Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease ...(ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL;
< 0.001) and lower lipoprotein(a) Lp(a) (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL;
< 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.
The use and production of chemical compounds are subjected to strong legislative pressure. Chemical toxicity and adverse effects derived from exposure to chemicals are key regulatory aspects for a ...multitude of industries, such as chemical, pharmaceutical, or food, due to direct harm to humans, animals, plants, or the environment. Simultaneously, there are growing demands on the authorities to replace traditional in vivo toxicity tests carried out on laboratory animals (e.g., European Union REACH/3R principles, Tox21 and ToxCast by the U.S. government, etc.) with in silica computational models. This is not only for ethical aspects, but also because of its greater economic and time efficiency, as well as more recently because of their superior reliability and robustness than in vivo tests, mainly since the entry into the scene of artificial intelligence (AI)‐based models, promoting and setting the necessary requirements that these new in silico methodologies must meet. This review offers a multidisciplinary overview of the state of the art in the application of AI‐based methodologies for the fulfillment of regulatory‐related toxicological issues.
This article is categorized under:
Data Science > Chemoinformatics
Data Science > Artificial Intelligence/Machine Learning
Artificial Intelligence for Toxicological Predictions
This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of ...pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.
The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.
Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.
Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.
A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A highly sensitive electrochemical methodology for end-point detection of loop-mediated isothermal nucleic acid amplification reactions was developed. It is based on the oxidation process of phenol ...red (PR), commonly used as a visual indicator. The dependence of its redox process on pH, which changes during amplification, allows performing quantitative measurements. Thus, the change in the oxidation potential of PR during the amplification is used, for the first time, as the analytical signal that correlates with the number of initial DNA copies. As a proof-of-concept, the amplification of the pneumolysin gene from Streptococcus pneumoniae, one of the main pathogens causing community-acquired pneumonia, is performed. Combination of isothermal amplification with electrochemical detection, performed on small-size flexible electrodes, allows easy decentralization. Adaptation to the detection of other pathogens causing infectious diseases would be very useful in the prevention of future epidemics.
Quantitative polymerase chain reaction (qPCR) is considered the gold standard for pathogen detection. However, improvement is still required, especially regarding the possibilities of ...decentralization. Apart from other reasons, infectious diseases demand on‐site analysis to avoid pathogen spreading and increase treatment efficacy. In this paper, the detection of SARS‐CoV‐2 is carried out by reverse transcription loop‐mediated isothermal amplification, which has the advantage of requiring simple equipment, easily adaptable to decentralized analysis. It is proposed, for the first time, the use of palladium nanoclusters (PdNCs) as indicators of the amplification reaction at end point. The pH of the medium decreases during the reaction and, in turn, a variation in the catalytic activity of PdNCs on the oxygen reduction reaction (ORR) can be electrochemically observed. For the detection, flexible and small‐size screen‐printed electrodes can be premodified with PdNCs, which together with the use of a simple and small electrochemical equipment would greatly facilitates their integration in field‐deployable devices. This would allow a faster detection of SARS‐CoV‐2 as well as of other future microbial threats after an easy adaptation.
In this article, authors propose an innovative methodology for electrochemical COVID‐19 diagnosis using palladium nanoclusters (PdNCs)‐based voltammetry. The product of the isothermal loop‐mediated amplification (LAMP) is transferred to a card with screen‐printed electrodes, previously modified with PdNCs. The change in the pH that occurs during a LAMP reaction produces a variation in the catalytic activity of PdNCs.
Introduction
Scalp cooling (SC) aims to prevent chemotherapy‐induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC.
Methods
...A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings.
Results
A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor–patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility.
Conclusion
Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed.
Patient or Public Contribution
In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer AECC and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation FECMA) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).
The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple ...sclerosis. Recently, a group of patients have been described who have an NMO spectrum disorder (NMOsd) and who are seronegative for AQP4 antibodies but positive for IgG aquaporin-1 (AQP1) or myelin oligodendrocyte glycoprotein (MOG) antibodies. The purpose of this study was to determine whether AQP1 and MOG could be considered new biomarkers of this disease; and if point mutations in the gDNA of
,
and
genes could be associated with the etiology of NMOsd. We evaluated the diagnostic capability of ELISA and cell-based assays (CBA), and analyzed their reliability, specificity, and sensitivity in detecting antibodies against these three proteins. The results showed that both assays can recognize these antigen proteins under appropriate conditions, but only anti-AQP4 antibodies, and not AQP1 or MOG, appears to be a clear biomarker for NMOsd. CBA is the best method for detecting these antibodies; and serum levels of AQP4 antibodies do not correlate with the progression of this disease. So far, the sequencing analysis has not revealed a genetic basis for the etiology of NMOsd, but a more extensive analysis is required before definitive conclusions can be drawn.
A comprehensive characterization of the culturable mycobiota associated to all stages of lignocellulose-based composting was achieved. A total of 77 different isolates were detected, 69 of which were ...identified on the basis of the 5.8-ITS region sequencing. All the isolates were assigned to the phyla Ascomycota and Basidiomycota, with prevalence of the Sordariomycetes (19) and Eurotiomycetes (17) classes. Penicillium was the most represented genus (11 species), while the species Gibellulopsis nigrescens and Microascus brevicaulis were detected at all the composting stages and showed the highest relative abundances. Fungal diversity decreased as the process proceed, while similarity between fungal communities associated to different samples were maximal for those phases closely connected chronologically and showing similar biological activity degree. Thus, the structure of the lignocellulose-based composting mycobiota can be divided into two major stages corresponding to bio-oxidative phase and maturation phase together with the final product, with a transitional cooling stage joining both of them.
Resumen Objetivo Evaluar la composición nutricional de las máquinas vending (MV) localizadas en edificios públicos y hospitales en Asturias. Diseño Descriptivo transversal. Emplazamiento Se ...analizaron las MV ubicadas en edificios públicos, hospitales y centros universitarios de Asturias. Mediciones principales Se realizó un mapeo de los edificios y posteriormente se acudió a cada uno de ellos para comprobar la presencia de MV, en cuyo caso se tomó una fotografía de los alimentos contenidos en ellas. Las variables analizadas fueron la ubicación, el tipo de alimento y su composición nutricional. Resultados Se incluyeron 215 alimentos identificados en 19 edificios, 12 universitarios y 7 hospitalarios, y se agruparon en 11 categorías. Los más frecuentes fueron los «chocolates y chocolatinas» (30,2%), «galletas» (11,6%) y «patatas fritas» (11,6%). La media de kcal fue de 216 (DE = 133,1). La media, en gramos de grasas 12,52 (DE = 11,21), grasas saturadas 4,48 (DE = 3,83), azúcares 11,88 (DE = 31,13), fibra 1,9 (DE = 2,47), proteínas 3,38 (DE = 3,62) y sal 0,3 (DE = 0,62). Se observó un exceso alto de grasa, grasa saturada y sal, y medio de azúcares. Conclusiones La calidad nutricional de las MV de los hospitales y centros universitarios públicos del Principado de Asturias no puede ser definida como saludable. Por tanto, se podrían desarrollar estrategias de promoción de la salud con el objetivo de mejorar su composición nutricional u orientar a la población hacia la selección y consumo de alimentos saludables.
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