In this paper a new integral mathematical model for volcanic plumes, named PLUME-MoM, is presented. The model describes the steady-state dynamics of a plume in a 3-D coordinate system, accounting for ...continuous variability in particle size distribution of the pyroclastic mixture ejected at the vent. Volcanic plumes are composed of pyroclastic particles of many different sizes ranging from a few microns up to several centimeters and more. A proper description of such a multi-particle nature is crucial when quantifying changes in grain-size distribution along the plume and, therefore, for better characterization of source conditions of ash dispersal models. The new model is based on the method of moments, which allows for a description of the pyroclastic mixture dynamics not only in the spatial domain but also in the space of parameters of the continuous size distribution of the particles. This is achieved by formulation of fundamental transport equations for the multi-particle mixture with respect to the different moments of the grain-size distribution. Different formulations, in terms of the distribution of the particle number, as well as of the mass distribution expressed in terms of the Krumbein log scale, are also derived. Comparison between the new moments-based formulation and the classical approach, based on the discretization of the mixture in N discrete phases, shows that the new model allows for the same results to be obtained with a significantly lower computational cost (particularly when a large number of discrete phases is adopted). Application of the new model, coupled with uncertainty quantification and global sensitivity analyses, enables the investigation of the response of four key output variables (mean and standard deviation of the grain-size distribution at the top of the plume, plume height and amount of mass lost by the plume during the ascent) to changes in the main input parameters (mean and standard deviation) characterizing the pyroclastic mixture at the base of the plume. Results show that, for the range of parameters investigated and without considering interparticle processes such as aggregation or comminution, the grain-size distribution at the top of the plume is remarkably similar to that at the base and that the plume height is only weakly affected by the parameters of the grain distribution. The adopted approach can be potentially extended to the consideration of key particle–particle effects occurring in the plume including particle aggregation and fragmentation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Prolactin in inflammatory response Pereira Suarez, Ana Laura; López-Rincón, Gonzalo; Martínez Neri, Priscila A ...
Advances in experimental medicine and biology,
01/2015, Volume:
846
Journal Article
Peer reviewed
Prolactin (PRL) is a peptide hormone produced by the pituitary gland and diverse extrapituitary sites, which triggers activation of various signaling pathways after binding to its receptor (PRLr) ...resulting in the activation of specific genes associated with the pleiotropic activities of PLR. To date, various PRLr isoforms have been described, generated by post-transcriptional or post-translational processes. PRL has been associated with the modulation of a variety of actions in the immune response and inflammatory processes in several physiologic and pathologic conditions. However, PRL can have opposite effects, which might be regulated by interaction with the various isoforms of PRLR and PRL variants, as well as the cellular and molecular microenvironment influence.
Hypoxia-inducible transcription factor-1 (HIF-1α) is overexpressed in multiple myeloma (MM) cells within the hypoxic microenvironment. Herein, we explored the effect of persistent HIF-1α inhibition ...by a lentivirus short hairpin RNA pool on MM cell growth either in vitro or in vivo and on the transcriptional and pro-angiogenic profiles of MM cells. HIF-1α suppression did not have a significant impact on MM cell proliferation and survival in vitro although, increased the antiproliferative effect of lenalidomide. On the other hand, we found that HIF-1α inhibition in MM cells downregulates the pro-angiogenic genes VEGF, IL8, IL10, CCL2, CCL5 and MMP9. Pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1α. The effect of HIF-1α inhibition was assessed in vivo in nonobese diabetic/severe combined immunodeficiency mice both in a subcutaneous and an intratibial MM model. HIF-1α inhibition caused a dramatic reduction in the weight and volume of the tumor burden in both mouse models. Moreover, a significant reduction of the number of vessels and vascular endothelial growth factors (VEGFs) immunostaining was observed. Finally, in the intratibial experiments, HIF-1α inhibition significantly blocked bone destruction. Overall, our data indicate that HIF-1α suppression in MM cells significantly blocks MM-induced angiogenesis and reduces MM tumor burden and bone destruction in vivo, supporting HIF-1α as a potential therapeutic target in MM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adenosine modulates cardiovascular functions reducing blood pressure and heart rate. Adenosine deaminase (ADA) by the irreversible deamination of adenosine to inosine contributes to the regulation of ...adenosine concentration in body fluids. We have studied the interaction between smoking and ADA genetic variability concerning their effects on blood pressure.
We have studied 344 subjects admitted to the hospital for cardiovascular diseases. The genotypes of two polymorphic loci within the ADA gene were determined: ADA
1
and ADA
2
. Both loci show two alleles: ADA
1
*1 and ADA
1
*2 in ADA
1
locus and ADA
2
*1 and ADA
2
*2 in ADA
2
locus.
In the absence of smoking, the proportion of subjects with hypertension tends to be lower in carriers of the ADA
1
*2 allele. In smoking subjects, the pattern is reversed and the proportion of those with hypertension tends to be higher in carriers of the ADA
1
*2 allele. A similar pattern is observed for ADA
2
locus.
