Gamma Knife radiosurgery for the management of glomus jugulare tumors: A systematic review and report of the experience of a radioneurosurgery unit in Latin America.

Background: Glomus jugulare tumors (GJTs) are rare and mainly affect women between the 5th and 6th decades of life. Its localization and anatomic relationships make conventional surgical treatment difficult and with a considerable risk of complications. This manuscript aims to describe the results of Gamma Knife radiosurgery (GKR) in patients with GJT treated in a single center in Latin America, as well as to systematically review the literature to determine the clinical and radiological effectiveness of this technique. Methods: A search of information from January 1995 to June 2023 was performed. Twenty-two articles reporting 721 GJT patients treated with GKR were included in the study. Variables such as symptomatic control, control of tumor size, and complications were evaluated. These variables were described using measures of central tendency and proportions. For the institutional experience, 77 patients with GJT tumors were included in the study. Pre-treatment clinical variables and follow-up data were collected from medical charts and phone interviews. The Short Form-36 scale was applied to assess the quality of life. The data were analyzed using the statistical program STATA17.0. Results: A total of 721 patients were considered. The median of patients included in these studies was 18.5. The mean age was 58.4 years. The median of symptom control was 89%, and the median of imaging control was 95.7%. In our institution, 77 patients were included in the study. The mean age was 53.2 years. The median hospital stay was 4.92 hours. For the clinical follow-up, information on 47 patients was obtained. An improvement in pre-treatment symptoms was described in 58%, with general symptomatic control of 97%. The tumor-control rate was 95%, and there were statistically significant differences in six of the nine Short Form-36 scale domains. Conclusion: GKR is an effective, safe, and cost-effective technique that offers a high degree of symptomatic and tumor size control in patients with GJT.

PSMA-targeted small-molecule drug-conjugates with valine-citrulline and phosphoramidate cleavable linkers.

In this study, we present a modular synthesis and evaluation of two prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugates (SMDCs) incorporating the potent chemotherapeutic agent monomethyl auristatin E (MMAE). These SMDCs are distinguished by their cleavable linker modules: one utilizing the widely known valine-citrulline linker, susceptible to cleavage by cathepsin B, and the other featuring a novel acid-labile phosphoramidate-based (PhosAm) linker. Both SMDCs maintained nanomolar affinity to PSMA. Furthermore, we confirmed the selective release of the payload and observed chemotherapeutic efficacy specifically within PSMA-positive prostate cancer cells, while maintaining cell viability in PSMA-negative cells. These findings not only validate the efficacy of our approach but also highlight the potential of the innovative pH-responsive PhosAm linker. This study contributes significantly to the field and also paves the way for future advancements in targeted cancer therapy.

ß-Phase Enhancement of Force Spun Composite Nanofibers for Sensing Applications.

In this study, a piezoelectric harvesting device was developed using polyvinylidene fluoride (PVDF) nanofibers reinforced with either BaTiO3 nanoparticles or graphene powder. BaTiO3 nanoparticles were synthesized through the sol-gel method with an average size of approximately 32 nm. The PVDF nanofibers, along with the nanoparticle composites in an acetone-N,N-dimethylformamide mixture, were produced using a centrifugal Forcespinning™ machine, resulting in a heterogeneous arrangement of fiber meshes, with an average diameter of 1.6 µm. Experimental tests revealed that the electrical performance of the fabricated harvester reached a maximum value of 35.8 Voc, demonstrating the potential of BaTiO3/ PVDF-based piezoelectric devices for designing wearable applications such as body-sensing and energy-harvesting devices.

Magnetic and Viscoelastic Response of Magnetorheological Elastomers Based on a Combination of Iron Nano- and Microparticles.

In this paper, we discuss the creation of a hybrid magnetorheological elastomer that combines nano- and microparticles. The mixture contained 45 wt.% fillers, with combinations of either 0% nanoparticles and 100% microparticles or 25% nanoparticles and 75% microparticles. TGA and FTIR testing confirmed the materials' thermal and chemical stability, while an SEM analysis determined the particles' size and morphology. XRD results were used to determine the crystal size of both nano- and microparticles. The addition of reinforcing particles, particularly nanoparticles, enhanced the stiffness of the composite materials studied, but their overall strength was only minimally affected. The computed interaction parameter relative to the volume fraction was consistent with the previous literature. Furthermore, the study observed a magnetic response increment in composite materials reinforced with nanoparticles above 30 Hz. The isotropic material containing only microparticles had a lower storage modulus than the isotropic sample with nanoparticles without a magnetic field. However, when a magnetic field was applied, the material with only microparticles exhibited a higher storage modulus than the samples with nanoparticles.

Modeling the Ultrasonic Micro-Injection Molding Process Using the Buckingham Pi Theorem.

Dimensional analysis through the Buckingham Pi theorem was confirmed as an efficient mathematical tool to model the otherwise non-linear high order ultrasonic micro-injection molding process (UMIM). Several combinations of processing conditions were evaluated to obtain experimental measurements and validate the derived equations. UMIM processing parameters, output variable energy consumption, and final specimen's Young modulus were arranged in dimensionless groups and formulated as functional relationships, which lead to dimensionless equations that predict output variables as a function of the user-specified processing parameters and known material properties.

Ferroptosis of Microglia in Aging Human White Matter Injury.

OBJECTIVE: Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia. METHODS: We analyzed postmortem human brain tissue to define a population of DM in aging WM lesions. We used immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM. RESULTS: We found that DM, which accumulated myelin debris were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. We identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in WM injury relative to gray matter neurodegeneration. INTERPRETATION: Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment. ANN NEUROL 2023;94:1048-1066.

Inducing Magnetic Properties with Ferrite Nanoparticles in Resins for Additive Manufacturing.

Additive manufacturing and nanotechnology have been used as fundamental tools for the production of nanostructured parts with magnetic properties, expanding the range of applications in additive processes through tank photopolymerization. Magnetic cobalt ferrite (CoFe2O4) and barium ferrite (BaFe12O19) nanoparticles (NPs) with an average size distribution value (DTEM) of 12 ± 2.95 nm and 37 ± 12.78 nm, respectively, were generated by the hydroxide precipitation method. The dispersion of the NPs in commercial resins (Anycubic Green and IRIX White resin) was achieved through mechanochemical reactions carried out in an agate mortar for 20 min at room temperature, with limited exposure to light. The resulting product of each reaction was placed in amber vials and stored in a box to avoid light exposure. The photopolymerization process was carried out only at low concentrations (% w/w NPs/resin) since high concentrations did not result in the formation of pieces, due to the high refractive index of ferrites. The Raman spectroscopy of the final pieces showed the presence of magnetic NPs without any apparent chemical changes. The electron paramagnetic resonance (EPR) results of the pieces demonstrated that their magnetic properties were maintained and not altered during the photopolymerization. Although significant differences were observed in the dispersion process of the NPs in each piece, we determined that the photopolymerization did not affect the structure and superparamagnetic behavior of ferrite NPs during processing, successfully transferring the magnetic properties to the final 3D-printed piece.

Polypropylene-Based Polymer Locking Ligation System Manufacturing by the Ultrasonic Micromolding Process.

In recent years, there has been a growing demand for biocompatible medical devices on the microscale. However, the manufacturing of certain microfeatures has posed a significant challenge. To address this limitation, a new process called ultrasonic injection molding or ultrasonic molding (USM) has emerged as a potential solution. In this study, we focused on the production of a specific microdevice known as Hem-O-Lok, which is designed for ligation and tissue repair during laparoscopic surgery. Utilizing USM technology, we successfully manufactured the microdevice using a nonabsorbable biopolymer that offers the necessary flexibility for easy handling and use. To ensure high-quality microdevices, we extensively investigated various processing parameters such as vibration amplitude, temperature, and injection velocity. Through careful experimentation, we determined that the microdevice achieved optimal quality when manufactured under conditions of maximum vibrational amplitude and temperatures of 50 and 60 °C. This conclusion was supported by measurements of critical microfeatures. Additionally, our materials characterization efforts revealed the presence of a carbonyl (C=O) group resulting from the thermo-oxidation of air in the plasticizing chamber. This finding contributes to the enhanced thermal stability of the microdevices within a temperature range of 429-437 °C.

A Novel Approach for Optimization of Soft Material Constitutive Model Parameters Based on a Genetic Algorithm and Drucker's Stability Criterion.

The growing interest in soft materials to develop flexible devices involves the need to create accurate methodologies to determine parameter values of constitutive models to improve their modeling. In this work, a novel approach for the optimization of constitutive model parameters is presented, which consists of using a genetic algorithm (GA) to obtain a set of solutions from data of uniaxial tensile tests, which are later used to simulate the mechanical test using finite element analysis (FEA) software to find an optimal solution considering Drucker's stability criterion. This approach was applied to the elastomer Ecoflex 00-30 considering the Warner and Yeoh models and Rivlin's phenomenological theory. The correlation between the experimental and the predicted data by the models was determined using the root mean squared error (RMSE), where the found parameter sets provided a close fit to the experimental data with RMSE values of 0.022 (ANSYS) and 0.024 (ABAQUS) for Warner's model, while for Yeoh's model were 0.014 (ANSYS) and 0.012 (ABAQUS). It was found that the best parameter values accurately follow the experimental material behavior using FEA. The proposed GA not only optimizes the material parameters but also has a high reproducibility level with average RMSE values of 0.024 for Warner's model and 0.009 for Yeoh's model, fulfilling Drucker's stability criterion.

Prefrontal engrams of long-term fear memory perpetuate pain perception.

A painful episode can lead to a life-long increase in an individual's experience of pain. Fearful anticipation of imminent pain could play a role in this phenomenon, but the neurobiological underpinnings are unclear because fear can both suppress and enhance pain. Here, we show in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex determines whether a painful episode shapes pain experience later in life. Furthermore, under conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia. These results reveal that a discrete subset of prefrontal cortex neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself.

Quality contract 'prevention of postoperative delirium in the care of elderly patients' study protocol: a non-randomised, pre-post, monocentric, prospective trial.

INTRODUCTION: Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a 'quality contract' (QC) as a new instrument to improve healthcare in Germany. One of the four areas for improvement of in-patient care is the 'Prevention of POD in the care of elderly patients' (QC-POD), as a means to reduce the risk of developing POD and its complications.The Institute for Quality Assurance and Transparency in Health Care identified gaps in the in-patient care of elderly patients related to the prevention, screening and treatment of POD, as required by consensus-based and evidence-based delirium guidelines. This paper introduces the QC-POD protocol, which aims to implement these guidelines into the clinical routine. There is an urgent need for well-structured, standardised and interdisciplinary pathways that enable the reliable screening and treatment of POD. Along with effective preventive measures, these concepts have a considerable potential to improve the care of elderly patients. METHODS AND ANALYSIS: The QC-POD study is a non-randomised, pre-post, monocentric, prospective trial with an interventional concept following a baseline control period. The QC-POD trial was initiated on 1 April 2020 between Charité-Universitätsmedizin Berlin and the German health insurance company BARMER and will end on 30 June 2023. INCLUSION CRITERIA: patients 70 years of age or older that are scheduled for a surgical procedure requiring anaesthesia and insurance with the QC partner (BARMER). Exclusion criteria included patients with a language barrier, moribund patients and those unwilling or unable to provide informed consent. The QC-POD protocol provides perioperative intervention at least two times per day, with delirium screening and non-pharmacological preventive measures. ETHICS AND DISSEMINATION: This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/054/20). The results will be published in a peer-reviewed scientific journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04355195.

Industrial bioelectrochemistry for waste valorization: State of the art and challenges.

Bioelectrochemistry has gained importance in recent years for some of its applications on waste valorization, such as wastewater treatment and carbon dioxide conversion, among others. The aim of this review is to provide an updated overview of the applications of bioelectrochemical systems (BESs) for waste valorization in the industry, identifying current limitations and future perspectives of this technology. BESs are classified according to biorefinery concepts into three different categories: (i) waste to power, (ii) waste to fuel and (iii) waste to chemicals. The main issues related to the scalability of bioelectrochemical systems are discussed, such as electrode construction, the addition of redox mediators and the design parameters of the cells. Among the existing BESs, microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) stand out as the more advanced technologies in terms of implementation and R&D investment. However, there has been little transfer of such achievements to enzymatic electrochemical systems. It is necessary that enzymatic systems learn from the knowledge reached with MFC and MEC to accelerate their development to achieve competitiveness in the short term.

Enzymatic Synthesis of Ascorbyl Palmitate in a Rotating Bed Reactor.

Ascorbyl palmitate, an ascorbic acid ester, is an important amphipathic antioxidant that has several applications in foods, pharmaceuticals, and cosmetics. The enzymatic synthesis of ascorbyl palmitate is very attractive, but few efforts have been made to address its process scale-up and implementation. This study aimed at evaluating the enzymatic synthesis of ascorbyl palmitate in a rotating basket reactor operated in sequential batches. Different commercial immobilized lipases were tested, and the most suitable reaction conditions were established. Among those lipases studied were Amano Lipase PS, Lipozyme® TL IM, Lipozyme® Novo 40086, Lipozyme® RM IM and Lipozyme® 435. Initially, the enzymes were screened based on previously defined synthesis conditions, showing clear differences in behavior. Lipozyme® 435 proved to be the best catalyst, reaching the highest values of initial reaction rate and yield. Therefore, it was selected for the following studies. Among the solvents assayed, 2-methyl-2-butanol and acetone showed the highest yields, but the operational stability of the catalyst was better in 2-methyl-2-butanol. The tests in a basket reactor showed great potential for large-scale application. Yields remained over 80% after four sequential batches, and the basket allowed for easy catalyst recycling. The results obtained in basket reactor are certainly a contribution to the enzymatic synthesis of ascorbyl palmitate as a competitive alternative to chemical synthesis. This may inspire future cost-effectiveness studies of the process to assess its potential as a viable alternative to be implemented.

Operationalizing and automating Data Governance.

The ability to cross data from multiple sources represents a competitive advantage for organizations. Yet, the governance of the data lifecycle, from the data sources into valuable insights, is largely performed in an ad-hoc or manual manner. This is specifically concerning in scenarios where tens or hundreds of continuously evolving data sources produce semi-structured data. To overcome this challenge, we develop a framework for operationalizing and automating data governance. For the first, we propose a zoned data lake architecture and a set of data governance processes that allow the systematic ingestion, transformation and integration of data from heterogeneous sources, in order to make them readily available for business users. For the second, we propose a set of metadata artifacts that allow the automatic execution of data governance processes, addressing a wide range of data management challenges. We showcase the usefulness of the proposed approach using a real world use case, stemming from the collaborative project with the World Health Organization for the management and analysis of data about Neglected Tropical Diseases. Overall, this work contributes on facilitating organizations the adoption of data-driven strategies into a cohesive framework operationalizing and automating data governance.

Simultaneous CO2 reduction and NADH regeneration using formate and glycerol dehydrogenase enzymes co-immobilized on modified natural zeolite.

In this work, the co-immobilization of formate dehydrogenase (FDH) and glycerol dehydrogenase (GlyDH) enzymes is proposed to reduce CO2 into formic acid, an important chemical intermediate. The reduction of carbon dioxide is carried out by FDH to obtain formic acid, simultaneously, the GlyDH regenerated the nicotinamide cofactor in the reduced form (NADH) by the oxidation of glycerol into dihydroxyacetone. Natural zeolite was selected as immobilization support given its good properties and low cost. The natural zeolite was modified with subsequent acid-alkaline attacks to obtain a mesostructurization of the clinoptilolite. The two enzymes were co-immobilized on clinoptilolite, previously hetero-functionalized with amino and glyoxyl groups. The distribution of the enzymes was confirmed by fluorescence microscopy analysis. Furthermore, a great increase in the retained activity for the formate dehydrogenase enzyme was noted, passing from 18% to 89%, when the mesostructured clinoptilolite was used as support. The immobilization yield of formate dehydrogenase and glycerol dehydrogenase is around 100% with all the supports studied. The promising results suggest a possible development of this procedure in enzyme immobilization and biocatalysis. The biocatalysts were characterized to find the optimal pH and temperature. Furthermore, a thermal stability test at 50 °C was carried out on both enzymes, in free and immobilized forms. Finally, it was shown that the biocatalyst is effective in reducing CO2, both by using the cofactor in the reduced form (NADH) or the oxidized form (NAD+), obtaining NADH through the regeneration with glycerol in this latter case.

Toward the Industrial Application of Aluminum-Based Nanocomposite Material: A Study of Zn-Plating Process in Circuit Breaker Application.

This article explores the industrial application of an Al-based nanocomposite reinforced with 0.5 wt.% of multiwalled carbon nanotubes with a Zn mechanical plating applied to fulfill the field requirements of electrical devices. The performance of electric devices made from this nanocomposite material and with a Zn plating was compared with that of MCCB devices using a normal Cu compound. MCCB devices with the Al-based nanocomposites compound showed a better performance, with less heat generated due to a flow of electrical charge passing through the device. The presence of MWCNTs in the Al nanocomposite dissipates heat, maintaining a stable electrical resistance in the MCCB, in contrast to what happens with Cu compound, which increases its electrical resistance as the temperature in the device increases.

Modular Smart Molecules for PSMA-Targeted Chemotherapy.

New targeted chemotherapeutics are urgently needed to minimize off-target toxicity and reduce the high-mortality rate associated with metastatic prostate cancer. Herein, we report on the modular synthesis, pharmacokinetics, and efficacy of two small-molecule-drug conjugates (SMDC) targeted to prostate-specific membrane antigen (PSMA) incorporating either: (i) a cathepsin-B-cleavable valine-citrulline (Val-Cit), or (ii) an acid-cleavable phosphoramidate linker. Crucial components used in the design of the conjugates include: (i) CTT1298, a nanomolar affinity ligand that binds irreversibly to PSMA and has proven in past studies to rapidly internalize and shuttle payloads into PSMA-expressing prostate cancer cells, (ii) MMAE, a known potent cytotoxic payload, and (iii) an albumin-binder, proven to improve residence time of drug conjugates. At dose of 0.8 mg/kg (∼250 nmol/kg), the two SMDCs showed significant efficacy in a PSMA(+) PC3-PIP mouse model of human prostate cancer compared with controls, without inducing systemic toxicity. Though localization of the SMDCs was observed in tissues apart from the tumor, release of MMAE was observed predominantly in tumor tissue, at levels that were 2-3 orders of magnitude higher than non-target tissues. Furthermore, SMDC2, which incorporated a novel pH-responsive phosporamidate linker, demonstrated significantly improved efficacy over SMDC1 that has a Val-Cit linker, with a 100% survival over 90 days and 4 out of 8 mice showing complete tumor growth inhibition after 6 weekly doses of 0.8 mg/kg (244 nmol/kg). Our findings demonstrate the potential of irreversible PSMA inhibitors combined with pH-responsive linkers as a way to specifically deliver chemotherapeutic drugs to prostate cancer tumors with minimal toxicity.

Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations.

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein-energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid's biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences.

Soft Tissue Hybrid Model for Real-Time Simulations.

In this article, a recent formulation for real-time simulation is developed combining the strain energy density of the Spring Mass Model (SMM) with the equivalent representation of the Strain Energy Density Function (SEDF). The resulting Equivalent Energy Spring Model (EESM) is expected to provide information in real-time about the mechanical response of soft tissue when subjected to uniaxial deformations. The proposed model represents a variation of the SMM and can be used to predict the mechanical behavior of biological tissues not only during loading but also during unloading deformation states. To assess the accuracy achieved by the EESM, experimental data was collected from liver porcine samples via uniaxial loading and unloading tensile tests. Validation of the model through numerical predictions achieved a refresh rate of 31 fps (31.49 ms of computation time for each frame), achieving a coefficient of determination R2 from 93.23% to 99.94% when compared to experimental data. The proposed hybrid formulation to characterize soft tissue mechanical behavior is fast enough for real-time simulation and captures the soft material nonlinear virgin and stress-softened effects with high accuracy.

Influence of Epoxy Resin Curing Kinetics on the Mechanical Properties of Carbon Fiber Composites.

In this study, the kinetic parameters belonging to the cross-linking process of a modified epoxy resin, Aerotuf 275-34™, were investigated. Resin curing kinetics are crucial to understanding the structure-property-processing relationship for manufacturing high-performance carbon-fiber-reinforced polymer composites (CFRPCs). The parameters were obtained using differential scanning calorimetry (DSC) measurements and the Flynn-Wall-Ozawa, Kissinger, Borchardt-Daniels, and Friedman approaches. The DSC thermograms show two exothermic peaks that were deconvoluted as two separate reactions that follow autocatalytic models. Furthermore, the mechanical properties of produced carbon fiber/Aerotuf 275-34™ laminates using thermosetting polymers such as epoxies, phenolics, and cyanate esters were evaluated as a function of the conversion degree, and a close correlation was found between the degree of curing and the ultimate tensile strength (UTS). We found that when the composite material is cured at 160 °C for 15 min, it reaches a conversion degree of 0.97 and a UTS value that accounts for 95% of the maximum value obtained at 200 °C (180 MPa). Thus, the application of such processing conditions could be enough to achieve good mechanical properties of the composite laminates. These results suggest the possibility for the development of strategies towards manufacturing high-performance materials based on the modified epoxy resin (Aerotuf 275-34™) through the curing process.