The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38ß MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38ß MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Sociodemographic and clinical characteristics associated with maternal and congenital syphilis - A prospective study in Peru.

OBJECTIVES: The objective of this study was to explore the factors and outcomes associated with gestational syphilis in Peru. METHODS: Women from the miscarriage, vaginal delivery, and C-section wards from a large maternity hospital in Lima with or without syphilis diagnosis were enrolled and their pregnancy outcomes compared. Maternal syphilis status using maternal blood and child serostatus using cord blood were determined by rapid plasma reagin (RPR) and rapid syphilis tests. The newborns' clinical records were used to determine congenital syphilis. RESULTS: A total of 340 women were enrolled, 197 were positive and 143 were negative for RPR/rapid syphilis tests. Antibody titers in sera from cord and maternal blood were comparable with RPR titers and were highly correlated (rho = 0.82, P <0.001). Young age (P = 0.009) and lower birth weight (P = 0.029) were associated with gestational syphilis. Of the women with gestational syphilis, 76% had received proper treatment. Mothers of all newborns with congenital syphilis also received appropriate treatment. Treatment of their sexual partners was not documented. CONCLUSIONS: Syphilis during pregnancy remains a major cause of the fetal loss and devastating effects of congenital syphilis in newborns.

Enhanced recovery and same-day discharge after brain tumor surgery under general anesthesia: initial experience with Hospital-at-Home-based postoperative follow-up.

OBJECTIVE: The objective of this study was to describe the outcomes of outpatient oncological neurosurgery (OON) in a European clinical setting and to compare them with the conventional inpatient protocol. METHODS: Patients who had undergone OON (either tumor removal or biopsy) at the authors' center since 2019 were analyzed. A matched cohort of patients was selected from patients undergoing tumor surgery in the same period. Collected data included patient demographics, postoperative progress, specific location of the target lesion, and the procedure performed. RESULTS: There were 18 patients in the case group and 59 patients in the control group. The outpatient surgeries had a same-day discharge rate of 89%, and all ambulatory patients successfully completed the Enhanced Recovery After Surgery program within 6.24 hours of the procedure. All ambulatory patients underwent Hospital-at-Home postoperative follow-up for an average of 4.12 days. Radiological complications were present in 11% of the case group and 8% of the control group. Postoperative neurological deficit occurred in 6% of the same-day discharge group and 3% of the control group. Among the patients in the control group, 3% suffered from postoperative seizures, whereas no seizures were observed in the case group. These differences were not statistically significant. General anesthesia-related complications were not observed in any of the patients. CONCLUSIONS: The authors' findings demonstrate that Enhanced Recovery After Surgery protocols and same-day discharge craniotomy for tumor resection and image-guided biopsy under general anesthesia, when patients are carefully selected, can be safely performed with excellent outcomes in a European clinical setting. The OON program proved to be a viable alternative to conventional hospitalization, showing comparable safety records and offering advantages in terms of patient recovery.

Self-Supported Spray-Coated NiFe-LDH Catalyst on a Stainless Steel Substrate for Efficient Oxygen Evolution Reaction.

In the quest for more efficient and cost-effective electrocatalytic systems, careful selection of catalysts and substrates plays a pivotal role. This study introduces an approach by synthesizing and depositing NiFe-layered double hydroxide (NiFe-LDH) catalysts on commercial AISI 304 substrates by using a low-temperature spray-coating technique. Through systematic investigations, the influence of processing conditions, such as the synthesis, ultrasonic power for having a stable nanoparticle's dispersion, and spray cycle optimization on the electrochemical and morphological properties of the coatings, is thoroughly explored. The results showcase exceptional catalytic performance, achieving an overpotential of 230 mV at 10 mA/cm2, with enhanced stability even at high current densities of 500 mA/cm2. The study highlights the significance of meticulous processing optimization and presents a scalable methodology that holds great potential for developing catalysts for oxygen evolution reactions (OER) and facilitates their integration into industrial processes.

