionally or continuously. Unfortunately, there is often scarce evidence of trustworthy information about how a specific molecule might affect the physiology of lactation. This is the reason that brought a European public-private partnership to fund the development of a reliable platform to provide women and health-care professionals a helpful instrument to reduce uncertainty about the effects of medication used during breastfeeding. On April 1st 2019, the ConcePTION project (Grant Agreement n°821520) started to develop such envisaged platform. The 3rd Work Package was in charge of the validation of in vitro, in vivo and in silico lactation models. Between the numerous species currently used in preclinical studies, pigs’ similarities with humans’ anatomy, physiology and genomics make them extremely useful as translational models, when proper veterinary expertise is applied. The ASA team from the University of Bologna, went first to characterize the translational lactation model using the swine species, chosen upon literature review. The aim of this work was to lay the foundations of a porcine lactation model that could be suitable for application within pharmaceutical tests, to study drug transfer through milk prior approval and commercialization. The obtained results highlighted both strengths and critical points of the study design, allowing a significant improvement in the knowledge of pharmacokinetic physiology in lactating mammals. Lastly, this project allowed the assessment of microbial changes in gut resident bacteria of newborns through an innovative in vitro colonic model. Indeed, even if there were no evident adverse effects determined by drug residues in milk, possible alterations in the delicate microbial ecology of newborns’ gastrointestinal tract was considered pivotal, giving its possible impact on the individual health and growth.

Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird

Acknowledgements This study was funded by a BBSRC studentship (MA Wenzel) and NERC grants NE/H00775X/1 and NE/D000602/1 (SB Piertney). The authors are grateful to Fiona Leckie, Andrew MacColl, Jesús Martínez-Padilla, François Mougeot, Steve Redpath, Pablo Vergara† and Lucy M.I. Webster for samples; Keliya Bai, Daisy Brickhill, Edward Graham, Alyson Little, Daniel Mifsud, Lizzie Molyneux and Mario Röder for fieldwork assistance; Gillian Murray-Dickson and Laura Watt for laboratory assistance; Heather Ritchie for helpful comments on manuscript drafts; and all estate owners, factors and keepers for access to field sites, most particularly Stuart Young and Derek Calder (Edinglassie), Simon Blackett, Jim Davidson and Liam Donald (Invercauld and Glas Choille), Richard Cooke and Fred Taylor† (Invermark) and T. Helps (Catterick).

Nat2, Xrcc1 And Hogg1 Polymorphisms, Cigarette Smoking, Alcohol Consumption And Risk Of Upper Aerodigestive Tract Cancer.

To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048). Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Quantification of prolactin-releasing peptide (PrRP) mRNA expression in specific brain regions of the rat during the oestrous cycle and in lactation

Real-time Taqman(TM) RT-PCR was used to make quantitative comparisons of the levels of PrRP mRNA expression in micropunch brain samples from rats at different stages of the oestrous cycle and in lactation. The nucleus of the solitary tract and ventrolateral reticular nuclei of the medulla oblongata contained significantly (P < 0.05) greater levels of PrRP mRNA than any hypothalamic region. Within the hypothalamus, the highest level of PrRP expression was localised to the dorsomedial aspect of the ventromedial hypothalamus. All other hypothalamic regions exhibited significantly (P < 0.05) lower levels of expression, including the rostral and caudal dorsomedial hypothalamus. Very low levels of PrRP expression were observed in the arcuate nucleus, paraventricular nucleus, medial preoptic nucleus and ventrolateral aspect of the ventromedial hypothalamus. No significant changes in PrRP expression were noted in any sampled region between proestrus, oestrus or dioestrus. Similarly, PrRP expression in hypothalamic regions did not differ between lactating and non-lactating (dioestrous) animals. During validation of RT-PCR techniques we cloned and sequenced a novel splice variant of PrRP from the hypothalamus. This variant arises from alternative splicing of the donor site within exon 2, resulting in an insert of 64 base pairs and shift in the-codon:reading frame with the introduction of an early stop codon. In the hypothalamus and brainstem, mRNA expression of the variant was restricted to regions that expressed PrRP. These results suggest that PrRP expression in the hypothalamus may be more Widespread than previously reported. However, the relatively low level of PrRP in the hypothalamus and the lack of significant changes in expression during the oestrous cycle and lactation provides further evidence that PrRP is unlikely to be involved in the regulation of prolactin, secretion. (C) 2003 Elsevier Science B.V. All rights reserved.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulatioin in BD. Objective: To use tract-based spatial statistics (TBSS) to examine VVM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design: Cross-sectional, case-control, whole-brain DTI using TBSS. Setting: University research institute. Participants: Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type 1 (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures: Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results: Subjects with BD vs controls had significantly greater FA (t > 3.0, P <=.05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <=.05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P <.01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P <.01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions: To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II)

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.

