Interdisciplinary Therapeutic Approaches to Atypical and Malignant Meningiomas.

Meningiomas have the highest incidence among brain tumors. In contrast to benign tumors that constitute the majority of this tumor entity, the treatment of aggressive meningiomas (WHO Grade 2 and 3) is more challenging, requiring gross total removal of the tumor and the affected dura and adjuvant radiotherapy. Sometimes the location and/or the configuration of the tumor do not favor radical surgical resection without endangering the patient's clinical condition after surgery and pharmacological therapy has, until now, not been proven to be a reliable alternative. Discussion: In this narrative review, we discuss the current literature with respect to the management of meningiomas, discussing the importance of the grade of resection in the overall prognosis of the patient and in the planning of adjuvant therapy. Conclusions: According to the location and size of the tumor, radical resection should be taken into consideration. In patients with aggressive meningiomas, adjuvant radiotherapy should be performed after surgery. In cases of skull base meningiomas, a maximal, though safe, resection should take place before adjuvant therapy. An interdisciplinary approach is beneficial for patients with primary or recurrent meningioma.

Traumatic carotid cavernous fistulas. Rare and life threatening.

Purpose: Carotid-cavernous fistulas (CCFs) are often underdiagnosed or misdiagnosed. In polytraumatized patients, the focus is primarily on treating potentially life-threatening conditions such as increased intracranial pressure and hemorrhages. This case report aims to identify common diagnostic mistakes in rare pathologies. Objective: We present a case of a young female patient who was admitted to the emergency room after a motorbike accident. The patient's vital parameters were successfully stabilized, and she spent approximately four weeks in the ICU and neurosurgical ward. The patient exhibited limited communication, ophthalmoplegia, and a swollen, red left eye. After four weeks, the patient's parents initiated admission to our department due to the suspicious red swollen eye. Angiography revealed a complete rupture of the internal carotid artery (ICA) into the cavernous sinus, and occlusion of the ICA showed significant improvement in the eye edema and the patient's mental state. Two days later, the patient was able to communicate with complex sentences. Three months after the occlusion, the patient showed positive progress, posting dancing videos on TikTok. Conclusion and Importance: A carotid-cavernous fistula presenting with a red swollen eye can be misdiagnosed as retrobulbar hematoma or conjunctivitis. Failure to recognize and treat it promptly can lead to severe morbidity.

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.

Association of aneurysmatic subarachnoid hemorrhage rate with environmental changes or emotional bursts.

INTRODUCTION: In the present letter we share the results of an analysis of more than 140,000 non traumatic arterial subarachnoid hemorrhages whereas the majority of them is expected to be after aneurysm rupture, in which we investigate a possible correlation of climatic changes and emotional bursts as correlating factors for such a rupture. METHODS: We obtained the daily number of SAH from 2006 to 2018 for males and females from the German National statistics agency. The ICD codes provided to us were I60.1-I60.7, which are SAHs originating from intracranial arteries and excluding traumatic SAH and other not specified SAH. RESULTS: An increase of mean SAH per day could be seen in winter compared to summer and family events seemed to have a protective effect against aneurysmal SAH. Additionally 6.55 more women per day suffer an SAH compared to men. CONCLUSION: There is a statistical significant higher risk of aneurysm ruptures in winter and in females, and a statistical lower number in Mother's day.

Profile and Prognosis of Spontaneous Lobar Intracerebral Hemorrhage: Comparison of 6-month Survival with STICH II and the MISTIE III Lobar Hemorrhage Subset.

BACKGROUND: Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model. METHODS: Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier. RESULTS: One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set. CONCLUSIONS: In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

The rupture of an anterior communicating artery aneurysm does not associate with an asymmetry in the A1 or A2 arteries: a retrospective study of radiological features.

BACKGROUND AND OBJECTIVES: Although the formation and rupture risk of an anterior communicating artery (ACoA) aneurysm has been the subject of many studies, no previous study has primarily searched for the relationship of the parent and daughter vessels and the impact of their size/diameter ratio on the potential rupture risk of an AcoA aneurysm. The objective of this study is to explore this link and to further analyse the surrounding vasculature of the anterior communicating artery aneurysm. MATERIALS AND METHODS: We conducted a retrospective analysis of 434 patients: 284 patients with an ACoA aneurysm (121 unruptured and 162 ruptured) and 150 control patients without an ΑCoA aneurysm. Radiological angiography investigations were used to assess the diameter ratios of the parent vessels in addition to ACoA aneurysm morphology parameters. RESULTS: When comparing the ruptured to the unruptured cases, we observed no significant difference in the parent or daughter vessel diameter ratios. Younger patient age (OR 0.96, p = 0.00) and a higher aneurysm size ratio (OR 1.10, p = 0.02) were of prognostic importance concerning the rupture risk of the aneurysm. The A1 diameter ratio and the A2 diameter were not statistically significant (OR 1.00, p = 0.99, and OR 3.38, p = 0.25 respectively). CONCLUSIONS: In our study, we focused on asymmetry in the parent and daughter vessels as well as traditional ACoA aneurysm morphological characteristics. We were able to label younger patient age and a greater size ratio as independent prognostic factors for ACoA aneurysm rupture. We were unable to label parent and daughter vessel asymmetry as prognostic factors. To validate our findings, parent and daughter vessel asymmetry should be subjected to future prospective studies.

Evidence for Quantum Chemical Effects in Receptor-Ligand Binding Between Integrin and Collagen Fragments - A Computational Investigation With an Impact on Tissue Repair, Neurooncolgy and Glycobiology.

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin - NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin-carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co2+ ions seem to bind stronger to integrin than Mg2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological-glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.

Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms.

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Asymmetry of P1 and vertebral arteries is not related to basilar tip aneurysm development or rupture.

OBJECTIVE: Lately, morphological parameters of the surrounding vasculature aside from aneurysm size, specific for the aneurysm location, e.g., posterior cerebral artery angle for basilar artery tip aneurysms, could be identified to correlate with the risk of rupture. We examined further image-based morphological parameters of the aneurysm surrounding vasculature that could correlate with the growth or the risk of rupture of basilar artery tip aneurysms. METHODS: Data from 83 patients with basilar tip aneurysms (27 not ruptured; 56 ruptured) and 100 control patients were assessed (50 without aneurysms and 50 with aneurysms of the anterior circle of Willis). Anatomical parameters of the aneurysms were assessed and analyzed, as well as of the surrounding vasculature, namely the asymmetry of P1 and the vertebral arteries. RESULTS: Patients with basilar tip aneurysm showed no significant increase in P1 or vertebral artery asymmetry compared with the control patients or patients with aneurysms of the anterior circulation, neither was there a significant difference in asymmetry between cases with ruptured and unruptured aneurysms. Furthermore, we observed no significant correlations between P1 asymmetry and the aneurysm size or number of lobuli in the aneurysms. CONCLUSION: We observed no significant difference in aneurysm size, rupture, or lobulation associated with P1 or vertebral artery (surrounding vasculature) asymmetry. Therefore, the asymmetry of the surrounding vessels does not seem to be a promising morphological parameter for the evaluation of probability of rupture and growth in basilar tip aneurysms in future studies.

Rupture of intracranial aneurysms in patients with blunt head trauma: Review of the literature.

INTRODUCTION: With a prevalence of 1-5 %, intracranial aneurysms are common. However, only 20-50 % of these aneurysms will rupture during a person's lifetime. This often happens spontaneously without exogenous factors. In the present study we reviewed the literature concerning the relation between trauma and rupture of a pre-existing aneurysm. METHODS: All studies that reported a causal relation between trauma and rupture of a pre-existing aneurysm were included, irrespective of study design. They were limited though to those written in English or German. Excluded were studies with traumatic aneurysms, studies where the rupture of an aneurysm lead to trauma and studies with doubts about the order of events. RESULTS: Thirteen studies with twenty-two cases of ruptured aneurysm in context with trauma and two unpublished cases were included. Fourteen patients were involved in a fight, seven patients in a bike/motorbike/bus accident and three got hit on the head in a setting outside of interpersonal violence. The aneurysm was located in internal carotid artery in most cases (7/24). The clear majority of patients (19/24) did not survive. CONCLUSION: Arteries and aneurysms can rupture in context with head trauma although this is rarely the case. Patients after head trauma with typical blood pattern for aneurysmal SAH in the native CT scan should receive conventional angiography to exclude a vascular or aneurysmal rupture, even when CT-angiography is inconspicuous.

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recently, ketogenic diet (KD) supplementation has attracted great interest. Therefore, we established the cuprizone (CPZ)-induced demyelination mouse model to investigate the possible neuroprotective effect of KD on the hippocampus of mice. We found that KD significantly elevated the level of serum ß-hydroxybutyric acid, improved behavioral and motor abnormalities, and impaired the spatial learning and memory of CPZ-induced demyelination mice. Meanwhile, KD lessened the hippocampal demyelination by enhancing the expression of mature oligodendrocytes (OLs), which was revealed by the elevated expression of MBP and CNPase, as well as the luxol fast blue-staining intensity. Furthermore, KD inhibits the activation of microglia (especially M1-like microglia) and reactive astrocytes. Interestingly, KD attenuated the CPZ-induced oxidative stress by decreasing the malondialdehyde (MDA) content and restoring the glutathione (GSH) levels. In addition, the double immunofluorescence staining revealed that KD enhanced the expression of SIRT1 in astrocytes, microglia, and mature oligodendrocytes. Concomitantly, Western blot demonstrated that KD increased the expression of SIRT1, phosphorylated-AKT, mTOR, and PPAR-γ. In conclusion, KD exerted a neuroprotective effect on CPZ-induced demyelination mice, and this activity was associated with the modulation of the SIRT1/PPAR-γ and SIRT1/P-Akt/mTOR pathways.

Amelioration of clinical course and demyelination in the cuprizone mouse model in relation to ketogenic diet.

Ketogenic diet (KD) is defined as a high-fat, low-carbohydrate diet with appropriate amounts of protein, which has broad neuroprotective effects. However, the mechanisms of ameliorating the demyelination and of the neuroprotective effects of KD have not yet been completely elucidated. Therefore, the present study investigated the protection mechanism of KD treatment in the cuprizone (bis-cyclohexanone oxalydihydrazone, CPZ)-induced demyelination mice model, with special emphasis on neuroinflammation. After the KD treatment, an increased ketone body level in the blood of mice was detected, and a significant increase in the distance traveled within the central area was observed in the open field test, which reflected the increased exploration and decreased anxiety of mice that received CPZ. The results of Luxol fast blue and myelin basic protein (MBP) immunohistochemistry staining for the evaluation of the myelin content within the corpus callosum revealed a noticeable increase in the number of myelinated fibers and myelin score after KD administration in these animals. Concomitant, the protein expressions of glial fibrillary acidic protein (GFAP, an astrocyte marker), ionized calcium-binding adaptor molecule 1 (Iba-1, a microglial marker), CD68 (an activated microglia marker) and CD16/32 (a M1 microglial marker) were down-regulated, while the expression of oligodendrocyte lineage transcription factor 2 (OLIG2, an oligodendrocyte precursor cells marker) was up-regulated by the KD treatment. In addition, the KD treatment not only reduced the level of the C-X-C motif chemokine 10 (CXCL10), which is correlated to the recruitment of activated microglia, but also inhibited the production of proinflammatory cytokines, including interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), which are closely correlated to the M1 phenotype microglia. It is noteworthy, that the expression levels of histone deacetylase 3 (HADC3) and nod-like receptor pyrin domain containing 3 (NLRP3) significantly decreased after KD administration. In conclusion, these data demonstrate that KD decreased the reactive astrocytes and activated the microglia in the corpus callosum, and that KD inhibited the HADC3 and NLRP3 inflammasome signaling pathway in CPZ-treated mice. This suggests that the inhibition of the HADC3 and NLRP3 signaling pathway may be a novel mechanism by which KD exerts its protective actions for the treatment of demyelinating diseases.

Comparison of Different Hybrid Techniques for the Treatment of Multilevel Cervical Degenerative Disc Disease-Analysis of Prospectively Collected Clinical, Radiologic, and Psychological Parameters.

OBJECTIVE: Conventional surgical treatment of multilevel cervical disc disease is based on anterior cervical discectomy and fusion (ACDF). However, fusion alters the biomechanics of the spine, potentially resulting in accelerated adjacent segment degeneration. To improve clinical outcomes, hybrid surgery, combining cervical disc arthroplasty with fusion, has been developed. Cervical total disc replacement (TDR) has been shown to keep the motion of adjacent segment, and a dynamic cervical implant (DCI) was shown to provide cervical dynamic stability under nonfusion. However, curative and unwanted side effects of the new therapy options TDR and DCI for treating multilevel cervical degenerative disc disease are still unknown. PATIENTS AND METHODS: This analysis is based on 88 patients treated for multilevel cervical degenerative disc disease with ACDF only (56 patients), DCI hybrid (17 patients), and TDR hybrid (15 patients) between June 2008 and November 2015. The mean follow-up was 19.5 months. Visual analog scale (VAS), Neck Disability Index, and quality-of-life measurements were assessed via questionnaires. RESULTS: The VAS scores decreased significantly in all 3 groups (P < 0.001), but the TDR group showed the greatest reduction in VAS score compared with ACDF and DCI (both P < 0.05). The overall range of motion (ROM) and the segmental ROM at the treated levels showed significant decreases in all 3 groups. Although there was no difference in the overall ROM at final follow-up among the operatively treated groups, the ROM of the treated segment was lowest in the ACDF group (P = 0.002). In terms of heterotopic ossification, patients undergoing TDR showed the best prognosis. CONCLUSIONS: These results indicate that both TDR hybrid and DCI hybrid are effective and safe procedures for the treatment of multilevel degenerative disc disease. However, there is no definitive evidence that DCI or TDR arthroplasty lead to better intermediate-term results than ACDF over an average observation time of 19.5 months.

Association between aneurysm hemodynamics and wall enhancement on 3D vessel wall MRI.

OBJECTIVE: Aneurysm wall enhancement (AWE) on 3D vessel wall MRI (VWMRI) has been suggested as an imaging biomarker for intracranial aneurysms (IAs) at higher risk of rupture. While computational fluid dynamics (CFD) studies have been used to investigate the association between hemodynamic forces and rupture status of IAs, the role of hemodynamic forces in unruptured IAs with AWE is poorly understood. The authors investigated the role and implications of abnormal hemodynamics related to aneurysm pathophysiology in patients with AWE in unruptured IAs. METHODS: Twenty-five patients who had undergone digital subtraction angiography (DSA) and VWMRI studies from September 2016 to September 2017 were included, resulting in 22 patients with 25 IAs, 9 with and 16 without AWE. High-resolution CFD models of hemodynamics were created from DSA images. Univariate and multivariate analyses were performed to investigate the association between AWE and conventional morphological and hemodynamic parameters. Normalized MRI signal intensity was quantified and quantitatively associated with wall shear stresses (WSSs) for the entire aneurysm sac, and in regions of low, intermediate, and high WSS. RESULTS: The AWE group had lower WSS (p < 0.01) and sac-averaged velocity (p < 0.01) and larger aneurysm size (p < 0.001) and size ratio (p = 0.0251) than the non-AWE group. From multivariate analysis of both hemodynamic and morphological factors, only low WSS was found to be independently associated with AWE. Sac-averaged normalized MRI signal intensity correlated with WSS and was significantly different in regions of low WSS compared to regions of intermediate (p = 0.018) and high (p < 0.001) WSS. CONCLUSIONS: The presence of AWE was associated with morphological and hemodynamic factors related to rupture risk. Low WSS was found to be an independent predictor of AWE. Our findings support the hypothesis that low WSS in IAs with AWE may indicate a growth and remodeling process that may predispose such aneurysms to rupture; however, a causality between the two cannot be established.

Transcranial Doppler Ultrasound, Perfusion Computerized Tomography, and Cerebral Angiography Identify Different Pathological Entities and Supplement Each Other in the Diagnosis of Delayed Cerebral Ischemia.

INTRODUCTION: There is still controversial discussion of the value of transcranial Doppler (TCD) in predicting vasospasms in patients with aneurysmal SAH (aSAH). A newer method of predicting a delayed ischemic deficit (DCI) is CT perfusion (CTP), although it is not quite understood which kind of perfusion deficit is detected by this method since it seems to also identifying microcirculatory disturbances. We compared the TCD and CTP values with angiography and evaluated TCD and CTP changes before and after patients received intra-arterial spasmolytic therapy. MATERIAL AND METHODS: Retrospective analysis of TCD, CTP, and angiographies of N = 77 patients treated from 2013 to 2016. In 38 patients intra-arterial spasmolysis had been performed, and in these cases TCD and CTP data were compared before and after lysis. Thirty-nine patients had a pathological CTP but no angiographically seen vasospasm. RESULTS: There was no correlation between the known thresholds of mean transit time (MTT) in CTP and vasospasm or with mean velocities in TCD and vasospasm. After spasmolysis in patients with vasospasms, only the MTT showed significant improvement, whereas TCD velocities and Lindegaard index remained unaffected. CONCLUSION: TCD and CTP seem to identify different pathological entities of DCI and should be used supplementary in order to identify as many patients as possible with vasospasms after aSAH.

Meteorological factors for subarachnoid hemorrhage in the greater Düsseldorf area revisited: a machine learning approach to predict the probability of admission of patients with subarachnoid hemorrhage.

BACKGROUND: Reported data regarding the relation between the incidence of spontaneous subarachnoid hemorrhage (SAH) and weather conditions are conflicting and do so far not allow prognostic models. METHODS: Admissions for spontaneous SAH (ICD I60.*) 2009-2018 were retrieved form our hospital data base. Historical meteorological data for the nearest meteorological station, Düsseldorf Airport, was retrieved from the archive of the Deutsche Wetterdienst (DWD). Airport is in the center of our catchment area with a diameter of approximately 100 km. Pearson correlation matrix between mean daily meteorological variables and the daily admissions of one or more patients with subarachnoid hemorrhage was calculated and further analysis was done using deep learning algorithms. RESULTS: For the 10-year period from January 1, 2009 until December 31, 2018, a total of 1569 patients with SAH were admitted. No SAH was admitted on 2400 days (65.7%), 1 SAH on 979 days (26.7%), 2 cases on 233 days (6.4%), 3 SAH on 37 days (1.0%), 4 in 2 days (0.05%), and 5 cases on 1 day (0.03%). Pearson correlation matrix suggested a weak positive correlation of admissions for SAH with precipitation on the previous day and weak inverse relations with the actual mean daily temperature and the temperature change from the previous days, and weak inverse correlations with barometric pressure on the index day and the day before. Clustering with admission of multiple SAH on a given day followed a Poisson distribution and was therefore coincidental. The deep learning algorithms achieved an area under curve (AUC) score of approximately 52%. The small difference from 50% appears to reflect the size of the meteorological impact. CONCLUSION: Although in our data set a weak correlation of the probability to admit one or more cases of SAH with meteorological conditions was present during the analyzed time period, no helpful prognostic model could be deduced with current state machine learning methods. The meteorological influence on the admission of SAH appeared to be in the range of only a few percent compared with random or unknown factors.

The Sialic Acid-Dependent Nematocyst Discharge Process in Relation to Its Physical-Chemical Properties Is A Role Model for Nanomedical Diagnostic and Therapeutic Tools.

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices.

Nanomedical Relevance of the Intermolecular Interaction Dynamics-Examples from Lysozymes and Insulins.

Insulin and lysozyme share the common features of being prone to aggregate and having biomedical importance. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation.