Publications by authors named "Joao Malva"

79 Publications

Methylmercury Impact on Adult Neurogenesis: Is the Worst Yet to Come From Recent Brazilian Environmental Disasters?

Front Aging Neurosci 2020 23;12:591601. Epub 2020 Nov 23.

Faculty of Medicine, Center for Innovative Biomedicine and Biotechnology (CIBB) and Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal.

Worldwide environmental tragedies of anthropogenic origin causing massive release of metals and other pollutants have been increasing considerably. These pollution outbreaks affect the ecosystems and impact human health. Among those tragedies, recent large-scale environmental disasters in Brazil strongly affected riverside populations, leading to high-risk exposure to methylmercury (MeHg). MeHg is highly neurotoxic to the developing brain. This toxicant causes neural stem cell dysfunction and neurodevelopmental abnormalities. However, less is known about the effects of MeHg in the postnatal neurogenic niche, which harbors neural stem cells and their progeny, in the adult brain. Therefore, taking in consideration the impact of MeHg in human health it is urgent to clarify possible associations between exposure to mercury, accelerated cognitive decline, and neurodegenerative diseases. In this perspectives paper, we discuss the neurotoxic mechanisms of MeHg on postnatal neurogenesis and the putative implications associated with accelerated brain aging and early-onset cognitive decline in populations highly exposed to this environmental neurotoxicant.
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http://dx.doi.org/10.3389/fnagi.2020.591601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719787PMC
November 2020

Methylmercury Interactions With Gut Microbiota and Potential Modulation of Neurogenic Niches in the Brain.

Front Neurosci 2020 3;14:576543. Epub 2020 Nov 3.

Laboratory of Tissue Healing, Ontogeny and Nutrition, Department of Morphology, School of Medicine, Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil.

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http://dx.doi.org/10.3389/fnins.2020.576543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670038PMC
November 2020

Editorial: Interplay Between Nutrition, the Intestinal Microbiota and the Immune System.

Front Immunol 2020 6;11:1758. Epub 2020 Aug 6.

Institute for Clinical and Biomedical Research (iCBR), Center for Innovative Biomedicine and Biotechnology (CIBB) and Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.3389/fimmu.2020.01758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423988PMC
August 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Calcium Signaling in Aging and Neurodegenerative Diseases 2019.

Int J Mol Sci 2020 Feb 7;21(3). Epub 2020 Feb 7.

Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Faculty of Medicine, Polo I, 1st floor, 3004-504 Coimbra, Portugal.

The European Calcium Society (ECS) workshop, which is held every 2 years, is a dedicated meeting of scientists interested in the elucidation of the action of calcium binding, calcium signaling and the study of proteins and organelles, such as mitochondria and endoplasmic reticulum, thereby involved, either in health and disease conditions. The 8 edition of the ECS workshop was organized by a group of researchers from the University of Coimbra, Portugal, in close collaboration with ECS board members. Thanks to the central role of "Calcium Signaling in Aging and Neurodegenerative Disorders", the ECS 2019 workshop was attended by 62 experts who presented their results in a plenary lecture and five regular symposia, two oral communication sessions and two poster sessions, followed by a hands-on session on calcium imaging. All the scientific and social events were fully participated by the scientific community that allowed a close and fruitful interaction and discussion between junior researchers and senior experts in the field. In this report, the contributions in individual sessions are summarized.
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http://dx.doi.org/10.3390/ijms21031125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037616PMC
February 2020

Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases-Meeting Report (Part 2).

J Thorac Dis 2019 Sep;11(9):4072-4084

Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin and Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Member of GA2LEN, Berlin, Germany.

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http://dx.doi.org/10.21037/jtd.2019.09.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790426PMC
September 2019

What Do Microglia Really Do in Healthy Adult Brain?

Cells 2019 10 22;8(10). Epub 2019 Oct 22.

Laboratório de Farmacologia Molecular (Instituto de Ciências Biológicas), Universidade Federal do Pará, Belém 66075-110, Brasil.

Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease.
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http://dx.doi.org/10.3390/cells8101293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829860PMC
October 2019

Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases-Meeting Report (Part 1).