Fulminant gastrointestinal hemorrhage due to Strongyloides stercoralis hyperinfection in an AIDS patient

Strongyloides stercoralis is an endemic nematode to tropical and subtropical regions of the globe. The parasite is capable of autoinfection, which is limited by an intact immune response. In immunocompromised hosts, hyperinfection and dissemination can occur and have a high index of mortality. A hyperinfection syndrome with dissemination is frequently associated with corticosteroid administration and other conditions (malignancies and organ transplantation). Interestingly, although strongyloidiasis is common among AIDS patients in endemic areas, the hyperinfection syndrome is rarely noted. We report here on a rare manifestation of fulminant gastrointestinal hemorrhage due to hyperinfection of strongyloidiasis in a female drug-abusing, alcoholic HIV/AIDS patient.

Flexible gastrointestinal motility pressure sensors based on aluminum thin-film strain-gauge arrays

This paper reports on an innovative approach to measuring intraluminal pressure in the upper gastrointestinal (GI) tract, especially monitoring GI motility and peristaltic movements. The proposed approach relies on thin-film aluminum strain gauges deposited on top of a Kapton membrane, which in turn lies on top of an SU-8 diaphragm-like structure. This structure enables the Kapton membrane to bend when pressure is applied, thereby affecting the strain gauges and effectively changing their electrical resistance. The sensor, with an area of 3.4 mm2, is fabricated using photolithography and standard microfabrication techniques (wet etching). It features a linear response (R2 = 0.9987) and an overall sensitivity of 2.6 mV mmHg−1. Additionally, its topology allows a high integration capability. The strain gauges’ responses to pressure were studied and the fabrication process optimized to achieve high sensitivity, linearity, and reproducibility. The sequential acquisition of the different signals is carried out by a microcontroller, with a 10-bit ADC and a sample rate of 250 Hz. The pressure signals are then presented in a user-friendly interface, developed using the Integrated Development Environment software, QtCreator IDE, for better visualization by physicians.

Deteção e classificação de regiões de interesse em vídeos de endoscopia

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)

Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI) is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI) broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%), followed by Klebsiella spp. (7%), Proteus mirabilis (6.4%), Enterococcus spp. (5.6%), and Pseudomonas aeruginosa (4.6%). Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%), TMP/SMX (40.4%), ciprofloxacin (21.6%), and gatifloxacin (17.1%). Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively), and P. mirabilis (71.8 and 84.6%, respectively). For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events.

Background: Recently, more clinical trials are being conducted in Africa and Asia, therefore, background morbidity in the respective populations is of interest. Between 2000 and 2007, the International AIDS Vaccine Initiative sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub-Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers.   Objective To assess background morbidity as reflected by unsolicited adverse events (AEs), unrelated to study vaccine, reported in clinical trials from four continents. Methods All but three clinical trials were double-blind, randomized, and placebo-controlled. Study procedures and data collection methods were standardized. The frequency and severity of AEs reported during the first year of the trials were analyzed. To avoid confounding by vaccine-related events, solicited reactogenicity and other AEs occurring within 28 d after any vaccination were excluded. Results In total, 2134 AEs were reported by 76% of all participants; 73% of all events were mild. The rate of AEs did not differ between placebo and vaccine recipients. Overall, the percentage of participants with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and India (65%), while the percentage of participants with AEs of moderate or greater severity was similar in all regions except India. In all regions, the most frequently reported AEs were infectious diseases, followed by gastrointestinal disorders. Conclusions Despite some regional differences, in these healthy participants selected for low risk of HIV infection, background morbidity posed no obstacle to clinical trial conduct and interpretation. Data from controlled clinical trials of preventive interventions can offer valuable insights into the health of the eligible population.

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.