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| 2. |
- Carraminana, Albert, et al.
(author)
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Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
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Journal article (peer-reviewed)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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| 3. |
- Vasudevan, Shashank, et al.
(author)
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Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
- 2019
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In: Advanced Science. - : Wiley. - 2198-3844. ; 6:24
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Journal article (peer-reviewed)abstract
- In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro-optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin-2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro-optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real-time using chronoamperometry.
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| 4. |
- Bruzelius, Andreas, et al.
(author)
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The human bone marrow harbors a CD45− CD11B+ cell progenitor permitting rapid microglia-like cell derivative approaches
- 2021
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In: Stem cells translational medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 10:4, s. 582-597
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Journal article (peer-reviewed)abstract
- Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches.
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| 5. |
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| 6. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 7. |
- Cunha, André B., et al.
(author)
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Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant
- 2024
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In: Sensors. - 1424-8220. ; 24:2
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Journal article (peer-reviewed)abstract
- Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.
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| 8. |
- Krzyzanowska, Agnieszka, et al.
(author)
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Reelin Immunoreactivity in the Adult Spinal Cord : A Comparative Study in Rodents, Carnivores, and Non-human Primates
- 2020
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In: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 13
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Journal article (peer-reviewed)abstract
- Reelin is a large extracellular matrix (ECM) glycoprotein secreted by several neuronal populations in a specific manner in both the developing and the adult central nervous system. The extent of Reelin protein distribution and its functional role in the adult neocortex is well documented in different mammal models. However, its role in the adult spinal cord has not been well characterized and its distribution in the rodent spinal cord is fragmentary and has not been investigated in carnivores or primates as of yet. To gain insight into which neuronal populations and specific circuits may be influenced by Reelin in the adult spinal cord, we have conducted light and confocal microscopy study analysis of Reelin-immunoreactive cell types in the adult spinal cord. Here, we describe and compare Reelin immunoreactive cell type and distribution in the spinal cord of adult non-human primate (macaque monkeys, Macaca mulatta), carnivore (ferret, Mustela putorius) and rodent (rat, Rattus norvegicus). Our results show that in all three species studied, Reelin-immunoreactive neurons are present in the intermediate gray matter, ventricular zone and superficial dorsal horn and intermedio-lateral nucleus, while positive cells in the Clarke nucleus are only found in rats and primates. In addition, Reelin intermediolateral neurons colocalize with choline acetyltransferase (ChAT) only in macaque whilst motor neurons also colocalize Reelin and ChAT in macaque, ferret and rat spinal cord. The different expression patterns might reflect a differential role for Reelin in the pathways involved in the coordination of locomotor activity in the fore- and hind limbs.
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| 9. |
- Martínez-Serrano, Alberto, et al.
(author)
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Short-term grafting of human neural stem cells : Electrophysiological properties and motor behavioral amelioration in experimental Parkinson’s disease
- 2016
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In: Cell Transplantation. - 0963-6897. ; 25:12, s. 2083-2097
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Journal article (peer-reviewed)abstract
- Cell replacement therapy in Parkinson’s disease (PD) still lacks a study addressing the acquisition of electrophysiological properties of human grafted neural stem cells and their relation with the emergence of behavioral recovery after transplantation in the short term. Here we study the electrophysiological and biochemical profiles of two ventral mesencephalic human neural stem cell (NSC) clonal lines (C30-Bcl-XL and C32-Bcl-XL) that express high levels of Bcl-XL to enhance their neurogenic capacity, after grafting in an in vitro parkinsonian model. Electrophysiological recordings show that the majority of the cells derived from the transplants are not mature at 6 weeks after grafting, but 6.7% of the studied cells showed mature electrophysiological profiles. Nevertheless, parallel in vivo behavioral studies showed a significant motor improvement at 7 weeks postgrafting in the animals receiving C30-Bcl-XL, the cell line producing the highest amount of TH+ cells. Present results show that, at this postgrafting time point, behavioral amelioration highly correlates with the spatial dispersion of the TH+ grafted cells in the caudate putamen. The spatial dispersion, along with a high number of dopaminergic-derived cells, is crucial for behavioral improvements. Our findings have implications for long-term standardization of stem cell-based approaches in Parkinson’s disease.
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| 10. |
- Ramos-Moreno, Tania, et al.
(author)
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Autoimmunity and mental health in William’s syndrome
- 2017
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In: Advances in Health and Disease. - 9781536126952 - 9781536126969 ; 2, s. 81-114
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Book chapter (peer-reviewed)abstract
- William’s Syndrome (WS) is described as a genetic disorder characterized by mild to moderate mental retardation, engaging personalities, distinctive facial features and heart and blood vessel (cardiovascular) problems. People affected by WS present also difficulties with visual-spatial tasks and are mostly known by their unique music and language skills, the latter being the reason why WS has been mainly studied for language formation. The presence of attention deficit disorder, problems with anxiety and phobias are usually less characterized in WS although more attention is starting to be given to these issues. Moreover, little attention has been paid to autoimmunity problems prevalent in WS such as celiac or Crohn’s disease. Autoimmune diseases (AID) are accepted to be possible pathogenic mechanisms that lead to mental deterioration and dementia. In people affected by WS, both AID and retardation are developing alongside each other whilst, in addition, AID can stimulate inflammatory brain states and deterioration. In the present chapter I will revise the different AID reported in patients with WS and will talk about the reasons why some AID are prevalent in WS. Next, I will explain how AID interfere with the normal development of the brain highlighting the pathways that might be affected in patients with WS suffering from AID, which can lead to mental health deterioration, obsessive-compulsive disorders and/or anxiety. Finally, and based on the above, I will suggest some guidance for clinicians and caregivers to decrease the risk for worsening mental health deterioration in WS.
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