Dynamic Workflow Proposal for Continuous Frameless Electromagnetic Neuronavigation in Rigid Neuroendoscopy.

BACKGROUND: Ventriculoscopic neuronavigation has been described in several articles. However, there are different ventriculoscopes and navigation systems. Due to these different combinations, it is difficult to find detailed neuronavigation protocols. We describe, step-by-step, a simple method to navigate both the trajectory until reaching the ventricular system, as well as the intraventricular work. METHODS: We use a rigid ventriculoscope (LOTTA, KarlStorz) with an electromagnetic stylet (S8-StealthSystem, Medtronic). The protocol is based on a modified or 3-dimensionally printed trocar for navigating the extraventricular step and on a modified pediatric nasogastric tube for the intraventricular navigation. RESULTS: This protocol can be set up in less than 10 minutes. The extraventricular part is navigated by introducing the electromagnetic stylet inside the modified or 3-dimensionally printed trocar. Intraventricular navigation is done by combining a modified pediatric nasogastric tube with the electromagnetic stylet inside the endoscope's working channel. The most critical point is to obtain a blunt-bloodless ventriculostomy while achieving perfect alignment of all targeted structures via pure straight trajectories. CONCLUSIONS: This protocol is easy-to-set-up, avoids head rigid-fixation and bulky optical-based attachments to the ventriculoscope, and allows continuous navigation of both parts of the surgery. Since we have implemented this protocol, we have noticed a significant enhancement in both simple and complex ventriculoscopic procedures because the surgery is dramatically simplified.

Neuroendoscopic access to the third ventricle in patients with narrow foramen of monro without stenosis/obstruction: role of foraminoplasty.

OBJECT: One of the critical steps for the success of intraventricular neuroendoscopic procedures is the entry into the third ventricle and passage of the endoscopy system through the foramen of Monro (FM). A diameter larger than that of the instrument used is considered a prerequisite for safely performing the technique, as damage to this structure can lead to alterations in the fornix and vascular structures. When the foramen diameter is narrow and there is no obstruction/stenosis, the role of foraminoplasty in reducing the risk of complications has not been adequately assessed in the literature. METHODS: A review of endoscopic procedures conducted at our center since 2018 was undertaken. Cases in which preoperative imaging indicated a FM diameter < 6 mm and foraminoplasty technique was applied were examined to determine the technical and functional success of the procedure. The technical success was determined by completing the neuroendoscopic procedure with the absence of macroscopic lesions in the various structures comprising the foramen and without complications in the follow-up imaging tests. Functional success was defined as the absence of cognitive/memory alterations during the 3-month postoperative follow-up. Additionally, a review of the various forms of foraminoplasty described in the literature is conducted. RESULTS: In our cohort, six patients were identified with a preoperative FM diameter < 6 mm without obstruction or stenosis. Foraminoplasty was planned for these cases to facilitate various intraventricular neuroendoscopic procedures. In all instances, the technique was successfully performed without causing macroscopic damage to the structures comprising the foramen. Follow-up visits included various cognitive tests to assess potential sequelae related to microscopic damage to the fornix. None of the patients exhibited anomalies. CONCLUSION: Foraminoplasty in patients with a narrow FM without signs of stenosis/obstruction is a useful technique to reduce the risk of complications during the passage of the endoscopy system through this structure, enabling the safe performance of neuroendoscopic procedures.

Entrenamiento microneuroquirúrgico en el espécimen anatómico. Propuesta de un plan estructurado de disección endoscópica y microquirúrgica basicraneal durante la residencia / Microneurosurgical training in the anatomical specimen: A structured plan for endoscopic and microsurgical skull base training during the residency

