Atrial fibrosis identification with unipolar electrogram eigenvalue distribution analysis in multi-electrode arrays

Atrial fbrosis plays a key role in the initiation and progression of atrial fbrillation (AF). Atrial fbrosis is typically identifed by a peak-to-peak amplitude of bipolar electrograms (b-EGMs) lower than 0.5 mV, which may be considered as ablation targets. Nevertheless, this approach disregards signal spatiotemporal information and b-EGM sensitivity to catheter orientation. To overcome these limitations, we propose the dominant-to-remaining eigenvalue dominance ratio (EIGDR) of unipolar electrograms (u-EGMs) within neighbor electrode cliques as a waveform dispersion measure, hypothesizing that it is correlated with the presence of fbrosis. A simulated 2D tissue with a fbrosis patch was used for validation. We computed EIGDR maps from both original and time-aligned u-EGMs, denoted as R and RA, respectively, also mapping the gain in eigenvalue concentration obtained by the alignment, ΔRA. The performance of each map in detecting fbrosis was evaluated in scenarios including noise and variable electrode-tissue distance. Best results were achieved by RA, reaching 94% detection accuracy, versus the 86% of b-EGMs voltage maps. The proposed strategy was also tested in real u-EGMs from fbrotic and non-fbrotic areas over 3D electroanatomical maps, supporting the ability of the EIGDRs as fbrosis markers, encouraging further studies to confrm their translation to clinical settings

Age at first episode modulates diagnosis-related structural brain abnormalities in psychosis

Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12–35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15–20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18–20 y). The AFP group also had age-constant (12–35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis

Targeting L-type amino acid transporter 1 in innate and adaptive T cells efficiently controls skin inflammation

BACKGROUND: Psoriasis is a frequent inflammatory skin disease that is mainly mediated by IL-23, IL-1β, and IL-17 cytokines. Although psoriasis is a hyperproliferative skin disorder, the possible role of amino acid transporters has remained unexplored. OBJECTIVE: We sought to investigate the role of the essential amino acid transporter L-type amino acid transporter (LAT) 1 (SLC7A5) in psoriasis. METHODS: LAT1 floxed mice were crossed to Cre-expressing mouse strains under the control of keratin 5, CD4, and retinoic acid receptor-related orphan receptor γ. We produced models of skin inflammation induced by imiquimod (IMQ) and IL-23 and tested the effect of inhibiting LAT1 (JPH203) and mammalian target of rapamycin (mTOR [rapamycin]). RESULTS: LAT1 expression is increased in keratinocytes and skin-infiltrating lymphocytes of psoriatic lesions in human subjects and mice. LAT1 deletion in keratinocytes does not dampen the inflammatory response or their proliferation, which could be maintained by increased expression of the alternative amino acid transporters LAT2 and LAT3. Specific deletion of LAT1 in γδ and CD4 T cells controls the inflammatory response induced by IMQ. LAT1 deletion or inhibition blocks expansion of IL-17-secreting γ4+δ4+ and CD4 T cells and dampens the release of IL-1β, IL-17, and IL-22 in the IMQ-induced model. Moreover, inhibition of LAT1 blocks expansion of human γδ T cells and IL-17 secretion by human CD4 T cells. IL-23 and IL-1β stimulation upregulates LAT1 expression and induces mTOR activation in IL-17+ γδ and TH17 cells. Deletion or inhibition of LAT1 efficiently controls IL-23- and IL-1β-induced phosphatidylinositol 3-kinase/AKT/mTOR activation independent of T-cell receptor signaling. CONCLUSION: Targeting LAT1-mediated amino acid uptake is a potentially useful immunosuppressive strategy to control skin inflammation mediated by the IL-23/IL-1β/IL-17 axis.Funding This manuscript has been funded by grants SAF 2017-82886-R (FS-M) and SAF 2013-42850-R (MF) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD-3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M); CIBERCV, BIOIMID PIE13/041 from Instituto de Salud Carlos III and Fundación La Marató TV3 (20152330 31). The project leading to these results has also received funding from FUNDACIÓN BBVA A EQUIPOS DE INVESTIGACIÓN CIENTÍFICA 2018 and from “la Caixa” Banking Foundation under the project code HR17-00016 (FS-M), and from Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional PI17/01972 (E.D).S

A chirality-induced alpha phase and a novel molecular magnetic metal in the BEDT-TTF/tris(croconate)ferrate(III) hybrid molecular system

The novel paramagnetic and chiral anion [Fe(C5O5)3]32 has been combined with the organic donor BEDT-TTF (= ET = bis(ethylenedithio)tetrathiafulvalene) to yield the first chirality- induced α phase and a paramagnetic metal.Gomez Garcia, Carlos, [email protected] ; Coronado Miralles, Eugenio, [email protected] ; Gimenez Saiz, Carlos, [email protected]

Considerations for future modification of The Association for the Study of Reproductive Biology embryo grading system incorporating time-lapse observations

10 Pág.The Association for the Study of Reproductive Biology (ASEBIR) Interest Group in Embryology (in Spanish 'Grupo de Interés de Embriología') reviewed key morphokinetic parameters to assess the contribution of time-lapse technology (TLT) to the ASEBIR grading system. Embryo grading based on morphological characteristics is the most widely used method in human assisted reproduction laboratories. The introduction and implementation of TLT has provided a large amount of information that can be used as a complementary tool for morphological embryo evaluation and selection. As part of IVF treatments, embryologists grade embryos to decide which embryos to transfer or freeze. At the present, the embryo grading system developed by ASEBIR does not consider dynamic events observed through TLT. Laboratories that are using TLT consider those parameters as complementary data for embryo selection. The aim of this review was to evaluate review time-specific morphological changes during embryo development that are not included in the ASEBIR scoring system, and to consider them as candidates to add to the scoring system.Peer reviewe

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Carbon dioxide (CO2) emissions and adherence to Mediterranean diet in an adult population: the Mediterranean diet index as a pollution level index

Background Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. Aim To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. Design and population Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. Methods Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (= 2.80 kg CO2). Results More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). Conclusions The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index