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The pharmacological inhibition of soluble epoxide hydrolase (sEH) has been suggested as a potential therapy for the treatment of pain and inflammatory diseases through the stabilization of epoxyeicosatrienoic acids, endogenous chemical mediators derived from arachidonic acid that show anti-inflammatory and analgesic effects.1 Although several potent sEH inhibitors (sEHI) have been developed, including clinical candidates AR9281, GSK2256294, and EC5026, so far no sEHI has reached the market.2 Recently, a new series of benzohomoadamantane-based ureas endowed with potent inhibitory activity for the human and murine sEH was reported. However, their very low microsomal stability prevented further development.3 Herein, novel series of benzohomoadamantane-based ureas were synthesized, fully characterized, and evaluated as sEHI. Most of them were endowed with subnanomolar inhibitory potencies at the human and murine enzymes. Further in vitro profiling (solubility, cytotoxicity, metabolic stability, CYP450s, hLOX-5, hCOX-2, hERG inhibition, permeability) allowed us to select a candidate for efficacy studies. In summary, these novel results and the previously reported studies using other families of sEHI, strongly suggest that sEH may be a target of clinical interest for the treatment of inflammatory and pain-related disorders.4 References: 1-Morisseau, C.; Hammock, B. D. Annu.Rev. Pharmacol. Toxicol. 2013, 53, 37-58. 2-Sun, C.-P.; Zhang, X.-Y.; Morisseau, C.; Hwang, S. H.; Zhang, Z.-J.; Hammock, B. D.; Ma, X.-C. J. Med. Chem. 2021, 64, 184-215. 3-Codony, S.; Calvó-Tusell, C.; Valverde, E.; Osuna, S.; Morisseau, C.; Loza, M. I.; Brea, J.; Pérez, C.; Rodríguez-Franco, M. I.; Pizarro-Delgado, J.; Corpas, R.; Griñán-Ferré, C.; Pallàs, M.; Sanfeliu, C.; Vázquez-Carrera, M.; Hammock, B. D.; Feixas, F.; Vázquez, S. J. Med. Chem., 2021, 64, 5429-5446. 4-McReynolds, C.; Morisseau, C.; Wagner, K.; Hammock, B. D. Adv. Exp. Med. Biol. 2020, 1274, 71-99.

Background: Chagas disease is endemic in Latin America and affects 8 million people worldwide. In 2010, Catalonia introduced systematic public health surveillance to detect and treat congenital Chagas disease. Aim: The objective was to evaluate the health outcomes of the congenital Chagas disease screening programme during the first 6 years (2010-2015) after its introduction in Catalonia. Methods: In a surveillance system, we screened pregnant women and newborns and other children of positive mothers, and treated Chagas-positive newborns and children. Diagnosis was confirmed for pregnant women and children with two positive serological tests and for newborns with microhaematocrit and/or PCR at birth or serology at age 9 months. Results: From 2010 to 2015, the estimated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were tested for Trypanosoma cruzi and 937 positive cases were diagnosed. The overall prevalence was 2.8 cases per loo pregnancies per year (15.8 in Bolivian women). We followed 82.8% of newborns until serological testing at age 9-12 months and 28 were diagnosed with Chagas disease (congenital transmission rate: 4.17%). Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) were positive for T. cruzi. Having other children with Chagas disease and the heart clinical form of Chagas disease were maternal risk factors associated with congenital T. cruzi infection (p < 0.05). Conclusion: The increased screening coverage rate indicates consolidation of the programme in Catalonia. The rate of Chagas disease congenital transmission in Catalonia is in accordance with the range in non-endemic countries.

To study the evolution of the incidence of early-onset neonatal sepsis (EOS) by Streptococcus agalactiae in the area of Barcelona and to analyze failure of compliance with the prevention protocol.

Objectives: To study the evolution of the incidence of early-onset neonatal sepsis (EOS) by Streptococcus agalactiae in the area of Barcelona and to analyze failure of compliance with the prevention protocol. Methods: A retrospective review was carried out on EOS cases in 8 Health-Care Centers in the Barcelona area between 2004 and 2010. Results: Forty-nine newborns from 48 mothers were diagnosed with EOS. The incidence was 0.29% living newborns (0.18-0.47%.), with no significant differences in the fluctuations along the 7 years. The mortality rate was 8.16%. In 68.5% cases the maternal colonization studies were negative, and in 21% these studies were not performed. No risk factors were detected in 58.3% of pregnant women, and 22.9% of births were premature. In 58% of cases intra-partum antibiotic prophylaxis was not administered because it was not indicated, and in 42% due to failure to follow the protocol (3 strains were resistant to erythromycin). Resistance to clindamycin was 33.3%. The Streptococcus agalactiae serotypes more frequently isolated were in, v, and ia. Conclusions: No significant changes were detected in the incidence of Streptococcus agalactiae EOS in the 7 years of the study. The increased sensitivity of screening methods with the use of molecular techniques, the performance of susceptibility testing of strains isolated from pregnant women, and the improvement of communication between Health-Care Centers, can contribute to a better implementation of the protocol, as well as to reduce the incidence of EOS.(C) 2014 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

La demanda creixent d’energia elèctrica i la destrucció del medi ambient, han impulsat a la investigació de noves formes de generar energia. En aquest projecte, es fa especial interès al “Energy Harvesting” o recol·lecció d’energia. S’estudia el “Energy Harvesting” a través de generadors piezoelèctrics, els quals generen càrregues elèctriques al ser deformats mecànicament. Com a objectiu principal es dissenya un sistema per aconseguir recol·lectar la energia mecànica que els vehicles perden al impactar amb els badens de les carreteres. I poder transformar aquesta energia recol·lectada en energia elèctrica. Es fa un estudi de en quin punt de la carretera és millor instal·lar el sistema dissenyat segons la energia elèctrica que pugui arribar a generar i segons on pugui afectar al mínim possible a la circulació dels vehicles que en facin el seu ús. En aquest informe es dissenya un sistema que contribueixi en els grans avantatges que implicaria la reducció de les emissions, modernització de la tecnologia i producció d’energia neta, és a dir, una millora de la localització i el desenvolupament de les energies renovables d’avui en dia, degut a que la major part de la producció d’energia que hi ha actualment depèn de les fonts no renovables d’energia.

This is an open access article distributed under the Creative Commons Attribution License., The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid β42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies. Copyright © 2010 Lydia Giménez-Llort et al., This work received financial support from Fundación La Marató de TV3 2006-062930 and 2006-062931; Red Envejecimiento y Fragilidad, RD06/0013/0003 and RD06/0013/1004 from ISCIII; SAF2006-13642 and SAF2009-13093-C02-02 from MICINN.

Streptococcus agalactiae or streptococcus group B (SGB) is the main etiologic agent of early neonatal sepsis. A multicenter study was performed with the aim of determining the incidence and characteristics of this disease in our medium and contribute the design of an adequate prevention protocol.Ten hospitals and two primary health care centers were implicated in the study; 103 microbiology confirmed episodes of SGB neonatal sepsis (blood and/or LCR positive) were reported from 1994 to 1996.The incidence of early SGB neonatal sepsis was 1.48/1,000 live births with a mortality of 8.7%. The cultures, for detecting the state of the SGB carrier were performed in only 26 (25%) of the patients. At least one of the factors described for risk of perinatal SGB infection was observed in 46% of the mothers, with the most frequent being prolonged amniorrhea (26%), intrapartum fever (17%), and early delivery (14%). At the time of delivery only 10.7% of the mothers received endovenous antibiotherapy.From these results the following recommendations have been made: a) detection of SGB carriers by the systematic practice of blood cultures in the last weeks of gestation and b) the administration of intrapartum antibiotic prophylaxis in both early births (37 weeks) and in all the SGB carriers should be undertaken. With these measures we aim to decrease the neonatal infections by streptococcus group B.

With innumerable clinical failures of target-specific drug candidates for multifactorial diseases, such as Alzheimer's disease (AD), which remains inefficiently treated, the advent of multitarget drug discovery has brought a new breath of hope. Here, we disclose a class of 6-chlorotacrine (huprine)-TPPU hybrids as dual inhibitors of the enzymes soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), a multitarget profile to provide cumulative effects against neuroinflammation and memory impairment. Computational studies confirmed the gorge-wide occupancy of both enzymes, from the main site to a secondary site, including a so far non-described AChE cryptic pocket. The lead compound displayed in vitro dual nanomolar potencies, adequate brain permeability, aqueous solubility, human microsomal stability, lack of neurotoxicity, and it rescued memory, synaptic plasticity, and neuroinflammation in an AD mouse model, after low dose chronic oral administration., This work was supported by grants PID2020-118127RB-I00, SAF2017-82771-R, PID2020-115683GA-I00, PGC2018- 102192-B-I00, PID2019-106285RB, and RTI2018-101032-JI00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, ED431C 2018/21 and ED431G 2019/02 from Xunta de Galicia, and 2017SGR106, 2017SGR1707, and 2019LLAV00017 from AGAUR. Partial support was provided by NIH-NIEHS River Award R35 ES03443, NIH-NIEHS Superfund Program P42 ES004699, NINDS R01 DK107767, and NIDDK R01 DK103616 to B.D.H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Fellowships from Ministerio de Educación, Cultura y Deporte to C.P. (FPU15/01131), from the University of Barcelona to S.C., and a starting grant from the European Research Council (ERC-2015-StG-679001- NetMoDEzyme) to S.O. are gratefully acknowledged. We thank Ms. Cecilia Mariani for technical assistance in the assays with mAChE.

Cumulative evidence shows that modifications in lifestyle factors constitute an effective strategy to modulate molecular events related to neurodegenerative diseases, confirming the relevant role of epigenetics. Accordingly, Environmental Enrichment (EE) represents an approach to ameliorate cognitive decline and neuroprotection in Alzheimer’s disease (AD). AD is characterized by specific neuropathological hallmarks, such as β-amyloid plaques and Neurofibrillary Tangles, which severely affect the areas of the brain responsible for learning and memory. We evaluated EE neuroprotective influence on 5xFAD mice. We found a better cognitive performance on EE vs. Control (Ct) 5xFAD mice, until being similar to Wild-Type (Wt) mice group. Neurodegenerative markers as β-CTF and tau hyperphosphorylation, reduced protein levels whiles APPα, postsynaptic density 95 (PSD95) and synaptophysin (SYN) protein levels increased protein levels in the hippocampus of 5xFAD-EE mice group. Furthermore, a reduction in gene expression of Il-6, Gfap, Hmox1 and Aox1 was determined. However, no changes were found in the gene expression of neurotrophins, such as Brain-derived neurotrophic factor (Bdnf), Nerve growth factor (Ngf), Tumor growth factor (Tgf) and Nerve growth factor inducible (Vgf) in mice with EE. Specifically, we found a reduced DNA-methylation level (5-mC) and an increased hydroxymethylation level (5-hmC), as well as an increased histone H3 and H4 acetylation level. Likewise, we found changes in the hippocampal gene expression of some chromatin-modifying enzyme, such as Dnmt3a/b, Hdac1, and Tet2. Extensive molecular analysis revealed a correlation between neuronal function and changes in epigenetic marks after EE that explain the cognitive improvement in 5xFAD., This study was supported by Ministerio de Economía y Competitividad of Spain SAF2016-33307. Authors belong to 2017SGR106 (Agencia de Gestió d’Ajuts Universitaris i de Recerca, AGAUR, Catalonia).