Antecedentes y objetivo: El desarrollo de una elevada capacidad crítica y competencia técnica constituye uno de los objetivos principales de todo programa de formación en Neurocirugía. Por múltiples factores, esta adquisición progresiva de habilidades técnicas puede resultar compleja durante la residencia. A pesar de su elevado coste y necesidad de infraestructura, existe un interés renovado respecto al papel de los laboratorios de anatomía. El estudio y disección del espécimen anatómico ha sido el contexto donde muchos neurocirujanos han desarrollado y perfeccionado la técnica microneuroquirúrgica. Proponemos un plan estructurado de disección y entrenamiento endoscópico y microquirúrgico que permita al residente obtener el máximo provecho durante su estancia en un laboratorio.Material y métodosDurante los meses de septiembre, octubre y noviembre de 2021 se realizó una estancia en el Laboratorio de Microneurocirugía y Base Craneal de la Universidad Miguel Hernández de Alicante. Se emplearon un total de 2 especímenes formolados e inyectados con silicona roja y azul. En el primer espécimen se realizó una primera fase de disección endoscópica endonasal. Tras completar la fase endonasal se plantearon un conjunto de incisiones para realizar los abordajes transcraneales. En el segundo espécimen se realizó primero la parte transcraneal dejando el trabajo endoscópico endonasal para la segunda fase.ResultadosSe muestran los resultados de la disección de los 2 especímenes. Durante la fase endoscópica endonasal se simuló el abordaje transesfenoidal a la silla incidiendo sobre los abordajes extendidos en el plano sagital. Durante la fase transcraneal se realizaron abordajes anterolaterales derecho e izquierdo, un abordaje interhemisférico transcalloso anterior izquierdo, un abordaje posterolateral transcondilar izquierdo y un abordaje lateral derecho combinado. (AU)

Background and objective: The development of a high level of competence and technical proficiency is one of the main objectives of any neurosurgical training program. Due to many factors, this progressive skill development can be complex during the residency. Despite its high cost and infrastructure requirements, there is renewed interest regarding the role of anatomy labs. The study and dissection of the human cadaver has been the environment where many surgeons have developed the necessary skills for microneurosurgery. We propose a structured endoscopic and microsurgical training dissection program to enable residents to maximize the benefits of their training in the lab.Material and methodsDuring the months of September, October and November 2021, a stay was done at the Microneurosurgery and Skull Base Laboratory of the Miguel Hernández University of Alicante. A total of 2 specimens were used. The first specimen underwent a first endoscopic endonasal dissection phase. After completing the endonasal part, a set of incisions were made to perform the transcranial part. In the second specimen, the transcranial part was performed first, leaving the endonasal endoscopic work for the last phase.ResultsThe results of the dissection program are presented. During the endonasal endoscopic phase, the transsphenoidal approach to the sella was simulated while focusing on the extended approaches in the sagittal plane. During the transcranial phase, right and left anterolateral approaches, a left anterior transcallosal interhemispheric approach, a left transcondylar posterolateral approach and a combined right lateral approach were performed. (AU)

Transcortical transcatheter ultrasound-assisted technique for deep-seated brain tumors. Technical note.

PURPOSE: Surgery of deep-seated brain tumors can be challenging. Several methods have been described to facilitate transcortical approaches, including ultrasound-assisted resection. Ultrasound-guided placement of a standard ventricular catheter is a widely reported technique and has been used to approach these lesions via the transcortical route. We describe how we usually perform this useful technique to assist and enhance the transcortical resection of some deep-seated brain tumors. METHODS: Standard electromagnetic frameless navigation (S8 Neuronavigation System, Medtronic, Minneapolis, USA) was employed to focus the craniotomy and to plan the trajectory of the ventricular catheter. After dural opening, an ultrasound device (Arietta 850, Hitachi-Aloka Medical, Tokyo, Japan) was used for intraoperative ultrasound (IOUS) assessment. A ventricular catheter was placed from the cortex to the lateral wall of the tumor under direct real-time IOUS visualization to guide the further transcortical dissection. RESULTS: Transcortical transcatheter ultrasound-assisted technique involved minimal time and infrastructure requirements. There were no major technical difficulties during its use, providing confidence and improving subcortical white matter dissection by guiding the route to the tumor. CONCLUSIONS: Recent improvement of IOUS image-quality devices offers several attractive options for real-time navigation. The combination of conventional neuronavigation systems with real-time IOUS assessment during the intradural step provides a higher degree of control by improving the execution of the surgery. We hope this description may be a useful tool for some selected cases and contribute to the further enhancement and improvement of this widely used technique.

Microneurosurgical training in the anatomical specimen: A structured plan for endoscopic and microsurgical skull base training during the residency.

