Determinants of Metabolic Health Across Body Mass Index Categories in Central Europe: A Comparison Between Swiss and Czech Populations.

Comparisons among countries can help to identify opportunities for the reduction of inequalities in cardiometabolic health. The present cross-sectional analysis and meta-analysis aim to address to what extent obesity traits, socioeconomic, and behavioral factors determine poor metabolic health across body mass index (BMI) categories in two urban population-based samples from Central Europe. Data from the CoLaus (~6,000 participants; Lausanne, Switzerland) and the Kardiovize Brno 2030 (~2,000 participants; Brno, Czech Republic) cohorts. For each cohort, logistic regression analyses were performed to identify the main determinants of poor metabolic health overall and stratified by body mass index (BMI) categories. The results of each cohort were then combined in a meta-analysis. We first observed that waist circumference and body fat mass were associated with metabolic health, especially in non-obese individuals. Moreover, increasing age, being male, having low-medium educational level, abdominal obesity, and high body fat mass were the main determinants of the metabolically unhealthy profile in both cohorts. Meta-analysis stratified by BMI categories confirmed the previous results with slight differences across BMI categories. In fact, increasing age and being male were the main determinants of poor metabolic health independent of obesity status. In contrast, low educational level and current smoking were associated with poor metabolic health only in non-obese individuals. In line, public health strategies against obesity and related comorbidities should aim to improve social conditions and to promote healthy lifestyles before the progression of metabolic disorders

Role of color doppler imaging in early diagnosis and prediction of progression in glaucoma

This longitudinal and prospective study analyzes the ability of orbital blood flow measured by color Doppler imaging (CDI) to predict glaucoma progression in patients with glaucoma risk factors. Patients with normal perimetry but having glaucoma risk factors and patients in the initial phase of glaucoma were prospectively included in the study and divided, after a five-year follow-up, into two groups: “Progression” and “No Progression” based on the changes in the Moorfields regression analysis (MRA) classification of Heidelberg retina tomograph (HRT). An orbital CDI was performed in all patients and the parameters obtained were correlated with changes in HRT. A logistic discrimination function (LDF) was calculated for ophthalmic artery (OA) and central retinal artery (CRA) parameters. Receiver operating characteristics curves (ROC) were used to assess the usefulness of LDFs to predict glaucomatous progression. A total of 71 eyes were included. End-diastolic velocity, time-averaged velocity, and resistive index in the OA and CRA were significantly different ( ) between the Progression and No Progression groups. The area under the ROC curves calculated for both LDFs was of 0.695 (OA) and 0.624 (CRA). More studies are needed to evaluate the ability of CDI to perform early diagnosis and to predict progression in glaucoma in eyes

Short-term effects of traffic noise on suicides and emergency hospital admissions due to anxiety and depression in Madrid (Spain)

Studies show a relationship between some mental illnesses and suicides and different environmental variables such as air pollution, characterized by stress at the neuropsychological level. Despite the fact that traffic noise is also a powerful neurological stressor, studies that relate traffic noise to these mental disorders are practically non-existent. The objective is to analyze the short-term impact that chemical air pollution, traffic noise and thermal extremes have on emergency hospital admissions due to anxiety, dementia and suicides in the city of Madrid. This ecological, longitudinal study uses generalized linear models with Poisson link to analyze the short-term impact of the average daily concentrations of chemical pollutants (NO2, PM10, PM2.5, O3), noise pollution indicators (Leqday, Leqnight and Leq24h) and temperatures during heat waves (Theat) and cold waves (Tcold) on daily admissions to emergency services in the city of Madrid from 2010 to 2013 due to anxiety (ICD-10: F32), depression (ICD-10: F40-F42) and suicide (ICD-10: X60-X84). The results show no association between any of the chemical pollutants considered and the dependent variables studied. On the contrary, the values of Leqday are associated with the three variables analyzed in lag 0 for the cases of anxiety and depression and in lag 1 for suicides, with RR: 1.20 (IC95% 1.14 1.26), RR: 1.11 (IC95% 1.06 1.16) and RR: 1.17 (IC95% 1.05 1.30), respectively, for increases of 1 dB(A) in the values of Leqday. An association was also found between Tcold and admissions for anxiety in lag 9 with RR: 1.62 (IC95% 1.18 2.22) for increases of 1 °C in the values of Tcold. Traffic noise can be considered an important risk factor related to the illnesses and anxiety and depression and for suicides in the city of Madrid, although new studies are needed to support the findings shown here.The authors gratefully acknowledge Project ENPY 376/18 and Project ENPY 107/18 grants from the Institute of Health Carlos III.S

Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of MamC protein of Magnetococcus marinus MC-1

Magnetite Nanoparticles (MNPs) find many applications, including biotechnology, as they can be manipulated by an external magnetic field and functionalized with different molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome production is still challenging, so bio-mimetics, i.e. in vitro magnetite synthesis mediated by magnetosome-associated proteins is being explored. Our group is working with MamC from Magnetococcus marinus MC-1 that controls the morphology and size of the crystals, producing well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody (mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells, while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a targeted local treatment of tumors with a decrease in the deleterious systemic side effects

Meta-Analysis of the Relation of Body Mass Index to All-Cause and Cardiovascular Mortality and Hospitalization in Patients With Chronic Heart Failure

Clinical studies have indicated the existence of an "obesity paradox" in patients with chronic heart failure (HF), that is, reduced mortality in patients who have elevated body mass index (BMI) scores compared with normal-weight reference groups. The aim of this study was to investigate the relation of BMI with all-cause and cardiovascular (CV) mortality and hospitalization in patients with chronic HF though a systematic review and meta-analysis of published research. PubMed, the Cumulative Index to Nursing and Allied Health Literature, Cochrane Central, Scopus, web of science and Embase were searched for studies reporting rates of total mortality, cardiac mortality, and risk for hospitalization in patients with HF in various BMI categories

