Hiatal hernia (HH) is a common disease in the general population. It is often asymptomatic, but if it does present clinical manifestations, these are usually gastrointestinal. Gastroesophageal reflux ...is the main symptom that accompanies it. Depending on the severity of the hernia, it is classified into several subtypes from I-IV. Especially, IV type (giant HH) can lead to various cardiopulmonary symptoms with several degrees of severity. It is necessary to keep this possibility in mind among the various differential diagnoses that may occur in this clinical setting. The current paper aims to review the literature on classic and novel information on the HH - cardiovascular system relationship. Epidemiological data, physiological aspects of the heart compressed by HH, cardiovascular symptoms, electrocardiographic changes, echocardiographic alterations and clinical implications are discussed.
The influenza A virus (IAV) nonstructural protein 1 (NS1) contributes to disease pathogenesis through the inhibition of host innate immune responses. Dendritic cells (DCs) release interferons (IFNs) ...and proinflammatory cytokines and promote adaptive immunity upon viral infection. In order to characterize the strain-specific effects of IAV NS1 on human DC activation, we infected human DCs with a panel of recombinant viruses with the same backbone (A/Puerto Rico/08/1934) expressing different NS1 proteins from human and avian origin. We found that these viruses induced a clearly distinct phenotype in DCs. Specifically, viruses expressing NS1 from human IAV (either H1N1 or H3N2) induced higher levels of expression of type I (IFN-α and IFN-β) and type III (IFN-λ1 to IFNλ3) IFNs than viruses expressing avian IAV NS1 proteins (H5N1, H7N9, and H7N2), but the differences observed in the expression levels of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) were not significant. In addition, using imaging flow cytometry, we found that human and avian NS1 proteins segregate based on their subcellular trafficking dynamics, which might be associated with the different innate immune profile induced in DCs by viruses expressing those NS1 proteins. Innate immune responses induced by our panel of IAV recombinant viruses were also characterized in normal human bronchial epithelial cells, and the results were consistent with those in DCs. Altogether, our results reveal an increased ability of NS1 from avian viruses to antagonize innate immune responses in human primary cells compared to the ability of NS1 from human viruses, which could contribute to the severe disease induced by avian IAV in humans.
Influenza A viruses (IAVs) cause seasonal epidemics which result in an important health and economic burden. Wild aquatic birds are the natural host of IAV. However, IAV can infect diverse hosts, including humans, domestic poultry, pigs, and others. IAVs circulating in animals occasionally cross the species barrier, infecting humans, which results in mild to very severe disease. In some cases, these viruses can acquire the ability to be transmitted among humans and initiate a pandemic. The nonstructural 1 (NS1) protein of IAV is an important antagonist of the innate immune response. In this study, using recombinant viruses and primary human cells, we show that NS1 proteins from human and avian hosts show intrinsic differences in the modulation of the innate immunity in human dendritic cells and epithelial cells, as well as different cellular localization dynamics in infected cells.
Abstract
We discuss the origin of the Large Magellanic Cloud (LMC) stellar bar by comparing the star formation histories (SFHs) obtained from deep colour–magnitude diagrams (CMDs) in the bar and in a ...number of fields in different directions within the inner disc. The CMDs, reaching the oldest main-sequence turn-offs in these very crowded fields, have been obtained with VIMOS on the Very Large Telescope in the service mode, under very good seeing conditions. We show that the SFHs of all fields share the same patterns, with consistent variations of the star formation rate as a function of time in all of them. We therefore conclude that no specific event of star formation can be identified with the formation of the LMC bar, which instead likely formed from a redistribution of disc material which occurred when the LMC disc became bar unstable, and shared a common SFH with the inner disc thereafter. The strong similarity between the SFH of the centre and edge of the bar rules out the expected significant spatial variations of the SFH across the bar.
In recent years, machine and deep learning models have attracted significant attention for electricity price forecast in global wholesale electricity markets. Yet, a predominant focus on point ...forecast in most parts of literature limits the practical application of these models due to the absence of uncertainty quantification. In this study, we first perform an analysis of the electricity price trends in the Mexican wholesale electricity market to determine the influence of key variables. Using independent component analysis and wavelet coherence analysis, we were able to identify primary determinants influencing locational marginal electricity prices. Subsequently, we applied four different models covering the most important algorithms proposed in the literature for electricity price forecast. Our findings revealed that the most accurate forecasting results were achieved using a deep learning‐based method with a decision tree‐based model trailing closely. Finally, we incorporate conformal prediction for uncertainty quantification by calculating the prediction intervals with a target coverage level of 95%. The conformal prediction intervals provide a more comprehensive view of the possible future scenarios, enhancing economic efficiency, risk management, and decision‐making processes. This is particularly important because of the dynamic nature of electricity markets, where prices are strongly influenced by multiple factors.
This study demonstrates the potential of using hybrid models for electricity price forecasting The findings suggest that natural gas prices would be sufficient for electricity price forecast in the Mexican market resulting in a simple model for deployment thus significantly reducing the computational costs. LSTM‐based and decision tree‐based models outperformed the ‘classical’ models in terms of accuracy and uncertaninty. This research offers significant insights for policymakers, energy traders, the academic community, and other key stakeholders, enhancing their understanding of the impact of exogenous variables on electricity prices. Finally, we incorporate conformal prediction for uncertainty quantification by calculating the predication intervals with a target coverage level of 95%.
Leishmaniases are a group of neglected tropical parasitic diseases, mainly affecting vulnerable populations of countries with poor socioeconomic status. Development of efficient vaccines is a ...priority due to the increasing incidence of drug resistance and toxicity to current treatments. In the search for a safe and efficient protective vaccine for human and dog visceral leishmaniases, we analyzed the suitability of the immunomodulatory drug sirolimus (SIR) to boost a preventive DNA vaccine against leishmaniasis. SIR is an already marketed drug that has been described to boost immune protection against different disease models and has also emerged as a promising therapeutic drug against L. major.
Syrian hamsters were treated with SIR concomitantly with the administration of a DNA vaccine formulation consisting in four plasmids carrying the Leishmania genes LACK, TRYP, PAPLE22 and KMPII, respectively. Two weeks after the last vaccination, the animals were infected intraperitoneally with L. infantum parasites. Five weeks post-infection the parasite load was measured by real-time PCR in target tissues and immune response was evaluated by determining anti-Leishmania specific antibodies in combination with cytokine expression in the spleen.
Our results show that the DNA vaccine itself efficiently reduced the burden of parasites in the skin (P = 0.0004) and lymph nodes (P = 0.0452). SIR administration also enhanced the protection by reducing the parasite load in the spleen (P = 0.0004). Vaccinated animals with or without SIR co-treatment showed lower IFN-γ expression levels than those found in the spleen of control animals. mRNA expression levels of NOS2 and IL-10 were found to be significantly higher in the vaccinated plus SIR treated group.
Co-administration of SIR enhances a DNA vaccination regimen against L. infantum, improving the reduction of parasite load in skin, lymph node and spleen. The analysis of immune markers in the spleen after challenge suggests that the trend to recover naïve levels of IFN-γ and IL-10, and the concurrent higher expression of NOS2, may be responsible for the protection induced by our vaccine co-administered with SIR.
African swine fever (ASF) is a pathology of pigs against which there is no treatment or vaccine. Understanding the equilibrium between innate and adaptive protective responses and immune pathology ...might contribute to the development of strategies against ASFV. Here we compare, using a proteomic approach, the course of the in vivo infection caused by two homologous strains: the virulent E75 and the attenuated E75CV1. Our results show a progressive loss of proteins by day 7 post-infection (pi) with E75, reflecting tissue destruction. Many signal pathways were affected by both infections but in different ways and extensions. Cytoskeletal remodelling and clathrin-endocytosis were affected by both isolates, while a greater number of proteins involved on inflammatory and immunological pathways were altered by E75CV1. 14-3-3 mediated signalling, related to immunity and apoptosis, was inhibited by both isolates. The implication of the Rho GTPases by E75CV1 throughout infection is also evident. Early events reflected the lack of E75 recognition by the immune system, an evasion strategy acquired by the virulent strains, and significant changes at 7 days post-infection (dpi), coinciding with the peak of infection and the time of death. The protein signature at day 31 pi with E75CV1 seems to reflect events observed at 1 dpi, including the upregulation of proteosomal subunits and molecules described as autoantigens (vimentin, HSPB1, enolase and lymphocyte cytosolic protein 1), which allow the speculation that auto-antibodies could contribute to chronic ASFV infections. Therefore, the use of proteomics could help understand ASFV pathogenesis and immune protection, opening new avenues for future research.