J Thorac Dis 2019 Aug;11(8):3633-3642

Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin and Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Member of GA2LEN, Berlin, Germany.

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http://dx.doi.org/10.21037/jtd.2019.08.64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753463PMC
August 2019

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

Development of a Healthy Lifestyle Assessment Toolkit for the General Public.

Front Med (Lausanne) 2019 27;6:134. Epub 2019 Jun 27.

Faculty of Medicine, Institute of Pharmacology & Experimental Therapeutics, University of Coimbra, Coimbra, Portugal.

The prevalence of age-related non-communicable chronic diseases has increased worldwide, being the leading causes of morbidity and death in many world regions, including in Europe. Innovative models and strategies focused on preventive care, including early identification of risk factors underlying disease onset and progression, and proper modification of lifestyle habits and behaviors, might contribute to promote quality of life, healthy living and active aging. Healthy Lifestyle Innovative Quarters for Cities and Citizens (HeaLIQs4cities) is an EIT Health-funded project aiming to engage, empower and educate citizens toward healthy lifestyles. One of the major objectives of this project was to develop a toolkit for a rapid and informal assessment of healthy lifestyles, to be used at different levels of care pathways, including in informal public environments. In this paper, we describe the methodology underlying the development of the toolkit, which resulted from the collaboration of an interdisciplinary focus group of academic experts, from medicine, sport sciences, psychology, health economics, and innovative technologies applied to health. The following eight components were included in the toolkit: (1) anthropometric assessment and cardiometabolic parameters; (2) physical activity and exercise; (3) well-being, social cohesion, and functional independence; (4) nutrition; (5) mental health; (6) smoking, drinking, and use of illicit substances; (7) sleep habits and quality; and (8) health and disease. A traffic light rating system indicating the risk score was used (low: green; moderate: yellow; and relevant: orange) for each of the 8 components, together with recommendations for the toolkit users. After completing the reduced version of the toolkit, individuals showing moderate or relevant risk in one or more of the 8 dimensions, were invited to participate in a more detailed assessment (toolkit long version), based on deeper and scientifically validated tools. The toolkit was incorporated in eVida, a web-based platform that focuses on delivering services to personalized health and well-being. The validation of the current toolkit has been applied in wide-ranging public events in three different European Regions. Large scale deployment of the toolkit is expected to profit from the Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Aging (EIP on AHA).
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http://dx.doi.org/10.3389/fmed.2019.00134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610478PMC
June 2019

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

J Allergy Clin Immunol 2019 07 3;144(1):135-143.e6. Epub 2019 Apr 3.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France; University Hospital, Montpellier, France; INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, and Euforea, Brussels, Belgium. Electronic address:

Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control.

Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR.

Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-antihistamines were studied.

Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-antihistamines were found.

Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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http://dx.doi.org/10.1016/j.jaci.2019.01.053DOI Listing
July 2019

Adult Hippocampal Neurogenesis in Different Taxonomic Groups: Possible Functional Similarities and Striking Controversies.

Cells 2019 02 5;8(2). Epub 2019 Feb 5.

Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil.

Adult neurogenesis occurs in many species, from fish to mammals, with an apparent reduction in the number of both neurogenic zones and new neurons inserted into established circuits with increasing brain complexity. Although the absolute number of new neurons is high in some species, the ratio of these cells to those already existing in the circuit is low. Continuous replacement/addition plays a role in spatial navigation (migration) and other cognitive processes in birds and rodents, but none of the literature relates adult neurogenesis to spatial navigation and memory in primates and humans. Some models developed by computational neuroscience attribute a high weight to hippocampal adult neurogenesis in learning and memory processes, with greater relevance to pattern separation. In contrast to theories involving neurogenesis in cognitive processes, absence/rarity of neurogenesis in the hippocampus of primates and adult humans was recently suggested and is under intense debate. Although the learning process is supported by plasticity, the retention of memories requires a certain degree of consolidated circuitry structures, otherwise the consolidation process would be hampered. Here, we compare and discuss hippocampal adult neurogenesis in different species and the inherent paradoxical aspects.
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http://dx.doi.org/10.3390/cells8020125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406791PMC
February 2019

Effect of Hypoproteic and High-Fat Diets on Hippocampal Blood-Brain Barrier Permeability and Oxidative Stress.

Front Nutr 2018 9;5:131. Epub 2019 Jan 9.

Laboratory of Tissue Healing, Ontogeny and Nutrition, Department of Morphology, School of Medicine, Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil.

Worldwide, millions of people are exposed to dietary imbalance that impacts in health and quality of life. In developing countries, like in Brazil, in poor settings, dietary habits, traditionally hypoproteic, are changing rapidly to western-type high-fat foods. These rapidly changing dietary habits are imposing new challenges to human health and there are many questions in the field that remain to be answered. Accordingly, we currently do not know if chronic consumption of hypoproteic (regional basic diet, RBD) or high-fat diets (HFD) may impact the brain physiology, contributing to blood-brain barrier (BBB) dysfunction and neuroinflammatory events. To address this issue, mice were challenged by breastfeeding from dams receiving standard, RBD or HFD from suckling day 10 until weaning. Immediately after weaning, mice continued under the same diets until post-natal day 52. Herein, we show that both RBD and HFD cause not only a peripheral but also a consistent central neuroinflammatory response, characterized by an increased production of Reactive Oxygen Species (ROS) and pro-inflammatory cytokines. Additionally, BBB hyperpermeability, accounted by an increase in hippocampal albumin content, a decrease in claudin-5 protein levels and collagen IV immunostaining, was also observed together with an upregulation of vascular cell adhesion molecule 1 (VCAM-1). Interestingly, we also identified a significant astrogliosis, manifested by upregulation of GFAP and S100β levels and an intensification of arbor complexity of these glial cells. In sum, our data show that dietary imbalance, related with hypoproteic or high-fat content, impairs BBB properties potentially favoring the transmigration of peripheral immune cells and induces both a peripheral and central neuroinflammatory status. Noteworthy, neuroinflammatory events in the hippocampus may cause neuronal malfunction leading to cognitive deficits and long-term persistence of this phenomenon may contribute to age-related neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnut.2018.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333637PMC
January 2019

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

Clin Exp Allergy 2019 04 12;49(4):442-460. Epub 2019 Mar 12.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France.

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries.

Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App.

Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach.

Results: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users.

Conclusion And Clinical Relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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http://dx.doi.org/10.1111/cea.13333DOI Listing
April 2019

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Authors:
Sinthia Bosnic-Anticevich Elisio Costa Enrica Menditto Olga Lourenço Ettore Novellino Slawomir Bialek Vitalis Briedis Roland Buonaiuto Henry Chrystyn Biljana Cvetkovski Stefania Di Capua Vicky Kritikos Alpana Mair Valentina Orlando Ema Paulino Johanna Salimäki Rojin Söderlund Rachel Tan Dennis M Williams Piotr Wroczynski Ioana Agache Ignacio J Ansotegui Josep M Anto Anna Bedbrook Claus Bachert Mike Bewick Carsten Bindslev-Jensen Jan L Brozek Giorgio Walter Canonica Victoria Cardona Warner Carr Thomas B Casale Niels H Chavannes Jaime Correia de Sousa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Pascal Demoly Philippe Devillier Mark S Dykewicz Mina Gaga Yehia El-Gamal João Fonseca Wytske J Fokkens Maria Antonieta Guzmán Tari Haahtela Peter W Hellings Maddalena Illario Juan Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Nikolai Khaltaev Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Désirée E Larenas-Linnemann Daniel Laune Lan T T Le Karin C Lodrup Carlsen Bassam Mahboub Dieter Maier Joao Malva Patrick J Manning Mário Morais-Almeida Ralph Mösges Joaquim Mullol Lars Münter Ruth Murray Robert Naclerio Leyla Namazova-Baranova Kristof Nekam Tshipukane Dieudonné Nyembue Kimi Okubo Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikolaos G Papadopoulos Hae-Sim Park Ruby Pawankar Oliver Pfaar Jim Phillips Davor Plavec Todor A Popov Paul C Potter Emmanuel P Prokopakis Regina E Roller-Wirnsberger Menachem Rottem Dermot Ryan Bolesław Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan Carlos Sisul David Somekh Cristiana Stellato Teresa To Ana Maria Todo-Bom Peter Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Errka Valovirta Maria Teresa Ventura Martin Wagenmann Dana Wallace Susan Waserman Magnus Wickman Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heather J Zar Mario E Zernotti Luo Zhang Mihaela Zidarn Torsten Zuberbier Jean Bousquet

Allergy 2019 07 30;74(7):1219-1236. Epub 2019 Apr 30.

