Endocrine disruption in Crohn’s disease: Bisphenol A enhances systemic inflammatory response in patients with gut barrier translocation of dysbiotic microbiota products

This study has been partially funded by PID2019-107036RB-I00, from Ministerio de Ciencia, Innovacion y Universidades, Madrid, Spain, and 2020-0287, from IIS ISABIAL, Hospital General Universitario, Alicante, Spain. RL is recipient of a grant (FPU 18/00063) by Ministerio de Ciencia, Innovacion y Universidades, Madrid, Spain.The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine disruptors, short-chain fatty acids, tryptophan and cytokines were measured. Bacterial-DNA and serum endotoxin levels were also evaluated. Gene expression of ER-α, ER-β and GPER was measured in PBMCs. All patients were genotyped for NOD2 and ATG16L1 polymorphisms. A series of 200 CD patients (140 in remission, 60 with active disease) was included in the study. Bisphenol A was significantly higher in patients with active disease versus remission and in colonic versus ileal disease. GPER was significantly increased in active patients and correlated with BPA levels. BPA was significantly increased in patients with bacterial-DNA and correlated with serum endotoxin levels, (r = 0.417; P = .003). Serum butyrate and tryptophan levels were significantly lower in patients with bacterial-DNA and an inverse relationship was present between them and BPA levels (r = −0.491; P = .001) (r = −0.611; P = .001). Serum BPA levels correlated with IL-23 (r = 0.807; P = .001) and IL-17A (r = 0.743; P = .001). The multivariate analysis revealed an independent significant contribution of BPA and bacterial-DNA to serum levels of IL-23 and IL-17A. In conclusion, bisphenol A significantly affects systemic inflammatory response in CD patients with gut barrier disruption and dysbiotic microbiota secretory products in blood. These results provide evidence of an endocrine disruptor playing an actual pathogenic role on CD.Ministerio de Ciencia, Innovacion y Universidades, Madrid, Spain PID2019-107036RB-I00 FPU 18/00063IIS ISABIAL, Hospital General Universitario, Alicante, Spain 2020-028

Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the “NELA” birth cohort

Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigeneticmechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentrationwas measured by dispersive liquid–liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration ofmaternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta= 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend=0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance.Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science, Innovation and Universities, Fondos FEDER MS14/00046 CP14/00046 PIE15/00051 PI16/00422 FI17/00086 PI19/00863Fundacion Seneca, Agencia de Ciencia y Tecnologia Region de Murcia 20877/PI/18Ministry of Science and Innovation, Spain (MICINN)Spanish Government FPU18/01990ISCIII, Spanish Ministry of Science, Innovation and Universities, and Fondos FEDER MS14/00046 CPII19/0001

Estructuras reproductoras y epífitas del género Avrainvillea en aguas cubanas

Se describen las estructuras reproductivas en Avrainvillea elliottii A. Gepp et E. S. Gepp, A. longicaulis f. laxa D. S. Littler et M. M. Littler y A. digitata Littler et Littler para aguas cubanas. Se revisaron materiales de herbario del género Avrainvillea, así como ejemplares de reciente colecta y se registraron un total de 41 táxones, 23 Rhodopyta, 4 Ochrophyta y 14 Chlorophyta como epífitas. A. levis Howe presentó como epífitas a miembros de su misma especie, tanto en la lámina como en la porción apical del estipe. Los rizoides pegados a los talos epifitos de A. levis tiene forma de disco. El estipe fue la región del talo que presentó el mayor número de especies epífitas. Se adicionan siete especies de algas marinas a la flora ficológica de Cuba: Rhodogorgon ramosissima N. Norris et Bucher, Botryocladia spinulifera W. R. Taylor et I. A. Abbott, Ceratodictyon scoparium (Mont. et Millardet) R.E. Norris, Ulva rigida C. Agardh, Caulerpa prolifera f. obovata (J. Agardh) Weber Bosse, H. monile f. robusta (Børgesen) Collins et Herv., y Udotea cyathiformis var. cyathiformis f. infundibulum (J. Agardh) D. S. Littler et M.M. Littler

Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach

This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors acknowledge the European Union's Horizon 2020 research and innovation program HBM4EUfor the financial support under Grant Agreement #733032. The study was also supported by the ISCIII with grants no. CP16/00085 and FIS 17/01526, and the Human Genotyping Laboratory at the Spanish National Cancer Research Center (CeGen-PRB3). The authors also thank the support of the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), and the University of Granada (Grant "UNETE," UCE-PP2017-06). A. Rodriguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education, Spain, and Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EUproject. C. Freire received a grant under the Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (MS16/00085; ISCIII/FEDER). This article forms part of the doctoral thesis developed by Andrea Rodriguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain).Background: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. Objectives: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. Methods: The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide carbaryl 1-naphthol (1-N), and the metabolite of ethylene-bis-dithiocarbamate fungicides ethylene thiourea (ETU) were measured in spot urine samples, as well as serum BDNF protein levels and blood DNA methylation of Exon IV of BDNF gene in 15–17-year-old boys from the INMA-Granada cohort in Spain. Adolescents’ behavior was reported by parents using the Child Behavior Check List (CBCL/ 6–18). This study included 140 adolescents of whom 118 had data on BDNF gene DNA methylation. Multivariable linear regression, weighted quantile sum (WQS) for mixture effects, and mediation models were fit. Results: IMPy, MDA, DCCA, and ETU were detected in more than 70% of urine samples, DETP in 53%, and TCPy, 3-PBA, and 1-N in less than 50% of samples. Higher levels of IMPy, TCPy, and ETU were significantly associated with more behavioral problems as social, thought problems, and rule-breaking symptoms. IMPy, MDA, DETP, and 1-N were significantly associated with decreased serum BDNF levels, while MDA, 3-PBA, and ETU were associated with higher DNA methylation percentages at several CpGs. WQS models suggest a mixture effect on more behavioral problems and BDNF DNA methylation at several CpGs. A mediated effect of serum BDNF within IMPy-thought and IMPy-rule breaking associations was suggested. Conclusion: BDNF biomarkers measured at different levels of biological complexity provided novel information regarding the potential disruption of behavioral function due to contemporary pesticides, highlighting exposure to diazinon (IMPy) and the combined effect of IMPy, MDA, DCCA, and ETU. However, further research is warranted.European Union's Horizon 2020 research and innovation program HBM4EU 733032Instituto de Salud Carlos III CP16/00085 FIS 17/01526Human Genotyping Laboratory at the Spanish National Cancer Research Center (CeGen-PRB3)Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP)University of Granada UCE-PP2017-06Spanish Government FPU 16/03011Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) MS16/0008

Effect of a dietary intervention based on the mediterranean diet on the quality of life of patients recovered from depression: analysis of the PREDIDEP randomized trial

Introduction: There is substantial evidence supporting that improving diet quality leads to improved healthrelated quality of life (HRQoL). Our major aim was to assess the effectiveness of a Mediterranean diet–based nutritional intervention to improve HRQoL in the context of a secondary prevention trial of depression. Secondarily to assess its effectiveness among adults aged 60 or more years. Methods: The PREDIDEP study is a 2-year multicentre, randomized, single-blinded nutritional trial. At baseline and at 1-year and 2-year follow-up, SF-36 health survey questionnaire was collected to evaluate participants' HRQoL (total and specific range for each of the 8 dimensions: 0 to 100 points). Mixed effect linear models were used to assess changes in HRQoL according to adherence to the Mediterranean diet. The trial was registered at ClinicalTrials.gov NCT03081065. Results: After 2 years of intervention, the Mediterranean Diet intervention group compared to control group (without nutritional intervention, only usual clinical care) showed an improvement in some dimensions of HRQoL such as Mental Health (7.22; 95 % CI = 2.22–12.22) (between-group difference: 6.79; 95 % CI − 0.14–13.73, p = 0.055); Vitality (9.51; 95 % CI = 4.00–15.03) (between-group difference: 9.00; 95 % CI 1.75–16.25, p = 0.020); Mental Summary Component (2.83; 95 % CI = 0.55–5.11) (between-group difference: 1.17; 95 % CI = − 1.96–4.30, p = 0.462); and General Health (10.70; 95 % CI = 5.58–15.81) (between-group difference: 6.20; 95 % CI = − 0.89–13.28, p = 0.086). Similar results were observed for participants aged 60 or more years. Conclusion: The intervention based on Mediterranean diet in patients with previous depression seems to be effective in improving HRQoL, especially the mental dimensions. This effect is also observed among participants aged 60 or more years.This study was externally funded by the Spanish Ministry of Science and Innovation (Carlos III National Health Institute-ISCIII), PI16/01274

Inventario de la flora marina del Archipiélago Sabana Camagüey, Cuba

Se presenta un inventario de especies de macroalgas y angiospermas marinas del Archipiélago Sabana-Camagüey (ASC). Se identificaron 379 taxones infragenéricos: 177 Rhodophyta, 49 Ochrophyta, 147 Chlorophyta y seis Magnoliophyta. El acumulado de especies representó el 78% de las conocidas para Cuba hasta 2005, lo que muestra la alta diversidad de macroalgas que posee este archipiélago. Todas las angiospermas marinas conocidas en nuestro país se encontraron en el ASC. La mitad oriental de la zona de estudio acumuló más especies (348) que la occidental (278) lo que puede deberse a la alta heterogeneidad de condiciones ambientales existentes en la primera.The inventory of macroalgae and marine angiosperms species of the Sabana-Camagüey Archipelago (ASC) is presented. 379 infrageneric taxa: 177 Rhodophyta, 49 Ochrophyta, 147 Chlorophyta and six Magnoliophyta were identified. The species of macroalgae accumulated represents the 78% of the species known for Cuba until 2005, what demonstrates the high diversity of seaweeds that possesses this archipelago. All the known marine angiosperms in our country were found in the ASC. The oriental half of the study area accumulated more species (348) than the westerner (278) what can be due to the high environmental heterogeneity in the former

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss

Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in 1 (protein O -glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O -glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent 7 + cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells