Validity of CSF alpha-synuclein to predict psychosis in prodromal Alzheimer's disease

BackgroundAlzheimer's disease (AD) accompanied by psychotic symptoms (PS) has a poor prognosis and may be associated with imbalances in key neural proteins such as alpha-synuclein (AS).AimThe aim of the study was to evaluate the diagnostic validity of AS levels in the cerebrospinal fluid (CSF) as a predictor of the emergence of PS in patients with prodromal AD.Materials and methodsPatients with mild cognitive impairment were recruited between 2010 and 2018. Core AD biomarkers and AS levels were measured in CSF obtained during the prodromal phase of the illness. All patients who met the NIA-AA 2018 criteria for AD biomarkers received treatment with anticholinesterasic drugs. Follow-up evaluations were conducted to assess patients for the presence of psychosis using current criteria; the use of neuroleptic drugs was required for inclusion in the psychosis group. Several comparisons were made, taking into account the timing of the emergence of PS.ResultsA total of 130 patients with prodromal AD were included in this study. Of these, 50 (38.4%) met the criteria for PS within an 8-year follow-up period. AS was found to be a valuable CSF biomarker to differentiate between the psychotic and non-psychotic groups in every comparison made, depending on the onset of PS. Using an AS level of 1,257 pg/mL as the cutoff, this predictor achieved at least 80% sensitivity.ConclusionTo our knowledge, this study represents the first time that a CSF biomarker has shown diagnostic validity for prediction of the emergence of PS in patients with prodromal AD

COVIDGR Dataset and COVID-SDNet Methodology for Predicting COVID-19 Based on Chest X-Ray Images

Currently, Coronavirus disease (COVID-19), one of the most infectious diseases in the 21st century, is diagnosed using RT-PCR testing, CT scans and/or Chest X-Ray (CXR) images. CT (Computed Tomography) scanners and RT-PCR testing are not available in most medical centers and hence in many cases CXR images become the most time/cost effective tool for assisting clinicians in making decisions. Deep learning neural networks have a great potential for building COVID-19 triage systems and detecting COVID-19 patients, especially patients with low severity. Unfortunately, current databases do not allow building such systems as they are highly heterogeneous and biased towards severe cases. This article is three-fold: (i) we demystify the high sensitivities achieved by most recent COVID-19 classification models, (ii) under a close collaboration with Hospital Universitario Clínico San Cecilio, Granada, Spain, we built COVIDGR-1.0, a homogeneous and balanced database that includes all levels of severity, from normal with Positive RT-PCR, Mild, Moderate to Severe. COVIDGR-1.0 contains 426 positive and 426 negative PA (PosteroAnterior) CXR views and (iii) we propose COVID Smart Data based Network (COVID-SDNet) methodology for improving the generalization capacity of COVID-classification models. Our approach reaches good and stable results with an accuracy of 97.72%±0.95% , 86.90%±3.20% , 61.80%±5.49% in severe, moderate and mild COVID-19 severity levels. Our approach could help in the early detection of COVID-19. COVIDGR-1.0 along with the severity level labels are available to the scientific community through this link https://dasci.es/es/transferencia/open-data/covidgr/This work was supported by the project DeepSCOP-Ayudas Fundación BBVA a Equipos de Investigación Científica en Big Data 2018, COVID19_RX-Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID-19 2020, and the Spanish Ministry of Science and Technology under the project TIN2017-89517-P. S. Tabik was supported by the Ramon y Cajal Programme (RYC-2015-18136). A. Gómez-Ríos was supported by the FPU Programme FPU16/04765. D. Charte was supported by the FPU Programme FPU17/04069. J. Suárez was supported by the FPU Programme FPU18/05989. E.G was supported by the European Research Council (ERC Grant agreement 647038 [BIODESERT])

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation

In Alzheimer’s disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inactive forms could result from post-translational modifications, we analyzed the glycosylation of AChE by lectin binding in brain samples from sporadic and familial AD (sAD and fAD). Most of the enzymatically active AChE was bound to lectins Canavalia ensiformis (Con A) and Lens culinaris agglutinin (LCA) that recognize terminal mannoses, whereas Western blot assays showed a very low percentage of AChE protein being recognized by the lectin. This indicates that active and inactive forms of AChE vary in their glycosylation pattern, particularly in the presence of terminal mannoses in active ones. Moreover, sAD subjects showed reduced binding to terminal mannoses compared to non-demented controls, while, for fAD patients that carry mutations in the PSEN1 gene, the binding was higher. The role of presenilin-1 (PS1) in modulating AChE glycosylation was then studied in a cellular model that overexpresses PS1 (CHO-PS1). In CHO-PS1 cells, binding to LCA indicates that AChE displays more terminal mannoses in oligosaccharides with a fucosylated core. Immunocytochemical assays also demonstrated increased presence of AChE in the trans-Golgi. Moreover, AChE enzymatic activity was higher in plasmatic membrane of CHO-PS1 cells. Thus, our results indicate that PS1 modulates trafficking and maturation of AChE in Golgi regions favoring the presence of active forms in the membrane

Treatment of WASTEWATER from the Tannery Industry in a Constructed Wetland Planted with Phragmites australis

Constructed wetlands (CWs) can remove a high amount of pollutants from wastewater, and therefore play an important role in water purification. In this study, a pilot system to improve the traditional treatment of industrial wastewater from the tannery industry was tested. The main objective of this research was to remove nitrogen, phosphorus, boron, and chromium from a tannery&rsquo;s industrial wastewater using a horizontal subsurface flow constructed wetland (HSSFCW) formed from three cells, planted with Phragmites australis and operated in batch mode as an ecofriendly system. P. australis was selected due to its ability to adapt to climatic conditions, its wetland and management characteristics, and its high capacity for pollutant absorption. The concentrations of total Kjeldahl nitrogen (TKN), total phosphorus (TP), boron (B), and chromium (Cr) were analyzed in both wastewater and purified water, and the removal efficiencies were calculated. In addition, both the absorption capacity of P. australis in the aerial and root parts and the adsorption capacity of substrates (gravel and washed sand) were analyzed. Results showed that the concentrations of TP and Cr decreased in the wastewater at both hydraulic retention times (HRTs) tested (3 and 7 days), with 3 days being the most effective, showing removal efficiency values of 78% and 48% for TP and Cr, respectively. However, concentrations of TKN and B were not statistically reduced at either HRTs. Regarding the absorption capacity of P. australis, the highest absorption efficiencies for TKN and TP were reported at 7 days in the aerial part of the plants. In contrast, B was retained in roots at HRT of 3 days. Finally, Cr was more significantly absorbed at 3 days by P. australis. Moreover, the substrates also played important roles in the adsorption of nitrogen and boron. Therefore, CWs planted with P. australis could be used as an ecofriendly technique to the reduce pollution load of the wastewater from tannery industry, especially for P and Cr, although in order to increase the removal efficiency of B and N, the combination with other plant species and different retention times should be tested