[spa] La neuroinflamación sostenida es un factor de riesgo de enfermedades relacionadas con la edad, incluidas las lesiones cerebrovasculares y la enfermedad de Alzheimer (EA). De hecho, los procesos inflamatorios se consideran cada vez más los culpables de la fragilidad y la enfermedad de la población envejecida. Como resultado, se ha intensificado la búsqueda de biomarcadores inflamatorios fiables y objetivos de intervención para combatir la demencia y otras enfermedades discapacitantes. Cada año se registran cerca de 8 millones de nuevos casos de demencia, y se estima que, para el 2050, la demencia afecte a 150 millones de personas. La enfermedad de Alzheimer (EA) es la más prevalente de las demencias, suponiendo entre un 60 y un 70% de todos los casos de demencia. Esta enfermedad se caracteriza por la pérdida cognitiva y de memoria, junto a la presentación de síntomas conductuales y psicológicos asociados a la demencia (BPSD) que disminuyen de manera drástica la calidad de vida del paciente y sus cuidadores. La neuropatología de la EA se caracteriza por el depósito proteico del péptido amiloide y tau hiperfosforilada que, eventualmente, desembocan en la agregación de placas seniles y ovillos neurofibrilares. Esta patología además, suele ir acompañada de neuroinflamación, aumento del estrés oxidativo y disfunción mitocondrial, alteración neurovascular, pérdida sináptica y neurodegeneración. Actualmente no existe cura para el Alzheimer, por ello, nuevas terapias que aborden su prevención o presenten nuevas vías de investigación son imprescindibles. En esta tesis se ha pretendido evaluar la contribución de la proteína monomérica C-reactiva al desarrollo de demencia de tipo EA. La proteína C-Reactiva (CRP) es una pentraxina, secretada por el hígado en respuesta a la inflamación y ampliamente conocida por ser un marcador de procesos inflamatorios. Así cuando el pentámero que es la CRP se une a las membranas de los tejidos dañados, esta se disocia dando lugar a sus subunidades monoméricas, altamente pro-inflamatorias y poco solubles, que quedan depositadas de manera crónica en la matriz extracelular del tejido afectado. La proteína monomérica C-reactiva es, por lo tanto, una de las subunidades monoméricas de la CRP. Así, la mCRP depositada en la matriz extracelular del tejido dañado favorece un ambiente proinflamatorio crónico que, sumado a su alta capacidad angiogénica favorece el agravamiento de la enfermedad. Estudios recientes han confirmado la presencia de mCRP en el tejido cerebral de enfermos de EA, así como la capacidad de las placas amiloides para disociar CRP generando mCRP. Asimismo, se ha demostrado cómo mCRP favorece la fosforilización de tau in vitro y cómo la tau fosforilada colocaliza a nivel intraneuronal con mCRP en cerebros de pacientes de EA. Por otra parte, estudios previos de nuestro grupo de investigación demostraron que la mCRP inyectada en el hipocampo de ratones inducía pérdida de memoria después de 4 semanas, así como otros rasgos de la EA, como patología amiloide y de tau en neuronas del hipocampo y áreas corticales. Estos estudios también han confirmado a mCRP como un posible vínculo entre el ictus y el posterior desarrollo de demencia que aparece en un tercio de los casos de accidente cerebrovascular. Así, la hipótesis en que se basa esta tesis es que la mCRP, la forma activada de la CRP, contribuye al desarrollo y progresión de la enfermedad de EA. Con el fin de probar esta hipótesis, desarrollamos un modelo de ratón de demencia inducido mediante la infusión bilateral de mCRP en el hipocampo de los ratones. Los animales fueron evaluados tras 1, 3 y 6 meses de tratamiento con mCRP con el fin de caracterizar la pérdida cognitiva y de BPSD de este modelo, así como la neuropatología adyacente.