Autoimmune neurological conditions associated with Zika virus infection

Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection

Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review

Depressive disorders appear relatively frequently in older patients, and therefore represent an important disease burden worldwide. Given the high levels of inflammatory parameters found in depressed elderly patients, the "inflammaging" hypothesis is gaining strength. In this systematic review, we summarize current evidence regarding the relationship between inflammatory parameters and late-life depression, with a unique focus on longitudinal studies to guarantee temporality. According to the data summarized in this review, the levels of some proinflammatory parameters-especially interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-α-could serve as biomarkers for the future development of depressive symptoms in elderly patients. Proinflammatory cytokines seem to be associated with the future development of clinically significant depression, irrespective of baseline scores, thus indicating that inflammation temporally precedes and increases depression risk. As insufficient research has been conducted in this field, further prospective studies are clearly warranted.This study was funded by grants from Research Network Center of Mental Health-CIBERSAM (2010-P-02); the Government of Spain “Health Research Fund” FEDER (PI08-1213, PI11-01977, PI14-01900, PI08-0873; PI10-01746; PS09/02002; PI12/02077; PI15-00789; PI13/00451); Ministry of Health and Social Equality (20111064) Policy; Local funding from the Department of Education, Language Policy and Culture of the Basque Government (200911147, 2013111162, 2010111170, SAIO10-PC10BF01); European Comission funds (UE/2012/FI-STAR). We appreciate the support of the University of the Basque Country (GIC10/80, GIC12/84) and the Basque Foundation for Health Innovation and Research-BIOEF. The Psychiatry Research Unit of the University Hospital of Álava-Santiago is supported by the “Stanley Research Foundation” (03-RC-003). John O’Brien is supported by the NIHR Cambridge Biomedical Research Centre awarded to the University of Cambridge, Cambridge University Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Trust

From the Eukaryotic Molybdenum Cofactor Biosynthesis to the Moonlighting Enzyme mARC

All eukaryotic molybdenum (Mo) enzymes contain in their active site a Mo Cofactor (Moco), which is formed by a tricyclic pyranopterin with a dithiolene chelating the Mo atom. Here, the eukaryotic Moco biosynthetic pathway and the eukaryotic Moco enzymes are overviewed, including nitrate reductase (NR), sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and the last one discovered, the moonlighting enzyme mitochondrial Amidoxime Reducing Component (mARC). The mARC enzymes catalyze the reduction of hydroxylated compounds, mostly N-hydroxylated (NHC), but as well of nitrite to nitric oxide, a second messenger. mARC shows a broad spectrum of NHC as substrates, some are prodrugs containing an amidoxime structure, some are mutagens, such as 6-hydroxylaminepurine and some others, which most probably will be discovered soon. Interestingly, all known mARC need the reducing power supplied by different partners. For the NHC reduction, mARC uses cytochrome b5 and cytochrome b5 reductase, however for the nitrite reduction, plant mARC uses NR. Despite the functional importance of mARC enzymatic reactions, the structural mechanism of its Moco-mediated catalysis is starting to be revealed. We propose and compare the mARC catalytic mechanism of nitrite versus NHC reduction. By using the recently resolved structure of a prokaryotic MOSC enzyme, from the mARC protein family, we have modeled an in silico three-dimensional structure of a eukaryotic homologue

Endothelial Damage in Sepsis: The Importance of Systems Biology

The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis

Extensive assessment of blood glucose monitoring during postprandial period and its impact on closed-loop performance

[EN] Background: Closed-loop (CL) systems aims to outperform usual treatments in blood glucose control and continuous glucose monitors (CGM) are a key component in such systems. Meals represents one of the main disturbances in blood glucose control, and postprandial period (PP) is a challenging situation for both CL system and CGM accuracy. Methods: We performed an extensive analysis of sensor¿s performance by numerical accuracy and precision during PP, as well as its influence in blood glucose control under CL therapy. Results: During PP the mean absolute relative difference (MARD) for both sensors presented lower accuracy in the hypoglycemic range (19.4 ± 12.8%) than in other ranges (12.2 ± 8.6% in euglycemic range and 9.3 ± 9.3% in hyperglycemic range). The overall MARD was 12.1 ± 8.2%. We have also observed lower MARD for rates of change between 0 and 2 mg/dl. In CL therapy, the 10 trials with the best sensor spent less time in hypoglycemia (PG < 70 mg/dl) than the 10 trials with the worst sensors (2 ± 7 minutes vs 32 ± 38 minutes, respectively). Conclusions: In terms of accuracy, our results resemble to previously reported. Furthermore, our results showed that sensors with the lowest MARD spent less time in hypoglycemic range, indicating that the performance of CL algorithm to control PP was related to sensor accuracy.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has been partially supported by the Spanish Government through Grants DPI 2013-46982-C2-1-R, DPI 2016-78831-C2-1-R, DPI 2013-46982-C2-2-R, and DPI 2016-78831-C2-2-R, the National Council of Technological and Scientific Development, CNPq Brazil through Grants 202050/2015-7 and 207688/2014-1.Biagi, L.; Hirata-Bertachi, A.; Conget, I.; Quirós, C.; Giménez, M.; Ampudia-Blasco, F.; Rossetti, P.... (2017). Extensive assessment of blood glucose monitoring during postprandial period and its impact on closed-loop performance. Journal of Diabetes Science and Technology. 11(6):1089-1095. https://doi.org/10.1177/1932296817714272S10891095116Doyle, F. J., Huyett, L. M., Lee, J. B., Zisser, H. C., & Dassau, E. (2014). Closed-Loop Artificial Pancreas Systems: Engineering the Algorithms. Diabetes Care, 37(5), 1191-1197. doi:10.2337/dc13-2108Cengiz, E., & Tamborlane, W. V. (2009). A Tale of Two Compartments: Interstitial Versus Blood Glucose Monitoring. Diabetes Technology & Therapeutics, 11(S1), S-11-S-16. doi:10.1089/dia.2009.0002Cobelli, C., Schiavon, M., Dalla Man, C., Basu, A., & Basu, R. (2016). Interstitial Fluid Glucose Is Not Just a Shifted-in-Time but a Distorted Mirror of Blood Glucose: Insight from an In Silico Study. Diabetes Technology & Therapeutics, 18(8), 505-511. doi:10.1089/dia.2016.0112Castle, J. R., & Ward, W. K. (2010). Amperometric Glucose Sensors: Sources of Error and Potential Benefit of Redundancy. Journal of Diabetes Science and Technology, 4(1), 221-225. doi:10.1177/193229681000400127Basu, A., Dube, S., Veettil, S., Slama, M., Kudva, Y. C., Peyser, T., … Basu, R. (2014). Time Lag of Glucose From Intravascular to Interstitial Compartment in Type 1 Diabetes. Journal of Diabetes Science and Technology, 9(1), 63-68. doi:10.1177/1932296814554797Keenan, D. B., Grosman, B., Clark, H. W., Roy, A., Weinzimer, S. A., Shah, R. V., & Mastrototaro, J. J. (2011). Continuous Glucose Monitoring Considerations for the Development of a Closed-Loop Artificial Pancreas System. Journal of Diabetes Science and Technology, 5(6), 1327-1336. doi:10.1177/193229681100500603Van Bon, A. C., Jonker, L. D., Koebrugge, R., Koops, R., Hoekstra, J. B. L., & DeVries, J. H. (2012). Feasibility of a Bihormonal Closed-Loop System to Control Postexercise and Postprandial Glucose Excursions. Journal of Diabetes Science and Technology, 6(5), 1114-1122. doi:10.1177/193229681200600516Rossetti, P., Quirós, C., Moscardó, V., Comas, A., Giménez, M., Ampudia-Blasco, F. J., … Vehí, J. (2017). Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technology & Therapeutics, 19(6), 355-362. doi:10.1089/dia.2016.0443Bailey, T., Zisser, H., & Chang, A. (2009). New Features and Performance of a Next-Generation SEVEN-Day Continuous Glucose Monitoring System with Short Lag Time. Diabetes Technology & Therapeutics, 11(12), 749-755. doi:10.1089/dia.2009.0075Zschornack, E., Schmid, C., Pleus, S., Link, M., Klötzer, H.-M., Obermaier, K., … Freckmann, G. (2013). Evaluation of the Performance of a Novel System for Continuous Glucose Monitoring. Journal of Diabetes Science and Technology, 7(4), 815-823. doi:10.1177/193229681300700403Pleus, S., Schmid, C., Link, M., Zschornack, E., Klötzer, H.-M., Haug, C., & Freckmann, G. (2013). Performance Evaluation of a Continuous Glucose Monitoring System under Conditions Similar to Daily Life. Journal of Diabetes Science and Technology, 7(4), 833-841. doi:10.1177/193229681300700405Zisser, H. C., Bailey, T. S., Schwartz, S., Ratner, R. E., & Wise, J. (2009). Accuracy of the SEVEN® Continuous Glucose Monitoring System: Comparison with Frequently Sampled Venous Glucose Measurements. Journal of Diabetes Science and Technology, 3(5), 1146-1154. doi:10.1177/193229680900300519Obermaier, K., Schmelzeisen-Redeker, G., Schoemaker, M., Klötzer, H.-M., Kirchsteiger, H., Eikmeier, H., & del Re, L. (2013). Performance Evaluations of Continuous Glucose Monitoring Systems: Precision Absolute Relative Deviation is Part of the Assessment. Journal of Diabetes Science and Technology, 7(4), 824-832. doi:10.1177/193229681300700404Clarke, W. L., Cox, D., Gonder-Frederick, L. A., Carter, W., & Pohl, S. L. (1987). Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose. Diabetes Care, 10(5), 622-628. doi:10.2337/diacare.10.5.622Martin Bland, J., & Altman, D. (1986). STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT. The Lancet, 327(8476), 307-310. doi:10.1016/s0140-6736(86)90837-8Breton, M., & Kovatchev, B. (2008). Analysis, Modeling, and Simulation of the Accuracy of Continuous Glucose Sensors. Journal of Diabetes Science and Technology, 2(5), 853-862. doi:10.1177/193229680800200517Kropff, J., Bruttomesso, D., Doll, W., Farret, A., Galasso, S., Luijf, Y. M., … DeVries, J. H. (2014). Accuracy of two continuous glucose monitoring systems: a head‐to‐head comparison under clinical research centre and daily life conditions. Diabetes, Obesity and Metabolism, 17(4), 343-349. doi:10.1111/dom.12378Reddy, M., Herrero, P., Sharkawy, M. E., Pesl, P., Jugnee, N., Pavitt, D., … Oliver, N. S. (2015). Metabolic Control With the Bio-inspired Artificial Pancreas in Adults With Type 1 Diabetes. Journal of Diabetes Science and Technology, 10(2), 405-413. doi:10.1177/1932296815616134Pleus, S., Schoemaker, M., Morgenstern, K., Schmelzeisen-Redeker, G., Haug, C., Link, M., … Freckmann, G. (2015). Rate-of-Change Dependence of the Performance of Two CGM Systems During Induced Glucose Swings. Journal of Diabetes Science and Technology, 9(4), 801-807. doi:10.1177/193229681557871

IAOx induces the SUR phenotype and differential signalling from IAA under different types of nitrogen nutrition in Medicago truncatula roots

Indole-3-acetaldoxime (IAOx) is a particularly relevant molecule as an intermediate in the pathway for tryptophan-dependent auxin biosynthesis. The role of IAOx in growth-signalling and root phenotype is poorly studied in cruciferous plants and mostly unknown in non-cruciferous plants. We synthesized IAOx and applied it to M. truncatula plants grown axenically with NO3 -, NH4 + or urea as the sole nitrogen source. During 14 days of growth, we demonstrated that IAOx induced an increase in the number of lateral roots, especially under NH4 + nutrition, while elongation of the main root was inhibited. This phenotype is similar to the phenotype known as superroot previously described in SUR1- and SUR2-defective Arabidopsis mutants. The effect of IAOx, IAA or the combination of both on the root phenotype was different and dependent on the type of N-nutrition. Our results also showed the endogenous importance of IAOx in a legume plant in relation to IAA metabolism, and suggested IAOx long-distance transport depending on the nitrogen source provided. Finally, our results point out to CYP71A as the major responsible enzymes for IAA synthesis from IAOx, while they exclude indole-3-acetaldehyde oxidases. © 2019 Elsevier B.V.This work was supported by the grants AGL2017-86293-P and CGL2017-84723-P from the Spanish Ministry of Economy and Competitiveness (MINECO) , AGL2014-52396-P from the Ministry of Science Innovation and Universities (MICINN) , and IT932-16 from the Basque Government, Spain . JB and PL-G are holders of PhD fellowships from the Public University of Navarre. ACh received a Juan de la Cierva initiation grant FJCI-2016-27905 and RE received a Juan de la Cierva incorporation grant IJCI-2014-21452. This research was also supported by the Basque Government through the BERC 2018-2021 program, and by the Spanish Ministry of Science, Innovation and Universities through the BC3 María de Maeztu excellence accreditation (MDM-2017-0714)

Papel de los factores psicológicos en la diabetes mellitus: morbilidad psiquiátrica y perfil psicopatológico

Una población de diabéticos jóvenes, sus madres y hermanos completaron dos inventarios para determinar si existían diferencias en cuanto a morbilidad psiquiátrica y al perfil psicopatológico. Los resultados indican que los pacientes diabéticos mostraban menor morbilidad psiquiátrica que sus madres. Entre sus hermanos no se observó ninguno que cumpliera criterios de caso psiquiátrico. Se realizan pruebas t y análisis de la varianza para estudiar las diferencias entre los tres grupos y se detecta que las variables depresión y somatización distinguen entre diabéticos y no diabéticos, mientras que entre el grupo de madres y sus hijos diabéticos se observaron diferencias significativas en las escalas que conforman la triada neurótica, la psicastenia y la introversión social

Basal plus basal-bolus approach in type 2 diabetes

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2011 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.[EN] Type 2 diabetes is characterized by insulin resistance and progressive b-cell deterioration. As b-cell function declines, most patients with type 2 diabetes treated with oral agents, in monotherapy or combination, will require insulin therapy. Addition of basal insulin (glargine, detemir, or NPH/neutral protamine lispro insulin) to previous treatment is accepted as the simplest way to start insulin therapy in those patients. But even when basal insulin is adequately titrated, some patients will also need prandial insulin to achieve or maintain individual glycemic targets over time. Starting with premixed insulin is an effective option, but it is frequently associated with increased hypoglycemia risk, ¿xed meal schedules, and weight gain. As an alternative, a novel approached known as ``basal plus strategy¿¿ has been developed. This approach considers the addition of increasing injections of prandial insulin, beginning with the meal that has the major impact on postprandial glucose values. Finally, if this is not enough intensi¿cation to basal¿bolus will be necessary. In reducing hyperglycemia, this modality still remains the most effective option, even in people with type 2 diabetes. This article will review the currently evidence on the basal plus strategy and also its progression to basal¿bolus therapy. In addition, practical recommendations to start and adjust basal plus therapy will be provided.F.J.A.-B. has received honoraria as speaker and/or consultant from Abbott, AstraZeneca, Bristol-Myers Squibb, Glaxo-SmithKline, LifeScan, Lilly, Madaus, MannKind Corp., Medtronic, Menarini, Merch Farma y Quimica, SA, MSD, Novartis, Novo Nordisk, Pfizer, Roche, sanofi-aventis, Schering-Plough, and Solvay. In addition, F.J.A.-B. has participated in clinical trials supported totally or partially by AstraZeneca, Glaxo-SmithKline, LifeScan, Lilly, MSD, Novo Nordisk, Pfizer, sanofi-aventis, and Servier. P. R. has no potential conflicts of interest to declare. J.F.A. has received honoraria as speaker and/or consultant form AstraZeneca, Ferrer, Glaxo-SmithKline, Laboratorios Dr. Esteve, Lilly, MSD, and Solvay.Ampudia-Blasco, J.; Rossetti ., P.; Ascaso, JF. (2011). Basal plus basal-bolus approach in type 2 diabetes. Diabetes Technology & Therapeutics. 13:75-83. doi:10.1089/dia.2011.0001S75831

Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target

This is a copy of an article published in the Diabetes Technology & Therapeutics © 2017 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology & Therapeutics is available online at: https://www.liebertpub.com/.[EN] Background: Postprandial (PP) control remains a challenge for closed-loop (CL) systems. Few studies with inconsistent results have systematically investigated the PP period. Objective: To compare a new CL algorithm with current pump therapy (open loop [OL]) in the PP glucose control in type 1 diabetes (T1D) subjects. Methods: A crossover randomized study was performed in two centers. Twenty T1D subjects (F/M 13/7, age 40.7 -10.4 years, disease duration 22.6 +/- 9.9 years, and A1c 7.8% +/- 0.7%) underwent an 8-h mixed meal test on four occasions. In two (CL1/CL2), after meal announcement, a bolus was given followed by an algorithmdriven basal infusion based on continuous glucose monitoring (CGM). Alternatively, in OL1/OL2 conventional pump therapy was used. Main outcome measures were as follows: glucose variability, estimated with the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) and CGM values, and from the analysis of the glucose time series; mean, maximum (C-max), and time to C-max glucose concentrations and time in range (180 mg/dL). Results: CVs of the glucose AUCs were low and similar in all studies (around 10%). However, CL achieved greater reproducibility and better PG control in the PP period: CL1 = CL2 0.05) nor the need for oral glucose was significantly different (CL 40.0% vs. OL 22.5% of meals; P = 0.054). Conclusions: This novel CL algorithm effectively and consistently controls PP glucose excursions without increasing hypoglycemia. Study registered at ClinicalTrials.gov: study number NCT02100488.This work was supported by the Spanish Ministry of Economy and Competitiveness through Grants DPI2013-46982-C2-1-R and DPI2013-46982-C2-2-R, and the EU through FEDER funds. C.Q. is the recipient of a grant from the Hospital Clinic i Universitari of Barcelona ("Ajut a la recerca Josep Font 2014-2017").Rossetti, P.; Quirós, C.; Moscardo-Garcia, V.; Comas, A.; Giménez, M.; Ampudia-Blasco, F.; León, F.... (2017). Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technology & Therapeutics. 19(6):355-362. https://doi.org/10.1089/dia.2016.0443S35536219