Understanding the Importance of Blood-Brain Barrier Alterations in Brain Arteriovenous Malformations and Implications for Treatment: A Dynamic Contrast-Enhanced-MRI-Based Prospective Study.

BACKGROUND AND OBJECTIVES: The major clinical implication of brain arteriovenous malformations (bAVMs) is spontaneous intracranial hemorrhage. There is a growing body of experimental evidence proving that inflammation and blood-brain barrier (BBB) dysfunction are involved in both the clinical course of the disease and the risk of bleeding. However, how bAVM treatment affects perilesional BBB disturbances is yet unclear. METHODS: We assessed the permeability changes of the BBB using dynamic contrast-enhanced MRI (DCE-MRI) in a series of bAVMs (n = 35), before and at a mean of 5 (±2) days after treatment. A set of cerebral cavernous malformations (CCMs) (n = 16) was used as a control group for the assessment of the surgical-related collateral changes. The extended Tofts pharmacokinetic model was used to extract permeability (Ktrans) values in the lesional, perilesional, and normal brain tissues. RESULTS: In patients with bAVM, the permeability of BBB was higher in the perilesional of bAVM tissue compared with the rest of the brain parenchyma (mean Ktrans 0.145 ± 0.104 vs 0.084 ± 0.035, P = .004). Meanwhile, no significant changes were seen in the perilesional brain of CCM cases (mean Ktrans 0.055 ± 0.056 vs 0.061 ± 0.026, P = .96). A significant decrease in BBB permeability was evident in the perilesional area of bAVM after surgical resection (mean Ktrans 0.145 ± 0.104 vs 0.096 ± 0.059, P = .037). This benefit in BBB permeability reduction after surgery seemed to surpass the relative increase in permeability inherent to the surgical manipulation. CONCLUSION: In contrast to CCMs, BBB permeability in patients with bAVM is increased in the perilesional parenchyma, as assessed using DCE-MRI. However, bAVM surgical resection seems to reduce BBB permeability in the perilesional tissue. No evidence of the so-called breakthrough phenomenon was detected in our series. DCE-MRI could become a valuable tool to follow the longitudinal course of BBB damage throughout the natural history and clinical course of bAVMs.

A Scalable Synthesis of Ag Nanoporous Film As an Efficient SERS-Substrates for Sensitive Detection of Nanoplastics.

Nanoplastics pollution has led to a severe environmental crisis because of a large accumulation of these smaller nanoplastic particles in the aquatic environment and atmospheric conditions. Detection of these nanoplastics is crucial for food safety monitoring and human health. In this work, we report a simple and eco-friendly method to prepare a SERS-substrate-based nanoporous Ag nanoparticle (NP) film through vacuum thermal evaporation onto a vacuum-compatible deep eutectic solvent (DES) coated growth substrate for quantitative detection of nanoplastics in environmental samples. The nanoporous Ag NP films with controlled pores were achieved by the soft-templating role of DESs over the growth substrate, which enabled the self-assembly of deposited Ag NPs over the surface of DES. The optimized nanoporous Ag substrate provides high sensitivity in the detection of analyte molecules, crystal violet (CV), and rhodamine 6G (R6G) with a limit of detection (LOD) up to 1.5 × 10-13 M, excellent signal reproducibility, and storage stability. Moreover, we analyzed quantitative SERS detection of polyethene terephthalate (PET, size of 200 nm) and polystyrene (PS, size of 100 nm) nanoplastics with an LOD of 0.38 and 0.98 µg/mL, respectively. In addition, the SERS substrate efficiently detects PET and PS nanoplastics in real environmental samples, such as tap water, lake water, and diluted milk. The enhanced SERS sensing ability of the proposed nanoporous Ag NP film substrate holds immense potential for the sensitive detection of various nanoplastic contaminants present in environmental water.

The HSACat Project: A Prospective Multicenter Observational Study of Spontaneous Subarachnoid Hemorrhage in Catalonia, Spain.

