Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

NeuroVM: Dynamic Neuromorphic Hardware Virtualization

This paper introduces a novel approach in neuromorphic computing, integrating heterogeneous hardware nodes into a unified, massively parallel architecture. Our system transcends traditional single-node constraints, harnessing the neural structure and functionality of the human brain to efficiently process complex tasks. We present an architecture that dynamically virtualizes neuromorphic resources, enabling adaptable allocation and reconfiguration for various applications. Our evaluation, using diverse applications and performance metrics, provides significant insights into the system\u27s adaptability and efficiency. We observed scalable throughput increases across configurations of 1, 2, and 4 Virtual Machines (VMs), reaching up to 5.1 Gibibits per second (Gib/s) for different data transfer sizes. This scalability demonstrates the system\u27s capacity to handle tasks that require substantial amounts of data. The energy consumption of our virtualized accelerator environment increased nearly linearly with the addition of more NeuroVM accelerators, ranging from 25 to 45 millijoules (mJ) as the number of accelerators increased from 1 to 20. Further, our investigation of reconfiguration overheads revealed that partial reconfigurations significantly reduce the time spent on reconfigurations compared to full reconfigurations, particularly when there are more virtual machines, as indicated by the logarithmic scale of time measurements.Accepted at 2024 International Green and Sustainable Computing Conference (IGSC

RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells

Background Telomeric 3’ overhangs can fold into a four-stranded DNA structure termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase activation is crucial for telomere maintenance in most cancer cells, several classes of G4 ligands have been designed to directly disrupt telomeric structure. Methods We exposed brain tumor cells to the G4 ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) and investigated proliferation, cell cycle dynamics, telomere length, telomerase activity and activated c-Myc levels. Results Although all cell lines tested were sensitive to RHPS4, PFSK-1 central nervous system primitive neuroectodermal cells, DAOY medulloblastoma cells and U87 glioblastoma cells exhibited up to 30-fold increased sensitivity compared to KNS42 glioblastoma, C6 glioma and Res196 ependymoma cells. An increased proportion of S-phase cells were observed in medulloblastoma and high grade glioma cells whilst CNS PNET cells showed an increased proportion of G1-phase cells. RHPS4-induced phenotypes were concomitant with telomerase inhibition, manifested in a telomere length-independent manner and not associated with activated c-Myc levels. However, anti-proliferative effects were also observed in normal neural/endothelial cells in vitro and ex vivo. Conclusion This study warrants in vivo validation of RHPS4 and alternative G4 ligands as potential anti-cancer agents for brain tumors but highlights the consideration of dose-limiting tissue toxicities

The Mental Health of Women with Gestational Diabetes During the COVID-19 Pandemic: An International Cross-Sectional Survey

Background: There is evidence that women with gestational diabetes are at increased risk of the common mental disorders of anxiety and depression. The COVID-19 pandemic may have exerted an additional burden on the mental health of this population. The aim of this analysis was to compare levels of symptoms of common mental disorders and experiences during the COVID-19 pandemic between pregnant and postnatal women exposed and unexposed to gestational diabetes. Methods: Cross-sectional study utilizing quantitative data from an online survey administered across 10 countries to women who were pregnant or up to 6 months postpartum from 15 June to October 31, 2020. Women self-reported gestational diabetes and completed the Edinburgh Postnatal Depression Scale and GAD-7 (Generalized Anxiety Disorder 7 items) measures. The COPE-IS (Coronavirus Perinatal Experiences-Impact Survey) tool was also administered. Complete case analyses were conducted on a sample of 7,371 women. Results: There was evidence of an association between gestational diabetes and increased levels of depression symptoms, which was robust to adjustment for age, education, and employment status. There was only evidence of an association with anxiety in postnatal women. There was also evidence that women with gestational diabetes, particularly those in the postnatal period, experienced higher levels of pandemic-related distress, although they did not experience higher levels of COVID-19 infection in this sample. Conclusions: The increased risk of common mental disorders in women with gestational diabetes underscores the importance of integrated physical and mental health care for pregnant and postnatal women both during and beyond the pandemic. Clinical Trial Registration no. NCT04595123. © Claire A. Wilson et al. 2022; Published by Mary Ann Liebert, Inc. 2022.This paper is part of the European Cooperation in Science and Technology (COST) Action Riseup-PPD CA18138 and was supported by COST under COST Action Riseup-PPD CA18138. R.C. is supported by the FSE and FCT under an individual Post-Doctoral Grant SFRH/BPD/117597/2016. D.L. received funding from the Bar-Ilan Dangoor Centre for Personalized Medicine, Israel. C.A.W is supported by the UK's National Institute for Health and Care Research (NIHR). Open access fees from an NIHR senior investigator grant (NIHR200241)

Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the e cacy and adverse e ects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological e ects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse e ects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo

"Geo-characterization" of selected areas in Crete, Greece, towards realistic assessment of seismic design actions

Η ποσοτική εκτίμηση των χαρακτηριστικών παραμέτρων της ισχυρής εδαφικής κίνησης στους επιφανειακούς γεωλογικούς σχηματισμούς έχει ιδιαίτερη σημασία στην τεχνική σεισμολογία και την εδαφομηχανική. Στο έργο “GEO  -CHARACTERIZATION” ΘΑΛΗΣ, μελετώνται οι γεωτεχνικές και γεωφυσικές τεχνικές ως μέθοδοι διερεύνησης των γεωτεχνικών παραμέτρων του υπεδάφους. Ενώ οι γεωτεχνικές δοκιμές παρέχουν με ακρίβεια τις γεωτεχνικές παραμέτρους, η κατασκευή των γεωτρήσεων και η εκτίμηση των γεωτεχνικών παραμέτρων, είναι ιδιαίτερα δαπανηρή, ασαφής και χρονοβόρα διαδικασία. Οι γεωφυσικές μέθοδοι είναι αποτελεσματικές στη διερεύνηση του υπεδάφους, αλλά τα αποτελέσματά τους δεν μπορούν άμεσα να μεταφραστούν σε μεταβολή των γεωτεχνικών παραμέτρων. Με σκοπό τη πληρέστερη μελέτη του υπεδάφους, σε σταθμούς επιταχυνσιογράφων του Ε.Δ.Ε. (Εθνικού Δικτύου Επιταχυνσιογράφων), θα  εκτελεστούν  συμπληρωματικές  γεωτεχνικές  και τεχνικογεωλογικές εργασίες  ενώ ταυτόχρονα θα εκτελεστούν γεωφυσικές διασκοπήσεις. Το σύνολο των δεδομένων θα επιτρέ   ψει  τη  συσχέτιση  των  φυσικομηχανικών  παραμέτρων  (από  εργαστηριακές/επιτόπου δοκιμές) με τις γεωφυσικές παραμέτρους. Επιπλέον, τα δεδομένα αυτά θα επιτρέψουν τη dιερεύνηση γεωτεχνικών προβλημάτων καθώς και την απόκριση των σχηματισμών που δομούν την περιοχή σε ενδεχόμενη δυναμική – σεισμική φόρτιση, ενώ θα προταθούν και τοπικά   κανονικοποιημένα ελαστικά φασμάτα σχεδιασμούτα οποία θα συγκριθούν με τα αντίστοιχα φάσματα του Ευρωκόδικα 8 (EC8). The geo-characterization of site conditions is crucial for the estimation of regional elastic  spectra.  The  work  to  be  done  in  the  framework  of  the  “GEO-CHARACTERIZATION”  THALIS-project,  will  combine  geotechnical  and geophysical methods and evaluate them to estimate critical geotechnical parameters. Although  geotechnical  tests  in  lab  may  provide  more  accurate  estimates  of geotechnical  parameters,  they  require  costly  and  time  consuming  drilling procedures.  On  the  other  hand  geophysical  methods  are  useful  in  providing estimates in situ of subsurface physical properties, which are not directly related to geotechnical parameters. Within “GEO-CHARACTERIZATION” THALIS-project a pilot  survey  for  geotechnical  characterization  at  selected  sites  of  Hellenic Accelerometric  Network in  Crete  will  be  conducted  by  employing  geotechnical, geological  and  geophysical  techniques.  Subsequently,  by  correlating  “geo-data” collected within this project, relations of certain mechanical parameters obtained in laboratory  or/and  in  situ  with  geophysical  parameters  for  typical  geologic formations  and  soils  will  be  established.  The  “GEO-CHARACTERIZATION” project, will focus on the influence of dynamic loads on geotechnical phenomena related to the static stress field variation, the estimation of site effects due to seismic motion and the proposal of regional elastic spectra for seismic provisions as well as their comparison with the  corresponding elastic design spectra of  Eurocode 8 (EC8)