BACKGROUND AND OBJECTIVE: The development of a high level of competence and technical proficiency is one of the main objectives of any neurosurgical training program. Due to many factors, this progressive skill development can be complex during the residency. Despite its high cost and infrastructure requirements, there is renewed interest regarding the role of anatomy labs. The study and dissection of the human cadaver has been the environment where many surgeons have developed the necessary skills for microneurosurgery. We propose a structured endoscopic and microsurgical training dissection program to enable residents to maximize the benefits of their training in the lab. MATERIAL AND METHODS: During the months of September, October and November 2021, a stay was done at the Microneurosurgery and Skull Base Laboratory of the Miguel Hernández University of Alicante. A total of 2 specimens were used. The first specimen underwent a first endoscopic endonasal dissection phase. After completing the endonasal part, a set of incisions were made to perform the transcranial part. In the second specimen, the transcranial part was performed first, leaving the endonasal endoscopic work for the last phase. RESULTS: The results of the dissection program are presented. During the endonasal endoscopic phase, the transsphenoidal approach to the sella was simulated while focusing on the extended approaches in the sagittal plane. During the transcranial phase, right and left anterolateral approaches, a left anterior transcallosal interhemispheric approach, a left transcondylar posterolateral approach and a combined right lateral approach were performed. CONCLUSIONS: The structured dissection of the specimen allowed both endonasal endoscopic and transcranial microsurgical training in the same specimen. This design facilitated the realization of the core skull base approaches in the same specimen. According to our initial experience, we believe that developing common dissection programs is a powerful tool to maximize the results of our residents' laboratory training.

Dorsum Sellae as Key Landmark in ETV With Disminished Prepontine Cistern: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: One of the key aspects in the surgical technique of endoscopic third ventriculostomy (ETV) is the perforation of the floor of the third ventricle because of the high risk of injuring vital structures located in that region. According to the standard technique, this perforation should be performed in the midline halfway between mammillary bodies and the infundibular recess to avoid damage to the structures. This can be performed without excessive complications when the diameter of the prepontine cistern is wide. However, in situations where the diameter is reduced (defined in the literature as having a prepontine interval [PPI] ≤1 mm), the probability of complications increases exponentially.In this article, we propose using dorsum sellae as a key point to safely perform ETV in patients with a decreased PPI, guiding the trajectory and its marking using neuronavigation. METHODS: A review was conducted on the latest 100 ETV procedures performed by our team in the past 5 years. The measurement of the PPI was conducted using archived preoperative MRI imaging studies, specifically between the dorsum sellae and the basilar artery. In cases where the PPI was ≤1 mm and, therefore, the use of the dorsum sellae was applied as a reference point, the technical results and procedural functions were documented. RESULTS: In the cohort, 7 patients with a PPI ≤1 mm were identified. In all 7 cases, fenestration of the tuber cinereum was successfully performed without causing vascular damage or associated complications. ETV was successful in 6 patients, with only one experiencing ETV failure necessitating the placement of a ventriculoperitoneal shunt. CONCLUSION: The utilization of the dorsum sellae as a reference point to perform ETV in reduced PPI constitutes a safe alternative to the classical technique.

A snoRNA-tRNA modification network governs codon-biased cellular states.

The dynamic balance between tRNA supply and codon usage demand is a fundamental principle in the cellular translation economy. However, the regulation and functional consequences of this balance remain unclear. Here, we use PARIS2 interactome capture, structure modeling, conservation analysis, RNA-protein interaction analysis, and modification mapping to reveal the targets of hundreds of snoRNAs, many of which were previously considered orphans. We identify a snoRNA-tRNA interaction network that is required for global tRNA modifications, including 2'-O-methylation and others. Loss of Fibrillarin, the snoRNA-guided 2'-O-methyltransferase, induces global upregulation of tRNA fragments, a large group of regulatory RNAs. In particular, the snoRNAs D97/D133 guide the 2'-O-methylation of multiple tRNAs, especially for the amino acid methionine (Met), a protein-intrinsic antioxidant. Loss of D97/D133 snoRNAs in human HEK293 cells reduced target tRNA levels and induced codon adaptation of the transcriptome and translatome. Both single and double knockouts of D97 and D133 in HEK293 cells suppress Met-enriched proliferation-related gene expression programs, including, translation, splicing, and mitochondrial energy metabolism, and promote Met-depleted programs related to development, differentiation, and morphogenesis. In a mouse embryonic stem cell model of development, knockdown and knockout of D97/D133 promote differentiation to mesoderm and endoderm fates, such as cardiomyocytes, without compromising pluripotency, consistent with the enhanced development-related gene expression programs in human cells. This work solves a decades-old mystery about orphan snoRNAs and reveals a function of snoRNAs in controlling the codon-biased dichotomous cellular states of proliferation and development.