BACKGROUND: Incidence, clinical course, and fatality of spontaneous subarachnoid hemorrhage (SAH) are evolving, with prevalence of risk factors diminishing, implementation of early detection programs and strategies for priority aneurysm exclusion, technical refinement with less invasive procedures, and improvements in neurocritical care. Modern epidemiological and prognostic data are lacking, especially in southern European and Mediterranean populations. METHODS: A prospective multicenter observational study on SAH was held in Catalonia, Northeast Spain, from 2020 to 2022 (HSACat project). All public tertiary hospitals participated in a common registry. Primary end points were functional outcomes (modified Rankin Scale) and mortality at 12 months. Secondary aims included epidemiological data, passage of patients between referral and tertiary hospitals, diagnostic and treatment delays, and in-hospital complications. RESULTS: Of 550 SAH cases reported in Catalonia (2020-2022), a complete registry for analysis was available for 474. Death rate was 20.6% during hospital admission and 26.9% at 1 year. Good functional outcome (modified Rankin Scale score 0-2) was observed in 63.4%, 70.1%, and 76.0% at 3, 6, and 12 months. Age at presentation was younger in men, patients who smoked, and patients with hypertension (P < 0.05). The female-to-male ratio was 3:2 except in the nonaneurysmal group. Time from onset to tertiary hospital admission was longer in rural than in metropolitan areas (7.0 hours vs. 4.7 hours, P < 0.01). Aneurysm occlusion in the first 72 hours was achieved in 83.3%; mainly endovascularly (77.5%) followed by microsurgically (19.3%). CONCLUSIONS: Even when most patients received timely aneurysm treatment, case fatality rates were considerably high. Data provided by the HSACat project may have public health effects and be used to guide prevention programs and screening strategies.

Microsurgical and endovascular treatment of large and giant aneurysms of the anterior circulation: A systematic review.

Introduction: Large and Giant intracranial aneurysms (LGIAs) have become the paradigm for which endovascular techniques do not provide satisfactory results. Yet, microsurgery is followed by non-negligible rates of morbimortality. This scenario may have changed since the introduction of flow-diversion devices. Research question: Contemporary and standardised revision on microsurgical and endovascular results, with emphasis on anterior circulation LGIAs. Materials and methods: A systematic literature search was conducted in two databases (PubMed and Embase) on treatment outcomes of LGIAs of the anterior circulation, after the introduction of flow-diverters 2008/01/01, till 2023/05/20. Small case series (<5 cases), series including >15% of posterior circulation aneurysms, and studies not reporting clinical and/or angiographic outcomes were excluded. Results: 44 relevant studies (observational cohorts) were identified, including 2923 LGIAs predominantly from anterior circulation. Mean follow-up 22 (±20) months. 1494 (51%) LGIAs were treated endovascularly and 1427 (49%) microsurgically. According to the random effects model, pooled rates of favourable clinical outcomes were 85.8% (CI 95% 82.6-88.4), complete occlusion 69.4% (CI 95% 63.7-7.46), complications 19.6% (CI 95%16-23.9) and mortality 5.6% (CI 95% 4.4-7.1). Focusing on type of treatment, occlusion rates are higher with microsurgical (842/993, 85% vs 874/1,299, 67%), although good outcomes are slightly more frequent with endovascular (1045/1,135, 92% vs 1120/1,294, 87%). Discussion and conclusions: According to contemporary data about occlusion rates, functional outcomes, and complications, primary or secondary treatment of LGIAs of the anterior circulation seems justified. Microsurgical occlusion rates are higher in LGIAs. An expert consensus on reporting complications and management strategies is warranted.

Caffeine, Alcohol, and Drug Use as Work Adjuncts Among Neurosurgeons. Prevalence, Contributing Factors, and Proposed Strategies.

BACKGROUND: Neurosurgeons may resort to caffeine, alcohol, and various drugs to maintain peak performance as they grapple with work demands and escalated stress. The prevalence of this controversial strategy remains largely unexplored. METHODS: An anonymous survey of 23 questions formulated by our research group was distributed through personal contacts and neurosurgical societies. Inquiries revolved around the use of medications and other substances for job-related reasons. Data were analyzed via regression and descriptive statistics in python. RESULTS: In total, 215 neurosurgeons (43 residents) were included, with 213 disclosing their gender (94 females). Out of all, 9.3% were <30, 38.1% were 30-39, 44.6% were 40-59, and 7.9% were >60 years old. Most (70.7%) practiced in Europe, 18.6% in Asia, 6.5% in North and South America, and the rest in Africa or Australia. While 132 participants stated they consume caffeine to manage challenging schedules, drugs for cognitive and mood enhancement were utilized by 18 and 35 respectively. Alcohol was employed for stress relief by 28 with 4 reporting as heavy drinkers. Drugs posed a solution to sleep disorders for 82, and helped 8 others in strengthening their hand dexterity. Notably, 12 of those claiming drug use initiated it in medical school. Exercise, self-care activities, and relational support were the main alternatives sought. Ultimately, most responders recommended extending mental health assistance and raising awareness about drug use. CONCLUSIONS: Reflecting on our results on job-associated drug use by neurosurgeons, we propose the judicious use of pharmacological or nonpharmacological adjuncts, alongside the prioritization of neurosurgeons' well-being.

