We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve persons with HIV (PWH) who initiated first-line ...antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 Kg and 0.98 Kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.
Atherosclerosis remains the leading cause of ischemic syndromes such as myocardial infarction or brain stroke, mainly promoted by plaque rupture and subsequent arterial blockade. Identification of ...vulnerable or high-risk plaques constitutes a major challenge, being necessary to identify patients at risk of occlusive events in order to provide them with appropriate therapies. Clinical imaging tools have allowed the identification of certain structural indicators of prone-rupture plaques, including a necrotic lipidic core, intimal and adventitial inflammation, extracellular matrix dysregulation, and smooth muscle cell depletion and micro-calcification. Additionally, alternative approaches focused on identifying molecular biomarkers of atherosclerosis have also been applied. Among them, proteomics has provided numerous protein markers currently investigated in clinical practice. In this regard, it is quite uncertain that a single molecule can describe plaque rupture, due to the complexity of the process itself. Therefore, it should be more accurate to consider a set of markers to define plaques at risk. Herein, we propose a selection of 76 proteins, from classical inflammatory to recently related markers, all of them identified in at least two proteomic studies analyzing unstable atherosclerotic plaques. Such panel could be used as a prognostic signature of plaque instability.
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•Atheroma plaque rupture is responsible of ischemic stroke and myocardial infarction.•It is compulsory to identify patients at risk to avoid such acute events.•A single marker cannot explain the complex process of plaque rupture.•Herein, a panel of protein markers related to plaque vulnerability is shown.
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Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an ...active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of
and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.
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•Novel MBs with high magnetization were obtained by encapsulation of highly magnetic zinc doped magnetite ZnxFe3-xO4 nanoparticles (ZnFeNPs) into a polymeric matrix of ...PLGA.•Functionalization with affinity proteins was carefully investigated and compared with commercial MBs in terms of magnetic behavior.•The obtained MBs have an enhanced ability to capture antibodies and provide better reproducibility than commercial ones.•The immunosensor developed was successfully applied for the detection of Tau protein in real samples.
Magnetic beads (MBs) have been notably used as platforms in biosensing thanks to their magnetic behavior as they allow to simplify purification and separation by preconcentrating the sample and also to minimize matrix effects, what facilitates the analysis of real samples. Even though it exists a variety of commercially available ones, there is still great interest to develop alternative MBs with improved performance. In this work, we propose the synthesis of novel, reliable and low-cost MBs by colloidal assembly of zinc doped magnetite for their use as electrochemical immunosensing platforms. First, zinc doped magnetite ZnxFe3-xO4 nanoparticles (ZnFeNPs) of a diameter of 13 ± 3 nm and a saturation magnetization of 81 emu/g were synthesized and encapsulated in a polymeric matrix of poly(lactic-co-glycolic) acid (PLGA), generating polymeric MBs that were covered with polyethyleneimine (PEI) (MB@PEI), obtaining particles of 96 ± 16 nm. The PEI external layer provides MBs with a higher degree of encapsulation and stability and with functional groups that convert MB@PEI particles in versatile tools for their use as immunosensing platforms. In order to compare the suitability of the obtained MBs with commercially available ones, the affinity protein neutravidin (NAV) was linked to the MB@PEI surface through glutaraldehyde crosslinking. The obtained MB@NAV exhibited a significantly higher saturation magnetization than commercially available NAV-modified MBs, and also a better reproducibility (RSD of 4% for MB@NAV and 12% for commercial MBs) and enhanced surface functionalization ability when used as immunosensing platforms in a model assay using gold nanoparticle tags. As proof-of-concept of application in real samples, MB@NAV were finally applied for the detection of Tau protein, a well-known Alzheimer’s Disease (AD) biomarker, with a detection limit (LOD) of 63 ng/mL and an excellent performance in human serum samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases ...whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed.
The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP.
We studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained.
The mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes.
The mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.
El linfoma T paniculítico (LTP) es un linfoma de células T citotóxico poco frecuente, de comportamiento indolente, más frecuente en mujeres, relacionado con enfermedades autoinmunes, y cuyos antecedentes patogénicos aún no se conocen bien. Se asocia y se confunde histológicamente con la paniculitis lúpica (PL).
El objetivo de nuestro estudio fue identificar mutaciones implicadas en la patogénesis del LTP y de la PL.
Se estudiaron 10 pacientes con LTP y 10 con PL mediante secuenciación masiva (con un panel de genes customizados) y pirosecuenciación dirigida. Se investigaron diferencias en la expresión genética mediante NanoString entre diferentes subgrupos moleculares encontrados. Se recopilaron datos clínicos y se correlacionaron con los datos moleculares obtenidos.
El perfil mutacional del LTP y el de la LP son diferentes. El porcentaje de mutaciones encontradas en el subgrupo de LTP fue inferior al ya publicado en la literatura. Solo un paciente con LTP mostraba mutaciones en el gen HAVCR2. Curiosamente, el 40% de los LTP mostraron la variante patogénica TP53 (p.Pro72Arg) (P72R). Los pacientes con mutaciones en el gen HAVCR2 o con la variante TP53(P72R) sufrían enfermedad sintomática, aunque ninguno desarrolló síndrome hemofagocítico (SPH). El estudio de NanoString identificó que las muestras con alteración de TP53(P72R) se caracterizaban por una down-regulation de la vía de señalización del metabolismo y de una mayor expresión de los genes de las vías de señalización de CD28 y Treg si se comparaban con los casos negativos para TP53 (P72R). Además, el 30% de nuestros casos presentaban la misma mutación (T735C) en el gen modificador epigenético DNMT3A. Ninguno de los pacientes con PL mostró mutaciones en ninguno de los genes estudiados.
Ampliamos el perfil mutacional del LTP, describiendo por primera vez la implicación de la variante patogénica TP53 (P72R) en este subgrupo de tumores. Además, sugerimos el posible papel de un fondo genético en el desarrollo de los LTP. La aparición de PL no parece seguir la misma vía patogénica que la de los LTP.
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The present study reports the results of an investigation of an ejector refrigeration system working with refrigerant R-134a, aiming at the enhancement of the pressure recovery. The critical ...condition has been determined for three mixing chambers of equal internal diameter but different profiles and for several stagnation conditions of primary and secondary fluid. The influence of both the nozzle longitudinal position and the vapor superheating of the primary and secondary fluid stagnation states on the mass ratio has also been reported. Experimental results have shown a negligible performance increment of the new mixing chamber designs, “B” and “C”, with respect to a standard design one, “A”, with the mixing chamber “C” underperforming the other two over all the performed tests. A new performance parameter has been introduced being defined as the ratio between experimental and a 2nd law based theoretical mass ratio.
•Experimental results for the critical point of a R-134a ejector refrigerator.•Influence of the nozzle position and superheating on the mass ratio.•Study of two geometries with secondary throat to enhance pressure recovery.•Performance analysis comparison based on a dimensionless parameter.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study was to evaluate the effect of the addition of tomato paste (TP) to sausage mortadella in order to improve the nutritional properties and reduce the lipid oxidation associated ...with the content of lycopene. First, three different mortadellas without colourant were made with 2, 6 and 10% of TP, to optimise technologically the amount of this ingredient. Then, commercial product was compared with 10% of TP mortadella; both products were made with natural colourant. After a proximate analysis only total protein decreased due to the addition of TP. Lycopene content in mortadella and the total antioxidant activity were proportional to the amount of TP added. The presence of TP provided stability during meat grinding, cooking and storage of mortadella by reducing the lipid oxidation. In addition, TP provided yellowness and softness; however, when TP was added together with red colourant, the redness remained constant in the mortadella without effects on the consumer overall acceptance.
