Pathophysiology and therapeutic approaches for spinal cord injury

Spinal cord injury (SCI) is a disabling condition that disrupts motor, sensory, and autonomic functions. Despite extensive research in the last decades, SCI continues to be a global health priority affecting thousands of individuals every year. The lack of effective therapeutic strategies for patients with SCI reflects its complex pathophysiology that leads to the point of no return in its function repair and regeneration capacity. Recently, however, several studies started to uncover the intricate network of mechanisms involved in SCI leading to the development of new therapeutic approaches. In this work, we present a detailed description of the physiology and anatomy of the spinal cord and the pathophysiology of SCI. Additionally, we provide an overview of different molecular strategies that demonstrate promising potential in the modulation of the secondary injury events that promote neuroprotection or neuroregeneration. We also briefly discuss other emerging therapies, including cell-based therapies, biomaterials, and epidural electric stimulation. A successful therapy might target different pathologic events to control the progression of secondary damage of SCI and promote regeneration leading to functional recovery.This work has been funded by National funds, through the Foundation for Science and Technology (FCT)-project UIDB/50026/2020, UIDP/50026/2020 and project EXPL/MED-PAT/0931/2021. Financial support was also provided from Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021)

The central nervous system source modulates microglia function and morphology in vitro

The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.This work was funded by the Santa Casa Neuroscience Awards—Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021), and it was partially funded by the Wings for Life Spinal Cord Research Foundation (WFL-ES-03/19). This work was also funded by national funds through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020, UIDP/50026/2020, and EXPL/MED-PAT/0931/2021, and by the project NORTE-01-0145-FEDER-000039, supported by the Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). We would like to acknowledge the support given by the Portuguese Foundation of Science and Technology to AGP (2020.07534.BD), AM (UMINHO/BIL-CNCG/2022/16), SM (CEECIND/01902/2017), and NAS (CEECIND/04794/2007)

Induced Pluripotent Stem Cells from Human Placental Chorion for Perinatal Tissue Engineering Applications

The reliable derivation of induced pluripotent stem cells (iPSCs) from a noninvasive autologous source at birth would facilitate the study of patient-specific in vitro modeling of congenital diseases and would enhance ongoing efforts aimed at developing novel cell-based treatments for a wide array of fetal and pediatric disorders. Accordingly, we have successfully generated iPSCs from human fetal chorionic somatic cells extracted from term pregnancies by ectopic expression of OCT4, SOX2, KLF4, and cMYC. The isolated parental somatic cells exhibited an immunophenotypic profile consistent with that of chorionic mesenchymal stromal cells (CMSCs). CMSC-iPSCs maintained pluripotency in feeder-free systems for more than 15 passages based on morphology, immunocytochemistry, and gene expression studies and were capable of embryoid body formation with spontaneous trilineage differentiation. CMSC-iPSCs could be selectively differentiated in vitro into various germ layer derivatives, including neural stem cells, beating cardiomyocytes, and definitive endoderm. This study demonstrates the feasibility of term placental chorion as a novel noninvasive alternative to dermal fibroblasts and cord blood for human perinatal iPSC derivation and may provide additional insights regarding the reprogramming capabilities of extra-embryonic tissues as they relate to developmental ontogeny and perinatal tissue engineering applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140245/1/ten.tec.2013.0480.pd

Shoulder Torque Production and Muscular Balance after Long and Short Tennis Points

Tennis is an asymmetric sport characterized by a systematic repetition of specific movements that may cause disturbances in muscular strength, power, and torque. Thus, we assessed (i) the torque, power, ratio production, and bilateral asymmetries in the shoulder’s external and internal rotations at 90 and 180°/s angular velocities, and (ii) the point duration influence of the above-mentioned variables. Twenty competitive tennis players performed external and internal shoulder rotations; an isokinetic evaluation was conducted of the dominant and non-dominant upper limbs before and after five and ten forehands. A higher torque production in the shoulder’s internal rotations at 90 and 180°/s was observed for the dominant vs. non-dominant sides (e.g., 63.1 ± 15.6 vs. 45.9 ± 9.8% and 62.5 ± 17.3 vs. 44.0 ± 12.6% of peak torque/body mass, p < 0.05). The peak torque decreased only after ten forehands (38.3 ± 15.8 vs. 38.2 ± 15.8 and 39.3 ± 16.1 vs. 38.1 ± 15.6 Nm, respectively, p < 0.05), but without impacting speed or accuracy. Unilateral systematic actions of tennis players caused contralateral asymmetries, evidencing the importance of implementing compensatory training. The forehand kinematic assessment suggests that racket and wrist amplitude, as well as speed, are important success determinants in tennis.SIThis research received no external funding

New multifunctional push-pull converter operating with MPPT and integrated energy storage system for PV micro-inverter applications

This paper presents a novel multifunctional push-pull converter for micro-inverter applications, used to interface photovoltaic (PV) modules and an battery energy storage system with the power grid (PG). The push-pull DC-DC power converter requires only two switching devices. It uses a specific algorithm to control the batteries charging process, preserving their lifetime, and also to operate as maximum power point tracker, optimizing the energy production from the PVs modules. The push-pull DC-AC power converter operates in coordination with the DC-DC converter, injecting all available energy from the PVs modules into the PG. If the produced energy exceeds the consumed energy, the surplus is used to charge the batteries for latter consumption. The proposed topology aims to contribute to the technological development in terms of power converters for micro-inverter applications. Throughout the paper is given a detailed explanation on the principle of operation of the new topology, as well as on the proposed digital control algorithm.This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT - Fundação para a Ciância e Tecnologia within the Project Scope: UID/CEC/00319/2013. This work is financed by the ERDF - European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation - COMPETE 2020 Programme, and by National Funds through the Portuguese funding agency, FCT - Fundação para a Ciância e a Tecnologia, within project SAICTPAC/0004/2015- POCI- 01-0145-FEDER-016434.info:eu-repo/semantics/publishedVersio

A Potential Link Between Prolonged Cork Exposure and Intestinal-Type Sinonasal Adenocarcinoma – Special Findings of a Retrospective Cohort Analysis

Introduction: intestinal-type sinonasal adenocarcinoma (ITAC) is a rare epithelium tumor of the nasal cavities and paranasal sinuses. Exposure to wood and leather dusts is a strong etiological factor related to its development. Prolonged cork exposure has rarely been associated. Materials and methods: thirty-seven-year (1981-2018) retrospective cohort analysis of all consecutive patients with sinonasal cancer (SNC) followed at our institution. Medical records were reviewed to determine patient demographics, occupational/environmental exposure, location and extent of the tumor, stage, histopathology findings, treatment strategies, and oncologic outcomes. Survival analysis was done using Kaplan-Meier method. Results: we evaluated 379 patients with SNC, including 39 (10.3%) ITAC. Patient median age was 73 years (range 49-87), 56% male and 69% with identified professional occupational exposure (54% for cork; 69.2% considering only those for which an agent has been identified). Seventy-two percent had locally advanced disease (stage III or IVA-B). The initial treatment was surgery in 77%, and 54% received adjuvant radiotherapy. The median time to progression, progression-free survival, and overall-survival was 2.36 years (95% CI 1.54-8.70), 1.96 years (95% CI 1.43-3.74), and 3.51 years (95% CI 2.33-10.02), respectively. Conclusion: ITAC is an uncommon malignancy that grows silently, which contributes to delayed diagnosis, advanced stage and low survival rates. In our cohort, we observed a high prevalence of cork occupational exposure. This finding may lead to the implementation of protection measures and suggest a potential link to be further studied.info:eu-repo/semantics/publishedVersio

Citalopram administration does not promote function or histological recovery after spinal cord injury

