Geniposide and Harpagoside Functionalized Cerium Oxide Nanoparticles as a Potential Neuroprotective.

Alzheimer's disease is associated with protein aggregation, oxidative stress, and the role of acetylcholinesterase in the pathology of the disease. Previous investigations have demonstrated that geniposide and harpagoside protect the brain neurons, and cerium nanoparticles (CeO2 NPs) have potent redox and antioxidant properties. Thus, the effect of nanoparticles of Ce NPs and geniposide and harpagoside (GH/CeO2 NPs) on ameliorating AD pathogenesis was established on AlCl3-induced AD in mice and an aggregation proteins test in vitro. Findings of spectroscopy analysis have revealed that GH/CeO2 NPs are highly stable, nano-size, spherical in shape, amorphous nature, and a total encapsulation of GH in cerium. Treatments with CeO2 NPs, GH/CeO2 NPs, and donepezil used as positive control inhibit fibril formation and protein aggregation, protect structural modifications in the BSA-ribose system, have the ability to counteract Tau protein aggregation and amyloid-ß1-42 aggregation under fibrillation condition, and are able to inhibit AChE and BuChE. While the GH/CeO2 NPs, treatment in AD induced by AlCl3 inhibited amyloid-ß1-42, substantially enhanced the memory, the cognition coordination of movement in part AD pathogenesis may be alleviated through reducing amyloidogenic pathway and AChE and BuChE activities. The findings of this work provide important comprehension of the chemoprotective activities of iridoids combined with nanoparticles. This could be useful in the development of new therapeutic methods for the treatment of neurodegenerative diseases.

Small Cell Neuroendocrine Carcinoma of the Lung Discovered by Acute Appendicitis Metastasis: An Experience at Our Hospital.

Acute appendicitis is the most common cause of abdominal pain that requires surgery. Appendiceal cancer is rare, comprising nearly 4% of all gastrointestinal diagnoses. It is common to find neuroendocrine neoplasms due to metastasis in this site. Appendix tumors are usually asymptomatic; however, if they are advanced or have metastases, they can cause abdominal symptoms. Computed tomography (CT) is commonly used to diagnose acute appendicitis in these cases. CT usually shows an increased appendiceal diameter with thickening (>3 mm) of the appendiceal wall, an intraluminal fluid depth >2.6 mm, and periappendiceal inflammation. Histopathological findings confirm the diagnosis. Medical and surgical management depends on physical characteristics such as size, location, and degree of evolution. We present the case of a 77-year-old woman with a family history of well-controlled type 2 diabetes mellitus and hypertension. She was referred to our institution after four days of abdominal pain in the epigastrium and both flanks accompanied by fever. An abdominal CT showed left pleural effusion and appendicular thickening. Laboratory tests showed high blood glucose levels, leukocytosis at the expense of neutrophils, an increased platelet count, and decreased albumin and total proteins. The CT scan also showed a calcified granuloma in the anterior segment of the right upper lobe and an irregular image with partially defined hypodense borders in the liver in segment IVb. We report our experience with the diagnosis, management, and treatment decisions of this case. It is important to mention that the first diagnosis was acute appendicitis. This diagnosis motivated us to seek other symptoms and signs by direct questioning and imaging studies leading us to diagnose metastatic lung cancer.

Impact of physico-chemical properties on the toxicological potential of reduced graphene oxide in human bronchial epithelial cells.