► We study the effect of the addition of tomato paste (TP) in sausage mortadella. ► TP does not affect significantly nutritional profile of mortadella. ► Lycopene levels and the total antioxidant activity were proportional to TP added. ► The addition of TP improves the stability of mortadella during the shelf-life period. ► The addition TP does not affect the colour, taste, texture or overall acceptance.
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Most of the existing prediction models for COVID-19 lack validation, are inadequately reported or are at high risk of bias, a reason which has led to discourage their use. Few existing models have ...the potential to be extensively used by healthcare providers in low-resource settings since many require laboratory and imaging predictors. Therefore, we sought to develop and validate a multivariable prediction model of death in Mexican patients with COVID-19, by using demographic and patient history predictors. We conducted a national retrospective cohort study in two different sets of patients from the Mexican COVID-19 Epidemiologic Surveillance Study. Patients with a positive reverse transcription-polymerase chain reaction for SARS-CoV-2 and complete unduplicated data were eligible. In total, 83 779 patients were included to develop the scoring system through a multivariable Cox regression model; 100 000, to validate the model. Eight predictors (age, sex, diabetes, chronic obstructive pulmonary disease, immunosuppression, hypertension, obesity and chronic kidney disease) were included in the scoring system called PH-Covid19 (range of values: −2 to 25 points). The predictive model has a discrimination of death of 0.8 (95% confidence interval (CI) 0.796–0.804). The PH-Covid19 scoring system was developed and validated in Mexican patients to aid clinicians to stratify patients with COVID-19 at risk of fatal outcomes, allowing for better and efficient use of resources.
On the basis of a Plackett–Burman experimental design for a resolution IV level obtained via a foldover strategy, the effect of 11 factors on lycopene in vitro accessibility was investigated. The ...selected factors were thermal treatment (X1), olive oil addition (X2), gastric pH (X3), gastric digestion time (X4), pepsin concentration (X5), intestinal pH (X6), pancreatin concentration (X7), bile salts concentration (X8), colipase addition (X9), intestinal digestion time (X10), and intestinal digestion speed (X11). Tomato passata was used as a natural source of lycopene. Samples were collected after gastric and intestinal digestion, and from the micellar phase, to quantify the (all-E)-lycopene and its (Z)-isomers by HPLC. Except for X3, X6, X7, and X11, the other factors studied explained lycopene in vitro accessibility, mainly regarding intestinal digestion, with R 2 values ≥ 0.60. Our results showed that the accessibility of lycopene is influenced by the conditions applied during in vitro intestinal digestion.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
ABSTRACT
We characterize for the first time the torus properties of an ultra-hard X-ray (14–195 keV) volume-limited (DL < 40 Mpc) sample of 24 Seyfert (Sy) galaxies (BCS40 sample). The sample was ...selected from the Swift/BAT nine-month catalogue. We use high angular resolution nuclear infrared (IR) photometry and N-band spectroscopy, the CLUMPY torus models and a Bayesian tool to characterize the properties of the nuclear dust. In the case of the Sy1s, we estimate the accretion disc contribution to the subarcsecond resolution nuclear IR SEDs (∼0.4 arcsec) which is, on average, 46 ± 28, 23 ± 13, and 11 ± 5 per cent in the J, H, and K bands, respectively. This indicates that the accretion disc templates that assume a steep fall for longer wavelengths than 1 $\mu$m might underestimate its contribution to the near-IR emission. Using both optical (broad versus narrow lines) and X-ray (unabsorbed versus absorbed) classifications, we compare the global posterior distribution of the torus model parameters. We confirm that Sy2s have larger values of the torus covering factor (CT ∼ 0.95) than Sy1s (CT ∼ 0.65) in our volume-limited Seyfert sample. These findings are independent of whether we use an optical or X-ray classification. We find that the torus covering factor remains essentially constant within the errors in our luminosity range and there is no clear dependence with the Eddington ratio. Finally, we find tentative evidence that even an ultra-hard X-ray selection is missing a significant fraction of highly absorbed type 2 sources with very high covering factor tori.
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