Role of bulge epidermal stem cells and TSLP signaling in psoriasis

Psoriasis is a common inflammatory skin disease involving a cross-talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF-SCs) in psoriasis is not well defined. Here, we show reduced expression of c-JUN and JUNB in bulge HF-SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c-Jun and JunB, we found that mutant bulge HF-SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non-mutant epidermal cells, while mutant inter-follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis-like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF-SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.We thank Drs. M. Serrano and M. Perez-Moreno for the Gt(ROSA)26Sortrn4(ACTB-tdTomato,-EGFP)Luo/J and K15-Cre-PGR mouse lines. We are very grateful to Drs. M. Perez-Moreno, F. Real, O. Uluckan, L. Bakiri and the laboratory members of the Sibilia and Wagner groups for critical reading of the manuscript and valuable suggestions. We thank V. Bermeo, G. Medrano, S. Leceta, O. Grana, and M. Perez for their technical help and IT support. We acknowledge R. Paus laboratory members for the shipment of hair follicle samples. N.G.L. received funding from the People programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no 608765. A.I is funded by the Institute of Health Carlos III (PI16/01430). The Wagner laboratory was funded by a grant from the Spanish Ministry of Economy and competitiveness (SAF2015-70857RE, cofounded by the European Regional Development Fund) and is supported by the ERC (ERC-AdG 2016 CSI-Fun).S

Improving graph-based detection of singular events for photochemical smog agents

Recently, a set of graph-based tools have been introduced for the identification of singular events of O3, NO2 and temperature time series, as well as description of their dynamics. These are based on the use of the Visibility Graphs (VG). In this work, an improvement of the original approach is proposed, being called Upside-Down Visibility Graph (UDVG). It adds the possibility of investigating the singular lowest episodes, instead of the highest. Results confirm the applicability of the new method for describing the multifractal nature of the underlying O3, NO2, and temperature. Asymmetries in the NO2 degree distribution are observed, possibly due to the interaction with different chemicals. Furthermore, a comparison of VG and UDVG has been performed and the outcomes show that they describe opposite subsets of the time series (low and high values) as expected. The combination of the results from the two networks is proposed and evaluated, with the aim of obtaining all the information at once. It turns out to be a more complete tool for singularity detection in photochemical time series, which could be a valuable asset for future research.Comment: 35 pages, 7 figure

Spectroscopic Observations of Convective Patterns in the Atmospheres of Metal-Poor Stars

Convective line asymmetries in the optical spectrum of two metal-poor stars, Gmb1830 and HD140283, are compared to those observed for solar metallicity stars. The line bisectors of the most metal-poor star, the subgiant HD140283, show a significantly larger velocity span that the expectations for a solar-metallicity star of the same spectral type and luminosity class. The enhanced line asymmetries are interpreted as the signature of the lower metal content, and therefore opacity, in the convective photospheric patterns. These findings point out the importance of three-dimensional convective velocity fields in the interpretation of the observed line asymmetries in metal-poor stars, and in particular, urge for caution when deriving isotopic ratios from observed line shapes and shifts using one-dimensional model atmospheres. The mean line bisector of the photospheric atomic lines is compared with those measured for the strong Mg I b1 and b2 features. The upper part of the bisectors are similar, and assuming they overlap, the bottom end of the stronger lines, which are formed higher in the atmosphere, goes much further to the red. This is in agreement with the expected decreasing of the convective blue-shifts in upper atmospheric layers, and compatible with the high velocity redshifts observed in the chromosphere, transition region, and corona of late-type stars.Comment: 27 pages, LaTeX; 10 Figures (14 PostScript files); to be published in The Astrophysical Journa

Determination of heat wave definition temperatures in Spain at an isoclimatic level: time trend of heat wave duration and intensity across the decade 2009–2018

Background: In line with WHO guidelines for the implementation of public health prevention plans targeted at the impacts of high temperatures, a heat wave defnition temperature (Tthreshold) was calculated for 182 so called “isoclimatic zones” (IZ) in Spain. As the dependent variable for determining this Tthreshold, we analysed daily all-cause mortality data (ICD-10: A00-R99) for each IZ across the period 2009–2018. The independent variable used was the mean value of the maximum daily temperature of the summer months recorded at meteorological observatories in each IZ. We used Box–Jenkins models to ascertain mortality anomalies, and scatterplots to link these anomalies to the temperatures at which they occurred, thereby determining the Tthreshold for each IZ. We then calculated how many heat waves had occurred in each IZ, as well as their intensity, and analysed their time trend over this period. Results: The results showed that in 52.5% of the IZ, the percentile of the maximum temperatures series of the summer months to which Tthreshold corresponded was below the 95th percentile of the meteorological heat wave defnition in Spain: indeed, it only coincided in 30.7% of cases. The geographical distribution of these percentiles displayed great heterogeneity as a consequence of the local factors that infuence the temperature–mortality relationship. The trend in the number of heat waves analysed indicated an overall increase in Spain at a rate of 3.9 heat waves per decade, and a similar rise in mean annual intensity of 9.5 °C/decade. These time-trend values were higher than those yielded by analysing the trend in meteorological heat waves based on the 95th percentile. Conclusions: The results obtained in this study indicate the need to use a heat wave defnition based on epidemiological temperature–mortality studies, rather than on values based on meteorological percentiles. This could be minimising estimated health impacts in analyses of future impacts attributable to heat.Acknowledgements and funding The authors would like to express their gratitude for the following grants from the Carlos III Institute of Health (Instituto de Salud Carlos III/ISCIII) for the ENPY 304/20, and ENPY 436/21 projects.S