African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, ...African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain
Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed
correlated with the ability of BA71ΔCD2 to induce specific CD8
T cells capable of recognizing both BA71 and E75 viruses
Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.
African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.
This paper presents a detailed study of the influence of deposition conditions on structural and morphological properties of AlN thin films synthesized on c-sapphire substrates by radio frequency ...(RF) reactive sputtering. After the optimization of deposition parameters such as RF power and substrate temperature, the substrate bias has been identified as a critical variable to improve the structural properties of the AlN layers. The use of negative bias leads to a decrease of the full-width at half-maximum (FWHM) of the rocking curve of the AlN(0002) x-ray reflection and an increase of the grain size. However, 2θ/ω x-ray scans of layers grown under negative bias reveal lattice disorder at the AlN/sapphire interface, which is attributed to the highly accelerated positive ions (Al+, N+, N2+) arriving to the substrate at the initial stages of the deposition process. In order to prevent this interface degradation, we propose a twostep deposition method which consists of starting the growth with an unbiased AlN buffer layer, at least 30nm thick, followed by AlN deposition under negative bias. This procedure results in high-quality AlN layers with FWHM of the rocking curve of the (0002) reflection of 1.63°, grain size of ~40nm and root-mean-square surface roughness of 0.4nm.
•Highly c-axis-oriented AlN layers were grown on sapphire by RF sputtering.•The layer structural quality is enhanced when negatively biasing the substrate.•A lattice disorder is produced by high energetic ions reaching the substrate.•We report an optimized two-step AlN growth method to avoid the lattice disorder.
Heart failure (HF) is a health problem that particularly affects the elderly population. Its onset is associated with other chronic diseases, a circumstance that makes it a challenge for health care ...services. The aim of this study is to quantify the prevalence of HF in family medicine offices and describe the chronic co-morbidity associated with it.
A cross-sectional, observational descriptive study set in a health area of the Community of Madrid, Spain. The study was carried out in a population of 198,670 individuals over 14 years of age, attended to by 129 specialists in family medicine. The patient was considered to have HF when this diagnosis (ICPC code K77) appeared in his or her electronic medical record. The prevalence of HF was quantified and its association with another 25 chronic diseases was analysed.
The prevalence of HF was 6.9‰, 7.9‰ among women and 5.9‰ among men. Patients with HF had a high rate of chronic co-morbidity, with an average of 5.2 + 2.1 chronic diseases. Only 3% of the patients present with isolated HF and >60% have four or more additional chronic problems. Hypertension, cardiac arrhythmias, hyperlipidaemia, obesity and diabetes mellitus are the chronic diseases most frequently detected in HF patients.
Patients with HF frequently visit the offices of family physicians, presenting with a high rate of cardiac and non-cardiac co-morbidity that proves to be a challenge on the clinical level and in terms of the organization of health care services.
In order to ensure proper management of primary care (PC) services, the efficiency of the health professionals tasked with such services must be known. Patients with heart failure (HF) are ...characterized by advanced age, high co-morbidity and high resource utilization.
To ascertain PC resource utilization by HF patients and variability in the management of such patients by GPs.
Descriptive, cross-sectional study targeting a population attended by 129 GPs over the course of 1 year. All patients with diagnosis of HF in their clinical histories were included, classified using the Adjusted Clinical Group system and then grouped into six resource utilization bands (RUBs). Resource utilization and Efficiency Index were both calculated.
One hundred per cent of patients with HF were ranked in RUBs 3, 4 and 5. The highest GP visit rate was 20 and the lowest in excess of 10 visits per year. Prescription drug costs for these patients ranged from €885 to €1422 per patient per year. Health professional efficiency varied notably, even after adjustment for co-morbidity (Efficiency Index Variation Ratio of 28.27 for visits and 404.29 for prescription drug cost).
Patients with HF register a high utilization of resources, and there is great variability in the management of such patients by health professionals, which cannot be accounted for by the degree of case complexity.
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