The increasing use of graphene-based materials (GBM) requires their safety evaluation, especially in occupational settings. The same physico-chemical (PC) properties that confer GBM extraordinary functionalities may affect the potential toxic response. Most toxicity assessments mainly focus on graphene oxide and rarely investigate GBMs varying only by one property. As a novelty, the present study assessed the in vitro cytotoxicity and genotoxicity of six reduced graphene oxides (rGOs) with different PC properties in the human bronchial epithelial 16HBE14o - cell line. Of the six materials, rGO1-rGO4 only differed in the carbon-to-oxygen (C/O) content, whereas rGO5 and rGO6 were characterized by different lateral size and number of layers, respectively, but similar C/O content compared with rGO1. The materials were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, laser diffraction and dynamic light scattering, and Brunauer-Emmett-Teller analysis. Cytotoxicity (Luminescent Cell Viability and WST-8 assays), the induction of reactive oxygen species (ROS; 2',7'-dichlorofluorescin diacetate-based assay), the production of cytokines (enzyme-linked immunosorbent assays) and genotoxicity (comet and micronucleus assays) were evaluated. Furthermore, the internalization of the materials in the cells was confirmed by laser confocal microscopy. No relationships were found between the C/O ratio or the lateral size and any of the rGO-induced biological effects. However, rGO of higher oxygen content showed higher cytotoxic and early ROS-inducing potential, whereas genotoxic effects were observed with the rGO of the lowest density of oxygen groups. On the other hand, a higher number of layers seems to be associated with a decreased potential for inducing cytotoxicity and ROS production.

Intersexual Differences in the Gene Expression of Phoneutria depilata (Araneae, Ctenidae) Toxins Revealed by Venom Gland Transcriptome Analyses.

The wandering spider, Phoneutria depilata, is one of Colombia's most active nocturnal arthropod predators of vertebrates and invertebrates. Its venom has been a relevant subject of study in the last two decades. However, the scarcity of transcriptomic data for the species limits our knowledge of the distinct components present in its venom for linking the mainly neurotoxic effects of the spider venom to a particular molecular target. The transcriptome of the P. depilata venom gland was analyzed to understand the effect of different diets or sex and the impact of these variables on the composition of the venom. We sequenced venom glands obtained from ten males and ten females from three diet treatments: (i) invertebrate: Tenebrio molitor, (ii) vertebrate: Hemidactylus frenatus, and (iii) mixed (T. molitor + H. frenatus). Of 17,354 assembled transcripts from all samples, 65 transcripts relating to venom production differed between males and females. Among them, 36 were classified as neurotoxins, 14 as serine endopeptidases, 11 as other proteins related to venom production, three as metalloprotease toxins, and one as a venom potentiator. There were no differences in transcripts across the analyzed diets, but when considering the effect of diets on differences between the sexes, 59 transcripts were differentially expressed. Our findings provide essential information on toxins differentially expressed that can be related to sex and the plasticity of the diet of P. depilata and thus can be used as a reference for venomics of other wandering spider species.

Measurement of voluntary bite forces in large carnivores using a semi-automated reward-driven system.

Bite force is a key performance trait of the feeding system, but maximal in vivo bite force has been measured in few large mammals. The alternative, modelling of bite force from anatomy, cannot be validated without in vivo measurements. To overcome existing limitations of ethics, safety and animal well-being, we propose a semi-automated method to obtain voluntary maximum bite forces from large mammals using bite plates that automatically dispense a food reward if an incrementally increasing threshold force value is reached. We validated our method using two Malayan sun bears, two Andean spectacled bears and a lioness. We show that voluntary bite force measurement using positive reinforcement is a non-invasive and reliable method to record maximum voluntary bite force performance in large mammals. Our results further show that in vivo data are critical as modeling efforts from osteology have greatly underestimated bite forces in Andean spectacled bears.

The Edge Application of Machine Learning Techniques for Fault Diagnosis in Electrical Machines.

The advent of digitization has brought about new technologies that enable advanced condition monitoring and fault diagnosis under the Industry 4.0 paradigm. While vibration signal analysis is a commonly used method for fault detection in literature, it often involves the use of expensive equipment in difficult-to-reach locations. This paper presents a solution for fault diagnosis of electrical machines by utilizing machine learning techniques on the edge, classifying information coming from motor current signature analysis (MCSA) for broken rotor bar detection. The paper covers the process of feature extraction, classification, and model training and testing for three different machine learning methods using a public dataset to then export the results to diagnose a different machine. An edge computing approach is adopted for the data acquisition, signal processing and model implementation on an affordable platform, the Arduino. This makes it accessible for small and medium-sized companies, albeit with the limitations of a resource-constrained platform. The proposed solution has been tested on electrical machines in the Mining and Industrial Engineering School of Almadén (UCLM) with positive results.