Brain metabolism response to intrahospital transfers in neurocritical ill patients and the impact of microdialysis probe location.

Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 27 patients with severe brain injury (10 traumatic brain injury and 17 subarachnoid hemorrhage patients) were included, with a total of 67 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 h pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Our results suggest that brain metabolism is altered after an IHT of neurocritical ill patients particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.

Ionic Liquid-Assisted Thermal Evaporation of Bimetallic Ag-Au Nanoparticle Films as a Highly Reproducible SERS Substrate for Sensitive Nanoplastic Detection in Complex Environments.

Nanoplastic particles are emerging as an important class of environmental pollutants in the atmosphere that have adverse effects on our ecosystems and human health. While many methods have been developed to quantitatively detect nanoplastics; however, sensitive detection at low concentrations in a complex environment remains elusive. Herein, we demonstrate a greener method to fabricate a surface-enhanced Raman spectroscopy (SERS) substrate consisting of self-assembled plasmonic Ag-Au bimetallic nanoparticle (NP) films for quantitative SERS detection of nanoplastics in complex media. The self-assembly of Ag-Au bimetallic NPs was achieved through thermal evaporation onto a vapor-phase compatible ionic liquid based on deep eutectic solvent over the growth substrate. The finite-difference time-domain simulation revealed that the localized field enhancement is strong in the gaps, which generate uniform SERS "hotspots" in the obtained substrate. Benefiting from highly accessible SERS "hotspots" at the gaps, the SERS substrate exhibits excellent sensitivity for detecting crystal violet with a limit of detection (LOD) as low as 10-14 M and excellent reproducibility (RSD of 5.8%). The SERS substrate is capable of detecting PET nanoplastics with LOD as low as 1 µg/mL and about 100 µg/mL in real samples such as tap water, lake water, diluted milk, and wine. Moreover, we also validated the feasibility of the designed SERS substrate for the practical detection of PET nanoplastics collected from commercial drinking water bottles, and it showed great potential applications for sensitive detection in actual environments.

Parenthood and neurosurgery in Europe, a white paper from the European association of neurosurgical societies' diversity in neurosurgery committee, part II - practice with children.

Introduction: In the first part of this White Paper, the European Association of Neurosurgical Societies (EANS) Diversity in Neurosurgery Committee (DC) addressed the obstacles faced by neurosurgeons when planning to have a family and practice during pregnancy, attempting to enumerate potential, easily implementable solutions for departments to be more family-friendly and retain as well as foster talent of parent-neurosurgeons, regardless of their gender identity and/or sexual orientation. Attrition avoidance amongst parent-neurosurgeons is at the heart of these papers. Research question: In this second part, we address the obstacles posed by practice with children and measures to mitigate attrition rates among parent-neurosurgeons. For the methodology employed to compose this White Paper, please refer to Supplementary Electronic Materials (SEM) 1. Materials and methods: For composing these white papers, the European Association of Neurosurgical Societies (EANS)'s Diversity Committee (DC) recruited neurosurgeon volunteers from all member countries, including parents, aspiring parents, and individuals without any desire to have a family to create a diverse and representative working group (WG). Results: In spite of the prevailing heterogeneity in policies across the continent, common difficulties can be identified for both mothers and fathers considering the utilization of parental leave. Discussion and conclusion: Reconciliation of family and a neurosurgical career is challenging, especially for single parents. However, institutional support in form of childcare facilities and/or providers, guaranteed lactation breaks and rooms, flexible schedule models including telemedicine, and clear communication of policies can improve working conditions for parent-neurosurgeons, avoid their attrition, and foster family-friendly work environments.

European Medical Students' Views on Neurosurgery, with Emphasis on South-East Europe (Albania, Greece, Serbia, and Turkey).

BACKGROUND: Neurosurgery, an intricate and dynamic surgical specialty, faces challenges in attracting medical graduates. Despite its potential appeal, a decreasing trend in medical students opting for surgical specialties, including neurosurgery, is noted. This study aims to assess European medical students' perceptions of neurosurgery, focusing on South-East Europe, and address concerns about the declining interest in this field. METHODS: A comprehensive digital survey, comprising 33 questions, was distributed to 1115 medical students across 17 European countries. The survey, conducted over 9 months, gathered responses through European neurosurgical societies, the European Association of Neurosurgical Societies (EANS), and university channels. Statistical analysis utilized IBM Statistical Package for the Social Sciences, presenting data through counts, proportions, and χ2 tests. RESULTS: The study reveals that, over the survey period, 834 medical students completed the questionnaire, with a predominant representation from South-East Europe. While 43.2% of participants were considering a surgical career, neurosurgery emerged as the most preferred specialty (26.37%). Despite this interest, 80.2% reported insufficient knowledge about pursuing a neurosurgical career, with limited exposure during medical education. Concerns about work-life balance, heavy workload, and hierarchical structures were prominent among respondents. CONCLUSIONS: The findings underscore the need for targeted interventions to address concerns influencing medical students' decisions regarding neurosurgery. Improving neurosurgical education, dispelling misconceptions, and creating a supportive work environment are crucial steps to attract and retain diverse talented individuals in neurosurgery. These efforts will be vital in narrowing the gap between the demand for neurosurgeons and the number of medical graduates entering the field, ensuring a sustainable future for this essential surgical specialty.

Parenthood and neurosurgery in Europe a white paper from the European Association of Neurosurgical Societies' Diversity in Neurosurgery Committee Part I - Family Planning and Practice during Pregnancy.

Introduction: Family and work have immensely changed and become intertwined over the past half century for both men and women. Additionally, alongside to traditional family structures prevalent, other forms of families such as single parents, LGBTQ + parents, and bonus families are becoming more common. Previous studies have shown that surgical trainees regularly leave residency when considering becoming a parent due to the negative stigma associated with pregnancy during training, dissatisfaction with parental leave options, inadequate lactation and childcare support, and desire for greater mentorship on work-life integration. Indeed, parenthood is one of the factors contributing to attrition in surgical specialities, neurosurgery not being an exception. Research question: The Diversity in Neurosurgery Committee (DC) of the European Association of Neurosurgical Societies (EANS) recognizes the challenges individuals face in parenthood with neurosurgery and wishes to address them in this white paper. Materials and methods: In the following sections, the authors will focus on the issues pertaining to family planning and neurosurgical practice during pregnancy in itemized fashion based on an exhaustive literature search and will make recommendations to address the matters raised. Results: Potential solutions would be to further improve the work-family time ration as well as improving working conditions in the hospital. Discussion and conclusion: While many obstacles have been quoted in the literature pertaining to parenthood in medicine, and in neurosurgery specifically, initiatives can and should be undertaken to ensure not only retention of colleagues, but also to increase productivity and job satisfaction of those seeking to combine neurosurgery and a family life, regardless of their sexual identity and orientation.

Glucose oxidase virus-based nanoreactors for smart breast cancer therapy.

BACKGROUND: Breast cancer is the most common malignant tumor disease and the leading cause of female mortality. The evolution of nanomaterials science opens the opportunity to improve traditional cancer therapies, enhancing therapy efficiency and reducing side effects. METHODS AND MAJOR RESULTS: Herein, protein cages conceived as enzymatic nanoreactors were designed and produced by using virus-like nanoparticles (VLPs) from Brome mosaic virus (BMV) and containing the catalytic activity of glucose oxidase (GOx) enzyme. The GOx enzyme was encapsulated into the BMV capsid (VLP-GOx), and the resulting enzymatic nanoreactors were coated with human serum albumin (VLP-GOx@HSA) for breast tumor cell targeting. The effect of the synthesized GOx nanoreactors on breast tumor cell lines was studied in vitro. Both nanoreactor preparations VLP-GOx and VLP-GOx@HSA showed to be highly cytotoxic for breast tumor cell cultures. Cytotoxicity for human embryonic kidney cells was also found. The monitoring of nanoreactor treatment on triple-negative breast cancer cells showed an evident production of oxygen by the catalase antioxidant enzyme induced by the high production of hydrogen peroxide from GOx activity. CONCLUSIONS AND IMPLICATIONS: The nanoreactors containing GOx activity are entirely suitable for cytotoxicity generation in tumor cells. The HSA functionalization of the VLP-GOx nanoreactors, a strategy designed for selective cancer targeting, showed no improvement in the cytotoxic effect. The GOx containing enzymatic nanoreactors seems to be an interesting alternative to improve the current cancer therapy. In vivo studies are ongoing to reinforce the effectiveness of this treatment strategy.

Funnel Shaped Anterior Communicating Artery Fenestration Mistaken for an Aneurysm: A Cautionary Tale.

This report portrays a case of a funnel shaped anterior communicating artery (ACoA) fenestration which was mistaken as a small A1 aneurysm in a subarachnoid hemorrhage case. Although tridimensional rotational digital subtraction angiography improves aneurysm diagnosis specially at the ACoA complex, current spatial resolution might leave behind a considerable percentage of ACoA fenestrations. This may lead to diagnostic errors and unnecessary treatments risking iatrogenic complications. Luckily for our patient, a concomitant aneurysm warranted clipping and subsequent surgical exploration of the ACoA complex revealed the pitfall, thus preventing further action. Interestingly, another group of authors who reported similar misdiagnosis with ACoA aneurysms were able to prevent a third error, thanks to the experience acquired with 2 prior cases. Therefore, this clinical image aims to raise wider awareness of the need for very cautious consideration of imaging depicting small and/or atypical aneurysms in the ACoA complex.

A Comparative Study of Cancer Cells Susceptibility to Silver Nanoparticles Produced by Electron Beam.

INTRODUCTION: Silver nanoparticles (AgNPs) have a wide range of bioactivity, which is highly dependent on particle size, shape, stabilizer, and production method. Here, we present the results of studies of AgNPs cytotoxic properties obtained by irradiation treatment of silver nitrate solution and various stabilizers by accelerating electron beam in a liquid medium. METHODS: The results of studies of morphological characteristics of silver nanoparticles were obtained by transmission electron microscopy, UV-vis spectroscopy, and dynamic light scattering measurements. MTT test, alamar blue test, flow cytometry, and fluorescence microscopy were used to study the anti-cancer properties. As biological objects for standard tests, adhesive and suspension cell cultures of normal and tumor origin, including prostate cancer, ovarian cancer, breast cancer, colon cancer, neuroblastoma, and leukemia, were studied. RESULTS: The results showed that the silver nanoparticles obtained by irradiation with polyvinylpyrrolidone and collagen hydrolysate are stable in solutions. Samples with different stabilizers were characterized by a wide average size distribution from 2 to 50 nm and low zeta potential from -7.3 to +12.4 mV. All AgNPs formulations showed a dose-dependent cytotoxic effect on tumor cells. It has been established that the particles obtained with the combination of polyvinylpyrrolidone/collagen hydrolysate have a relatively more pronounced cytotoxic effect in comparison to samples stabilized with only collagen or only polyvinylpyrrolidone. The minimum inhibitory concentrations for nanoparticles were less than 1 µg/mL for various types of tumor cells. It was found that neuroblastoma (SH-SY5Y) is the most susceptible, and ovarian cancer (SKOV-3) is the most resistant to the action of silver nanoparticles. The activity of the AgNPs formulation prepared with a mixture of PVP and PH studied in this work was higher that activity of other AgNPs formulations reported in the literature by about 50 times. CONCLUSIONS: The results indicate that the AgNPs formulations synthesized with an electron beam and stabilized with polyvinylpyrrolidone and protein hydrolysate deserve deep study for their further use in selective cancer treatment without harming healthy cells in the patient organism.

Silver nanoparticles induce a non-immunogenic tumor cell death.

Immunogenic cell death (ICD) is a form of cell death characterized by the release of danger signals required to trigger an adaptive immune response against tumor-associated antigens. Silver nanoparticles (AgNP) display anti-proliferative and cytotoxic effects in tumor cells, but it has not been previously studied whether AgNP act as an ICD inductor. The present study evaluated the in vitro release of calreticulin as a damage-associated molecular pattern (DAMP) associated with the cytotoxicity of AgNP and their in vivo anti-cancer effects. In vitro, mouse CT26 colon carcinoma and MCA205 fibrosarcoma cells were exposed to AgNP and then cell proliferation, adhesion, and release of calreticulin were determined. The results indicated there were time- and concentration-related anti-proliferative effects of AgNP in both the CT26 and MCA205 lines. Concurrently, changes in cell adhesion were detected mainly in the CT26 cells. Regarding DAMP detection, a significant increase in calreticulin was observed only in CT26 cells treated with doxorubicin and AgNP; however, no differences were found in the MCA205 cells. In vivo, the survival and growth of subcutaneous tumors were monitored after vaccination of mice with cell debris from tumor cells treated with AgNP or after intra-tumoral administration of AgNP to established tumors. Consequently, anti-tumoral prophylactic immunization with AgNP-dead cells failed to protect mice from tumor re-challenge; intra-tumor injection of AgNP did not induce a significant effect. In conclusion, there was a noticeable anti-tumoral effect of AgNP in vitro in both CT26 and MCA205 cell lines, accompanied by the release of calreticulin in CT26 cells. In vivo, immunization with cell debris derived from AgNP-treated tumor cells failed to induce a protective immune response in the cancer model mice. Clearly, further research is needed to determine if one could combine AgNP with other ICD inducers to improve the anti-tumor effect of these nanoparticles in vivo.

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients.

Introduction: Delayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs)-small non-coding RNAs involved in clue gene regulation at the post-transcriptional level-as biomarkers of neurological outcomes in SAH patients. Methods: We analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples. Results: We found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes. Conclusion: These observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-ß inflammatory pathway and blood-brain barrier disruption.

Gender differences in work-life balance of European neurosurgeons.

Introduction: Neurosurgery is one of the most demanding medical specialties. For neurosurgeons, balancing professional activity with personal life can be challenging. Research question: To evaluate gender differences in contribution of neurosurgeons in the household and child-rearing, as well as their impact on personal life and career. Material and methods: An anonymous, electronic, 59-item web-based survey was administered to National Neurosurgical Societies of Europe, and European Member Societies of the European Association of Neurosurgical Societies (June-October 2021). Results: A total of 205 European neurosurgeons (87 females and 118 males, mean age 40.7) are included in our survey. In neurosurgery, females are significantly more likely to be alone (37.9%), while males are significantly more likely to have children (66.9%). In terms of household efforts, females spend more time than males on the same tasks. Most participants (71.2%) view gender issues as a disadvantage in career pursuing. Women feel less accepted (54.3%) and having fewer opportunities (58.6%), while men believe that pregnancy/child-rearing (65.8%) and having many roles (51.3%) are the main obstacles. Both genders (77.6%) favor more convenient working conditions for young parents.Discussion and Conclusion. In our study we found that, women neurosurgeons take more responsibilities at home, especially in the child-rearing years. Female neurosurgeons are more likely to live alone or stay childless more often compared to their male colleagues. Supportive facilities, flexible programs, universal life policies and presumably curbing of the social stereotypes are of importance to overcome gender inequities that women are still facing in neurosurgery.

Targeted Enzymatic VLP-Nanoreactors with ß-Glucocerebrosidase Activity as Potential Enzyme Replacement Therapy for Gaucher's Disease.

Gaucher disease is a genetic disorder and the most common lysosomal disease caused by the deficiency of enzyme ß-glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) is successfully applied using mannose-exposed conjugated glucocerebrosidase, the lower stability of the enzyme in blood demands periodic intravenous administration that adds to the high cost of treatment. In this work, the enzyme ß-glucocerebrosidase was encapsulated inside virus-like nanoparticles (VLPs) from brome mosaic virus (BMV), and their surface was functionalized with mannose groups for targeting to macrophages. The VLP nanoreactors showed significant GCase catalytic activity. Moreover, the Michaelis-Menten constants for the free GCase enzyme (KM =0.29 mM) and the functionalized nanoreactors (KM =0.32 mM) were similar even after chemical modification. Importantly, the stability of enzymes under physiological conditions (pH 7.4, 37 °C) was enhanced by ≈11-fold after encapsulation; this is beneficial for obtaining a higher blood circulation half-life, which may decrease the cost of therapy by reducing the requirement of multiple intravenous injections. Finally, the mannose receptor targeted enzymatic nanoreactors showed enhanced internalization into macrophage cells. Thus, the catalytic activity and cell targeting suggest the potential of these nanoreactors in ERT of Gaucher's disease.

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score.

BACKGROUND: Risk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding. METHODS: A retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort. RESULTS: 68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 . CONCLUSIONS: Venous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.