MACVIA-France, Fondation Partenariale FMC VIA-LR, Montpellier, France.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
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http://dx.doi.org/10.1111/all.13701DOI Listing
July 2019

Revisiting Inbred Mouse Models to Study the Developing Brain: The Potential Role of Intestinal Microbiota.

Front Hum Neurosci 2018 19;12:358. Epub 2018 Sep 19.

Division of Infectious Diseases and International Health, Center for Global Health, University of Virginia, Charlottesville, VA, United States.

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http://dx.doi.org/10.3389/fnhum.2018.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156437PMC
September 2018

The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

Front Med (Lausanne) 2018 8;5:132. Epub 2018 May 8.

Ageing@Coimbra, EIP on AHA Reference Site, Coimbra, Portugal.

Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens.
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http://dx.doi.org/10.3389/fmed.2018.00132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952223PMC
May 2018

A case study of polypharmacy management in nine European countries: Implications for change management and implementation.

PLoS One 2018 18;13(4):e0195232. Epub 2018 Apr 18.

Institute of General Practice, Hannover Medical School, Hannover, Germany.

Background: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained.

Methods: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases.

Results: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation.

Conclusion: Within the studied EU countries, polypharmacy management was not widely addressed. These results highlight the importance of change management and theory-based implementation strategies, and provide examples of polypharmacy management initiatives that can assist managers and policymakers in developing new programs or scaling up existing ones, particularly in places currently lacking such initiatives.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195232PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905890PMC
July 2018

A modified Delphi study to determine the level of consensus across the European Union on the structures, processes and desired outcomes of the management of polypharmacy in older people.

PLoS One 2017 20;12(11):e0188348. Epub 2017 Nov 20.

Institute for General Medicine, Medizinische Hochschule Hannover, Hannover, Germany.

Background: Inappropriate use of multiple medicines (inappropriate polypharmacy) is a major challenge in older people with consequences of increased prevalence and severity of adverse drug reactions and interactions, and reduced medicines adherence. The aim of this study was to determine the levels of consensus amongst key stakeholders in the European Union (EU) in relation to aspects of the management of polypharmacy in older people.

Methods: Forty-six statements were developed on aspects of healthcare structures, processes and desired outcomes, with consensus defined at ≥ 80% agreement. Panel members were strategists (e.g. directors, leading clinicians and commissioners) from each of the 28 EU member states, with a target recruitment of five per member state. Three Delphi rounds were conducted via email, with panel members being provided with summative results and collated, anonymised comments at the commencement of Rounds 2 and 3.

Results: Ninety panel members were recruited (64.3% of target), with high participation levels throughout the three Delphi rounds (91.1%, 83.3%, 72.2%). During Round 1, consensus was obtained for 27/46 statements (58.7%), with an additional two statements in Round 2 and none in Round 3. Consensus was obtained for statements relating to: potential gain arising from polypharmacy management (3/4 statements); strategic development (7/7); change management (5/7) indicator measures (4/6); legislation (0/3); awareness raising (5/5); polypharmacy reviews (5/7); and EU vision (0/7). Analysis of free text comments indicated that the vision statements were too ambitious and not achievable by the specified timeframe of 2025.

Conclusion: Consensus was obtained amongst key EU strategists around many aspects of polypharmacy management in older people. Notably, no consensus was achieved in relation to statements relating to the need to alter legislation in areas of healthcare delivery, remuneration and practitioner scope of practice. While the vision for the EU by 2025 was considered rather ambitious, there is great potential and clear opportunity to advance polypharmacy management throughout the EU and beyond.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188348PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695766PMC
December 2017

Silencing of P2X7R by RNA interference in the hippocampus can attenuate morphological and behavioral impact of pilocarpine-induced epilepsy.