Insulin and the kidneys: a contemporary view on the molecular basis.

Insulin is a hormone that is composed of 51 amino acids and structurally organized as a hexamer comprising three heterodimers. Insulin is the central hormone involved in the control of glucose and lipid metabolism, aiding in processes such as body homeostasis and cell growth. Insulin is synthesized as a large preprohormone and has a leader sequence or signal peptide that appears to be responsible for transport to the endoplasmic reticulum membranes. The interaction of insulin with the kidneys is a dynamic and multicenter process, as it acts in multiple sites throughout the nephron. Insulin acts on a range of tissues, from the glomerulus to the renal tubule, by modulating different functions such as glomerular filtration, gluconeogenesis, natriuresis, glucose uptake, regulation of ion transport, and the prevention of apoptosis. On the other hand, there is sufficient evidence showing the insulin receptor's involvement in renal functions and its responsibility for the regulation of glucose homeostasis, which enables us to understand its contribution to the insulin resistance phenomenon and its association with the progression of diabetic kidney disease.

3D-Printable PLA/Mg Composite Filaments for Potential Bone Tissue Engineering Applications.

Magnesium (Mg) is a promising material for bone tissue engineering applications due to it having similar mechanical properties to bones, biocompatibility, and biodegradability. The primary goal of this study is to investigate the potential of using solvent-casted polylactic acid (PLA) loaded Mg (WE43) composites as filament feedstock for fused deposition modeling (FDM) 3D Printing. Four PLA/Magnesium (WE43) compositions (5, 10, 15, 20 wt%) are synthesized and produced into filaments, then used to print test samples on an FDM 3D printer. Assessments are made on how Mg incorporation affected PLA's thermal, physicochemical, and printability characteristics. The SEM study of the films shows that the Mg particles are uniformly distributed in all the compositions. The FTIR results indicate that the Mg particles blend well with the polymer matrix and there is no chemical reaction between the PLA and the Mg particles during the blending process. The thermal studies show that the addition of Mg leads to a small increase in the melting peak reaching a maximum of 172.8 °C for 20% Mg samples. However, there are no dramatic variations in the degree of crystallinity among the Mg-loaded samples. The filament cross-section images show that the distribution of Mg particles is uniform up to a concentration of 15% Mg. Beyond that, non-uniform distribution and an increase in pores in the vicinity of the Mg particles is shown to affect their printability. Overall, 5% and 10% Mg composite filaments were printable and have the potential to be used as composite biomaterials for 3D-printed bone implants.

Discriminating Glioblastoma from Peritumoral Tissue by a Nanohole Array-Based Optical and Label-Free Biosensor.

In glioblastoma (GBM) patients, maximal safe resection remains a challenge today due to its invasiveness and diffuse parenchymal infiltration. In this context, plasmonic biosensors could potentially help to discriminate tumor tissue from peritumoral parenchyma based on differences in their optical properties. A nanostructured gold biosensor was used ex vivo to identify tumor tissue in a prospective series of 35 GBM patients who underwent surgical treatment. For each patient, two paired samples, tumor and peritumoral tissue, were extracted. Then, the imprint left by each sample on the surface of the biosensor was individually analyzed, obtaining the difference between their refractive indices. The tumor and non-tumor origins of each tissue were assessed by histopathological analysis. The refractive index (RI) values obtained by analyzing the imprint of the tissue were significantly lower (p = 0.0047) in the peritumoral samples (1.341, Interquartile Range (IQR) 1.339-1.349) compared with the tumor samples (1.350, IQR 1.344-1.363). The ROC (receiver operating characteristic) curve showed the capacity of the biosensor to discriminate between both tissues (area under the curve, 0.8779, p < 0.0001). The Youden index provided an optimal RI cut-off point of 0.003. The sensitivity and specificity of the biosensor were 81% and 80%, respectively. Overall, the plasmonic-based nanostructured biosensor is a label-free system with the potential to be used for real-time intraoperative discrimination between tumor and peritumoral tissue in patients with GBM.

