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Health-care personnel (HCP) are exposed to infectious diseases throughout the course of their work. The concerns of pregnant HCP are considerable because certain otherwise mild infections may affect fetal development. We studied 424 pregnant HCP at the University Hospital Frankfurt / Germany between March 2007 and July 2011. Serological tests were carried out for varicella zoster virus (VZV), measles, mumps, rubella (MMR), cytomegalovirus (CMV) and parvovirus B19. Our overall seroprevalence data with regard to VZV, MMR, CMV and parvovirus B 19 corresponded to the general population. It was striking that, only 57.1% of the study population was immune against the four vaccine-preventable diseases (MMR, VZV). Our study suggests that a comprehensive approach to improving the vaccination status of said HCP before pregnancy is paramount.
Nosocomial infectious diseases (e.g. influenza, pertussis) are a threat particularly for immunocompromised and vulnerable patients. Although vaccination of healthcare workers (HCWs) constitutes the most convenient and effective means to prevent nosocomial transmissions, vaccine uptake among HCWs remains unacceptably low. Worldwide, numerous studies have demonstrated that nurses have lower vaccination rates than physicians and that there is a relationship between receipt of vaccination by HCWs and knowledge. Measures to improve vaccination rates need to be profession-sensitive as well as specific in their approach in order to achieve sustained success.
Background: A growing interest exists in using polymeric nanoparticles (NPs) especially functionalized with surface-active substances as carriers across the blood brain barrier (BBB) for potentially effective drugs in traumatic brain injury (TBI). However, the organ distribution of intravenous administrated biodegradable and non-biodegradable NPs coated with different surfactants, how much of the administrated dose reach the brain parenchyma in areas with intact and opened BBB after trauma, as well as whether they elicit an inflammatory response is still to be clarified.
Methods: The organ distribution, brain penetration and eventual inflammatory activation of polysorbate-80 (Tw80) and sodium-lauryl-sulfate (SDS) coated poly l-lactide (PLLA) and perfluorodecyl acrylate (PFDL) nanoparticles were evaluated after intravenous administration in rats prior and after undergoing controlled cortical impact (CCI).
Results: A significant highest NP uptake at 4 and 24 hs was observed in the liver and spleen, followed by the brain and kidney, with minimal concentrations in the lungs and heart for all NPs. After CCI, a significant increase of NP uptake at 4 hs and 24 hs was observed within the traumatized hemisphere, especially in the perilesional area, although NPs were still found in areas away from CCI and the contralateral hemisphere in similar concentrations as in non-CCI subject. NPs were localized in neurons, glial and endovascular cells. Immunohistochemical staining against GFAP, Iba1, TNFα and IL1β demonstrated no glial activation or neuroinflamatory changes.
Conclusions: Tw80 and SDS coated biodegradable (PLLA) and non-biodegradrable (PFDL) NPs reach the brain parenchyma in both areas of traumatized and undamaged brain with disrupted and intact BBB, even though a high amount of them are retained in the liver and the spleen. No inflammatory reaction is elicited by these NPs within 24 hs after application. These preliminary promising results postulate the effectiveness and safety of these NPs as drug-carriers for the treatment of TBI.
Oral e-Poster Presentations - Booth 2: Neuro-Oncology C (Imaging&Monitoring), September 27, 2023, 1:00 PM - 2:30 PM
Background: Repetitive TMS (rTMS) can be used to non-invasively map cortical language areas. Commonly, frequencies of 5-10 Hz are used to induce speech errors. We could recently show that frequencies of 30 and 50 Hz are advantageous to achieve higher reliability. However, high-frequent rTMS applied over perisylvian regions still suffer from limited tolerability. Using short-train or paired-pulse TMS (pp-TMS) might offer a good alternative to rTMS to interfere with speech production. In this study, we, therefore, compared 30 Hz rTMS to pp-TMS aiming at improved language mapping.
Methods: 13 healthy, right-handed subjects (f=6, 25-41 years) were investigated using two different rTMS protocols: (i) 30 Hz rTMS and (ii) pp-TMS. TMS protocols were applied in a pseudo-randomized order during a picture naming task (picture-to-trigger interval: 0 ms) over cortical language areas. In a subsequent study, we compared pp-TMS also to short trains of three TMS pulses and repetitive paired pulse TMS. Language errors were post-hoc analysed by two independent raters and were assigned to eight different error categories. The level of pain was assessed on a subjective 0-10 numeric rating scale (NRS). Moreover, language error distribution was analysed using a cortical parcellation system.
Results: 30 Hz rTMS evoked a significantly higher number of errors than the pp-protocol, i.e., 18 ± 12 % vs. 10 ± 7 % (p<0.05). However, pp-TMS was significantly better tolerated with a mean NRS of 2.3 ± 1.6 vs. 3.4 ± 1.5 (p<0.05, FDR-corrected). Of note, pp-TMS could induce a higher number of anomias (15 ± 15 %) than repetitive TMS protocols (4 ± 7 %; p<0.1, FDR-corrected), but less dysarthria. The cortical distribution of errors differed between the two protocols. The results of train-of-three TMS were similar to the pp-TMS protocol.
Conclusions: Due to its better tolerability, pp-TMS might offer the possibility to stimulate regions which are particularly prone to direct facial / trigeminal nerve stimulation, e.g., the inferior frontal gyrus. Moreover, pp-TMS seems advantageous for mapping patients who are comparatively susceptible to rTMS side effects and with regard to safety in general.
TRENTOOL : an open source toolbox to estimate neural directed interactions with transfer entropy
(2011)
To investigate directed interactions in neural networks we often use Norbert Wiener's famous definition of observational causality. Wiener’s definition states that an improvement of the prediction of the future of a time series X from its own past by the incorporation of information from the past of a second time series Y is seen as an indication of a causal interaction from Y to X. Early implementations of Wiener's principle – such as Granger causality – modelled interacting systems by linear autoregressive processes and the interactions themselves were also assumed to be linear. However, in complex systems – such as the brain – nonlinear behaviour of its parts and nonlinear interactions between them have to be expected. In fact nonlinear power-to-power or phase-to-power interactions between frequencies are reported frequently. To cover all types of non-linear interactions in the brain, and thereby to fully chart the neural networks of interest, it is useful to implement Wiener's principle in a way that is free of a model of the interaction [1]. Indeed, it is possible to reformulate Wiener's principle based on information theoretic quantities to obtain the desired model-freeness. The resulting measure was originally formulated by Schreiber [2] and termed transfer entropy (TE). Shortly after its publication transfer entropy found applications to neurophysiological data. With the introduction of new, data efficient estimators (e.g. [3]) TE has experienced a rapid surge of interest (e.g. [4]). Applications of TE in neuroscience range from recordings in cultured neuronal populations to functional magnetic resonanace imaging (fMRI) signals. Despite widespread interest in TE, no publicly available toolbox exists that guides the user through the difficulties of this powerful technique. TRENTOOL (the TRansfer ENtropy TOOLbox) fills this gap for the neurosciences by bundling data efficient estimation algorithms with the necessary parameter estimation routines and nonparametric statistical testing procedures for comparison to surrogate data or between experimental conditions. TRENTOOL is an open source MATLAB toolbox based on the Fieldtrip data format. ...
Introduction: Spondylodiscitis is the commonest form of infectious disease of the spine and harbours a high mortality rate of up to 20%. Recent demographic trends in Germany, such as an aging population, immunosuppression, and intravenous drug use, suggest that the incidence of spondylodiscitis may be on the rise. However, the exact epidemiological development of the disease remains uncertain. This study aims to analyse the burden on the tertiary healthcare system in Germany using data from the Federal Statistical Office of Germany (FSOG) database.
Materials and Methods: All cases of spondylodiscitis diagnosed between 2005 and 2021 were identified from the FSOG database. The study characterised the mean duration of hospital stays, total and population-adjusted number of diagnoses made, age-stratified incidence, and outcomes of hospitalised patients.
Results: A total of 131,982 diagnoses for spondylodiscitis were identified between 2005 and 2021. The number of diagnoses for spondylodiscitis has doubled during this period, from 5.4/100,000 population in 2005 to 11/100,000 population in 2021. The highest increase in admissions was recorded for those aged 90 years and above (+1307%), 80-89 (+376%) and 70-79 (+99%). Hospital discharges to rehabilitation facilities have increased by 160%, and discharges against medical advice by 91%. On the other hand, during the analysed period, the in-hospital mortality rate has decreased by 52%.
Conclusion: The population-adjusted incidence of spondylodiscitis in Germany has more than doubled between 2005 and 2021, highlighting the clinical relevance of this disease. During the same period, in-hospital mortality dropped by half. These findings suggest the need for further investigation into optimal therapy, particularly the role and timing of surgical treatment.
Introduction: Ferroptosis has recently been identified as a form of programmed cell death caused by an accumulation of lipid reactive oxygen species (ROS). However, little is yet known about the role in hepatocellular carcinoma (HCC) and its signalling mechanism as well the modulation of ROS.
Material and methods: Human HCC cell lines were treated with different concentrations of ROS modulators (Auranofin, Erastin, BSO). Cell death was determined by analysis of PI-stained nuclei using flow cytometry. ROS production and lipid peroxidation were analysed at early time points before cell death starts. For mechanistic studies we performed Western Blot and a Proteome array. Different inhibitors of cell death target proteins, ROS-scavengers as well as lipoxygenase inhibitors were used. To investigate the functional relevance of NAPDH oxidases (NOX) 1 and 4 for ROS modulation and ferroptosis we genetically silenced its genes using three distinct siRNAs and we used the NOX1/4-inhibitor GKT137831.
Results and discussions: Compared to the single treatment, Auranofin/BSO-cotreatment as well as Erastin/BSO-cotreatment acted in concert to trigger cell death and to reduce cell viability of HCC cells in a dose- and time-dependent manner. Furthermore, both cotreatments induce ROS production, lipid peroxidation and ferroptotic cell death, which could be inhibited by the use of Ferrostatin-1 (inhibitor of lipid peroxidation) and Liproxstatin-1 (specific inhibitor of ferroptosis). The broad-range caspase inhibitor zVAD.fmk failed to rescue cells from Auranofin/BSO- or Erastin/BSO-cotreatment induced cell death. No activation of caspases-3 could be seen in the proteome profiler apoptosis assay. Importantly, the selective lipoxygenase (LOX) inhibitor Baicalain and the pan-LOX inhibitor NDGA protect HCC cells from Auranofin/BSO- and Erastin/BSO-cotreatment stimulated lipid peroxidation, ROS generation and cell death, indication that the induction of ferroptosis may bypass apoptosis resistance of HCC cells. Mechanistic studies showed that Auranofin/BSO-cotreatment decreased TrxR-activity, led to Nrf2 accumulation and promoted the activation of HO-1. In contrast, NOX 1 and 4 were involved in Erastin/BSO-mediated cell death and the use of the NOX1/4-inhibitor GKT137831 rescued HCC cells from the Erastin/BSO-induced cell death.
Conclusion: By providing new insights into the molecular regulation of ROS and ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in HCC cells.
Study Design: Cross-sectional survey
Objective: To determine the influence of surgeons’ level of experience and subspeciality training on the reliability, reproducibility, and accuracy of sacral fracture classification using the AO Spine Sacral Injury Classification System.
Summary of Background Data: An ideal classification system is easily comprehensible and reliable amongst the diverse group of surgeons. A surgeons’ level of experience may have a significant effect on the reliability and accuracy of a classification system. Moreover, surgeons of different subspecialities may have various levels of comfort with imaging assessment of sacral injuries required for accurate diagnosis and classification.
Methods: High-resolution computerized tomography (CT) images from 26 cases were assessed by 172 investigators from a diverse array of surgical subspecialities (general orthopaedics, neurosurgery, orthopaedic spine, orthopaedic trauma) and experience (<5, 5-10, 11-20, >20 years). Validation assessments were performed via web conference using high-resolution images, as well as axial/sagittal/coronal CT scan sequences. Two assessments were performed by each investigator independently three weeks apart in randomized order. Reliability and reproducibility were calculated with cohen’s kappa coefficient (k) and gold standard classification agreement was determined for each fracture morphology and subtype and stratified by experience and subspeciality.
Results: Respondents achieved an overall k = 0.87 for morphology and k = 0.77 for subtype classification, representing excellent and substantial intraobserver reproducibility, respectively. Respondents from all four practice experience groups demonstrated excellent interobserver reliability when classifying overall morphology (k=0.842/0.850, Assessment 1/Assessment 2) and substantial interobserver reliability in overall subtype (k=0.719/0.751) in both assessments. General orthopaedists, neurosurgeons, and orthopaedic spine surgeons exhibited excellent interobserver reliability in overall morphology classification and substantial interobserver reliability in overall subtype classification. Surgeons in each experience category and subspecialty correctly classified fracture morphology in over 90% of cases and fracture subtype in over 80% of cases according to the gold standard. Correct overall classification of fracture morphology (Assessment 1: p= 0.024, Assessment 2: p=0.006) and subtype (p2<0.001) differed significantly with surgeons with >20 years of experience demonstrating increased difficulty correctly classifying all fracture subtypes overall in comparison to the other experience groups. Correct overall classification did not significantly differ by subspecialty.
Conclusions: Overall, the AO Spine Sacral Injury Classification System appears to be universally applicable among surgeons of various subspecialties and levels of experience with acceptable reliability, reproducibility, and accuracy.
Disclosures: author 1: none; author 2: consultant=Medtronic, Nuvasive, ISD, Asutra, Stryker, Bioventus, Zimmer, teledocs, Clinical Spine Surgery, AOSpine ; author 3: none; author 4: grants/research support=AOSpine, consultant=DPS, icotec; author 5: none; author 6: none; author 7: grants/research support=DPS; author 8: none; author 9: grants/research support=NIH, RTI, CSRS, royalties=Inion ; author 10: stock/shareholder=Advanced Spinal Intellectual Properties; Atlas Spine; Avaz Surgical; Bonovo Orthopaedics; Computational Biodynamics; Cytonics; Deep Health; Dimension Orthotics LLC; Electrocore; Flagship Surgical; FlowPharma; Globus; Innovative Surgical Design; Insight Therapeutics; Jushi; Nuvasive; Orthobullets; Paradigm Spine; Parvizi Surgical Innovation; Progressive Spinal Technologies; Replication Medica; Spine Medica; Spineology; Stout Medical; Vertiflex; ViewFi Health, royalties=Aesculap; Atlas Spine; Globus; Medtronics; SpineWave; Stryker Spine,other financial report=AO Spine