Purinergic Signal 2017 Dec 13;13(4):467-478. Epub 2017 Jul 13.

Departamento de Neurologia e Neurocirurgia, Disciplina de Neurociência, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 2° andar, São Paulo, SP, CEP 04039-032, Brazil.

Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested to be involved in epileptogenesis, via modulation of intracellular calcium levels, excitotoxicity, activation of inflammatory cascades, and cell death, among other mechanisms. These processes have been described to be involved in pilocarpine-induced status epilepticus (SE) and contribute to hyperexcitability, resulting in spontaneous and recurrent seizures. Here, we aimed to investigate the role of P2X7R in epileptogenesis in vivo using RNA interference (RNAi) to inhibit the expression of this receptor. Small interfering RNA (siRNA) targeting P2X7R mRNA was injected into the lateral ventricles (icv) 6 h after SE. Four groups were studied: Saline-Vehicle, Saline-siRNA, Pilo-Vehicle, and Pilo-siRNA. P2X7R was quantified by western blotting and neuronal death assessed by Fluoro-Jade B histochemistry. The hippocampal volume (edema) was determined 48 h following RNAi. Behavioral parameters as latency to the appearance of spontaneous seizures and the number of seizures were determined until 60 days after the SE onset. The Saline-siRNA and Pilo-siRNA groups showed a 43 and 37% reduction, respectively, in P2X7R protein levels compared to respective vehicle groups. Neuroprotection was observed in CA1 and CA3 of the Pilo-siRNA group compared to Pilo-Vehicle. P2X7R silencing in pilocarpine group reversed the increase in the edema detected in the hilus, suprapyramidal dentate gyrus, CA1, and CA3; reduced mortality rate following SE; increased the time to onset of spontaneous seizure; and reduced the number of seizures, when compared to the Pilo-Vehicle group. Therefore, our data highlights the potential of P2X7R as a therapeutic target for the adjunct treatment of epilepsy.
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http://dx.doi.org/10.1007/s11302-017-9573-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714836PMC
December 2017

Impact of Neuroinflammation on Hippocampal Neurogenesis: Relevance to Aging and Alzheimer's Disease.

J Alzheimers Dis 2017 ;60(s1):S161-S168

Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

The cognitive reserve is associated with the capacity of the brain to maintain cognitive performance in spite of being challenged by stressful degenerative insults related to aging. Hippocampal neurogenesis is a life-long process of continuous addition of functional new neurons in the memory processing circuits. Accordingly, adult hippocampal neurogenesis is increasingly seen as a key determinant of cognitive reserve robustness. On the other side, neuroinflammation, by releasing a plethora of proinflammatory cytokines and other inflammatory molecules, is increasingly shown to be one of the key determinant pathophysiological factors that negatively impact on neurogenesis and on the cognitive reserve, playing a detrimental role in hippocampal neurogenic niche dynamics and in the progression of neurodegenerative diseases, such as Alzheimer's disease. In the present manuscript, we highlight the functional interplay between neuroinflammation, dynamics of the neurogenic niche, and spatial memory performance in healthy and age-related pathological processes, including progression of Alzheimer's disease.
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http://dx.doi.org/10.3233/JAD-170239DOI Listing
April 2018

Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity.

J Neurosci 2016 09;36(37):9558-71

Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France,

Unlabelled: Although we are beginning to understand the late stage of neurodegenerative diseases, the molecular defects associated with the initiation of impaired cognition are poorly characterized. Here, we demonstrate that in the adult brain, the coxsackievirus and adenovirus receptor (CAR) is located on neuron projections, at the presynapse in mature neurons, and on the soma of immature neurons in the hippocampus. In a proinflammatory or diseased environment, CAR is lost from immature neurons in the hippocampus. Strikingly, in hippocampi of patients at early stages of late-onset Alzheimer's disease (AD), CAR levels are significantly reduced. Similarly, in triple-transgenic AD mice, CAR levels in hippocampi are low and further reduced after systemic inflammation. Genetic deletion of CAR from the mouse brain triggers deficits in adult neurogenesis and synapse homeostasis that lead to impaired hippocampal plasticity and cognitive deficits. We propose that post-translational CAR loss of function contributes to cognitive defects in healthy and diseased-primed brains.

