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.

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.

Women's role in neurosurgical research: is the gender gap improving?

OBJECTIVE: The percentage of women publishing high-impact neurosurgical research might be perceived as a representation of our specialty and may influence the perpetuation of the existing gender gap. This study investigated whether the trend in women taking lead roles in neurosurgical research has mirrored the increase in female neurosurgeons during the past decade and whether our most prestigious publications portray enough female role models to stimulate gender diversity among the new generation of neurosurgeons. METHODS: Two of the most prominent neurosurgical journals-Journal of Neurosurgery and Neurosurgery-were selected for this study, and every original article that was published in 2009 and 2019 in each of those journals was investigated according to the gender of the first and senior authors, their academic titles, their affiliations, and their institutions' region. RESULTS: A total of 1328 articles were analyzed. The percentage of female authors was significantly higher in Europe and Russia compared with the US and Canada (first authors: 60/302 [19.9%] vs 109/829 [13.1%], p = 0.005; and senior authors: 32/302 [10.6%] vs 57/829 [6.9%], p = 0.040). Significantly increased female authorship was observed from 2009 to 2019, and overall numbers of both first and senior female authors almost doubled. However, when analyzing by regions, female authorship increased significantly only in the US and Canada. Female authors of neurosurgical research articles were significantly less likely to hold an MD degree compared with men. Female neurosurgeons serving as senior authors were represented in only 3.6% (48/1328) of articles. Women serving as senior authors were more likely to have a female colleague listed as the first author of their research (29/97 [29.9%] vs 155/1231 [12.6%]; χ2 = 22.561, p = 0.001). CONCLUSIONS: Although this work showed an encouraging increase in the number of women publishing high-impact neurosurgical research, the stagnant trend in Europe may suggest that a glass ceiling has been reached and further advances in equity would require more aggressive measures. The differences in the researchers' profiles (academic title and affiliation) suggest an even wider gender gap. Cultural unconscious bias may explain why female senior authors have more than double the number of women serving as their junior authors compared with men. While changes in the workforce happen, strategies such as publishing specific issues on women, encouraging female editorials, and working toward more gender-balanced editorial boards may help our journals to portray a more equitable specialty that would not discourage bright female candidates.

Validation of shunt dependency prediction scores after aneurysmal spontaneous subarachnoid hemorrhage.

BACKGROUND: Currently available scores for predicting shunt dependency after aneurysmal spontaneous subarachnoid hemorrhage (aSAH) are limited and not widely accepted. The key purpose of this study was to validate a recently created score for shunt dependency in aSAH (SDASH) in an independent population of aSAH patients. We compared this new SDASH score based on a combination of the Hunt and Hess grade, Barrow Neurological Institute (BNI) score, and the presence or not of acute hydrocephalus with other published predictive scores. METHODS: The SDASH score, Hijdra score, BNI grading system, chronic hydrocephalus ensuing from SAH score (CHESS), Graeb score, and modified Graeb score (mGS) were calculated for a cohort of aSAH patients. Logistic regression analysis was used to determine the reliability of the SDASH score, and the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to assess the discriminative ability of the model. RESULTS: In 214 patients with aSAH, 40 (18.7%) developed shunt-dependent hydrocephalus (SDHC). The AUC for the SDASH score was 0.816. The SDASH score reliably predicted SDHC in aSAH (odds ratio: 2.93, 95% CI: 1.99-4.31; p < 0.001) with no statistically significant differences being found between the SDASH score and the CHESS score (AUC: 0.816), radiological-based Graeb score (AUC: 0.742), or modified Graeb score (AUC: 0.741). However, the Hijdra score (AUC: 0.673) and BNI grading system (AUC: 0.616) showed lower predictive values than the SDASH score. CONCLUSIONS: Our findings support the ability of the SDASH score to predict shunt dependency after SAH in a population independent to that used to develop the score. The SDASH score may aid in the early management of hydrocephalus in aSAH, and it does not differ greatly from other predictive scores.

Growth prediction in asymptomatic meningiomas: the utility of the AIMSS score.

BACKGROUND: Management of asymptomatic meningiomas represents a challenge due to the absence of a solid consensus on which is the best management strategy. There are various known factors predicting meningiomas growth risk. However, the Asian Intracranial Meningioma Scoring System (AIMSS) is the only described score to quantify such risk thus emerging as a potential tool for management decisions. This study aims to validate this score on our series of asymptomatic meningiomas. METHOD: We performed a retrospective review of asymptomatic meningiomas diagnosed at our institution between January 2008 and October 2016 and followed by an annual cerebral Magnetic Resonance Imaging (MRI). For each lesion, the AIMSS score was calculated thus classifying them in low (0-2), intermediate (3-6) or high risk (7-11) of rapid growth (>2cm3/year). We investigated the correlation between the expected Average Growth Rate (AGR) according to the score and the one obtained in our study. The mean growth velocity over the different risk groups was also compared. RESULTS: Overall, 69 asymptomatic meningiomas found incidentally in 46 patients were included in the study; 31 were assigned to the low-risk group, 34 to the intermediate-risk group and 4 to the high-risk group. Attending to the AGR, 0% showed rapid growth in the low-risk group, 12% in the intermediate-risk group, and 25% in the high-risk group. The mean growth velocity showed a significant difference over the different risk groups (p < 0,001). CONCLUSIONS: According to our finding, the AIMSS score is a valid tool to estimate the risk of rapid growth of asymptomatic meningiomas. It is especially useful distinguishing between low- and intermediate-risk meningiomas. This feature would allow physicians to adjust the periodicity of radiological and clinical controls. Adding more known risk factors of rapid growth to the score might improve its predictive capabilities with the high-risk group.

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer.

BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. RESULTS: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. CONCLUSIONS: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.

Silver deposition on titanium surface by electrochemical anodizing process reduces bacterial adhesion of Streptococcus sanguinis and Lactobacillus salivarius.

OBJECTIVES: The aim of this study was to determine the antibacterial properties of silver-doped titanium surfaces prepared with a novel electrochemical anodizing process. MATERIAL AND METHODS: Titanium samples were anodized with a pulsed process in a solution of silver nitrate and sodium thiosulphate at room temperature with stirring. Samples were processed with different electrolyte concentrations and treatment cycles to improve silver deposition. Physicochemical properties were determined by X-ray photoelectron spectroscopy, contact angle measurements, white-light interferometry, and scanning electron microscopy. Cellular cytotoxicity in human fibroblasts was studied with lactate dehydrogenase assays. The in vitro effect of treated surfaces on two oral bacteria strains (Streptococcus sanguinis and Lactobacillus salivarius) was studied with viable bacterial adhesion measurements and growth curve assays. Nonparametric statistical Kruskal-Wallis and Mann-Whitney U-tests were used for multiple and paired comparisons, respectively. Post hoc Spearman's correlation tests were calculated to check the dependence between bacteria adhesion and surface properties. RESULTS: X-ray photoelectron spectroscopy results confirmed the presence of silver on treated samples and showed that treatments with higher silver nitrate concentration and more cycles increased the silver deposition on titanium surface. No negative effects in fibroblast cell viability were detected and a significant reduction on bacterial adhesion in vitro was achieved in silver-treated samples compared with control titanium. CONCLUSIONS: Silver deposition on titanium with a novel electrochemical anodizing process produced surfaces with significant antibacterial properties in vitro without negative effects on cell viability.

Intraoperative arteriovenous malformation rupture: causes, management techniques, outcomes, and the effect of neurosurgeon experience.

