Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLCMS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention

Insights into the single-particle composition, size, mixing state, and aspect ratio of freshly emitted mineral dust from field measurements in the Moroccan Sahara using electron microscopy

The chemical and morphological properties of mineral dust aerosols emitted by wind erosion from arid and semi-arid regions influence climate, ocean, and land ecosystems; air quality; and multiple socio-economic sectors. However, there is an incomplete understanding of the emitted dust particle size distribution (PSD) in terms of its constituent minerals that typically result from the fragmentation of soil aggregates during wind erosion. The emitted dust PSD affects the duration of particle transport and thus each mineral's global distribution, along with its specific effect upon climate. This lack of understanding is largely due to the scarcity of relevant in situ measurements in dust sources. To advance our understanding of the physicochemical properties of the emitted dust PSD, we present insights into the elemental composition and morphology of individual dust particles collected during the FRontiers in dust minerAloGical coMposition and its Effects upoN climaTe (FRAGMENT) field campaign in the Moroccan Sahara in September 2019. We analyzed more than 300 000 freshly emitted individual particles by performing offline analysis in the laboratory using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectrometry (EDX). Eight major particle-type classes were identified with clay minerals making up the majority of the analyzed particles both by number and mass, followed by quartz, whereas carbonates and feldspar contributed to a lesser extent. We provide an exhaustive analysis of the PSD and potential mixing state of different particle types, focusing largely on iron-rich (Fe oxide-hydroxides) and feldspar particles, which are key to the effects of dust upon radiation and clouds, respectively. Nearly pure or externally mixed Fe oxide-hydroxides are present mostly in diameters smaller than 2 µm, with the highest fraction below 1 µm at about 3.75 % abundance by mass. Fe oxide-hydroxides tend to be increasingly internally mixed with other minerals, especially clays, as particle size increases; i.e., the volume fraction of Fe oxide-hydroxides in aggregates decreases with particle size. Pure (externally mixed) feldspar represented 3.2 % of all the particles by mass, of which we estimated about a 10th to be K-feldspar. The externally mixed total feldspar and K-feldspar abundances are relatively invariant with particle size, in contrast to the increasing abundance of feldspar-like (internally mixed) aggregates with particle size with mass fractions ranging from 5 % to 18 %. We also found that overall the median aspect ratio is rather constant across particle size and mineral groups, although we obtain slightly higher aspect ratios for internally mixed particles. The detailed information on the composition of freshly emitted individual dust particles and quantitative analysis of their mixing state presented here can be used to constrain climate models including mineral species in their representation of the dust cycle.</p

COVID-19 in hospitalized HIV-positive and HIV-negative patients: A matched study

Objectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.This work was supported by the Instituto de Salud Carlos III (ISCII) (grant no. COV20/00108) and the Spanish AIDS Research Network (RD16/0025), which is included in the Spanish I+D+I Plan and is co- funded by ISCIII- Subdirección General de Evaluación and European Funding for Regional Development (FEDER)S

Impact of piglet oral vaccination against tuberculosis in endemic free-ranging wild boar populations

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe Eurasian wild boar (Sus scrofa) is the main wild reservoir of the Mycobacterium tuberculosis complex in Mediterranean woodlands and a key risk factor for cattle tuberculosis (TB) breakdowns. Wild boar vaccination therefore has the potential to be a valuable tool for TB control. We tested two orally delivered vaccines, heat-inactivated Mycobacterium bovis (IV) and BCG, in four sites (two per vaccine type: one Managed and one Natural or unmanaged) during four years. TB was also monitored in 15 unvaccinated sites (spatial control), as well as in all sites from one year prior to intervention (temporal control). The rationale is that by vaccinating 2-6 month old wild boar piglets we can reduce disease at the population level during the study period. This is achievable due to the fast turnover of wild boar populations. Vaccine baits were deployed using selective piglet feeders and this method proved highly successful with uptake rates of 50 to 74% in Natural sites and 89 to 92% in Managed sites. This is relevant for the potential delivery of vaccines to control other diseases, too. Local wild boar TB prevalence at the beginning of the study was already high ranging from 50 to 100%. TB prevalence increased in unvaccinated sites (6%), while a significant decline occurred in the Managed IV site (34%). Changes recorded in the remaining sites were not significant. The short-term impact of vaccination observed in the field was complemented by mathematical modelling, representative of the field system, which examined the long-term impact and showed that vaccination of piglets reduced prevalence and increased abundance at the population level. We conclude that IV could become part of integrated TB control schemes, although its application must be tailored for each specific site.Engineering and Physical Sciences Research Council (EPSRC)Scottish Funding CouncilHeriot-Watt UniversityUniversity of EdinburghMINEC

IVRIPARC project: a method for assessing the impact of global change on geoheritage of the Canary Islands national parks (Spain)

El patrimonio geológico y la geodiversidad de los parques nacionales contribuyen, junto con la biodiversidad, para que sean espacios naturales protegidos únicos en el país, pero también únicos a nivel mundial. El patrimonio geológico es de carácter no renovable, de tal forma que, si se pierden o degradan, lo hacen para siempre. Ante el escenario del cambio global, el patrimonio geológico de los parques nacionales canarios es muy vulnerable a los impactos rovocados por los cambios en la temperatura, avenidas torrenciales, tormentas extremas, sequías, desertificación y ascenso del nivel del mar, fundamentalmente, y a los impactos derivados de la actividad humana. Estos fenómenos provocan la activación de procesos geológicos que afectan directamente a su conservación, de tal forma que es necesario identificar los Lugares de Interés Geológico más amenazados, evaluar su incidencia y establecer los indicadores a escala de cada parque nacional para realizar su seguimiento. Conocer el estado de conservación actual, su vulnerabilidad y sus amenazas directas contribuirá a la gestión de los parques para el proceso de adaptación y mitigación del cambio global.The geoheritage and geodiversity of the national parks contribute, together with biodiversity, to make them protected natural areas that are unique in Spain, but also unique worldwide. Geoheritage is non-renewable and if it is lost or degraded it does so forever. Under the Global Change and Climate Change scenario, the geoheritage of the Canary national parks is highly vulnerable to the impacts caused by changes in temperature, flash floods, extreme storms, droughts, desertification, fires and sea level rise, fundamentally and to the impacts directly derived from human activity. These phenomena trigger the activation of geological processes that directly affect their conservation, in such a way that it is necessary to identify the geosites most threatened, to evaluate their impact and to establish the indicators at the scale of each national park for monitoring them. The knowledge of the current conservation status of geoheritage, its vulnerability and its direct threats will contribute to the management of the national parks for the process of adaptation and mitigation of Global Change.Depto. de Geodinámica, Estratigrafía y PaleontologíaDepto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEOrganismo Autónomo de Parques Nacionalespu

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study

Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4–11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0–64.9) when LOH was 11–15 days, and by 72.0% (95%CI = 42.6–107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4–36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Muticenter spanish study for perioperative stroke risk prediction after isolated coronary artery bypass surgery: The PACK2 score

