Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work ...was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the I
inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of I
on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Multiple variables determine holiday rentals' price composition in cultural tourism destinations. This study sought, first, to test a model including the variables with the greatest impact on tourism ...accommodations' prices in these destinations and, second, to demonstrate the proposed model's applicability to cultural city destinations by identifying the adaptations needed to apply it to different contexts. Two cities were selected for the model application - Seville in Spain and Porto in Portugal - both of which are located in different countries and are well-known cultural tourism destinations. The data were extracted from Booking.com because this accommodations platform has adapted its offer to the sharing economy, becoming one of the most important players in the market, and because research on holiday rentals using data from Booking.com is scarce. The results show that the variables used are relevant and highlight the adaptations necessary for specific cultural tourism destinations, thereby indicating that the model can be applied to all cultural tourism destinations. The proposed approach can help holiday rental managers select the correct tools for determining their accommodation units' daily rates according to their product and marketing context's characteristics.
Kojic acid (KA) is a fungal metabolite used as a topical treatment skin-whitening cosmetic agent for melasma in humans; however its potential as an anti-leishmanial agent is unknown. Chemotherapy is ...one of the most effective treatments for Leishmaniasis. However, the drugs available are expensive, invasive, require long-term treatment and have severe side effects. Thus, the development of new effective leishmanicidal agents is a necessity. In this study we investigated the anti-leishmanial effect of KA on L. amazonensis, following in vitro and in vivo infections. KA (50 μg/mL) was found to decrease the growth by 62% (IC50 34 μg/mL) and 79% (IC50 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of KA-treated amastigotes showed the presence of vesicles bodies into the flagellar pocket, and an intense intracellular vacuolization and swelling of the mitochondrion. During the in vitro interaction of parasites and the host cell, KA reverses the superoxide anions (O2-) inhibitory mechanism promoted by parasite. In addition, 4 weeks after KA-topical formulation treatment of infected animals, a healing process was observed with a high production of collagen fibers and a decrease in parasite burden. Thus, these results demonstrated the great potential of KA as an anti-leishmanial compound.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune ...process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes.
All patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes.
Forty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS.
Considering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Controlled or slow release fertilizers have been recommended to enhance crop yield, while minimizing environmental and economic issues related from current fertilizer applications. However, ...alternative biodegradable and non-toxic coating material should be suggested to produce biocoated fertilizers. Here we propose the use of lignin and poly(vinyl acetate) (PVAc) as biocoating materials for preparing slow release urea fertilizer. The blend of PVAc and lignin at a mass ratio of 75:25 improved the characteristics of the formed film and increased the nitrogen release time if compared to the pure polymers. The nitrogen release time from urea granules coated with a polymeric layer of 154.3 ± 5.5 μm formed by lignin and PVAc was 36 times greater than from bare urea. The increase in the polymeric coating from 52.6 ± 5.2 to 80.2 ± 6.1 μm decreased the curvature of the nitrogen release data by a factor of at least 1.7, while the curvature was decreased in at least 1.3 with the increase in the polymeric coating from 80.2 ± 6.1 to 158.9 ± 10.6 μm. The adjustment of nitrogen release data to the Peppas-Sahlin model indicated the Fickian diffusion is more predominant than relaxation contributions, since the used polymers did not present considerable swelling. Thus, the blending of PVAc and lignin at 25 wt% of lignin and 75 wt% of PVAc is suggested as a biocoating material for producing slow release fertilizers.
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•Lignin/PVAc biofilm improves the nitrogen release time from urea granules in 36 times.•Lignin in PVAc emulsion at concentrations up to 25 wt% increases nitrogen release time.•Nitrogen release time is improved by increasing the polymeric film thickness.
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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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•Pelleting improved the bulk density and enzymatic digestibility of corn stover.•Stover composition was not significantly altered by high moisture pelleting.•Pelleting decreased ...substrate surface area but increased protein accessibility.•Hydrolysis of cross-linking structures may occur during the pelleting process.
Pelleting of lignocellulosic biomass to improve its transportation, storage and handling impacts subsequent processing and conversion. This work reports the role of high moisture pelleting in the enzymatic digestibility of corn stover prior to pretreatment, together with associated substrate characteristics. Pelleting increases the digestibility of unpretreated corn stover, from 8.2 to 15.5% glucan conversion, at 5% solid loading using 1 FPU Cellic® CTec2 per g solids. Compositional analysis indicates that loose and pelleted corn stover have similar non-dissolvable compositions, although their extractives are different. Enzymatic hydrolysis of corn stover after size reduction to normalize particle sizes and removal of extractives confirms that pelleting improves corn stover digestibility. Such differences may be explained by the decreased particle size, improved substrate accessibility, and hydrolysis of cross-linking structures induced by pelleting. These findings are useful for the development of processing schemes for sustainable and efficient use of lignocellulose.
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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 conducts a bibliometric analysis of online customer and hotel review research, aiming to provide insights into where each field comes from, stands now and ought to go in the future. In ...particular, this study examines how the existing research on online customer reviews can benefit future hotel review research. Data collected from Web-of-Science and Scopus created an expanded network of 797 core articles and 19,374 citations to identify intellectual structures, developing trends, and future research gaps. This study offers a visual overview of journals, institutions, countries, research themes and authors to assess the overall directions hotels can take. It underscores the necessity for rigorous and relevant research amid the proliferation of online reviews and emphasises the imperative for academia to bridge the gap between theoretical insights and practical applications within the dynamic tourism industry. This study provides researchers and industry professionals with useful tools to understand and deal with the complexities of online reviews. It also highlights the important role these reviews play in shaping the future of tourism strategies.
Abstract Background Previous studies have associated neurohumoral excitation, as estimated by plasma norepinephrine levels, with increased mortality in heart failure. However, the prognostic value of ...neurovascular interplay in heart failure (HF) is unknown. We tested the hypothesis that the muscle sympathetic nerve activity (MSNA) and forearm blood flow would predict mortality in chronic heart failure patients. Methods One hundred and twenty two heart failure patients, NYHA II–IV, age 50 ± 1 ys, LVEF 33 ± 1%, and LVDD 7.1 ± 0.2 mm, were followed up for one year. MSNA was directly measured from the peroneal nerve by microneurography. Forearm blood flow was obtained by venous occlusion plethysmography. The variables were analyzed by using univariate, stepwise multivariate Cox proportional hazards analysis, and Kaplan–Meier analysis. Results After one year, 34 pts died from cardiac death. The univariate analysis showed that MSNA, forearm blood flow, LVDD, LVEF, and heart rate were significant predictors of mortality. The multivariate analysis showed that only MSNA ( P = 0.001) and forearm blood flow ( P = 0.003) were significant independent predictors of mortality. On the basis of median levels of MSNA, survival rate was significantly lower in pts with > 49 bursts/min. Similarly, survival rate was significantly lower in pts with forearm blood flow < 1.87 ml/min/100 ml ( P = 0.002). Conclusion MSNA and forearm blood flow predict mortality rate in patients with heart failure. It remains unknown whether therapies that specifically target these abnormalities will improve survival in heart failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives
To report clinical, angiographic characteristics, outcomes, and predictors of unsuccessful procedures in patients who underwent chronic total occlusion (CTO) percutaneous coronary ...interventions (PCI) in Latin America.
Background
CTO PCI has been increasingly performed worldwide, but there is a lack of information in this region.
Methods
An international multicenter registry was developed to collect data on CTO PCI performed in centers in Latin America. Patient, angiographic, procedural and outcome data were evaluated. Predictors of unsuccessful procedures were assessed by multivariable analysis.
Results
We have included data related to 1,040 CTO PCIs performed in seven countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, and Puerto Rico). The mean age was 64 ± 10 years, and CTO PCI was performed mainly for angina control (81%) or treatment of a large ischemic area (30%). Overall technical success rate was 82.5%, and it was achieved with antegrade wire escalation in 81%, antegrade dissection/re‐entry in 8% and with retrograde techniques in 11% of the successful procedures. Multivariable analysis identified moderate/severe calcification, a blunt proximal cap and a previous attempt as independent predictors of unsuccessful procedures. In‐hospital major adverse cardiovascular events (MACE) occurred in 3.1% of the cases, death in 1% and cardiac tamponade in 0.9%
Conclusions
CTO PCI in Latin America has been performed mainly for ischemia relief. Procedures were associated with a success rate above 80% and low incidence of MACE. Predictors of unsuccessful procedures were similar to those previously reported in the literature.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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