Smoking increases the proportion of subjects showing hypertension: such effect is more marked in those carrying the ADA
1
*2 allele as compared to subjects with ADA
1
*1/*1 genotype. The same pattern of association is observed for ADA
2
locus. The two loci show an additive effect. The odds ratio for hypertension in smokers vs nonsmokers is 1.450 in subjects carrying ADA
1
*1/*1 and ADA
2
*1/*1 genotypes, while it is 11.200 in subjects carrying the *2 alleles in both loci.
From a practical point, a view of our results suggest that smokers carrying both ADA
1
*2 and ADA
2
*2 alleles have a higher risk of hypertension.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antecedentes: En 2020, la Organización Mundial de la Salud declaró la COVID-19 como pandemia, por lo que se suspendieron los programas de tamizaje, afectando la detección oportuna del cáncer de mama ...en todo el mundo y generando un aumento de los casos posterior a la pandemia. Objetivo: Determinar la proporción de casos BI-RADS 4 y 5 en mastografías realizadas posterior a las restricciones por la COVID-19 comparadas con las del año 2019. Material y métodos: Estudio observacional, transversal y comparativo de pacientes con mastografías BI-RADS 4 o 5 tras las restricciones por la COVID-19 comparadas con las del año 2019 en una unidad de medicina familiar. Resultados: De un total de 5 945 mastografías, se realizaron 2 415 en 2019 y 3 530 en 2022. En 2019, 69 fueron BI-RADS > 4 (2.85%) y en 2022 aumentaron a 175 (4.95%) (p = 0.001). Este incremento fue proporcional para todos los grupos etarios (p < 0.045). Conclusiones: Hubo un 73% más mastografías clasificadas como BI-RADS 4 o 5 en el año posterior a la pandemia, en comparación con el año previo a ella.
The optimal management of localized gallbladder perforation (Neimeier type II) has yet to be defined. The aim of this systematic review was to identify factors associated with improved patient ...outcomes.
Systematic review of studies that described the management of Neimeier type II perforation, reported complications of the first intervention, necessity of added interventions, resolution of the pathology, and days of hospital stay were included. The search strategy was conducted in EMBASE, Mayo Journals, MEDLINE, SCOPUS, and Web of Science (December 2020)
A total of 122 patients (53% male) from case reports, series, and cohorts were included for analysis. In total 56 (46%) and 44 (36%)patients were treated with open and laparoscopic cholecystectomy respectively. Overall risk of bias was moderate. The need for another intervention was higher in the laparoscopic group (5 vs 17, p=<0.001) as well as prevalence of complications (4 vs 16, p=<0.001), but lower for days of hospital stay (median days 5. vs 15, p = 0.008) against open cholecystectomy. Preoperative percutaneous catheter drainage did not influence outcome.
Open cholecystectomy has a lower need for further surgical procedures and postoperative complications, but a longer hospital stay. These outcomes did not vary with preoperative percutaneous drainage. The effect of timing of cholecystectomy did not influence the outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
SCN5A gene encodes the α-subunit of Nav1.5, mainly found in the human heart. SCN5A variants are the most common genetic alterations associated with Brugada syndrome (BrS). In rare cases, compound ...heterozygosity is observed; however, its functional consequences are poorly understood. We aimed to analyze the functional impact of de novo Nav1.5 mutations in compound heterozygosity in distinct alleles (G400R and T1461S positions) previously found in a patient with BrS. Moreover, we evaluated the potential benefits of quinidine to improve the phenotype of mutant Na+ channels in vitro.
The functional properties of human wild-type and Nav1.5 variants were evaluated using whole-cell patch-clamp and immunofluorescence techniques in transiently expressed human embryonic kidney (HEK293) cells.
Both variants occur in the highly conservative positions of SCN5A. Although all variants were expressed in the cell membrane, a significant reduction in the Na+ current density (except for G400R alone, which was undetected) was observed along with abnormal biophysical properties, once the variants were expressed in homozygosis and heterozygosis. Interestingly, the incubation of transfected cells with quinidine partially rescued the biophysical properties of the mutant Na+ channel.
De novo compound heterozygosis mutations in SNC5A disrupt the Na+ macroscopic current. Quinidine could partially reverse the in vitro loss-of-function phenotype of Na+ current. Thus, our data provide, for the first time, a detailed biophysical characterization of dysfunctional Na+ channels linked to compound heterozygosity in BrS as well as the benefits of the pharmacological treatment using quinidine on the biophysical properties of Nav1.5.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic ...arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: − 0.66; 95% CI − 0.97 to − 0.34;
P
< .00001;
I
2
= 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: − 0.94 vs − 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: − 0.21; 95% CI − 0.25 to − 0.18;
P
< .00001;
I
2
= 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223.
Key Points
•
Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials.
•
The best available evidence on this particular outcome is currently at a moderate risk of bias.
•
Existing reports of the effect of DMARDs on structural damage must be taken with caution.
•
Further research is required to assess long-term outcomes and to control heterogeneity between studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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