Significance Statement: This study addressed the role of the coxsackievirus and adenovirus receptor (CAR), a single-pass cell adhesion molecule, in the adult brain. Our results demonstrate that CAR is expressed by mature neurons throughout the brain. In addition, we propose divergent roles for CAR in immature neurons, during neurogenesis, and at the mature synapse. Notably, CAR loss of function also affects hippocampal plasticity.
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http://dx.doi.org/10.1523/JNEUROSCI.0132-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601941PMC
September 2016

Operational definition of active and healthy ageing: Roadmap from concept to change of management.

Maturitas 2016 Feb 26;84:3-4. Epub 2015 Nov 26.

University Hospital, Montpellier, France; MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, EIP-AHA Reference Site, France.

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http://dx.doi.org/10.1016/j.maturitas.2015.11.004DOI Listing
February 2016

Operational Definition of Active and Healthy Aging (AHA): The European Innovation Partnership (EIP) on AHA Reference Site Questionnaire: Montpellier October 20-21, 2014, Lisbon July 2, 2015.

J Am Med Dir Assoc 2015 Dec 20;16(12):1020-6. Epub 2015 Oct 20.

Department of Health, Social Services and Public Safety, Belfast, Ireland.

A core operational definition of active and healthy aging (AHA) is needed to conduct comparisons. A conceptual AHA framework proposed by the European Innovation Partnership on Active and Healthy Ageing Reference Site Network includes several items such as functioning (individual capability and underlying body systems), well-being, activities and participation, and diseases (including noncommunicable diseases, frailty, mental and oral health disorders). The instruments proposed to assess the conceptual framework of AHA have common applicability and availability attributes. The approach includes core and optional domains/instruments depending on the needs and the questions. A major common domain is function, as measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). WHODAS 2.0 can be used across all diseases and healthy individuals. It covers many of the AHA dimensions proposed by the Reference Site network. However, WHODAS 2.0 does not include all dimensions proposed for AHA assessment. The second common domain is health-related quality of life (HRQoL). A report of the AHA questionnaire in the form of a spider net has been proposed to facilitate usual comparisons across individuals and groups of interest.
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http://dx.doi.org/10.1016/j.jamda.2015.09.004DOI Listing
December 2015

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice.

BMC Neurosci 2014 Aug 26;15:100. Epub 2014 Aug 26.

Department of Physiology, School of Medicine, University of Santiago de Compostela, 15710 Santiago de Compostela, Spain.

Background: Accumulating evidence suggests that growth hormone (GH) may play a major role in the regulation of postnatal neurogenesis, thus supporting the possibility that it may be also involved in promoting brain repair after brain injury. In order to gain further insight on this possibility, in this study we have investigated the pathways signaling the effect of GH treatment on the proliferation and survival of hippocampal subgranular zone (SGZ)-derived neurospheres.

Results: Our results demonstrate that GH treatment promotes both proliferation and survival of SGZ neurospheres. By using specific chemical inhibitors we have been also able to demonstrate that GH treatment promotes the activation of both Akt-mTOR and JNK signaling pathways, while blockade of these pathways either reduces or abolishes the GH effects. In contrast, no effect of GH on the activation of the Ras-ERK pathway was observed after GH treatment, despite blockade of this signaling path also resulted in a significant reduction of GH effects. Interestingly, SGZ cells were also capable of producing GH, and blockade of endogenous GH also resulted in a decrease in the proliferation and survival of SGZ neurospheres.

Conclusions: Altogether, our findings suggest that GH treatment may promote the proliferation and survival of neural progenitors. This effect may be elicited by cooperating with locally-produced GH in order to increase the response of neural progenitors to adequate stimuli. On this view, the possibility of using GH treatment to promote neurogenesis and cell survival in some acquired neural injuries may be envisaged.
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http://dx.doi.org/10.1186/1471-2202-15-100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155078PMC
August 2014

Can we talk about microglia without neurons? A discussion of microglial cell autonomous properties in culture.