OBJECT: Intraoperative rupture can transform an arteriovenous malformation (AVM) resection. Blood suffuses the field and visualization is lost; suction must clear the field and the hand holding the suction device is immobilized; the resection stalls while hemostasis is being reestablished; the cause and site of the bleeding may be unclear; bleeding may force technical errors and morbidity from chasing the source into eloquent white matter; and AVM bleeding can be so brisk that it overwhelms the neurosurgeon. The authors reviewed their experience with this dangerous complication to examine its causes, management, and outcomes. METHODS: From a cohort of 591 patients with AVMs treated surgically during a 15-year period, 32 patients (5%) experienced intraoperative AVM rupture. Their prospective data and medical records were reviewed. RESULTS: Intraoperative AVM rupture was not correlated with presenting hemorrhage, but had a slightly higher incidence infratentorially (7%) than supratentorially (5%). Rupture was due to arterial bleeding in 18 patients (56%), premature occlusion of a major draining vein in 10 (31%), and nidal penetration in 4 (13%). In 14 cases (44%), bleeding control was abandoned and the AVM was removed immediately ("commando resection"). The incidence of intraoperative rupture was highest during the initial 5-year period (9%) and dropped to 3% and 4% in the second and third 5-year periods, respectively. Ruptures due to premature venous occlusion and nidal penetration diminished with experience, whereas those due to arterial bleeding remained steady. Despite intraoperative rupture, 90% of AVMs were completely resected initially and all of them ultimately. Intraoperative rupture negatively impacted outcome, with significantly higher final modified Rankin Scale scores (mean 2.8) than in the overall cohort (mean 1.5; p < 0.001). CONCLUSIONS: Intraoperative AVM rupture is an uncommon complication caused by pathological arterial anatomy and by technical mistakes in judging the dissection distance from the AVM margin and in mishandling or misinterpreting the draining veins. The decrease in intraoperative rupture rate over time suggests the existence of a learning curve. In contrast, intraoperative rupture due to arterial bleeding reflects the difficulty with dysplastic feeding vessels and deep perforator anatomy rather than neurosurgeon experience. The results demonstrate that intraoperative AVM rupture negatively impacts patient outcome, and that skills in managing this catastrophe are critical.

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.

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.

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 non- adjuncts, alongside the prioritization of neurosurgeons' well-being.

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.

Nukbone® promotes proliferation and osteoblastic differentiation of mesenchymal stem cells from human amniotic membrane.

Bovine bone matrix Nukbone® (NKB) is an osseous tissue-engineering biomaterial that retains its mineral and organic phases and its natural bone topography and has been used as a xenoimplant for bone regeneration in clinics. There are not studies regarding its influence of the NKB in the behavior of cells during the repairing processes. The aim of this research is to demonstrate that NKB has an osteoinductive effect in human mesenchymal stem cells from amniotic membrane (AM-hMSCs). Results indicated that NKB favors the AM-hMSCs adhesion and proliferation up to 7 days in culture as shown by the scanning electron microscopy and proliferation measures using an alamarBlue assay. Furthermore, as demonstrated by reverse transcriptase polymerase chain reaction, it was detected that two gene expression markers of osteoblastic differentiation: the core binding factor and osteocalcin were higher for AM-hMSCs co-cultured with NKB in comparison with cultivated cells in absence of the biomaterial. As the results indicate, NKB possess the capability for inducing successfully the osteoblastic differentiation of AM-hMSC, so that, NKB is an excellent xenoimplant option for repairing bone tissue defects.

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.

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.

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.

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.

Nicotiana benthamiana resistance to non-adapted Melon necrotic spot virus results from an incompatible interaction between virus RNA and translation initiation factor 4E.

Nicotiana benthamiana has been described as non-host for Melon necrotic spot virus (MNSV). We investigated the basis of this resistance using the unique opportunity provided by strain MNSV-264, a recombinant virus that is able to overcome the resistance. Analysis of chimeric MNSV mutants showed that virulence in N. benthamiana is conferred by a 49 nucleotide section of the MNSV-264 3'-UTR, which acts in this host as a cap-independent translational enhancer (3'-CITE). Although the 3'-CITE of non-adapted MNSV-Mα5 is active in susceptible melon, it does not promote efficient translation in N. benthamiana, thus preventing expression of proteins required for virus replication. However, MNSV-Mα5 gains the ability to multiply in N. benthamiana cells if eIF4E from a susceptible melon variety (Cm-eIF4E-S) is supplied in trans. These data show that N. benthamiana resistance to MNSV-Mα5 results from incompatibility between the MNSV-Mα5 3'-CITE and N. benthamiana eIF4E in initiating efficient translation of the viral genome. Therefore, non-host resistance conferred by the inability of a host susceptibility factor to support viral multiplication may be a possible mechanism for this type of resistance to viruses.