"Geo-characterization" of selected areas in Crete, Greece, towards realistic assessment of seismic design actions

Η ποσοτική εκτίμηση των χαρακτηριστικών παραμέτρων της ισχυρής εδαφικής κίνησης στους επιφανειακούς γεωλογικούς σχηματισμούς έχει ιδιαίτερη σημασία στην τεχνική σεισμολογία και την εδαφομηχανική. Στο έργο “GEO  -CHARACTERIZATION” ΘΑΛΗΣ, μελετώνται οι γεωτεχνικές και γεωφυσικές τεχνικές ως μέθοδοι διερεύνησης των γεωτεχνικών παραμέτρων του υπεδάφους. Ενώ οι γεωτεχνικές δοκιμές παρέχουν με ακρίβεια τις γεωτεχνικές παραμέτρους, η κατασκευή των γεωτρήσεων και η εκτίμηση των γεωτεχνικών παραμέτρων, είναι ιδιαίτερα δαπανηρή, ασαφής και χρονοβόρα διαδικασία. Οι γεωφυσικές μέθοδοι είναι αποτελεσματικές στη διερεύνηση του υπεδάφους, αλλά τα αποτελέσματά τους δεν μπορούν άμεσα να μεταφραστούν σε μεταβολή των γεωτεχνικών παραμέτρων. Με σκοπό τη πληρέστερη μελέτη του υπεδάφους, σε σταθμούς επιταχυνσιογράφων του Ε.Δ.Ε. (Εθνικού Δικτύου Επιταχυνσιογράφων), θα  εκτελεστούν  συμπληρωματικές  γεωτεχνικές  και τεχνικογεωλογικές εργασίες  ενώ ταυτόχρονα θα εκτελεστούν γεωφυσικές διασκοπήσεις. Το σύνολο των δεδομένων θα επιτρέ   ψει  τη  συσχέτιση  των  φυσικομηχανικών  παραμέτρων  (από  εργαστηριακές/επιτόπου δοκιμές) με τις γεωφυσικές παραμέτρους. Επιπλέον, τα δεδομένα αυτά θα επιτρέψουν τη dιερεύνηση γεωτεχνικών προβλημάτων καθώς και την απόκριση των σχηματισμών που δομούν την περιοχή σε ενδεχόμενη δυναμική – σεισμική φόρτιση, ενώ θα προταθούν και τοπικά   κανονικοποιημένα ελαστικά φασμάτα σχεδιασμούτα οποία θα συγκριθούν με τα αντίστοιχα φάσματα του Ευρωκόδικα 8 (EC8). The geo-characterization of site conditions is crucial for the estimation of regional elastic  spectra.  The  work  to  be  done  in  the  framework  of  the  “GEO-CHARACTERIZATION”  THALIS-project,  will  combine  geotechnical  and geophysical methods and evaluate them to estimate critical geotechnical parameters. Although  geotechnical  tests  in  lab  may  provide  more  accurate  estimates  of geotechnical  parameters,  they  require  costly  and  time  consuming  drilling procedures.  On  the  other  hand  geophysical  methods  are  useful  in  providing estimates in situ of subsurface physical properties, which are not directly related to geotechnical parameters. Within “GEO-CHARACTERIZATION” THALIS-project a pilot  survey  for  geotechnical  characterization  at  selected  sites  of  Hellenic Accelerometric  Network in  Crete  will  be  conducted  by  employing  geotechnical, geological  and  geophysical  techniques.  Subsequently,  by  correlating  “geo-data” collected within this project, relations of certain mechanical parameters obtained in laboratory  or/and  in  situ  with  geophysical  parameters  for  typical  geologic formations  and  soils  will  be  established.  The  “GEO-CHARACTERIZATION” project, will focus on the influence of dynamic loads on geotechnical phenomena related to the static stress field variation, the estimation of site effects due to seismic motion and the proposal of regional elastic spectra for seismic provisions as well as their comparison with the  corresponding elastic design spectra of  Eurocode 8 (EC8)

Key dimensions of women’s and their partners’ experiences of childbirth: A systematic review of reviews of qualitative studies

Background The World Health Organization 2018 intrapartum guideline for a positive birth experience emphasized the importance of maternal emotional and psychological well-being during pregnancy and the need for safe childbirth. Today, in many countries birth is safe, yet many women report negative and traumatic birth experiences, with adverse effects on their and their families’ well-being. Many reviews have attempted to understand the complexity of women’s and their partners’ birth experience; however, it remains unclear what the key dimensions of the birth experience are. Objective To synthesize the information from reviews of qualitative studies on the experience of childbirth in order to identify key dimensions of women’s and their partners’ childbirth experience. Methods Systematic database searches yielded 40 reviews, focusing either on general samples or on specific modes of birth or populations, altogether covering primary studies from over 35,000 women (and >1000 partners) in 81 countries. We appraised the reviews’ quality, extracted data and analysed it using thematic analysis. Findings Four key dimensions of women’s and partners’ birth experience (covering ten subthemes), were identified: 1) Perceptions, including attitudes and beliefs; 2) Physical aspects, including birth environment and pain; 3) Emotional challenges; and 4) Relationships, with birth companions and interactions with healthcare professionals. In contrast with the comprehensive picture that arises from our synthesis, most reviews attended to only one or two of these dimensions. Conclusions The identified key dimensions bring to light the complexity and multidimensionality of the birth experience. Within each dimension, pathways leading towards negative and traumatic birth experiences as well as pathways leading to positive experiences become tangible. Identifying key dimensions of the birth experience may help inform education and research in the field of birth experiences and gives guidance to practitioners and policy makers on how to promote positive birth experiences for women and their partners

Transcriptomic profiles of muscle, heart, and spleen in reaction to circadian heat stress in Ethiopian highland and lowland male chicken

Temperature stress impacts both welfare and productivity of livestock. Global warming is expected to increase the impact, especially in tropical areas. We investigated the biological mechanisms regulated by temperature stress due to the circadian temperature cycle in temperature adapted and non-adapted chicken under tropical conditions. We studied transcriptome profiles of heart, breast muscle, and spleen tissues of Ethiopian lowland chicken adapted to high circadian temperatures and non-adapted Ethiopian highland chicken under lowland conditions at three points during the day: morning, noon, and evening. Functional annotations and network analyses of genes differentially expressed among the time points of the day indicate major differences in the reactions of the tissues to increasing and decreasing temperatures, and also the two chickens lines differ. However, epigenetic changes of chromatin methylation and histone (de)acetylation seemed to be central regulatory mechanisms in all tissues in both chicken lines. Finally, all tissues showed differentially expressed genes between morning and evening times indicating biological mechanisms that need to change during the night to reach morning levels again the next day.</p