Citalopram is a selective serotonin reuptake inhibitor, and although widely used as an antidepressant, this drug has also demonstrated interesting repairing properties leading to motor recovery and pathology amelioration in animal models of stroke and degeneration. Here, we tested the efficacy of both 7-day and 8-week citalopram treatment in a contusive spinal cord injury (SCI) rat model. A combination of behavioral tests, histological and serum cytokine analysis was used to assess overall recovery. Despite promoting a mild reduction of inflammatory cells as well as an early, but transient increase of specific serum cytokines, citalopram administration showed no overall beneficial effects on motor performance or lesion extension. Our results do not support citalopram treatment as a therapeutic strategy for SCI.This research was funded by Prémios Santa Casa Neurociências—Prize Melo e Castro for SpinalCord Injury Research, Grant Number MC-04/17 and the Portuguese Foundation for Science and Technology(FCT) through the Scientific Employment Stimulus to N. Silva and S. Monteiro (CEECIND/04794/2017 and CEECIND/01902/2017) and fellowships to RL (PD/BDE/127836/2016); EDG (SFRH/BD/103075/2014);NLV (SFRH/BD/136952/2018) and R.AS (PDE/BDE/113596/2015).This work was also funded by FEDER,through the Competitiveness Internalization Operational Program (POCI) and by National funds, throughthe Foundation for Sciences and Technology (FCT), under the scope of the projects POCI-01-0145-FEDER-007038,POCI-01-0145-FEDER-029206, POCI-01-0145-FEDER-029751 and PTDC/BTM-MAT/29968/2017. This work hasbeen funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - PortuguesePlatform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundationfor Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020; and by the projectsNORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Fully Automatic 3D-TEE Segmentation for the Planning of Transcatheter Aortic Valve Implantation

A novel fully automatic framework for aortic valve (AV) trunk segmentation in three-dimensional (3-D) transesophageal echocardiography (TEE) datasets is proposed. The methodology combines a previously presented semiautomatic segmentation strategy by using shape-based B-spline Explicit Active Surfaces with two novel algorithms to automate the quantification of relevant AV measures. The first combines a fast rotation-invariant 3-D generalized Hough transform with a vessel-like dark tube detector to initialize the segmentation. After segmenting the AV wall, the second algorithm focuses on aligning this surface with the reference ones in order to estimate the short-axis (SAx) planes (at the left ventricular outflow tract, annulus, sinuses of Valsalva, and sinotubular junction) in which to perform the measurements. The framework has been tested in 20 3-D-TEE datasets with both stenotic and nonstenotic AVs. The initialization algorithm presented a median error of around 3 mm for the AV axis endpoints, with an overall feasibility of 90%. In its turn, the SAx detection algorithm showed to be highly reproducible, with indistinguishable results compared with the variability found between the experts' defined planes. Automatically extracted measures at the four levels showed a good agreement with the experts' ones, with limits of agreement similar to the interobserver variability. Moreover, a validation set of 20 additional stenotic AV datasets corroborated the method's applicability and accuracy. The proposed approach mitigates the variability associated with the manual quantification while significantly reducing the required analysis time (12 s versus 5 to 10 min), which shows its appeal for automatic dimensioning of the AV morphology in 3-D-TEE for the planning of transcatheter AV implantation.This work was supported by the project "ON.2 SR&TD Integrated Program (Norte-07-0124-FEDER-000017)" cofunded by the Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referencia Estrategico Nacional, through Fundo Europeu de Desenvolvimento Regional. The work of S. Queiros and P. Morais was supported by the FCT-Fundacao para a Ciencia e a Tecnologia and the European Social Found through the Programa Operacional Capital Humano in the scope of the Ph.D. Grants SFRH/BD/93443/2013 and SFRH/BD/95438/2013, respectively. J. L. Vilaca and J. D'hooge are joint last authors. Asterisk indicates corresponding author.info:eu-repo/semantics/publishedVersio

Academics perception towards various water reuse options: University of Trás-os-Montes e Alto Douro - UTAD Campus (Portugal) as a case study

Any strategy of water reuse has to achieve social acceptance to be successful. This paper presents the results of a multiple choice survey that attempted to establish the general attitude toward water reuse by asking academics in UTAD (Portugal) a wide range of questions. The survey included 20 reuse options, which were clustered into three reuse categories, specifically: low, medium and high contact levels. Correlation analysis between the level of support of low, medium and high contact options and demographic characteristics, personal and environmental beliefs was performed. Results show that a high proportion of the participants supported low and medium contact reuse options. Correlation was found to exist between the income classes and to the level of support of medium and high reuse options and between education level and the support for high contact reuse options. The responses to the survey suggested that some beliefs influence the level of support