Bi-nasal sectors of ganglion cells complex and visual evoked potential amplitudes as biomarkers in pituitary macroadenoma management.

The study aimed to evaluate the retinal ganglion cell structure using optical coherence tomography and the visual pathway function employing visual evoked potentials in the diagnosis and monitoring of patients with pituitary macroadenoma. A descriptive, cross-sectional, and longitudinal study (3 and 12 months follow-up) was conducted on forty-two patients. Thirty-five age-matched healthy controls were used in the cross-sectional one. Full neuro-ophthalmological evaluation (structural and functional) was carried out including global and segmented retinal nerve fiber layer/ganglion cell complex analysis and amplitude and latency of P100 component in the electrophysiology. Statistical data analysis was conducted with R version 3.6.3 and Python version 3.8. Associations were evaluated using Spearman's correlations. Amplitude sensitivities were 0.999, and bi-nasal sectors of ganglion cell complex thickness specificities were 0.999. This structural parameter had the highest diagnostic value (area under curve = 0.923). Significant associations were found between bi-nasal sectors with amplitude at 12' (rho > 0.7, p < 0.01) and median deviation of the visual field (rho > 0.5, p < 0.01) at 3 months. Pre-surgical values of bi-nasal sectors and amplitude can predict post-surgically median deviation and amplitude (Oz, 12') at 3 months with r 2 > 0.5. Bi-nasal sectors of ganglion cell complex and visual evoked potentials P100 amplitude are efficient biomarkers of visual pathway damage for pituitary macroadenoma patients' management. Pre-surgical values of the bi-nasal sector and visual evoked potentials' amplitude could help to predict the restoration of parvocellular pathway traffic after decompression.

Pharmacokinetics of Vancomycin among Patients with Chemotherapy-Associated Febrile Neutropenia: Which Would Be the Best Dosing to Obtain Appropriate Exposure?

Previous research has determined that the required doses for treating febrile neutropenia with vancomycin are higher than the doses used conventionally. These recommendations have been made considering pharmacotherapeutic goals based on minimum concentration (Cmin) between 15-20 mg/L. This study was developed to evaluate dose recommendations based on the achievement of a target consisting of ratio of area under the curve over minimum inhibitory concentration (AUC24h/MIC) ≥400 in this population of individuals. This study was conducted in a referral hospital for cancer treatment, study participants received vancomycin doses of 1g every 12 h in 2-4-h infusions. Vancomycin was described by a two-compartment pharmacokinetic model with clearance dependent on the estimated glomerular filtration rate. Simulations were performed taking into account a reduced version of the model to establish the influence of controllable and non-controllable variables on the probability of achieving several PK-PD targets. A dose of 2.5g/day in patients with estimated glomerular filtration rate (eGFR) between 80 and 122mL/min/1.73m2 was adequate to achieve the pharmacotherapeutic target. A discrepancy was found between AUC-based and Cmin-based PK/PD indices, the former being affected by the dose and creatinine clearance while the latter highly influenced by the interval between doses.

Polyelectrolytes Enabled Reduced Graphite Oxide Water Dispersions: Effects of the Structure, Molecular Weight, and Charge Density.

The polyelectrolyte (PE)-based water dispersion of graphene-related materials (GRMs) represents an interesting intermediate for the development of advanced materials by sustainable processes. Although the proof of concept has been demonstrated, there is a lack of knowledge for what concerns the effects of parameters typical of PEs such as functionalization, molecular weight, and charge density. In this work, we evaluate the effects of such parameters on the quality and long-term stability of reduced graphite oxide (rGO) dispersion in aqueous media prepared by ultrasound sonication in the presence of different PEs. Four PEs were evaluated: polyacrylic acid (PAA), branched poly(ethylenimine) (BPEI), sodium carboxymethyl cellulose (CMC), and poly(sodium 4-styrenesulfonic acid) (PSS). The prepared dispersions were thoroughly characterized by means of UV-visible spectroscopy, thermogravimetric analysis, dynamic light scattering, and Raman spectroscopy. The highest concentrations of rGO were achieved by BPEI with a molecular weight of 25,000 and 270,000 Da (33 and 26 µg/mL, respectively). For other PEs, the rGO concentration was found to be independent of the molecular weight. The PAA-based dispersions displayed the best through-time stability while yielding homogeneous dispersion with a smaller average size and narrower size distribution.

Evaluation of Diabetes Effects of Selenium Nanoparticles Synthesized from a Mixture of Luteolin and Diosmin on Streptozotocin-Induced Type 2 Diabetes in Mice.

The absence of a treatment efficient in the control of type 2 diabetes mellitus requires more functional products to assist treatment. Luteolin (LU) and diosmin (DIO) have been known as bioactive molecules with potential for the treatment of diabetes. This work aimed to establish the role that a combination of LU and DIO in selenium nanoparticles (SeNPs) played in streptozotocin (STZ)- induced diabetes mice. Green synthesis of Se NPs was performed by mixing luteolin and diosmin with the solution of Na2SeO3 under continuous stirring conditions resulting in the flavonoids conjugated with SeNPs. The existence of flavonoids on the surface of SeNPs was confirmed by UV-Vis spectra, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) images, and DLS graphs via Zetasizer. The average diameter of GA/LU/DIO-SeNPs was 47.84 nm with a PDI of -0.208, a zeta potential value of -17.6, a Se content of 21.5% with an encapsulation efficiency of flavonoids of 86.1%, and can be stabilized by gum Arabic for approximately 175 days without any aggregation and precipitation observed at this time. Furthermore, The C57BL/6 mice were treated with STZ induced-diabetes and were exposed to LU/DIO, SeNPs, and GA/LU/DIO-SeNPs for six weeks. The treatment by nanospheres (GA/LU/DIO-SeNPs) in the mice with diabetes for a period of 6 weeks restored their blood glucose, lipid profile, glycogen, glycosylated hemoglobin, and insulin levels. At the same time, there were significant changes in body weight, food intake, and water intake compared with the STZ- untreated induced diabetic mice. Moreover, the GA/LU/DIO-SeNPs showed good antioxidant activity examined by catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) in liver and kidney and can prevent the damage in the liver evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. The nanospheres exhibited a significant anti-diabetic activity with a synergistic effect between the selenium and flavonoids. This investigation provides novel SeNPs nanospheres prepared by a high-efficiency strategy for incorporating luteolin and diosmin to improve the efficiency in type 2 diabetes.

Caracterización de las lesiones compresivas de la vía visualanterior / Characterization of Compressive Lesions of the Anterior VisualPathway

Objetivo: Determinar las características clínico-epidemiológicas de los pacientes diagnosticados con lesiones compresivas de la vía visual anterior. Métodos: Se realizó un estudio descriptivo transversal durante el período comprendido entre mayo de 2018 y marzo de 2020 con 41 pacientes con diagnóstico de síndrome compresivo de la vía visual anterior atendidos en el Servicio de Neuroftalmología del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Resultados: La mayor frecuencia en cuanto a síntomas fue la disminución progresiva de la visión central. Se encontraron lesiones de tipo tumoral en 39 pacientes para el 95,1 por ciento. Los defectos hemianópticos se detectaron en el campo visual del 45 por ciento de la muestra y el 33 por ciento presentó disminución difusa de la sensibilidad retiniana. Conclusiones: La mayoría de los pacientes fueron del sexo femenino en edades medias de la vida. Predominaron las lesiones tumorales sobre las vasculares. Los macroadenomas de hipófisis y los meningiomas fueron las etiologías más frecuentes y el sitio de compresión más encontrado fue el quiasma óptico. Se detectó disminución del grosor del complejo de células ganglionares maculares en la tomografía de coherencia óptica de la mayoría de los enfermos(AU)

Objective: To determine the clinical-epidemiological characteristics of patients diagnosed with compressive lesions of the anterior visual pathway. Methods: A cross-sectional descriptive study was conducted during the period from May 2018 to March 2020 with 41 patients diagnosed with compressive syndrome of the anterior visual pathway attended at the Neurophthalmology Service of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". Results: The most frequent symptom was the progressive decrease of central vision. Tumor type lesions were found in 39 patients for 95.1 percent. Hemianoptic defects were detected in the visual field of 45 percent of the sample and 33 percent presented diffuse decrease of retinal sensitivity. Conclusions: The majority of patients were female at middle ages of life. Tumor lesions predominated over vascular lesions. Pituitary macroadenomas and meningiomas were the most frequent etiologies and the most frequent site of compression was the optic chiasm. Decreased thickness of the macular ganglion cell complex was detected in the optical coherence tomography of most of the patients(AU)

Chagas disease reactivation after autologous stem cell transplant. Case report and literature review / Reactivación de la enfermedad de Chagas después de trasplante autólogo de progenitores hematopoyéticos. Reporte de caso y revisión de la literatura

Introduction: Chagas disease is an endemic parasitic infection in Latin America transmitted by triatomines. It is associated with risk factors such as poverty and rurality. After acute infection, a third of patients will present target organ involvement (heart, digestive tract, central nervous system). The remaining two thirds remain asymptomatic throughout their life. Pharmacological immunosuppression breaks the balance between the immune system and the parasite, favoring its reactivation. Clinical case: We present the case of a 58-year-old man from a Colombian rural area with a diagnosis of multiple myeloma refractory to the first line of treatment who required a new chemotherapy scheme and consolidation with autologous stem cell transplant. During the post-transplant period, he suffered from febrile neutropenia. Initial microbiological studies were negative but the peripheral blood smear evidenced trypomastigotes in blood. With a diagnosis of acute Chagas disease in a post-transplant patient, benznidazole was started. The evolution of the patient was satisfactory. Conclusions: Positive serology prior to transplantation makes it necessary to rule out reactivation of the pathology in the setting of febrile neutropenia. More studies are required to determine tools for estimating the probability of reactivation of the disease and defining the best cost-risk-benefit relation for the prophylactic therapy.

Introducción. La enfermedad de Chagas es una parasitosis endémica en Latinoamérica transmitida por triatominos. Está asociada a factores de riesgo como la pobreza y la ruralidad. Después de la infección aguda, un tercio de los pacientes presenta compromiso del corazón, el aparato digestivo o el sistema nervioso central, en tanto que los dos tercios restantes no presentan este tipo de compromiso secundario. La inmunosupresión farmacológica rompe el equilibrio entre el sistema inmunitario y el parásito, lo cual favorece su reactivación. Caso clínico. Se presenta el caso de un hombre de 58 años procedente de un área rural colombiana, con diagnóstico de mieloma múltiple resistente a los fármacos de primera línea de tratamiento, que requirió un nuevo esquema de quimioterapia y consolidación con trasplante autólogo de células madre. Después del trasplante, presentó neutropenia febril. Los estudios microbiológicos iniciales fueron negativos. En el frotis de sangre periférica, se demostraron tripomastigotes y se diagnosticó enfermedad de Chagas aguda posterior al trasplante. Se inició el tratamiento con benznidazol. La evolución del paciente fue satisfactoria. Conclusiones. La serología positiva para Chagas previa a un trasplante obliga a descartar la reactivación de la enfermedad en caso de neutropenia febril. Se requieren más estudios para determinar las herramientas que permitan estimar la probabilidad de reactivación de la enfermedad y decidir sobre la mejor opción de relación entre costo, riesgo y beneficio de la terapia profiláctica.

Pinching or stinging? Comparing prey capture among scorpions with contrasting morphologies.

Background: Scorpions can use their pincers and/or stingers to subdue and immobilize their prey. A scorpion can thus choose between strategies involving force or venom, or both, depending on what is required to subdue its prey. Scorpions vary greatly in the size and strength of their pincers, and in the efficacy of their venom. Whether this variability is driven by their defensive or prey incapacitation functionis unknown. In this study, we test if scorpion species with different pincer morphologies and venom efficacies use these weapons differently during prey subjugation. To that end, we observed Opisthacanthus elatus and Chactas sp. with large pincers and Centruroides edwardsii and Tityus sp. with slender pincers. Methods: The scorpion pinch force was measured, and behavioral experiments were performed with hard and soft prey (Blaptica dubia and Acheta domesticus). Stinger use, sting frequency and immobilization time were measured. Results: We found that scorpions with large pincers such as O. elatus produce more force and use the stinger less, mostly subjugating prey by crushing them with the pincers. In C. edwardsii and Tityus sp. we found they use their slender and relatively weak pincers for holding the prey, but seem to predominantly use the stinger to subjugate them. On the other hand, Chactas sp. uses both strategies although it has a high pinch force. Conclusions: Our results show that scorpionspecies with massive pincers and high pinch force as O. elatus use the stinger less for prey subjugation than scorpionspecies with slenderpincers.

Βio-Based Epoxy/Amine Reinforced with Reduced Graphene Oxide (rGO) or GLYMO-rGO: Study of Curing Kinetics, Mechanical Properties, Lamination and Bonding Performance.

In this work, we report the synthesis and study of nanocomposites with a biobased epoxy/amine (Epilok 60-600G/Curamine 30-952) matrix reinforced with reduced graphene oxide (rGO) or functionalised with 3-glycidoxypropyltrimethoxysilane (GLYMO-rGO). These graphene related materials (GRMs) were first dispersed into a Curamine hardener using bath ultrasonication, followed by the addition of epoxy resin. Curing kinetics were studied by DSC under non-isothermal and isothermal conditions. The addition of 1.5 wt% of GLYMO-rGO into the epoxy matrix was found to increase the degree of cure by up to 12% and glass transition temperature by 14 °C. Mechanical testing showed that the addition of 0.05 wt% GLYMO-rGO improves Young's modulus and tensile strength by 60% and 16%, respectively, compared to neat epoxy. Carbon fibre reinforced polymer (CFRP) laminates were prepared via hand lay up, using the nanocomposite system GRM/Epilok/Curamine as matrix, and were cut as CFRP adherents for lap shear joints. GRM/Epilok/Curamine was also used as adhesive to bond CFRP/CFRP and CFRP/aluminium adherents. The addition of 0.1 wt% GLYMO-rGO into the adhesive and CRFP adherents showed improved lap shear strength by 23.6% compared to neat resin, while in the case of CFRP/Aluminium joints the increase was 21.2%.

Comparison of biological activities of Tityus pachyurus venom from two Colombian regions.

BACKGROUND: In the present study, we have tested whether specimens of the medically relevant scorpion Tityus pachyurus, collected from two climatically and ecologically different regions, differ in the biological activities of the venom. METHODS: Scorpions were collected in Tolima and Huila, Colombia. Chemical profiles of the crude venom were obtained from 80 scorpions for each region, using SDS-PAGE and RP-HPLC. Assays for phospholipase A2, direct and indirect hemolytic, proteolytic, neuromuscular, antibacterial, and insecticidal activities were carried out. RESULTS: The electrophoretic profiles of venom from the two regions showed similar bands of 6-14 kDa, 36-45 kDa, 65 kDa and 97 kDa. However, bands between 36 kDa and 65 kDa were observed with more intensity in venoms from Tolima, and a 95 kDa band occurred only in venoms from Huila. The chromatographic profile of the venoms showed differences in the intensity of some peaks, which could be associated with changes in the abundance of some components between both populations. Phospholipase A2 and hemolytic activities were not observable, whereas both venoms showed proteolytic activity towards casein. Insecticidal activity of the venoms from both regions showed significant variation in potency, the bactericidal activity was variable and low for both venoms. Moreover, no differences were observed in the neuromuscular activity assay. CONCLUSION: Our results reveal some variation in the activity of the venom between both populations, which could be explained by the ecological adaptations like differences in feeding, altitude and/or diverse predator exposure. However more in-depth studies are necessary to determine the drivers behind the differences in venom composition and activities.