The current state of the art of primary motor mapping for tumor resection: A focused survey.

INTRODUCTION: Cortical and subcortical motor mapping has advanced the notion of maximal safe resection of intra-axial brain tumours, thereby preserving neurological functions as well as improving survival. Despite being an age-old and established neurosurgical procedure across the world, the strategy and techniques involved in motor mapping have a gamut of variation due to a lack of defined standard protocols. METHODS: We disseminated a structured survey among focused group of neurosurgeons with established practices involving brain mapping. It consisted of 40 questions, split into five sections assessing the practice description, general approach for motor mapping, preference for asleep versus awake mapping, operative techniques and approach to representative tumor cases. Practice-patterns during primary motor mapping for brain tumours were analysed from responses of 51 neurosurgeons. RESULTS: 60.8 % felt that any lesion even near (without infiltration) was suffice to define "involvement" of the cortical/subcortical motor pathways. 82.4 % felt that motor mapping was necessary for brain tumours involving motor pathways, irrespective of the tumor histology or patient age. 90.2 % opined that tumor location was the predominant factor affecting their choice between awake or asleep mapping. 31.4 % believed that all cases should be performed awake unless patient-related medical, psychological, or anaesthetic contraindications exist, whereas 45.1 % felt that all cases should be performed asleep unless language mapping is required. MRI, DTI-based tractography and intra-operative fluorescence were the most commonly employed surgical adjuncts. CONCLUSIONS: The data from this survey may serve as a preliminary foundation for a more standardized approach to patient selection and the approach to motor mapping for brain tumors.

Mind the Pulp: Environmental and economic assessment of a sugar beet pulp biorefinery for biobased chemical production.

Sugar beet pulp, a byproduct from sugar beet refining, is used by farmers as fertilizer or sold as animal feed. Both options underestimate the potential of sugar beet pulp as a platform to produce specialty and bulky chemicals as a promising pathway for sustainable biochemicals - mind the pulp. This study proposes a biorefinery concept to produce food additives (pectin-derived oligosaccharides) and bulky chemicals (terephthalic acid). Since the biorefinery has a low technology readiness level (TRL = 1), it is relevant to evaluate the feasibility of this biorefinery concept to provide guidance (at an early stage) on the environmental and economic advantages and limitations. For this purpose, the life cycle assessment and techno-economic assessment frameworks are used to assess the environmental impact and economic performance of the biobased terephthalic acid, respectively. Moreover, environmental impacts are accounted for in economic terms using different monetary valuation methods (environmental prices, Ecovalue12, and Ecotax). The environmental impact of biobased terephthalic acid was higher in most impact categories than the fossil counterpart, depending on the selected allocation approach (mass vs economic). The economic feasibility of the proposed biorefinery is highly dependent on the pectin-derived oligosaccharides market price and the valorization of byproducts (humins and levulinic acid). The selection of the monetary valuation method is critical for monetizing environmental impacts when comparing biobased against fossil-based alternatives.

Monitoring COVID-19 in Colombia during the first year of the pandemic.

Background: COVID-19 cases in Medellín, the second largest city in Colombia, were monitored during the first year of the pandemic using both mathematical models based on transmission theory and surveillance from each observed epidemic phase. Design and Methods: Expected cases were estimated using mandatory reporting data from Colombia's national epidemiological surveillance system from March 7, 2020 to March 7, 2021. Initially, the range of daily expected cases was estimated using a Borel-Tanner stochastic model and a deterministic Susceptible-Infected-Removed (SIR) model. A subsequent expanded version of the SIR model was used to include asymptomatic cases, severe cases and deaths. The moving average, standard deviation, and goodness of fit of estimated cases relative to confirmed reported cases were assessed, and local transmission in Medellin was contrasted with national transmission in Colombia. Results: The initial phase was characterized by imported case detection and the later phase by community transmission and increases in case magnitude and severity. In the initial phase, a maximum range of expected cases was obtained based on the stochastic model, which even accounted for the reduction of new imported cases following the closure of international airports. The deterministic estimate achieved an adequate fit with respect to accumulated cases until the conclusion of the mandatory national quarantine and gradual reopening, when reported cases increased. The estimated new cases were reasonably fit with the maximum reported incidence. Conclusion: Adequate model fit was obtained with the reported data. This experience of monitoring epidemic trajectory can be extended using models adapted to local conditions.

Barriers and facilitators in the implementation of a telemedicine-based outpatient brain tumor surgery program.

OBJECTIVE: Despite growing evidence on the benefits of outpatient oncological neurosurgery (OON), it is only performed in a few specialized centers and there are no previous descriptions of established OON programs in Europe. Moreover, increasing application of telemedicine strategies, especially after the start of the coronavirus disease 2019 (COVID-19) pandemic, is drastically changing neurosurgical management, particularly in the case of vulnerable populations such as neuro-oncological patients. In this context, the authors implemented an OON program in their hospital with telematic follow-up. Herein, they describe the protocol and qualitatively analyze the barriers and facilitators of the development process. METHODS: An OON program was developed through the following steps: assessment of hospital needs, specific OON training, multidisciplinary team organization, and OON protocol design. In addition, the implementation phase included training sessions, a pilot study, and continuous improvement sessions. Finally, barriers and facilitators of the protocol's implementation were identified from the feedback of all participants. RESULTS: An OON protocol was successfully designed and implemented for resection or biopsy of supratentorial lesions up to 3 cm in diameter. The protocol included the patient's admission to the day surgery unit, noninvasive anesthetic monitoring, same-day discharge, and admission to the hospital-at-home (HaH) unit for telematic and on-site postoperative care. After a pilot study including 10 procedures in 9 patients, the main barriers identified were healthcare provider resistance to change, lack of experience in outpatient neurosurgery, patient reluctance, and limitations in the recruitment of patients. Key facilitators of the process were the patient education program, the multidisciplinary team approach, and the HaH-based telematic postoperative care. CONCLUSIONS: Initiating an OON program with telematic follow-up in a European clinical setting is feasible. Nevertheless, it poses several barriers that can be overcome by identifying and maximizing key facilitators of the process. Among them, patient education, a multidisciplinary team approach, and HaH-based postoperative care were crucial to the success of the program. Future studies should investigate the cost-effectiveness of telemedicine to assess potential cost savings, from reduced travel and wait times, and the impact on patient satisfaction.

COVID-19, body weight and the neighbourhood: food system dimensions and consumption associated with changes in body weight of Peruvian adults during first wave lockdowns.

Objective: The objective of this study is to assess changes in the dimensions of the food system and consumption associated with body weight variations during the first month's lockdown in Peruvian adults in Metropolitan Lima. Methods: A cross-sectional study conducted during the first months of lockdowns in Peru. 694 adults completed a web-based survey about changes experienced in the process of acquiring food during lockdown, changes in their intake and self-perceived body weight. A multinomial logistic regression analysis was conducted to evaluate the factors associated with changes in body weight. Results: Weight gain was perceived in 38% of the participants and 22.8% perceived weight loss. 39.2% did not perceive changes in their weight. Risk factors for body weight gain were increased alcohol consumption (OR=4.510, 95% CI 1.764 to 11.531) and decreased fruit consumption (OR=2.129, 95% CI 1.290 to 3.515), while decreasing cereal intake (OR=0.498, 95% CI 0.269 to 0.922) and choosing nutritious food as a driver for purchase (OR=0.512, 95% CI 0.320 to 0.821) were found to be protective against gaining weight. Decreasing food intake during the pandemic (OR=2.188, 95% CI 1.348 to 3.550) and having to miss important foods (OR=2.354, 95% CI 1.393 to 3.978), were associated with weight loss. Conclusions: During confinement, weight gain was mostly associated with food consumption and personal food system factors. Meanwhile, weight loss was associated with external food system factors.

Visual Mapping for Tumor Resection: A Proof of Concept of a New Intraoperative Task and A Systematic Review of the Literature.

Homonymous hemianopia has been reported after brain tumor resection with a significant effect on quality of life. Nevertheless, no standardized methods exist for intraoperative optical radiation mapping. The purpose of this article is to describe a new intraoperative task for visual mapping and to review the existing literature. A Central and Peripheral Image task was used to map optic radiations during brain tumor resection in 3 patients. A systematic review was performed following PRISMA 2020 guidelines, with 25 of 449 articles included. Optic radiations were identified in all patients and preserved in all but one, in whom the extent of resection prevailed. The literature review exposed 2 methods to assess visual function: visual evoked potentials (VEP) and direct electric stimulation (DES), with 13 and 12 articles and 341 and 63 patients, respectively. Hemianopia was developed in 13.49% of patients with VEP versus 1.59% of patients with DES. The use of DES might be associated with a better outcome (level IV evidence). However, standardization of intraoperative tasks during DES could be improved. In this context, the Central and Peripheral Image task might be an adequate tool for the resection of tumors affecting the optic radiations.

Signaling Pathways Regulating the Expression of the Glioblastoma Invasion Factor TENM1.

Glioblastoma (GBM) is one of the most aggressive cancers, with dismal prognosis despite continuous efforts to improve treatment. Poor prognosis is mostly due to the invasive nature of GBM. Thus, most research has focused on studying the molecular players involved in GBM cell migration and invasion of the surrounding parenchyma, trying to identify effective therapeutic targets against this lethal cancer. Our laboratory discovered the implication of TENM1, also known as ODZ1, in GBM cell migration in vitro and in tumor invasion using different in vivo models. Moreover, we investigated the microenvironmental stimuli that promote the expression of TENM1 in GBM cells and found that macrophage-secreted IL-6 and the extracellular matrix component fibronectin upregulated TENM1 through activation of Stat3. We also described that hypoxia, a common feature of GBM tumors, was able to induce TENM1 by both an epigenetic mechanism and a HIF2α-mediated transcriptional pathway. The fact that TENM1 is a convergence point for various cancer-related signaling pathways might give us a new therapeutic opportunity for GBM treatment. Here, we briefly review the findings described so far about the mechanisms that control the expression of the GBM invasion factor TENM1.

HIF2α Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells.

Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.

Surrogate test performance for SARS-CoV-2 neutralizing antibodies (nAbs) for convalescent plasma (CCP): How useful could they be?

BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.

Unilateral and Bilateral Post-Activation Performance Enhancement on Jump Performance and Agility.

This study aimed to compare the effects of the post-activation performance enhancement (PAPE) of two different types of warm-ups, unilateral and bilateral, on the performance in vertical jumping and agility of healthy subjects with strength training experience. In the study, 17 subjects (12 men and 5 women) performed two different PAPE protocols: unilateral squat (UT) and bilateral squat (BT). The height of the subjects' countermovement jump (CMJ) and the subjects' time to perform the T-agility test (TAT) were measured before and after executing the PAPE warm-up. The squats were performed at a velocity of 0.59 m·s-1 with three sets of three repetitions, with a 3-min rest between sets and a 5-min rest after both uni- and bilateral PAPE warm-ups before taking the tests again. For statistical analysis, we applied ANOVA and calculated the effect size. The results showed that the PAPE for each case decreased the CMJ height but generated significant improvements in the total time taken for the T-agility test (p < 0.01); however, in both cases, the effect sizes were trivial. In conclusion, it is possible to observe that the PAPE, performed both unilaterally and bilaterally, negatively affects the performance in the vertical jump, showing moderate effect sizes. However, both PAPE protocols show performance benefits in agility tests, with a large effect size for the unilateral protocol and moderate for the bilateral protocol.

Análisis del modelo multicausal sobre el nivel de la anemia en niños de 6 a 35 meses en Perú / Analysis of the multicausal model of anemia level in children 6-35 months old in Peru

Introducción: La anemia ferropénica en niños de 6 a 35 meses es un problema de Salud Pública severa. Objetivo: Determinar la prevalencia del nivel de anemia y sus factores asociados en niños menores de tres años utilizando un modelo multicausal en la población peruana. Materiales y métodos Se realizó un estudio de nivel explicativo a través de un análisis secundario con los datos de la base de datos de la Encuesta Demográfica y de Salud Familiar del 2019. La variable principal fue el nivel de anemia utilizando el Hemocue® para su medición. Se consideraron valores ponderados; frecuencias, porcentajes, bondad de ajuste y un modelo de regresión ordinal. Resultados: Un 40.20% de niños menores de tres años presentaron anemia. Los factores como presencia de diarrea (OR=1,30), 12 meses de vida (OR: 3,33), no iniciar el control prenatal (OR:1,19), sexo masculino (OR: 1.25), madre con anemia (OR: 1.75), madre de 15 a 24 años (OR: 1.94), pozo de tierra como fuente de agua (OR: 1,53), lengua materna aymara (OR: 2,31) se asociaron al nivel de anemia. Conclusiones: Entre los factores de riesgo asociados a la anemia según el modelo multicausal resultan la diarrea en las últimas dos semanas como factor inmediato, entre los subyacentes son edad del niño, fuente de agua poTable, control prenatal, anemia y edad de la mujer. Asimismo, los factores protectores corresponden al amamantamiento por alguna vez y quintil de riqueza superior. (AU)

Transopercular Insular Approach, Overcoming the Training Curve Using a Cadaveric Simulation Model: 2-Dimensional Operative Video.

Transopercular approach to the insula is indicated for resection of insular low-grade gliomas, particularly for Yasargil's 3B, 5A, and 5B types. Nevertheless, the infrequent location and its challenging approach make it difficult to master the surgery. Consequently, a realistic laboratory training model might help to acquire key surgical skills. In this video, we describe a cadaveric-based model simulating the resection of a temporo-insular low-grade glioma. Kingler's fixation technique was used to fix the cadaver head before injecting red and blue colorants for a realistic vascular appearance. Hemisphere was frozen for white matter tract dissection. Tractography and intraoperative eloquent areas were extrapolated from a glioma patient by using a neuronavigation system. Then, a fronto-temporal craniotomy was performed through a question mark incision, exposing from inferior temporal gyrus up to middle frontal gyrus. After cortical anatomic landmark identification, eloquent areas were extrapolated creating a simulated functional cortical map. Then, transopercular noneloquent frontal and temporal corticectomies were performed, followed by subpial resection. Detailed identification of Sylvian vessels and insular cortex was demonstrated. Anatomic resection limits were exposed, and implicated white matter bundles, uncinate and fronto-occipital fascicles, were identified running through the temporal isthmus. Finally, a temporo-mesial resection was performed. In summary, this model provides a simple, cost-effective, and very realistic simulation of a transopercular approach to the insula, allowing the development of surgical skills needed to treat insular tumors in a safe environment. Besides, the integration of simulated navigation has proven useful in better understanding the complex white matter anatomy involved. Cadaver donation, subject or relatives, includes full consent for publication of the images. For the purpose of this video, no ethics committee approval was needed. Images correspond to a cadaver head donation. Cadaver donation, subject or relatives, includes full consent for any scientific purposes involving the corpse. The consent includes image or video recording. Regarding the intraoperative surgical video and tractography, the patient gave written consent for scientific divulgation prior to surgery.

Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway.

We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.