Neuronavigated endoscopic aqueductoplasty with panventricular stent plus septostomy for isolated fourth ventricle in complex hydrocephalus and syringomyelia associated with myelomeningocele: how I do it.

BACKGROUND: Isolated fourth ventricle (IFV) is a challenging entity to manage. In recent years, endoscopic treatment for aqueductoplasty has been on the rise. However, in patients with complex hydrocephalus and distorted ventricular system, its implementation can be complex. METHODS: We present a 3-year-old patient with myelomeningocele and postnatal hydrocephalus treated by ventriculoperitoneal shunt. In follow-up, a progressive IFV and isolated lateral ventricle with symptoms of the posterior fossa developed. An endoscopic aqueductoplasty (EA) with panventricular stent plus septostomy guided with neuronavigation was decided due to the complexity of the ventricular system. CONCLUSION: In IFV associated with complex hydrocephalus with distortion of the ventricular system, navigation can be of great help for planning and as a guide for performing EA.

An Inflection Point in Cancer Protein Biomarkers: What was and What's Next.

Biomarkers remain the highest value proposition in cancer medicine today-especially protein biomarkers. Despite decades of evolving regulatory frameworks to facilitate the review of emerging technologies, biomarkers have been mostly about promise with very little to show for improvements in human health. Cancer is an emergent property of a complex system, and deconvoluting the integrative and dynamic nature of the overall system through biomarkers is a daunting proposition. The last 2 decades have seen an explosion of multiomics profiling and a range of advanced technologies for precision medicine, including the emergence of liquid biopsy, exciting advances in single-cell analysis, artificial intelligence (machine and deep learning) for data analysis, and many other advanced technologies that promise to transform biomarker discovery. Combining multiple omics modalities to acquire a more comprehensive landscape of the disease state, we are increasingly developing biomarkers to support therapy selection and patient monitoring. Furthering precision medicine, especially in oncology, necessitates moving away from the lens of reductionist thinking toward viewing and understanding that complex diseases are, in fact, complex adaptive systems. As such, we believe it is necessary to redefine biomarkers as representations of biological system states at different hierarchical levels of biological order. This definition could include traditional molecular, histologic, radiographic, or physiological characteristics, as well as emerging classes of digital markers and complex algorithms. To succeed in the future, we must move past purely observational individual studies and instead start building a mechanistic framework to enable integrative analysis of new studies within the context of prior studies. Identifying information in complex systems and applying theoretical constructs, such as information theory, to study cancer as a disease of dysregulated communication could prove to be "game changing" for the clinical outcome of cancer patients.

ETV as treatment for obstructive hydrocephalus in an aneurysmal malformation of the vein of Galen in infants: case report and review of literature.

INTRODUCTION: A vein of Galen aneurysmal malformation (VGAM) is a high-flow arteriovenous malformation that typically presents in early childhood. Complications associated with this condition include heart failure and hydrodynamic disorders resulting from high blood flow. Hydrocephalus is one of the hydrodynamic disorders. It can present in a chronic form due to a defect in the absorption of cerebrospinal fluid (CSF) resulting from venous hypertension or in an acute/subacute form due to obstruction of normal circulation routes caused by the mass effect of the VGAM. Currently, endovascular closure of the lesion is considered the treatment of choice. However, in acute/subacute presentations of obstructive hydrocephalus, progression may occur despite endovascular treatment, necessitating a cerebrospinal fluid diversion procedure. Prior to the advent of endoscopic treatment, ventricular shunts were utilized, but outcomes were poor due to the pathological hydrodynamic parameters associated with the malformation. The role of endoscopic third ventriculostomy as a treatment option in these situations remains unclear, and there is limited literature available. Therefore, we present the case of a patient with a vein of Galen aneurysmal malformation and obstructive hydrocephalus, which was treated via ETV. Furthermore, a literature review was conducted. CASE DESCRIPTION: We present a 5-month-old infant who was diagnosed at birth with VGAM. At 2 months of age, a partial closure of the malformation was performed via endovascular. Subsequently, the patient presented at the emergency department with symptoms of irritability, lethargy, vomiting, feeding refusal, and "setting sun" sign of several days' duration due to obstructive hydrocephalus. The patient was successfully treated via ETV. Following this, a new arteriography was performed and revealed occlusion of the VGAM. The child clinically improved and currently exhibits mild psychomotor impairment after 1-year follow-up. CONCLUSION: In the literature, there are a limited number of reports on the treatment of obstructive hydrocephalus associated with VGAM via ETV. These reports have demonstrated good outcomes with minimal surgical complications. Our patient also exhibited good results. As such, ETV is a viable and safe option for the treatment of obstructive hydrocephalus associated with VGAM in pediatric patients. However, more research is needed to establish the effectiveness of ETV in comparison to other treatment options and to understand the long-term outcomes.

Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.

Liver cancer is a malignancy developed from underlying liver disease that encompasses liver injury and metabolic disorders. The progression from these underlying liver disease to cancer is accompanied by chronic inflammatory conditions in which liver macrophages play important roles in orchestrating the inflammatory response. During this process, bioactive lipids produced by hepatocytes and macrophages mediate the inflammatory responses by acting as pro-inflammatory factors, as well as, playing roles in the resolution of inflammation conditions. Here, we review the literature discussing the roles of bioactive lipids in acute and chronic hepatic inflammation and progression to cancer.

Intraoperative ultrasound-assisted surgery in orbital apex tumours: technical note.

BACKGROUND: Since the introduction of ultrasonography (US) in the operating theatre in the early 1970s, intraoperative ultrasound (IOUS) has become a very useful tool for real-time neurosurgical procedures. The main limitation of US is its innately reduced capacity to penetrate the intact skull. This is the reason why most IOUS-assisted procedures are usually performed via transfontanellar or after a craniotomy or laminotomy is done. OBJECTIVE: We present a 54-year-old woman with a right optic nerve sheath meningioma, who was operated on by a right cranio-orbital approach and IOUS-assisted tumour removal. METHODS: Data concerning the anamnesis and complementary studies were obtained from the clinical history. Surgical images were obtained in the operating room during surgery. Images obtained by US were compared with the preoperative and postoperative imaging scans. IOUS imaging was also compared with the intraoperative findings. RESULTS: The correlation between US and both preoperative and postoperative studies was very high. During surgery, both transpalpebral and transperiorbital IOUS facilitated the resection with no specific technical difficulties or significant time consumption. CONCLUSION: Recent improvements in the image quality of IOUS devices offer several attractive options for real-time neuronavigation. We describe our initial experience with the IOUS-assisted technique for orbital apex tumours. In our patient transpalpebral and transperiorbital IOUS provided an excellent source of control over location and over the extent of tumour resection. We hope that this description of how we usually perform this procedure may be useful for some selected cases and contribute to the further enhancement and improvement of the technique.

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.

Obesity confers an independent risk for carcinogenesis. Classically viewed as a genetic disease, owing to the discovery of tumor suppressors and oncogenes, genetic events alone are not sufficient to explain the progression and development of cancers. Tumor development is often associated with metabolic and immunological changes. In particular, obesity is found to significantly increase the mortality rate of liver cancer. As its role is not defined, a fundamental question is whether and how metabolic changes drive the development of cancer. In this review, we will dissect the current literature demonstrating that liver lipid dysfunction is a critical component driving the progression of cancer. We will discuss the involvement of inflammation in lipid dysfunction driven liver cancer development with a focus on the involvement of liver macrophages. We will first discuss the association of steatosis with liver cancer. This will be followed with a literature summary demonstrating the importance of inflammation and particularly macrophages in the progression of liver steatosis and highlighting the evidence that macrophages and macrophage produced inflammatory mediators are critical for liver cancer development. We will then discuss the specific inflammatory mediators and their roles in steatosis driven liver cancer development. Finally, we will summarize the molecular pattern (PAMP and DAMP) as well as lipid particle signals that are involved in the activation, infiltration and reprogramming of liver macrophages. We will also discuss some of the therapies that may interfere with lipid metabolism and also affect liver cancer development.

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78.

