Summary
Background
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline ...phosphatase ALP and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long‐term effectiveness of second‐line treatments remains uncertain.
Aims
To evaluate the long‐term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
Methods
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non‐responsive PBC patients (Paris‐II criteria) from Spain and Portugal who received OCA ± fibrates.
Results
Of 255 patients, median follow‐up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE‐PBC and 5‐year UK‐PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
Conclusion
Triple therapy was superior in achieving therapeutic goals in UDCA‐nonresponsive PBC. Decompensation was linked to pre‐existing portal hypertension.
Longitudinal, real‐world study on 255 UDCA‐nonresponsive PBC patients (Per Paris II criteria); median follow‐up of 35.1 months (IQR: 20–53). All patients received obeticholic acid (OCA), with 25% receiving later add‐on fibrate treatment (triple therapy). In multivariate analysis, triple therapy outperformed dual therapy across all surrogate biochemical endpoints of outcomes.
Resumen
La enfermedad de Alzheimer (EA) es la forma más común de demencia y tiene una elevada morbilidad y mortalidad. La EA se caracteriza principalmente por la presencia de dos estructuras ...aberrantes en el cerebro de los pacientes, placas seniles formadas por péptido-β-amiloide (Aβ) y ovillos neurofibrilares cuyo principal componente es la proteína tau fosforilada. Aunque actualmente no se conoce bien la etiopatogenia, cada vez son más los estudios que demuestran un efecto causal del microbioma intestinal sobre la EA y las funciones cognitivas, a través del "eje microbiota intestino-cerebro". Las evidencias científicas sugieren un posible efecto protector de los polifenoles del vino frente a los trastornos neurodegenerativos aunque se desconocen los mecanismos y, hasta el momento, los estudios para evaluar de forma exhaustiva el efecto del vino sobre la etiopatogenia de la EA son muy escasos. El objetivo principal de la línea de investigación que enmarca este trabajo es entender cómo la dieta, y especialmente los polifenoles presentes en los alimentos vegetales, y otros factores del estilo de vida interactúan con el microbioma oral e intestinal, en relación con la salud digestiva y el deterioro cognitivo. Para ello, se está llevando a cabo una aproximación experimental que tiene como finalidad evaluar el posible efecto protector de los polifenoles del vino, mediante la suplementación de la dieta en dos modelos murinos de la EA (patología Aß y Tau), y, por otro lado, se está profundizando en el estudio de los mecanismos de protección mediante la evaluación de los efectos del ácido protocatéquico sobre la actividad eléctrica del cerebro.
Alzheimer's disease (AD) is the most common form of age-related dementia with high morbidity and mortality. AD is mainly characterized by the presence of two aberrant structures in the brain of patients, senile plaques formed by peptide-β-amyloid (Aβ) and neurofibrillary tangles whose main component is phosphorylated tau protein. Although the etiopathogenesis is currently not well understood, an increasing number of studies demonstrate a causal effect of the gut microbiome on AD and cognitive functions, through the "gut-brain microbiota axis". Scientific evidence suggests a possible protective effect of wine polyphenols against neurodegenerative disorders although the mechanisms are unknown and, so far, studies to evaluate comprehensively the effect of wine on the etiopathogenesis of AD are very scarce. The main objective of the research line that frames this work is to understand how diet, and especially the polyphenols present in plant foods, and other lifestyle factors interact with the oral and intestinal microbiome in relation to digestive health and cognitive impairment. To this end, an experimental approach is being carried out to evaluate the possible protective effect of wine polyphenols through dietary supplementation in two murine models of AD (Aß and Tau pathology), and, on the other hand, the study of the protective mechanisms is being deepened by evaluating the effects of protocatechuic acid on the electrical activity of the brain.
High concentration photovoltaic technology promises the large-scale generation of clean-renewable energy with competitive costs. Like any other systems for electricity generation, it is important to ...know the electrical characteristics of the system. However, while there is a wide experience in modeling the behavior of traditional photovoltaic systems, not every model for flat-plate solar cells or modules is directly applicable to high concentration photovoltaic cells or modules because of the special features of these devices (use of multijunction cells, use of optics for high concentration, etc.). So, in recent years, the scientific community has devoted considerable efforts in developing models that reproduce the electrical behavior of high concentration cells and modules. These models allow calculating the main electrical parameters of the device from its operating conditions (irradiance, cell temperature, spectral distribution of the radiation, etc.). In this paper, a comprehensive review of existing models for the electrical characterization of high concentration photovoltaic cells and modules is presented with the aim of helping the photovoltaic professionals and researchers in the design, monitoring and energy prediction tasks.
Abstract Introduction In Parkinson's disease patients, impulse control disorders (ICDs) have been associated with younger age and early disease onset, yet the prevalence of ICDs in early-onset ...Parkinson's disease (EOPD) patients has yet to be studied. Thus, we set out to compare the prevalence of impulse control behaviors (ICBs) in a cohort of EOPD patients with that in age and gender matched healthy controls (HCs), as well as to analyze the association of these symptoms with the use of dopaminergic drugs and other clinical or demographic factors. Methods A cross-sectional, multicenter study was carried out on patients recruited from outpatient Movement Disorder Clinics, assessing ICBs using the short form of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). In addition, depression and quality of life (QoL) were measured, along with other demographic and clinical variables. Results Of the 87 EOPD patients, 49 (58.3%) displayed an ICB, as did 28 of the 87 HCs (32.9%; p = 0.001). Most of the EOPD patients that displayed an ICB (91.8%) were medicated with a dopamine agonist (DA) and accordingly, DA treatment was associated with a 7-fold increased risk of developing an ICB. Patients with ICBs had a higher depression score and a worse QoL. Conclusions ICBs are much more prevalent in EOPD patients than in HCs and they are associated with DA intake, depression and a worse QoL.
Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. Objective: Based on a systematic review, we aimed to explain differences in the reported ...incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies.
We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis death rate for the population of a country or for an administrative region. The research strategy was based on combining "anaphylaxis" with "death", "study design", and "main outcomes" (incidence).
A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02, 95%CI 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out.
The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.
A comparative study of three different ceria synthesis procedures (template- and MW- assisted hydrothermal synthesis and urea homogeneous precipitation) is reported in this paper. The obtained ...materials were employed as supports for Pt nanoparticles, and the Pt/CeO2 catalysts were evaluated in the WGS reaction under model and realistic conditions. The influence of the support, e.g., its morphology and electronic properties, has been studied in detail by means of XRD, H2-TPR, XPS, UV–Vis spectroscopy and toluene hydrogenation (for metal dispersion assessment). The catalytic performance of the samples is directly correlated with the modification of the electronic properties, as a result of the preparation method used. The conventional homogeneous precipitation method with urea resulted to be the best option, leading to enhanced ceria reducibility and adequate Pt dispersion, which in turns resulted in a very efficient WGS catalyst.
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•Three different ceria synthesis routes have been compared.•The synthesis procedure modulates the redox and electronic properties of CeO2.•Pt dispersion and metal-support interaction are depend on the morphology of CeO2.•The highest activity with realistic conditions was shown by the Pt/CeO2 urea catalyst.
Numerous exhaustive analyses of the economic assessment of conventional PV systems are available in the literature. However, there is a lack of these studies concerning High Concentrator Photovoltaic ...(HCPV) technology. Besides, future owners and potential investors on HCPV plant demand information relating to the economic feasibility of their investment. In this work the profitability and competitiveness of HCPV plants in several countries are analysed. To analyse the profitability the internal rate of return (IRR) criterion has been used, while the competitiveness has been analysed based on estimating the so-called HCPV generation parity. As a result of the economic profitability analysis conducted the group of countries where the investment in HCPV could be interesting has been identified. The results obtained could be also useful for researchers to identify the weaknesses of the HCPV technology and take actions at making it more competitive. From the competitiveness analysis carried out in several Eurozone countries and USA for two possible scenarios 2015 and 2020, the results show that HCPV could be competitive in some locations in 2020. Therefore, government organizations of the studied countries, which participate in the design or the selection of support mechanisms for HCPV, can be guided by the results obtained.
•The economic profitability of HCPV plants worldwide, using as the criterion the internal rate of return (IRR) has been studied.•The competitiveness of HCPV plants worldwide, based on estimating the so-called HCPV generation parity has been evaluated.•Detection of the more appropriate countries for investing in HCPV power plant in terms of the IRR has been investigated.•So-called parity generation HCPV will be achieved in some European countries and regions of USA for the year 2020.
Background
The management of melanocytic lesions with peripheral globules (MLPGs) is usually age‐dependent and can be challenging in high‐risk melanoma patients.
Objectives
To evaluate clinical, ...dermoscopic and reflectance confocal microscopy (RCM) features of MLPG in patients under digital dermoscopic surveillance. To know whether dermoscopic or RCM findings correlate with histologic diagnosis and the accuracy of the dermoscopy–RCM compared with histopathology.
Methods
During 24 months, we prospectively enrolled MLPG in patients under digital dermoscopy follow‐up. All were evaluated by dermoscopy and RCM and excised for histologic examination.
Results
We enrolled 154 patients, mean age 42.45 years (18.78–73.19). Three melanomas and 19 dysplastic naevi (DNs) were diagnosed. There were no significant differences in the age of the patients (P = 0.662). MLPGs with diameter of 6 mm or more and asymmetry in two axes were associated with melanoma (P = 0.01, P = 0.003). Patients with more than one MLPG were less likely to have melanoma. Blue‐grey and red colours were more frequent in melanoma (P = 0.013 and P = 0.000). Different sizes and shapes of PG were associated with DN and melanoma (P = 0.000 and P = 0.001). In a new lesion, PG in <25% of the circumference was related to malignancy (P = 0.010). RCM signs of malignancy were related to melanoma: pagetoid cells (P = 0.000), non‐edged papillae (P = 0.001), atypical junctional thickenings (P = 0.000) and atypical cells at the dermal‐epidermal junction (P = 0.000). Dense irregular nests were associated to melanoma (P = 0.019). Dermoscopy and confocal evaluation were able to diagnose 100% of melanomas and 84.21% of DNs. The kappa coefficient between dermoscopy–RCM vs. histology was 0.76.
Conclusions
We recommend to excise a MLPG when it presents asymmetry in two axes, 6 or more mm, new lesion with PG in less than the 25% of the circumference, irregular size and shape PGs and irregular dense nests on RCM, regardless of the patient's age.
Linked Commentary: E. Lazaridou et al. J Eur Acad Dermatol Venereol 2021; 35: 1040. https://doi.org/10.1111/jdv.17239.
Recent massive sky surveys in different bandwidths are providing new opportunities to modern astronomy. The Virtual Observatory (VO) represents the adequate framework to handle the huge amount of ...information available and filter out data according to specific requirements. In this work, we applied a selection strategy to find new, uncatalogued hot subdwarfs making use of VO tools. We used large area catalogues like GALEX, Sloan Digital Sky Survey (SDSS), SuperCosmos and Two Micron All Sky Survey (2MASS) to retrieve photometric and astrometric information of stellar objects. To these objects, we applied colour and proper motion filters, together with an effective temperature cutoff, aimed at separating hot subdwarfs from other blue objects such as white dwarfs, cataclysmic variables or main-sequence OB stars. As a result, we obtained 437 new, uncatalogued hot subdwarf candidates. Based on previous results, we expect our procedure to have an overall efficiency of at least 80 per cent. Visual inspection of the 68 candidates with SDSS spectrum showed that 65 can be classified as hot subdwarfs: 5 sdOs, 25 sdOBs and 35 sdBs. This success rate above 95 per cent proves the robustness and efficiency of our methodology. The spectral energy distribution of 45 per cent of the subdwarf candidates showed infrared excesses, a signature of their probable binary nature. The stellar companions of the binary systems so detected are expected to be late-type main-sequence stars. A detailed determination of temperatures and spectral classification of the cool companions will be presented in a forthcoming work.
Nutritional restriction early in life followed by catch-up growth has been associated with increased risk of metabolic syndrome in adulthood. To elucidate whether altered gut colonization underlies ...the mechanisms responsible of this predisposition gut microbiome was studied before or afterwards catch-up growth. Offspring of dams fed ad libitum (C) or undernourished during pregnancy and suckling (U), were weaned onto high-fat diet (HFD) for 22 weeks (CHF and UHF, respectively) or continued on their diet. HF-feeding induced glucose intolerance (P<.05), insulin resistance (P<.001), and white adipose tissue inflammation (P<.001) in UHF rats compared to CHF. Analyses of gut microbial composition before catch-up growth revealed reduced F/B ratio and significant expansion of the mucolytic genera Akkermansia (P<.05) and Desulfovibrio (P<.05) in U pups. Although relative abundance of Akkermansia remained elevated to adulthood in U rats, HFD normalized its levels to C and CHF. Food-restriction increased intestinal permeability causing disorganization on the tight-junction proteins of colonic epithelium, Zonula Occludens-1 (ZO-1) and occludin, and reducing the mucus thickness layer in U adult rats. The levels of ZO-1 and occludin were not recovered in U rats after HF-feeding. This event was correlated with increased circulating levels of bacterial lipopolysaccharides in both U and UHF adult rats. Even more, serum lipopolysaccharides were already elevated in U rats compared to C group (P<.001) at weaning. Thus, gut dysbiosis and chronic endotoxemia observed in U rats, even before catch-up growth, might anticipate a pro-inflammatory milieu promoting metabolic diseases when fed hyperlipidic diets.
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