49 research outputs found
Long-term effects of bosentan therapy in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical and haemodynamic impact
No full textFirst and second authors equally contributed to the study. The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in HEART editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://heart.bmjjournals.com/ifora/licence.pdf). Affiliation
Lipoleiomyosarcoma with pleomorphic liposarcoma of the uterus: Computed tomography findings with pathological correlation. A case report and review of literature
No full textUterine lipoleiomyosarcomas (L-LMS) are rare malignant tumors with only few cases descripted in literature. As well, liposarcomas (LPS) arising from uterine corpus are extremely rare since fat tissue is commonly poor or absent in uterus. We report a case of L-LMS of the uterine corpus with an associated component of pleomorphic LPS. As for other female pelvic malignancies, these neoplasms are more common in postmenopausal women and clinical findings are nonspecific. Most frequent signs and symptoms are metrorrhagia and abdominal pain often associated with pelvic distension/mass. We describe diagnostic and therapeutic steps of our patient from acceptation to conclusive diagnosis. In this case, contrast-enhanced computed tomography (CECT) depicted pivotal diagnostic findings and showed a clear distinction between different tumor components. Therefore, our goal with this essay is to stress the role of CECT imaging for diagnosis of these rare neoplasms. We also perform a review of current literature about liposarcomas of the uterine corpus
Adipokines and redox signaling: impact on fatty liver disease.
No full textAdipokines (adipose tissue cytokines) are polypeptide factors secreted by adipose tissue in a highly regulated manner. The 'classical' adipokines (leptin, adiponectin, and resistin) are expressed only by adipocytes, but other adipokines have been shown to be released by resident and infiltrating macrophages, as well as by components of the vascular stroma. Indeed, adipose tissue inflammation is known to be associated with a modification in the pattern of adipokine secretion. Several studies indicate that adipokines can interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Moreover, plasma levels of adipokines have been investigated in patients with nonalcoholic fatty liver disease in order to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. In this Forum article, we provide a review of recent data that suggest a significant role for oxidative stress, reactive oxygen species, and redox signaling in mediating actions of adipokines that are relevant in the pathogenesis of nonalcoholic fatty liver disease, including hepatic insulin resistance, inflammation, and fibrosis
Correction to: Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research
No full textIn the original publication of the article, the author name has been incorrectly published as Maria C. Santagati in the Review (2022). The correct name is Maria Santagati. The original article has been corrected
Enantiopurity‐Dependent Peptide Coacervates and Asymmetric Organocatalysis
No full textInternational audienceABSTRACT Membraneless compartmentalization via liquid–liquid phase separation (LLPS) has emerged as a powerful strategy to organize biochemical reactions. Recently, peptide‐based coacervates demonstrated the potential to function as microreactors by enhancing reaction kinetics through increased local concentrations and altered microenvironments. Here, we introduce an O‐methylated diphenylalanine‐based tripeptide LLL PFF‐OCH 3 containing an N‐terminal proline, designed to undergo LLPS, and simultaneously function as an enantioselective organocatalyst. Comprehensive characterization via confocal microscopy, fluorescence recovery after photobleaching (FRAP), micro‐Raman and attenuated total reflection infrared (ATR‐IR) spectroscopy, diffusion‐surface plasmon resonance ( D ‐SPR), and molecular dynamics (MD) simulations revealed the formation of stable liquid droplets. In contrast, a racemic mixture of LLL PFF‐OCH 3 and DDD PFF‐OCH 3 failed to form liquid droplets and instead formed a solid precipitate, unveiling a critical role of enantiopurity in LLPS. Proof‐of‐concept catalytic studies proved enantioselective organocatalytic activity of the LLL PFF‐OCH 3 liquid coacervates. Beyond catalysis these results may have broader implications in understanding prebiotic chemistry and neurodegeneration
Solid carbon dioxide to promote the extraction of extra-virgin olive oil
No full textThe use of solid carbon dioxide (dry ice) as a cryogen is widespread in the food industry to produce high quality wines, rich in color and perfumes. The direct addition of carbon dioxide to olives in the solid state before milling represents a fundamental step which characterizes this innovative extraction system.
At room temperature conditions solid carbon dioxide evolves directly into the air phase (sublimation), and the direct contact between the cryogen and the olives induces a partial solidification of the cellular water inside the fruits. Since the volume occupied by water in the solid state is higher than that in the liquid state, the ice crystals formed are incompatible with the cellular structure and induce the collapse of the cells, besides promoting the diffusion of the cellular substances in the extracted oil, which is thus enriched with cellular metabolites characterized by a high nutraceutical value. Furthermore, a layer of CO2 remains over the olive paste to preserve it from oxidative degradation. The addition of solid carbon dioxide to processed olives induced a statistically significant increase in oil yield and promoted the accumulation of tocopherols in the lipid phase, whereas a not significant increase in the phenolic fraction of the oil occurred
Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults
No full textAcuin, Cecilia (IRRI author
POPULATION-BASED SERO-EPIDEMIOLOGICAL STUDY PROTOCOL FOR THE IMPACT OF SMOKING ON SARS-COV-2 INFECTION AND COVID-19 OUTCOMES – THE TROINA STUDY
No full textAfter the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness remains uncertain. In this context, this project aims at quantifying the proportion of SARS-CoV-S antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between smoking status and infection using seroprevalence data.
The added value of this research is that the current smoking status of the population to be studied will be biochemically verified, in order to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide actionable metric to study the role of smoking in SARS-CoV-2 spread, and therefore implement the most appropriate public health measures to control the pandemic.
The research design involves a 6-month prospective cohort study with serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (namely, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2 specific antibodies and serum cotinine.
Overall, we expect to find a higher prevalence of antibodies in individuals at high-risk for viral exposure (i.e., healthcare or other essential workers), according to previous literature, and to refine current estimates on the association between smoking status and SARS-CoV-2/COVID-19. Our results may serve as a reference for future clinical research and the methodology could be exploited in public health sectors and policies.
Competing Interest Statement
RP is full tenured professor of Internal Medicine at the University of Catania (Italy) and Medical Director of the Institute for Internal Medicine and Clinical Immunology at the same University. In relation to his recent work in the area of respiratory diseases, clinical immunology, and tobacco control, RP has received lecture fees and research funding from Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A/S, Sandoz, MSD, Boehringer Ingelheim, Novartis, Duska Therapeutics, and Forest Laboratories. Lecture fees from a number of European EC industry and trade associations (including FIVAPE in France and FIESEL in Italy) were directly donated to vaper advocacy no−profit organizations. RP has also received grants from European Commission initiatives (U−BIOPRED and AIRPROM) and from the Integral Rheumatology & Immunology Specialists Network (IRIS) initiative. He has also served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, CV Therapeutics, Boehringer Ingelheim, Novartis, Duska Therapeutics,ECITA (Electronic Cigarette Industry Trade Association, in the UK), Arbi Group Srl., and Health Diplomats. RP has served on the Medical and Scientific Advisory Board of Cordex Pharma, Inc., CV Therapeutics, Duska Therapeutics Inc, Pfizer, and PharmaCielo. RP is also founder of the Center for Tobacco prevention and treatment (CPCT) at the University of Catania and of the Center of Excellence for the acceleration of Harm Reduction (CoEHAR) at the same University, which has received support from Foundation for a Smoke Free World to conduct 8 independent investigator−initiated research projects on harm reduction. RP is also currently involved in the following pro bono activities, scientific advisor for LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti−Smoking League), the Consumer Advocates for Smoke−free Alternatives (CASAA) and the International Network of Nicotine Consumers Organizations (INNCO), Chair of the European Technical Committee for standardization on Requirements and test methods for emissions of electronic cigarettes (CEN/TC 437, WG4). JR: Research support from Foundation for a Smoke−Free World, Philip Morris International, Altria, JUUL Labs. Consulting with Revive pharmaceuticals, and consulting and patent purchase agreement with Philip Morris International. All other authors have no relevant conflict of interest to declare in relation to this study.This investigator-initiated research protocol was produced with the help of a grant from the Foundation for a Smoke Free World. The funder had no role in the study design, or the writing of the protocol. The contents, selection and presentation of facts, as well as any opinions expressed in the protocol are the sole responsibility of the author and under no circumstances shall be regarded as reflecting the positions of the funder
Machine learning model to predict the risk of adverse event in opioid analgesics using next-generation sequencing (NGS) data in a population of Colombian patients
No full textilustracionesOBJETIVO: Desarrollar un modelo basado en aprendizaje automático para la predicción del riesgo de evento adverso, a partir del genotipo en farmacogenes asociados con la farmacocinética y farmacodinámica de analgésicos opioides, a partir de datos de secuenciación de última generación (NGS), en una cohorte de pacientes colombianos.
MÉTODOS: Se desarrolló un pipeline de anotación de variantes y anotación funcional en 39 genes asociados a la farmacocinética y farmacodinamia de 17 analgésicos opioides de uso común en Colombia a partir de 2080 VCF de exomas provenientes de la secuenciación de nueva generación (NGS). Se realizó un modelo de aprendizaje automático para la clasificación del riesgo efecto adverso utilizando bosques aleatorios, naive Bayes y perceptrón multicapa.
RESULTADOS: El pipeline de anotación de variantes y anotación funcional en 39 genes asociados a la farmacocinética y farmacodinamia de 17 analgésicos opioides de uso común en Colombia detecta 9 variantes de riesgo. Los algoritmos de aprendizaje automático se entrenan y evalúan a partir de un dataset compuesto por 1900 variantes genéticas con score de riesgo desde 0.5 a 1.5, 50 variantes genéticas con un escore de 1.5 a 2 y 9 variantes genéticas con score de 2.5 a 4, las cuales están asociadas con efecto adverso, se analizan empleando bosques aleatorios, naive bayes y perceptrón multicapa, obteniendo resultados deficientes en la clasificación de la clase 2 y clase 3 debido al desbalance de datos en estas clase, con lo cual se realiza un enriquecimiento del dataset a partir de variantes de la base de datos PharmGKB, ampliando la data de la clase 3. Se evalúan varias combinaciones de clases por medio de bosques aleatorios y perceptrón multicapa, obteniendo los mejores resultados de clasificación, considerado únicamente dos clases, clase 1, suprimiendo valores de score de 0.5 y 1 y clase 2 compuesta por la unión de datos con score de 2.5 a 5.
CONCLUSIONES: Fue posible desarrollar modelos computacionales de clasificación del riesgo de efecto adverso. Sin embargo, se concluye que el desequilibrio en las clases, genera problemas de clasificación, lo que resulta en una reducción significativa de la sensibilidad y la precisión de los modelos de aprendizaje automático. Para poder generar relaciones entre variantes genéticas y su asociación con la presentación de efecto adverso se hace indispensable considerar variables de diversas ómicas que le den un peso importante a la asociación, acompañado de la información clínica y de seguimiento de los pacientes. (Texto tomado de la fuente)GOAL: To develop a model based on machine learning for prediction of the risk of
adverse event, from the genotype in associated pharmacogenes with the
pharmacokinetics and pharmacodynamics of opioid analgesics, based on data from nextgeneration sequencing (NGS), in a cohort of colombian patients.
METHODS: A variant annotation and functional annotation pipeline was developed
for 39 genes associated with the pharmacokinetics and pharmacodynamics of 17
commonly used opioid analgesics in Colombia from 2080 VCF exomes from
nextgeneration sequencing (NGS). A machine learning model was performed for
risk adverse effect classification using random forest, naive Bayes, and multilayer
perceptron.
RESULTS: The variant annotation and functional annotation pipeline in 39 genes
associated with the pharmacokinetics and pharmacodynamics of 17 commonly
used opioid analgesics in Colombia detected 9 risk variants. Machine learning
algorithms are trained and evaluated from a dataset composed of 1,900 genetic
variants with risk scores from 0.5 to 1.5, 50 genetic variants with scores from 1.5
to 2, and 9 genetic variants with scores from 2.5 to 4. , which are associated with
an adverse effect, will be analyzed using occasional forests, naive bayes and
multilayer perceptron, obtaining poor results in the classification of class 2 and
class 3 due to the imbalance of data in these classes, with which an enrichment is
performed. of the dataset from variants of the PharmGKB database, expanding the
data of class 3. Various combinations of classes are evaluated by means of random
forests and multilayer perceptron, obtaining the best classification results,
considering only two classes, class 1, suppressing score values of 0.5 and 1 and
class 2 composed of the union of data with scores from 2.5 to 5.
CONCLUSIONS: It was possible to develop computational models for classifying
the risk of adverse effects. However, it is concluded that the imbalance in the
classes generates classification problems, which results in a significant reduction
in the sensitivity and accuracy of the machine learning models. In order to generate
relationships between genetic variants and their association with the presentation
of adverse effects, it is essential to consider variables of various omics that give
significant weight to the association, accompanied by clinical information and
patient follow-up.MaestríaMagíster en BioinformáticaFarmacogenómic
Venetian cardinals at the Papal Court during the pontificates of Sixtus IV and Innocent VIII : 1471-1492
No full textThe histories of particular cities and states within that myriad-faceted
slice of civilisation, the Renaissance in Italy, have received
more scholarly attention than have the diplomatic, ecclesiastical and
cultural connections between them. This study is part of a balance-redressing
process. Senior clerics traversed frontiers, owing
allegiance to their native state, their benefices and, above all, to
the Papacy. The purpose of this exploration of the curial careers of
four later quattrocento Venetian cardinals is essentially twofold : to
account for relations between Venice and the Papacy with reference to
individuals who were at once Venetian patricians and princes of the
Church; and to examine the cardinals' responses to this situation in
terms of political, ecclesiastical and cultural patronage. Where did
their loyalty lie? To Venice, with its perennial suspicion of the
Church and peculiar notion of the characteristics of a Venetian
cardinal? Or to the Pope, expressing overt hostility towards the
Republic in the War of Ferrara and placing it under an interdict?
Chapter one sets Merco Barbo, Pietro Foscari, Giovanni Michiel and
Giovanni Battista Zeno in a Venetian context. Chapters two and three
chart relations between the two powers, from the exposure of Cardinal
Zeno's involvement in a scheme to transmit Venetian state secrets to
Rome in exchange for ecclesiastical preferment, through to Ermolao
Barbaro's controversial appointment to the patriarchate of Aquileia,
via the short-lived Papal-Venetian league negotiated by Cardinal
Foscari in 1480. The fourth chapter considers their proximity to the
Supreme Pontiff and how their material fortunes varied under popes
Sixtus and Innocent, after which an assessment of the nature, extent
and effectiveness of their patronage is divided between chapters five
and six, focussing pa.rticularly on Venetian connections. Despite
diverging careers, it is concluded that all were bound by variations
of the Venetian inheritance