Front Cell Neurosci 2014 24;8:202. Epub 2014 Jul 24.

Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, University of Coimbra Coimbra, Portugal ; Institute for Interdisciplinary Research, University of Coimbra Coimbra, Portugal.

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http://dx.doi.org/10.3389/fncel.2014.00202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109436PMC
August 2014

New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis.

Front Neurosci 2014 16;8:142. Epub 2014 Jun 16.

Faculty of Health Sciences, Health Sciences Research Center, University of Beira Interior Covilhã, Portugal.

The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine.
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http://dx.doi.org/10.3389/fnins.2014.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058902PMC
July 2014

Long-term effects of an acute and systemic administration of LPS on adult neurogenesis and spatial memory.

Front Neurosci 2014 21;8:83. Epub 2014 Apr 21.

Faculty of Medicine, Institute for Biomedical Imaging and Life Sciences, University of Coimbra Coimbra, Portugal.

The cognitive reserve is the capacity of the brain to maintain normal performance while exposed to insults or ageing. Increasing evidences point to a role for the interaction between inflammatory conditions and cognitive reserve status during Alzheimer's disease (AD) progression. The production of new neurons along adult life can be considered as one of the components of the cognitive reserve. Interestingly, adult neurogenesis is decreased in mouse models of AD and following inflammatory processes. The aim of this work is to reveal the long-term impact of a systemic inflammatory event on memory and adult neurogenesis in wild type (WT) and triple transgenic mouse model of AD (3xTg-AD). Four month-old mice were intraperitoneally injected once with saline or lipopolysaccharide (LPS) and their performance on spatial memory analyzed with the Morris water maze (MWM) test 7 weeks later. Our data showed that a single intraperitoneal injection with LPS has a long-term impact in the production of hippocampal neurons. Consistently, LPS-treated WT mice showed less doublecortin-positive neurons, less synaptic contacts in newborn neurons, and decreased dendritic volume and complexity. These surprising observations were accompanied with memory deficits. 3xTg-AD mice showed a decrease in new neurons in the dentate gyrus compatible with, although exacerbated, the pattern observed in WT LPS-treated mice. In 3xTg-AD mice, LPS injection did not significantly affected the production of new neurons but reduced their number of synaptic puncta and impaired memory performance, when compared to the observations made in saline-treated 3xTg-AD mice. These data indicate that LPS treatment induces a long-term impairment on hippocampal neurogenesis and memory. Our results show that acute neuroinflammatory events influence the production of new hippocampal neurons, affecting the cognitive reserve and leading to the development of memory deficits associated to AD pathology.
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http://dx.doi.org/10.3389/fnins.2014.00083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001049PMC
May 2014

Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?

Front Cell Neurosci 2014 27;8:59. Epub 2014 Feb 27.

Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra Coimbra, Portugal ; Center of Investigation in Environment, Genetics and Oncobiology, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra Coimbra, Portugal.

Neural stem cells (NSCs) from the subventricular zone (SVZ) have been indicated as a source of new oligodendrocytes to use in regenerative medicine for myelin pathologies. Indeed, NSCs are multipotent cells that can self-renew and differentiate into all neural cell types of the central nervous system. In normal conditions, SVZ cells are poorly oligodendrogenic, nevertheless their oligodendrogenic potential is boosted following demyelination. Importantly, progressive restriction into the oligodendrocyte fate is specified by extrinsic and intrinsic factors, endocannabinoids being one of these factors. Although a role for endocannabinoids in oligodendrogenesis has already been foreseen, selective agonists and antagonists of cannabinoids receptors produce severe adverse side effects. Herein, we show that hemopressin (Hp), a modulator of CB1 receptors, increased oligodendroglial differentiation in SVZ neural stem/progenitor cell cultures derived from neonatal mice. The original results presented in this work suggest that Hp and derivates may be of potential interest for the development of future strategies to treat demyelinating diseases.
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http://dx.doi.org/10.3389/fncel.2014.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936357PMC
February 2014