Efectos de la pérdida de peso preoperatoria mediante una dieta muy baja en calorías versus una dieta mixta, en pacientes obesos mórbidos candidatos a cirugía bariátrica laparoscópica

L'obesitat ha anat en augment en les últimes dècades, especialment en les seves formes més extremes. Aquesta patologia s'associa amb algunes comorbiditats i se sap que el mètode més efectiu en la seva millora o resolució és la cirurgia bariàtrica. No obstant, la malaltia del fetge gras no alcohòlic, present en gairebé el 90% dels subjectes pendents de cirurgia bariàtrica, és una comorbiditat que fa que el fetge sigui més friable i de major grandària, dificultant així l'acte quirúrgic. L'objectiu principal d'aquesta tesi és avaluar quin tipus d'estratègia dietètica preoperatòria, una dieta molt baixa en calories (VLCD) o bé una dieta baixa en calories (LCD), és més efectiva per reduir el volum hepàtic. Els objectius específics tracten d’avaluar l'efecte de les dues dietes sobre el pes i la composició corporal, la tolerància i el compliment de la dieta, els paràmetres bioquímics, les complicacions quirúrgiques i l’estada hospitalària; així com també l'efecte d'incrementar o disminuir l'adherència a la dieta mediterrània i / o el nivell d'activitat física després de la cirurgia bariàtrica sobre la pèrdua ponderal, la qualitat de vida o la tolerància alimentària durant l'any posterior a la intervenció. Els resultats obtinguts mostren que ambdues dietes són efectives en la pèrdua ponderal precirurgia, essent aquesta més gran en la dieta VLCD. També, seguir una dieta VLCD o LCD té efectes similars en la reducció del volum hepàtic, en els paràmetres bioquímics, en les complicacions quirúrgiques i en la durada de l'hospitalització. A més, incrementar l'adherència a una dieta saludable com la mediterrània s'associa a una major pèrdua ponderal a l'any de la cirurgia. En conclusió, no és necessari realitzar dietes excessivament restrictives prèvies a la cirurgia per a la disminució del volum hepàtic. A més, augmentar l'adherència a la dieta mediterrània pot incrementar la pèrdua ponderal postcirurgia.La obesidad ha ido en aumento en las últimas décadas, especialmente en sus formas más extremas. Esta patología se asocia con algunas comorbilidades, sabiéndose que el método más efectivo en su mejora o resolución es la cirugía bariátrica. Sin embargo, la enfermedad del hígado graso no alcohólico, presente en casi el 90% de los sujetos pendientes de cirugía bariátrica, es una comorbilidad que deriva en un hígado más friable y de mayor tamaño, dificultando así el acto quirúrgico. El objetivo principal de esta tesis es evaluar qué tipo de estrategia dietética preoperatoria, una dieta muy baja en calorías (VLCD) o una dieta baja en calorías (LCD), es más efectiva para reducir el volumen hepático. Los objetivos específicos evalúan el efecto de ambas dietas sobre el peso y la composición corporal, la tolerancia y el cumplimiento de la dieta, los parámetros bioquímicos, las complicaciones quirúrgicas y la estancia hospitalaria; así como también el efecto de incrementar o disminuir la adherencia a la dieta mediterránea y/o el nivel de actividad física después de la cirugía bariátrica sobre la pérdida ponderal, la calidad de vida o la tolerancia alimentaria durante el año posterior a la intervención. Los resultados obtenidos muestran que ambas dietas son efectivas en la pérdida ponderal precirugía, siendo ésta mayor en la dieta VLCD. Asimismo, se observa también que ambas tienen efectos similares en la reducción del volumen hepático, en los parámetros bioquímicos, en lasObesity has been on the rise in recent decades, especially in its most extreme forms. While this pathology is associated with some comorbidities, it is known that the most effective method for its improvement or resolution is bariatric surgery. Nontheless, nonalcoholic fatty liver disease, which is present in almost 90% of subjects pending bariatric surgery, is a comorbidity that turns the liver more friable and larger, thus making the surgical act more difficult. The main objective of this dissertation is to evaluate which type of preoperative dietary strategy, either a Very Low Calorie Diet (VLCD) or a Low Calorie Diet (LCD), is more effective in reducing liver volume. The specific objectives evaluate the effect of both diets on weight and body composition, tolerance and diet compliance, biochemical parameters, surgical complications and hospital stay; as well as the effect of increasing or decreasing adherence to the Mediterranean diet and / or the level of physical activity

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Update on the Combined Analysis of Muon Measurements from Nine Air Shower Experiments

Over the last two decades, various experiments have measured muon densities in extensive air showers over several orders of magnitude in primary energy. While some experiments observed differences in the muon densities between simulated and experimentally measured air showers, others reported no discrepancies. We will present an update of the meta-analysis of muon measurements from nine air shower experiments, covering shower energies between a few PeV and tens of EeV and muon threshold energies from a few 100 MeV to about 10GeV. In order to compare measurements from different experiments, their energy scale was cross-calibrated and the experimental data has been compared using a universal reference scale based on air shower simulations. Above 10 PeV, we find a muon excess with respect to simulations for all hadronic interaction models, which is increasing with shower energy. For EPOS-LHC and QGSJet-II.04 the significance of the slope of the increase is analyzed in detail under different assumptions of the individual experimental uncertainties

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication i

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates

Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials