393 research outputs found

    Técnicas de biopsia para el diagnóstico de lesiones mamarias no palpables

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    Facing a non-palpable mammary lesion requiring a diagnostic biopsy, consideration must be given to the most suitable guiding method for obtaining the latter. Three methods are employed at present: stereotaxy (basically in cases of microcalcifications), echography (above all in the nodules), and magnetic resonance (for lesions not made visible through the previous systems). The next step is to select the most suitable biopsy technique. The most classical and reliable technique is the surgical biopsy with prior marking using a metallic harpoon, but, besides its high cost, it has the drawback of being an aggressive technique for the diagnosis of a benign pathology. Numerous systems of puncture have been developed as alternatives. Puncture with a fine needle is technically simple to carry out and can provide good results in the mammary nodules, but the existence of positive and negative false results has progressively limited its use. As an alternative, the systems of biopsy with a broad needle have made it possible to obtain multiple cylinders with a high diagnostic reliability, above all in the case of mammary nodules. However, their use in microcalcifications continues to show negative false results. The arrival of systems of vacuum-assisted biopsy has made it possible to obtain cylinders of greater quality, above all in cases of microcalcifications. Finally, the systems of percutaneous resection biopsy by means of cannulas with a diameter of 22 mm make it possible to completely extract lesions of a size below that of the cannula, with a reliability similar to that of the surgical biopsy

    Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I

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    Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging findings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissure

    Multi-ancestry genome-wide association study of asthma exacerbations

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    Asthma exacerbations; Single-nucleotide polymorphismExacerbaciones del asma; Polimorfismo de un solo nucleótidoExacerbacions de l'asma; Polimorfisme d'un sol nucleòtidBackground Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10−5) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele) = 0.82, p = 9.05 × 10−6 and replication: ORT allele = 0.89, p = 5.35 × 10−3) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele = 0.85, p = 3.10 × 10−5 and replication: ORC allele = 0.89, p = 1.30 × 10−2). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.This work was funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033, and the European Regional Development Fund “ERDF A way of making Europe” by the European Union (SAF2017-83417R), by MCIN/AEI/10.13039/501100011033 (PID2020-116274RB-I00) and by the Allergopharma-EAACI award 2021. This study was also supported by the SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020. GALA II and SAGE studies were supported by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, Harry Wm. and Diana V. Hind Distinguished Professor in Pharmaceutical Sciences II, the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, and R01HL141845), National Institute of Health and Environmental Health Sciences (R01ES015794 and R21ES24844); the National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, and R56MD013312); the National Institute of General Medical Sciences (NIGMS) (RL5GM118984); the Tobacco-Related Disease Research Program (24RT-0025 and 27IR-0030); and the National Human Genome Research Institute (NHGRI) (U01HG009080) to EGB. The PACMAN study was funded by a strategic alliance between GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences. The Slovenia study was financially supported by the Slovenian Research Agency (research core funding No. P3-0067) and from SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (contract number C3330-16-500106). The SHARE Bioresource (GoSHARE) and SHARE have ongoing funding from NHS Research Scotland and were established by funding from The Wellcome Trust Biomedical Resource [Grant No. 099177/Z/12/Z]. Genotyping of samples from BREATHE, PAGES, and GoSHARE was funded by AC15/00015 and conducted at the Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII; supported by ISCIII and European Regional Development Fund (ERDF) (PT17/0019). ALSPAC was supported by the UK Medical Research Council and Wellcome (102215/2/13/2) and the University of Bristol. The Swedish Heart-Lung Foundation, the Swedish Research Council, and Region Stockholm (ALF project and database maintenance) funded the BAMSE study. The PASS study was funded by the NHS Chair of Pharmacogenetics via the UK Department of Health. U-BIOPRED was funded by the Innovative Medicines Initiative (IMI) Joint Undertaking, under grant agreement no. 115010, resources for which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and kind contributions from companies in the European Federation of Pharmaceutical Industries and Associations (EFPIA). Genotyping of samples from GEMAS and MEGA studies was funded by the Spanish Ministry of Science and Innovation (SAF2017-87417R) at the Spanish National Cancer Research Centre, in the Human Genotyping lab, a member of CeGen, PRB3, and was supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. The genotyping of GEMAS was also partially funded by Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17). The Rotterdam Study was funded by Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. ALLIANCE Cohort was funded by grants from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) as part of the German Centre for Lung Research (DZL) funding. The Hartford-Puerto Rico study was funded by the U.S. National Institutes of Health (grant HL07966 to JCC). MP-Y was funded by the Ramón y Cajal Program (RYC-2015-17205) by MCIN/AEI/10.13039/501100011033 and by the European Social Fund “ESF Investing in your future”. MP-Y and JV were supported by CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain (CB/06/06/1088). EH-L was supported by a fellowship awarded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future” (PRE2018-083837). JP-G was supported by a fellowship awarded by Spanish Ministry of Universities (FPU19/02175). AE-O reports funding from the Spanish Ministry of Science, Innovation, and Universities (MICIU) and Universidad de La Laguna (ULL). NH-P was supported by a Medium-Term Research Fellowship by the European Academy of Allergy and Clinical Immunology (EAACI) and a Long-Term Research Fellowship by the European Respiratory Society (ERS) (LTRF202101-00861). UP and MG were supported by the Ministry of Education, Science and Sport of the Republic of Slovenia, grant PERMEABLE (contract number C3330-19-252012). SCSGES results were contributed by authors FTC and YYS. FTC has received research support from the Singapore Ministry of Education Academic Research Fund, Singapore Immunology Network (SIgN), National Medical Research Council (NMRC) (Singapore), Biomedical Research Council (BMRC) (Singapore), and the Agency for Science Technology and Research (A*STAR) (Singapore); Grant Numbers: N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, and H17/01/a0/008. F.T.C. has received consulting fees from Sime Darby Technology Centre; First Resources Ltd; Genting Plantation, and Olam International, outside the submitted work. YYS has received research support from the NUS Resilience & Growth Postdoctoral Fellowships with grant number: R-141-000-036-281. QY conducted the analysis from Hartford-Puerto Rico and United Kingdom Biobank studies. QY was funded by the U.S. National Institutes of Health (HL138098)

    Functional bold MRI: advantages of the 3 T vs. the 1.5 T

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    We quantitatively evaluate the benefits of a higher field strength for functional brain MRI (fMRI) based on the blood oxygenation level-dependent contrast. The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm

    Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

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    Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients

    Gastroduodenal injury after radioembolization of hepatic tumors

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    Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. METHODS: We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. RESULTS: We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. CONCLUSIONS: We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complicatio

    A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

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    Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

    Biocompatibility, Inflammatory Response, and Recannalization Characteristics of Nonradioactive Resin Microspheres: Histological Findings

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    Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10–30 microspheres (15–30 μm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 μm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization

    Clustering patterns of physical activity, sedentary and dietary behavior among European adolescents: The HELENA study.

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    Evidence suggests possible synergetic effects of multiple lifestyle behaviors on health risks like obesity and other health outcomes. A better insight in the clustering of those behaviors, could help to identify groups who are at risk in developing chronic diseases. This study examines the prevalence and clustering of physical activity, sedentary and dietary patterns among European adolescents and investigates if the identified clusters could be characterized by socio-demographic factors. METHODS: The study comprised a total of 2084 adolescents (45.6% male), from eight European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. Physical activity and sedentary behavior were measured using self-reported questionnaires and diet quality was assessed based on dietary recall. Based on the results of those three indices, cluster analyses were performed. To identify gender differences and associations with socio-demographic variables, chi-square tests were executed. RESULTS: Five stable and meaningful clusters were found. Only 18% of the adolescents showed healthy and 21% unhealthy scores on all three included indices. Males were highly presented in the cluster with high levels of moderate to vigorous physical activity (MVPA) and low quality diets. The clusters with low levels of MVPA and high quality diets comprised more female adolescents. Adolescents with low educated parents had diets of lower quality and spent more time in sedentary activities. In addition, the clusters with high levels of MVPA comprised more adolescents of the younger age category. CONCLUSION: In order to develop effective primary prevention strategies, it would be important to consider multiple health indices when identifying high risk groups.Peer Reviewe
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