Realización y postproducción de un cortometraje. Análisis de la influencia de la imagen-sonora en la percepción del relato cinematográfico

La fusión creativa de música, ambientes y efectos sonoros en combinación con las imágenes proporciona una ventana a nuevos mundos y formas de percibir una narración. Dicha tarea recae sobre el proceso de edición. Nuestro objetivo es acercarnos a la “obra de arte total” que propugnaba Richard Wagner, mediante el uso de técnicas de montaje, como el monólogo interior y el contrapunto sonoro, y así producir un cortometraje que ofrezca toda una experiencia sensorial al espectador. Gesamtkunstwerk narra un drama reflexivo que trata sobre la vida, el paso del tiempo y la capacidad individual para escribir nuestra propia historia, al margen de lo que dicta la sociedad. La protagonista es una niña cuya inocencia y pureza le ayudan a afrontar los problemas y a prepararse para la vida. En este texto se exponen las diferentes tareas que exige cada fase de la producción, el flujo de trabajo necesario para cumplir las expectativas y las metodologías aplicadas en el desarrollo del producto.The creative fusion of music, environments and sound effects in combination with images provides a window into new worlds and ways of perceiving a narrative. This task falls on the editing process. Our goal is to approach the "Total artwork" advocated by Richard Wagner, by using montage techniques such as interior monologue and sound counterpoint, and thus produce a short film that offers a complete sensory experience to the viewer. Gesamtkunstwerk tells a thoughtful drama about life, about the passage of time and individual ability to write our own history, apart from what society dictates. The protagonist is a girl whose innocence and purity help her to confront the problems and to get ready for life. In this text are presented the different tasks required for each stage of production, the workflow necessary to achieve the expectations and methodologies applied in the product development.Soldevila Amaré, B. (2016). Realización y postproducción de un cortometraje. Análisis de la influencia de la imagen-sonora en la percepción del relato cinematográfico. Universitat Politècnica de València. http://hdl.handle.net/10251/75594TFG

Epithelial-Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors

Thyroid Hormone Upregulates Zinc-α-glycoprotein Production in the Liver but Not in Adipose Tissue

Overproduction of zinc-α-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α-glycoprotein expression in adipose tissue could be the reason why zinc-α-glycoprotein is not related to weight loss in hyperthyroidism

The relationship between social support and self-reported health status in immigrants: an adjusted analysis in the Madrid Cross Sectional Study

<p>Abstract</p> <p>Background</p> <p>Social support is an important factor in the adaptation process of immigrants, helping for their integration in a new environment. The lack of social support may influence on well-being and health status. The aim of this study is to describe the social support of immigrant and native population and study the possible association between immigration and lack social support after adjusting for sociodemographic factors, income, stress and self-reported health status.</p> <p>Methods</p> <p>Cross-sectional population based study of immigrants and national patients without mental disorders of 15 urban primary health centers in the north-eastern area of Madrid. Participants provided information on social support, stress level, perceived health status and socio-economic characteristics. Descriptive and multiple logistic regression were conducted.</p> <p>Results</p> <p>The proportion of the global perception of social support among immigrants and natives was 79.2% and 94.2%, respectively. The lack of global social support adjusted prevalence ratio (PR) of immigrant was 2.72 (95% Confidence Interval = 1.81-4.09), showing a significant association with being male (PR = 2.26), having monthly income below 500 euros (PR = 3.81) and suffering stress (PR = 1.94). For the dimensions of lack of social support the higher association was being an immigrant and suffering stress.</p> <p>Conclusions</p> <p>We conclude that with regardless of the level of monthly income, stress level, self-reported health status, and gender, immigrant status is directly associated with lack social support. The variable most strongly associated with lack social support has been monthly income below 500 euros.</p

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population

Background: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D). Aim: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers.Methods: Concentrations of YKL-40, adiponectin, IL-6, IL-1β, TNF- α, hsCRP and homocysteine were determined in 150 T1D patients (58 % men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m2; HbA1c 8.1 ± 2.3 %, 48 % smokers; 26 % retinopathy, microalbuminuria 9 %) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS). Results: 82 % of T1D patients and 92 % of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008). Conclusions: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background

Advanced lipoprotein profle disturbances in type 1 diabetes mellitus: a focus on LDL particles

Background: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profle in T1DM individuals, and analysed diferences with non-diabetic counterparts. Methods: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed. Results: The median (interquartile range) age of the study participants was 45 (38–53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16–31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p<0.001). The T1DM group had a better conventional (all parameters, p<0.001) and NMR-lipid profle than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p<0.001 for all). While non-diabetic women had a more favourable lipid profle than non-diabetic men, women with T1DM had a similar concentration of LDL-par‑ ticles compared to men with T1DM (1231 [1125–1383] vs. 1257 [1128–1383] nmol/L, p=0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2–733.9] vs. 671.2 [593.5–761.4] nmol/L, respectively; p=0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDLcholesterol than non-diabetic subjects (prevalence of LDL-cholesterol1000 nmol/L: 38 vs. 21.2%; p<0.001). All these diferences were largely unchanged in participants without lipid-lowering drugs (T1DM, n=275; controls, n=317).This research was supported by grants from the Carlos III National Institute of Health (PI12/0183 and PI15/0625). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) and CIBER on Pathophysiology of Obesity and Nutrition (CIBEROBN) are initiatives of ISCIII, Spain. AJA received a research grant from the Associació Catalana de Diabetis (ACD), “Ajut per a la recerca en diabetis modalitat clínica 2018”

Reference Intervals of Thyroid Function Tests Assessed by Immunoassay and Mass Spectrometry in Healthy Pregnant Women Living in Catalonia

Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect ® immunoassay (Abbott) and FT4 by two immunoassays, Architect ® (Abbott) and Cobas ® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03-3.78; 2T: 0.51-3.53; 3T: 0.50-4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect ® 1T: 10.42-15.96; 2T: 8.37-12.74; 3T: 8.24-12.49; p < 0.0001; and Cobas ® : 1T: 11.46-19.05; 2T: 9.65-14.67; 3T: 8.88-14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75-18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable. Conclusions: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile

Factors associated with critical care requirements in diabetic patients treated with dexamethasone for COVID-19 infection in the first wave of the pandemia

Diabetes mellitus (DM) and hyperglycemia are important risk factors for poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to analyze the factors associated with the composite outcome of the necessity of invasive mechanical ventilation (IMV) or admission to the intensive care unit (ICU) in subjects with severe COVID-19 infection treated with dexamethasone comparing patients with DM vs. patients without DM. An observational retrospective cohort study was performed, including hospitalized subjects with a diagnosis of SARS-CoV-2 pneumonia. Inclusion criteria were: age ≥18 years old with severe COVID-19 disease requiring daily intravenous 6 mg dexamethasone treatment for 10 days. Exclusion criteria were: <18 years old, non-severe illness and/or patients in charge of ICU. Variables related to clinical and analytical parameters, glycemic control, acquired-hospital superinfections, mortality, IMV requirement, ICU admission and length of stay were included. Two hundred and nine individuals with COVID-19 disease treated with dexamethasone were included. One hundred twenty-five out of these subjects (59.8%) were patients with DM. Overall, from the 209 subjects, 66 (31.6%) required IMV or were admitted to the ICU, with significant differences between patients with DM (n=50) vs. patients without DM (n=16) (76% vs. 24%, p=0.002). Among the group of subjects with DM (n=125), those who required IMV or were admitted to the ICU showed higher serum concentrations of C-reactive protein, interleukin-6, D-dimer, ferritin and pro-calcitonin and significantly lower serum concentrations of albumin compared to those who did not require IMV or were not admitted to the ICU. Besides, between these two groups of patients with DM, we observed no differences in glycemic parameters, including median capillary blood glucose values, glycosylated hemoglobin, coefficient of variability and hypoglycemic episodes. In the multinomial analysis, factors independently associated with the composite outcome of IMV or admission to the ICU in the insulin-treated group were the National Early Warning Score (NEWS) 2 score (OR 1.55 [1.17-2.17], p=0.005) and the presence of hospital-acquired superinfections (OR 35.21 [5.11-386.99], p=0.001). In our study, parameters related to glycemic control were not associated with IMV requirement nor admission to the ICU in patients with DM and severe COVID-19 disease receiving daily 6 mg of dexamethasone for 10 days. However, hospital-acquired superinfections and disease severity at admission were independent factors associated with this composite outcome

Pasireotide in the Personalized Treatment of Acromegaly

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects : A population-based study

To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD