The structural dynamics of the interactions between defensins or lysozymes and various saccharide chains that are covalently linked to lipids or proteins were analyzed in relation to the sub-molecular architecture of the carbohydrate binding sites of lectins. Using tissue materials from rare and endangered domestic animals as well as from dogs it was possible to compare these results with data obtained from a human glioblastoma tissue. The binding mechanisms were analyzed on a cellular and a sub-molecular size level using biophysical techniques (e.g. NMR, AFM, MS) which are supported by molecular modeling tools. This leads to characteristic structural patterns being helpful to understand glyco-biochemical pathways in which galectins, defensins or lysozymes are involved. Carbohydrate chains have a distinct impact on cell differentiation, cell migration and immunological processes. The absence or the presence of sialic acids and the conformational dynamics in glycans are often correlated with zoonoses such as influenza- and coronavirus-infections. Receptor-sensitive glycomimetics could be a solution. The new findings concerning the function of galectin-3 in the nucleus in relation to differentiation processes can be understood when the binding specificity of neuroleptic molecules as well as the interactions between proteins and nucleic acids are describable on a sub-molecular size level.

BACKGROUND A conjoined nerve root is a rare condition with numerous variants. The diagnosis can be challenging, especially when the condition coexists with other pathologies. In cases where a disc herniation affects these nerve roots, any miscalculation or inexperience of the surgeon can irreversibly injure them. Numerous reports have described the dismay of surgeons during discectomy in patients with a conjoined nerve root. Many surgical techniques have been suggested but without the good results following typical discectomies. OBSERVATIONS In this case report, the authors describe a 53-year-old female patient who presented with radicular pain due to a large disc herniation at the level of L5–S1 on the left side. Intraoperatively, the authors identified a conjoined nerve root, forcing them to employ a novel approach with very good results. LESSONS In some cases, the only possible way to remove a disc herniation is the contralateral approach, as described in this report. https://thejns.org/doi/10.3171/CASE24301

BackgroundIntracranial hemorrhage due to a ruptured aneurysm is one of the most serious neurosurgical emergencies. The patient mostly presents with severe headaches and neurological deterioration. A rapid diagnosis and an interdisciplinary approach play a major role in the fate of these patients. The treatment can vary from endovascular to surgical and must be carefully and individually planned. Neurovascular expertise and an interdisciplinary approach are of vital importance and obligatory for the best possible outcome.MethodsIn this narrative review, we scrutinize the current literature and discuss the actual data and guidelines in order to emphasize the importance of the interdisciplinary expertise and approach in patients with ruptured intracranial aneurysm.ResultsThe current approach to patients with ruptured aneurysm is inhomogeneous and often ineffective due to internal disputes between different disciplines. Although there is plenty of literature and hard evidence to “show the way,” many still choose to base their decisions on personal experience or opinion.ConclusionsEvery ruptured brain aneurysm should be approached in an interdisciplinary manor and treated according to the current evidence and guidelines.

Background and Aim: Vascular neurosurgical expertise is highly in demand in African countries.To create a sustainable environment for treating the patients, local neurosurgeons have tobe trained and be able to operate under the local circumstances, and equipment and on-sitefellowship programs are needed. We have reported the results of the first completed on-sitecerebrovascular fellowship in Cameroon and to our knowledge, in central Africa. Methods and Materials/Patients: Forty-two cerebrovascular cases (38 aneurysms) wereoperated by the cerebrovascular expert and his fellows microsurgically from April 2021to November 2022. The expert traveled to Cameroon four times. Online conferences andtheoretical courses were organized.Results: The overall morbidity rate was 10.5% with a long-term functional morbidity rate of5.2%. The intraoperative mortality rate was 0 and the 30-day mortality rate was 2.7%. Aftercompletion of the program, the fellow’s surgical skills concerning operating time, intraoperativecomplications, and mortality improved significantly. Conclusion: The on-site cerebrovascular fellowship program in sub-Saharan countries is feasibleand provides the patient with high-quality surgery with outcomes similar to Western countries.The caseload in two years is sufficient enough to provide excellent training to the local fellows.There is a high demand for further fellowships, like the one we described. It is important for thetrainer to stay dedicated to the program until the completion of it. To provide the fellows with ahigh caseload, only two fellows should be trained, which are participating in every case

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.

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.

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.

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.

BACKGROUND: The hemorrhage risk of unruptured and untreated cerebral arteriovenous malformations (AVMs) has been shown to be higher for female patients than male patients in their child bearing ages. Although it has been neurosurgical practice to advise female patients in their childbearing ages to postpone pregnancy until proven AVM obliteration, there is no literature consensus regarding this potential hemorrhage risk increase.OBJECTIVE: To accurately quantify the risk increase for AVM hemorrhage during pregnancy.METHODS: This study is based on data from previous publications, consisting of known age at the first AVM hemorrhage in 3425 patients. The risk increase during pregnancy could be calculated from the difference in age distribution for the first AVM hemorrhage between male patients and female patients, taking the average pregnancy time per female into account. A comparison was also made with data for all hospital discharges (13 751) in Germany 2008 to 2018 with the diagnosis brain AVM.RESULTS: The average pregnancy and puerperium time was 1.54 years per female in the patient population, which was used to determine the annual AVM hemorrhage risk during pregnancy to be around 9%. The increased risk during pregnancy was further evidenced by analysis of a subgroup of 105 female patients, for which pregnancy status at the time of hemorrhage was known.CONCLUSION: The quantified annual risk for AVM hemorrhage during pregnancy is about 3 times higher than that of male patients at corresponding age. This provides an important basis for advising female patients with patent AVMs about the increased risk for hemorrhage that a pregnancy would entail.

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 Dusseldorf 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 42mL in the conservative cohort, compared with 38 and 36mL in the STICH II trial, and 46 and 47mL 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 bioactivities of collagen-hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study 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 were 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. Nutraceuticals data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameters were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen-hydrolysates or sulfated glucosamines. 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.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, and results in the degradation of the myelin sheath. The study investigates the neuroprotective effects of krill oil (KO) on the cuprizone (CPZ)-induced demyelination of the MS mouse model. The results suggested that KO treatment can improve the motor abnormalities and cognitive deficit of MS mice, as demonstrated by the open field, rotarod and Morris water maze tests. Meanwhile, the CPZ-induced demyelination of mice was alleviated after KO treatment and KO can attenuate the CPZ-induced oxidative stress. Furthermore, KO reduces M1 microglia activation and promotes M2 microglia polarization in the corpus callosum. Moreover, our studies indicated that KO diminished histone deacetylase (HDAC)3, phosphorylated signal transducer and activator of transcription (STAT) 3 and NF-κB p65 protein expression levels. In conclusion, KO exerts its neuroprotective actions in mice with CPZ-induced demyelination possibly by modulating the HDAC3/STAT3/NF-κB signaling pathways.

Violent content seems prevalent in mass media and popular culture; however, the effects of these representations of aggressive behaviour and violence in real life should not be underestimated. Violent scenes are getting ever more brutal and are sometimes displayed in minute detail. In particular, assault-related traumatic brain injury (TBI) is notably prevalent in many films and TV series, displaying typical injury patterns of severe TBI that are usually lethal in real life. Notwithstanding, in these fictional representations the victims often recover in a short time without many physical or psychological consequences.

The collagen-integrin interactions are mediated by the doubly charged Mg 2+ 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 Co 2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co 2+ 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 Co 2+ 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 Co 2+ ions seem to bind stronger to integrin than Mg 2+ 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.

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.

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.

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 β-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.