Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Ischemic etiopathogenesis as the possible origin of post-double baloon enteroscopy pancreatitis: a porcine model study

The aim is to evaluate the pancreatic vascular-ischemic effects related to double balloon enteroscopy in the porcine model as a possible etiopathogenesis of post-enteroscopic pancreatitis. For this reason we carry out two independent experiments in a porcine animal model. In the first arm protocol (group I), 10 animals underwent 90 minutes of oral enteroscopy with 7 days follow-up. The levels of amylase, lipase and C-reactive protein were measured at T0 basal-T1 -90 min, T2-24, T3-7 days. Also we perform upper gastrointestinal endoscopy in a control group. At 7 days, the animals of experimental protocol-I had their pancreases removed for a pathological and immunohistochemical study to evaluate vascular epithelial growth factor (VEGF) expression. The second experimental protocol in this study aims to evaluate possible changes in vascular topography due to the double balloon enteroscopy (DBE). Group-II (10 animals) underwent oral enteroscopy and selective angiography of the cranial mesenteric artery and celiac trunk. None of the group I or control group animals presented pancreatitis, although the biochemical results for group-I showed increases in the levels of amylase, lipase and C reactive protein at 24 hours. The microscopic study for group-I showed pancreatic necrotic foci and positive VEGF expression, though these changes were not expressed in the control group. These foci were found in 50 % of the group I animals and in relation to the total of the parenchyma were quantified at 6 % of the pancreas. The results for group-II showed that the enteroscopy caused mobilization of the mesenteric vascular axis, with signs of both intestinal and pancreatic hypoperfusion. The conclusions of this study are that, after enteroscopy in the porcine model, pancreatic necrotic foci are produced, in addition to ischemic phenomena causing VEGF expression. This could be related to episodes of visceral hypoperfusion caused by vascular alterations on a topographic level. This can be related to the possible ischemic etiopathogenesis described for post-enteroscopic pancreatitis

Estudios americanos: revista de síntesis e interpretación 10 (50-51)

El ser histórico del mundo hispanoamericanoUna nueva etapa culturalMisiones protestantesAproximación a los problemas socialesPresente y futuro de la Filosofía HispanoamericanaEl momento teatralHacia una reforma del Derecho ProcesalLa empresa universitariaEl sentido religioso de la música en los Estados UnidosProblemas de enseñanza secundariaLas concepciones internacionalistasReflexiones sobre la familia norteamericanaEl libro de Cristóbal Colón, de Paul ClaudelBreve historia de una RevistaPeer reviewe

Bioactive organocopper compound from Pseudomonas aeruginosa inhibits the growth of Xanthomonas citri subsp. citri

Citrus canker is a lot destructive disease of citrus species. The challenge is to find new compounds that show strong antibiotic activity, low toxicity to plants and the environment. The objectives of the present study are (1) produce, purify and evaluate the antibiotic activity of secondary metabolites produced by induction by P. aeruginosa LV strain in vitro against Xanthomonas citri subsp. citri (strain 306), (2) study the potential for semi-purified secondary metabolites on foliar application to control citrus canker under greenhouse conditions, (3) identify the antibiotic activity in orange leaf mesophyll infected with strain 306 by electron microscopy. Two pure bioactive compounds were isolated, organocopper antibiotic compound and phenazine-1-carboxamide. The phenazine-1-carboxamide did not show any antibiotic activity under the experimental conditions used in this study. The organocopper antibiotic compound showed a high level of antibiotic activity with a minimum inhibitory concentration of 0.12 µg mL-1. In greenhouse tests for control of citrus canker in orange trees, the semi-purified fraction F3d, reduced lesion formation about 97%. The concentration used was five hundred times lower than recommended commercial product of metallic copper-based. Electron microscopy showed that F3d altered the exopolysaccharide matrix and causing cell lysis of the pathogen inside the citrus canker lesions. These results suggest that secondary metabolites produced by induction by P. aeruginosa LV strain has a high potential to be used as a bioproduct to control citrus canker

The Lockman-SpReSO project

Context. Extragalactic surveys are a key tool for better understanding the evolution of galaxies. Both deep and wide-field surveys serve to provide a clearer emerging picture of the physical processes that take place in and around galaxies, and to identify which of these processes are the most important in shaping the properties of galaxies. Aims. The Lockman Spectroscopic Redshift Survey using Osiris (Lockman-SpReSO) aims to provide one of the most complete optical spectroscopic follow-ups of the far-infrared (FIR) sources detected by the Herschel Space Observatory in the Lockman Hole (LH) field. The optical spectroscopic study of the FIR-selected galaxies supplies valuable information about the relation between fundamental FIR and optical parameters, including extinction, star formation rate, and gas metallicity. In this article, we introduce and provide an in-depth description of the Lockman-SpReSO project and of its early results. Methods. We selected FIR sources from Herschel observations of the central 24 arcmin ×24 arcmin of the LH field with an optical counterpart up to 24.5 RC(AB). The sample comprises 956 Herschel FIR sources, plus 188 additional interesting objects in the field. These are point X-ray sources, cataclysmic variable star candidates, high-velocity halo star candidates, radio sources, very red quasi-stellar objects, and optical counterparts of sub-millimetre galaxies. The faint component of the catalogue (RC(AB) ≥ 20) was observed using the OSIRIS instrument on the 10.4 m Gran Telescopio Canarias in multi-object spectroscopy (MOS) mode. The bright component was observed using two multi-fibre spectrographs: the AF2-WYFFOS at the William Herschel Telescope and the HYDRA instrument at the WYIN telescope. Results. From an input catalogue of 1144 sources, we measured a secure spectroscopic redshift in the range 0.03 ≲ z ≲ 4.96 for 357 sources with at least two identified spectral lines. In addition, for 99 sources that show only one emission or absorption line, a spectroscopic redshift was postulated based on the line and object properties, and photometric redshift. In both cases, properties of emission and absorption lines were measured. Furthermore, to characterize the sample in more depth with determined spectroscopic redshifts, spectral energy distribution (SED) fits were performed using the CIGALE software. The IR luminosity and the stellar mass estimations for the sample are also presented as a preliminary description

Visual impairment in aging and cognitive decline: experience in a memory Clinic

Visual impairment is common in people living with dementia and regular ophthalmological exams may improve their quality of life. We evaluated visual function in a cohort of elderly individuals and analyzed its association with their degree of cognitive impairment. Participants underwent neurological and neuropsychological exams, neuro-ophthalmological assessment (visual acuity, intraocular pressure, rates of past ophthalmological pathologies, use of ocular correction, treatments and surgeries) and optical coherence tomography (OCT) scan. We analyzed differences in ophthalmological characteristics among diagnostic groups. The final sample of 1746 study participants aged ≥ 50 comprised 229 individuals with Subjective Cognitive Decline (SCD), 695 with mild cognitive impairment (MCI) and 833 with Dementia (Alzheimer disease: n = 660; vascular dementia: n = 92, Lewy body dementia: n = 34; frontotemporal dementia: n = 19 and other: n = 28). Age, gender and education were used as covariates. Patients with Dementia, compared to those with SCD and MCI, presented worse visual acuity (p < 0.001), used less visual correction (p = 0.02 and p < 0.001, respectively) and fewer ophthalmological treatments (p = 0.004 and p < 0.001, respectively) and underwent fewer ocular surgeries (p = 0.009 and p < 0.001, respectively). OCT image quality worsened in parallel to cognitive decline (Dementia vs SCD: p = 0.008; Dementia vs MCI: p < 0.001). No group differences in past ophthalmological disorders or abnormal OCT findings were detected. Efforts should be made to ensure dementia patients undergo regular ophthalmological assessments to correct their visual function in order to improve their quality of life.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 796706 awarded to MM; from Fundació ACE Institut Català de Neurociències Aplicades in Barcelona, Spain and from a donation of “La nit de l’Alzheimer”, a charity dinner initiative that took place on August 8th 2016 as part of the “Festival Castell de Peralada”. The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of CH

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial

Abstract Background Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. Methods This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. Discussion This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. Trial registration ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b]