[ES] Objetivos: Desarrollar un modelo predictivo multivariante del accidente cerebrovascular (ACV) intrahospitalario tras cirugía de bypass coronario. Métodos: Veintiséis mil trescientos cuarenta y siete pacientes incluidos en el estudio procedentes de 21 bases de datos de hospitales españoles. El análisis de regresión logística fue utilizado para predecir el riesgo de ACV perioperatorio (ictus o accidente isquémico transitorio). El modelo predictivo fue desarrollado a partir de un subgrupo de datos «de prueba» y validado en otro subgrupo independiente, ambos seleccionados aleatoriamente del total de la muestra. La capacidad predictiva del modelo se relacionó con el área bajo la curva ROC (ABC). Las variables consideradas fueron: preoperatorias (edad, sexo, diabetes mellitus, hipertensión arterial, ACV previo, insuficiencia cardiaca y/o fracción de eyección del ventrículo izquierdo < 40%, prioridad de la intervención no electiva, arteriopatía extracardiaca, insuficiencia renal crónica y/o creatininemia &#8805; 2 mg/dl y fibrilación auricular) e intraoperatorias (cirugía coronaria con/sin circulación extracorpórea). Resultados: Incidencia global de ACV perioperatorio 1,38%. La prioridad no electiva de la cirugía (priority; OR = 2,32), arteriopatía extracardiaca (arteriopathy; OR = 1,37), insuficiencia cardiaca (cardiac; OR = 3.64) e insuficiencia renal crónica (kidney; OR = 6,78) fueron identificados como factores de riesgo independientes de ACV perioperatorio en los modelos uni y multivariante en el subgrupo de prueba; p < 0,0001; ABC = 0,77, IC del 95%, 0,73-0,82. El modelo PACK2 de ACV perioperatorio tras cirugía de bypass coronario se estableció con 1 punto para cada ítem, excepto para la insuficiencia renal crónica que se le otorgaron 2 puntos (rango 0-5 puntos); ABC = 0,76, IC del 95%, 0,72-0,80. En pacientes con puntuación PACK2 &#8805; 2 puntos, la cirugía coronaria sin circulación extracorpórea redujo la incidencia de ACV en un 2,3% cuando se comparó con el grupo con cirugía realizada con circulación extracorpórea. Conclusiones: La escala de riesgo PACK2 muestra una buena capacidad predictiva en los datos analizados y podría ser útil en la toma de decisiones y selección de pacientes de la práctica clínica.[EN] Objectives: To develop a multivariate predictive risk score of perioperative in-hospital stroke after coronary artery bypass grafting (CABG) surgery. Methods: A total of 26,347 patients were enrolled from 21 Spanish hospital databases. Logistic regression analysis was used to predict the risk of perioperative stroke (stroke or transient ischaemic attack). The predictive scale was developed from a training set of data and validated by an independent test set, both selected randomly from the global sample. The assessment of the accuracy of prediction was related to the area under the ROC curve (AUC). The variables considered were: preoperative (age, gender, diabetes mellitus, arterial hypertension, previous stroke, cardiac failure and/or left ventricular ejection fraction < 40%, non-elective priority of surgery, extracardiac arteriopathy, chronic kidney failure and/or serum creatinine ≥2 mg/dl, and atrial fibrillation) and intra-operative (on/off-pump). Results: The overall perioperative stroke incidence was 1.38%. Non-elective priority of surgery (priority; OR = 2.32), vascular disease (arteriopathy; OR = 1.37), heart failure (cardiac; OR = 3.64), and chronic kidney failure (kidney; OR = 6.78) were found to be independent risk factors for perioperative stroke in uni- and multivariate models in the training set of data; P < .0001; AUC = 0.77, 95% CI 0.73–0.82. The PACK2 stroke CABG score was established with 1 point for each item, except for chronic kidney failure with 2 points (range 0–5 points); AUC = 0.76, 95% CI 0.72–0.80. In patients with PACK2 score ≥2 points, off-pump reduced perioperative stoke incidence by 2.3% when compared with on-pump CABG. Conclusions: PACK2 risk scale shows good predictive accuracy in the data analysed and could be useful in clinical practice for decision making and patient selection.Martín, E.; Hornero, F.; Rodríguez, R.; Castellà, M.; Porras, C.; Romero, B.; Maroto, L.... (2014). Estudio multicéntrico español para la predicción del riesgo perioperatorio de accidente cerebrovascular tras cirugía de bypass coronario aislada: el modelo PACK2. Cirugia Cardiovascular. 21(3):175-180. doi:10.1016/j.circv.2014.02.009S17518021

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect