Removal and toxicity evaluation of a diverse group of drugs from water by a cyclodextrin polymer/pulsed light system

The presence of pharmaceutical compounds (PhCs) in the effluents of wastewater treatment plants (WWTPs) is an ecological concern. The issue could be alleviated by trapping those substances by cyclodextrin (CD) polymers or photolyzing them by pulsed light (PL). Consequently, a sequential CD polymer/PL system was tested for the removal of PhCs. Firstly, a survey detected the presence of recurrent PhCs in the effluents of local WWTPs. Then, pure water was spiked with 21 PhCs, 100 μg/L each one. The three-dimensional network provides amphiphilic features to the CD polymer that reduced the pollutant concentration by 77 %. Sorption involves a plead of physical and chemical mechanisms hindering the establishment of a general removal model for all compounds. The performed simulations hint that the retention capacity mainly correlates with the computed binding energies, so that theoretical models are revealed as valuable tools for further improvements. The complementary action of PL rose the elimination to 91 %. The polymer can be reused at least 10 times for ibuprofen (model compound) removal, and was able to eliminate the ecotoxicity of an ibuprofen solution. Therefore, this novel sequential CD polymer/PL process seems to be an efficient alternative to eliminate PhCs from wastewater.Ciencias Ambientale

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. OBJECTIVES 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. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

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La noblesse, bien qu’elle ait cédé au clergé la première place dans les hiérarchies sociales de l’époque, occupait cependant une place éminente au sein de cette même société. C’est un état dont les effectifs sont difficiles à quantifier de façon globale, mais qui, incontestablement, était assez nombreux surtout si on compare avec les autres pays de l’Europe occidentale. Un recensement castillan de 1591 établissait le nombre d’hidalgos, catégorie que l’on peut assimiler à la noblesse au sens l..

MIB3G

Estágio realizado na OptimusRelatório do Estágio Curricular da LEIC 2004/200

Genetic and constitutional factors are major contributors to substantia nigra hyperechogenicity

9 páginas, 2 figuras, 4 tablasHyperechogenicity of substantia nigra (SNh) is a frequent finding in amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and other movement disorders (MD) patients, but its meaning is unclear. To ascertain the contribution of different factors to SNh area, we measured it in 108 ALS, 102 PD, 91 other MD patients and 91 healthy controls. Demographical data were collected in all patients and controls. In ALS patients, we also recorded clinical variables, performed genetic analysis and measured baseline levels of ferritin. After family history and genetic testing, ALS patients were classified as familial (15) or sporadic (93). ALS, PD and other MD patients had a larger SNh area than controls. Left SNh and male gender, but not age, associated with larger SNh area in both patients and controls. Familial ALS patients showed larger SNh area than sporadic ones and familial ALS was the only clinical variable in the multivariate analysis to be associated with larger SNh area in ALS patients. Our results suggest that SNh associates with genetic and constitutional factors (male gender, handedness), some of which predispose to certain neurodegenerative diseases. This evidence supports the idea of SNh as an inborn marker of unspecific neuronal vulnerability.The research leading to these results has received funding from Instituto de Investigación Sanitaria La Fe (2013/0332, PI JFVC/TS), from Instituto de Salud Carlos III (ISCIII, PI12/0946, PI TS) and from Ministerio de Economía, Industria y Competitividad (SAF2014-59469-R, PI: JPT). The Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED, group 209) are initiatives from the ISCIII.Peer reviewe

Rare variants in calcium homeostasis modulator 1 (CALHM1) found in early onset alzheimer's disease patients alter calcium homeostasis

Calcium signaling in the brain is fundamental to the learning and memory process and there is evidence to suggest that its dysfunction is involved in the pathological pathways underlying Alzheimer’s disease (AD). Recently, the calcium hypothesis of AD has received support with the identification of the non-selective Ca2+-permeable channel CALHM1. A genetic polymorphism (p. P86L) in CALHM1 reduces plasma membrane Ca2+ permeability and is associated with an earlier age-at-onset of AD. To investigate the role of CALHM1 variants in early-onset AD (EOAD), we sequenced all CALHM1 coding regions in three independent series comprising 284 EOAD patients and 326 controls. Two missense mutations in patients (p.G330D and p.R154H) and one (p.A213T) in a control individual were identified. Calcium imaging analyses revealed that while the mutation found in a control (p.A213T) behaved as wild-type CALHM1 (CALHM1-WT), a complete abolishment of the Ca2+ influx was associated with the mutations found in EOAD patients (p.G330D and p.R154H). Notably, the previously reported p. P86L mutation was associated with an intermediate Ca2+ influx between the CALHM1-WT and the p.G330D and p.R154H mutations. Since neither expression of wild-type nor mutant CALHM1 affected amyloid ß-peptide (Aß) production or Aß-mediated cellular toxicity, we conclude that rare genetic variants in CALHM1 lead to Ca2+ dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Aß cascade.This study was supported by grants from Instituto de Salud Carlos III (PI12/01311, PI10/000587, Red HERACLES RD12/0042/0014), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain), Spanish Ministry of Economy and Competiveness (SAF2012-38140), FEDER Funds, and Generalitat de Catalunya (SGR05-266). Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital, the Strategic Funding of the University on Eastern Finland (UEF-Brain) (to M.H and H.S). M.A.V. is the recipient of an ICREA Academia Awar