Rapalogues are powerful therapeutic modalities for breast cancer; however, they suffer from low solubility and dose-limiting side effects. To overcome these challenges, we developed a long-circulating multiheaded drug carrier called 5FA, which contains rapamycin-binding domains linked with elastin-like polypeptides (ELPs). To target these "Hydra-ELPs" toward breast cancer, we here linked 5FA with four distinct peptides which are reported to engage the cell surface form of the 78 kDa glucose-regulated protein (csGRP78). To determine if these peptides affected the carrier solubility, this library was characterized by light scattering and mass spectrometry. To guide in vitro selection of the most potent functional carrier for rapamycin, its uptake and inhibition of mTORC1 were monitored in a ductal breast cancer model (BT474). Using flow cytometry to track cellular association, it was found that only the targeted carriers enhanced cellular uptake and were susceptible to proteolysis by SubA, which specifically targets csGRP78. The functional inhibition of mTOR was monitored by Western blot for pS6K, whereby the best carrier L-5FA reduced mTOR activity by 3-fold compared to 5FA or free rapamycin. L-5FA was further visualized using super-resolution confocal laser scanning microscopy, which revealed that targeting increased exposure to the carrier by ∼8-fold. This study demonstrates how peptide ligands for GRP78, such as the L peptide (RLLDTNRPLLPY), may be incorporated into protein-based drug carriers to enhance targeting.

De novo determination of mosquitocidal Cry11Aa and Cry11Ba structures from naturally-occurring nanocrystals.

Cry11Aa and Cry11Ba are the two most potent toxins produced by mosquitocidal Bacillus thuringiensis subsp. israelensis and jegathesan, respectively. The toxins naturally crystallize within the host; however, the crystals are too small for structure determination at synchrotron sources. Therefore, we applied serial femtosecond crystallography at X-ray free electron lasers to in vivo-grown nanocrystals of these toxins. The structure of Cry11Aa was determined de novo using the single-wavelength anomalous dispersion method, which in turn enabled the determination of the Cry11Ba structure by molecular replacement. The two structures reveal a new pattern for in vivo crystallization of Cry toxins, whereby each of their three domains packs with a symmetrically identical domain, and a cleavable crystal packing motif is located within the protoxin rather than at the termini. The diversity of in vivo crystallization patterns suggests explanations for their varied levels of toxicity and rational approaches to improve these toxins for mosquito control.

Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR.

High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage beta-cells under different circumstances. Here, by feeding mice a high-fat diet (HFD) for 2 weeks to up to 14 months, the study showed that HFD initially causes the beta-cells to expand in population, whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge. To prevent the failure of beta-cells and the development of type 2 diabetes, the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure were explored. Using palmitic acid (PA) in cultured beta-cells and islets, the study demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with down-regulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT down-regulation by PA is correlated with the induction of mTOR/S6K activity. Inhibiting mTOR activity with rapamycin induced Raptor and restored AKT activity, allowing beta-cells to gain proliferation capacity that was lost after HFD exposure. In summary, a novel mechanism in which lipid exposure may cause the dipole effects on beta-cell growth was elucidated, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.

Sincronía de diferentes tumores radioinducidos en superviviente de leucemia linfoblástica aguda / Different radioinducid tumors synchrony in an acute lymphoblastic leukemia survivor

La aparición de tumores craneales inducidos por radiación en pacientes pediátricos tratados de enfermedades hematológicas como la leucemia/linfoma linfoblástico T (T-ALL/LBL) es un fenómeno conocido que puede incluir lesiones de diferentes grados de malignidad y precisar tratamiento neuroquirúrgico. Presentamos el caso de un varón de 38 años remitido a nuestro servicio por la aparición brusca de diplopía con hemiparesia izquierda progresiva de 6 meses de evolución y caídas frecuentes. Tras realización de pruebas de imagen, se objetivan distintas lesiones intraaxiales y extraaxiales con diferente comportamiento radiológico decidiéndose un abordaje quirúrgico único para su exéresis. La anatomía patológica confirma cuatro variantes histológicas: meningioma (grado 1 y 2 [atípico]), subependimoma y cavernoma. Discutimos el papel teratogénico y efectos biológicos de las radiaciones ionizantes (AU)

The cranial radiation-induced tumors appearance in pediatric patients treated for hematological diseases such as leukemia/T-lymphoblastic lymphoma (T-ALL/LBL) is a known phenomenon that may include lesions of different malignant degrees and require neurosurgical treatment. We present the case of a 38-year-old man referred to our department for a sudden diplopia with 6-month progressive left hemiparesis and frequent falls. After imaging tests, different intra and extraxial lesions with different radiological behavior were observed, performing a single surgical approach for their resection. The pathological anatomy confirms four histological variants: meningioma (grade 1 and 2 [atypical]), subependymoma, and cavernoma. We discuss the teratogenic role of ionizing radiation (AU)