Rose Bengal Labeled Bovine Serum Albumin for Protein Transport Imaging in Subcutaneous Tissues Using Computed Tomography and Fluorescence Microscopy.

Subcutaneous (SC) injection of protein-based therapeutics is a convenient and clinically established drug delivery method. However, progress is needed to increase the bioavailability. Transport of low molecular weight (Mw) biotherapeutics such as insulin and small molecule contrast agents such as lipiodol has been studied using X-ray computed tomography (CT). This analysis, however, does not translate to the investigation of higher Mw therapeutics, such as monoclonal antibodies (mAbs), due to differences in molecular and formulation properties. In this study, an iodinated fluorescein analog rose bengal (RB) was used as a radiopaque and fluorescent label to track the distribution of bovine serum albumin (BSA) compared against unconjugated RB and sodium iodide (NaI) via CT and confocal microscopy following injection into ex vivo porcine SC tissue. Importantly, the high concentration BSA-RB exhibited viscosities more like that of viscous biologics than the small molecule contrast agents, suggesting that the labeled protein may serve as a more suitable formulation for the investigation of injection plumes. Three-dimensional (3D) renderings of the injection plumes showed that the BSA-RB distribution was markedly different from unconjugated RB and NaI, indicating the need for direct visualization of large protein therapeutics using conjugated tags rather than using small molecule tracers. Whereas this proof-of-concept study shows the novel use of RB as a label for tracking BSA distribution, our experimental approach may be applied to high Mw biologics, including mAbs. These studies could provide crucial information about diffusion in SC tissue and the influence of injection parameters on distribution, transport, and downstream bioavailability.

In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway.

Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of Crotalus durissus collilineatus venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet. Methods: We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP+ (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models. Results: Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP+ on cell viability and differentiation. Conclusion: These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models.

Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.

PURPOSE: To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data. METHODS: Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy. RESULTS: The majority of patients were female, with the age of symptom onset ranging from 1 year and 6 months to 40 years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration. CONCLUSIONS: VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

Assessment of U-Net in the segmentation of short tracts: Transferring to clinical MRI routine.

Accurately studying structural connectivity requires precise tract segmentation strategies. The U-Net network has been widely recognized for its exceptional capacity in image segmentation tasks and provides remarkable results in large tract segmentation when high-quality diffusion-weighted imaging (DWI) data are used. However, short tracts, which are associated with various neurological diseases, pose specific challenges, particularly when high-quality DWI data acquisition within clinical settings is concerned. Here, we aimed to evaluate the U-Net network ability to segment short tracts by using DWI data acquired in different experimental conditions. To this end, we conducted three types of training experiments involving 350 healthy subjects and 11 white matter tracts, including the anterior, posterior, and hippocampal commissure, fornix, and uncinated fasciculus. In the first experiment, the model was exclusively trained with high-quality data of the Human Connectome Project (HCP) dataset. The second experiment focused on images of healthy subjects acquired from a local hospital dataset, representing a typical clinical routine acquisition. In the third experiment, a hybrid training approach was employed, combining data of the HCP and local hospital datasets. Then, the best model was also tested in unseen DWIs of 10 epilepsy patients of the local hospital and 10 healthy subjects acquired on a scanner from another company. The outcomes of the third experiment demonstrated a notable enhancement in performance when contrasted with the preceding trials. Specifically, the short tracts within the local hospital dataset achieved Dice scores ranging between 0.60 and 0.65. Similar intervals were obtained with HCP data in the first experiment, and a substantial improvement compared to the scores between 0.37 and 0.50 obtained with the local hospital dataset at the same experiment. This improvement persisted when the method was applied to diverse scenarios, including different scanner acquisitions and epilepsy patients. These results indicate that combining datasets from different sources, coupled with resolution standardization strengthens the neural network ability to generalize predictions across a spectrum of datasets. Nevertheless, short tract segmentation performance is intricately linked to the training composition, to validation, and to testing data. Moreover, curved tracts have intricate structural nature, which adds complexities to their segmenting. Although the network training approach tested herein has provided promising results, caution must be taken when extrapolating its application to datasets acquired under distinct experimental conditions, even in the case of higher-quality data or analysis of long or short tracts.

Long-term effectiveness of eliglustat treatment: A real-world analysis from the International Collaborative Gaucher Group Gaucher Registry.

Gaucher disease type 1 (GD1) is known for phenotypic heterogeneity and varied natural history. Registrational clinical trials enrolled narrowly defined phenotypes, but greater diversity is encountered in clinical practice. We report real-world outcomes with long-term eliglustat treatment in adults with GD1 in the International Collaborative Gaucher Group Gaucher Registry. Among 5985 GD1 patients in the Registry as of January 6, 2023, 872 started eliglustat at ≥18 years old; of these, 469 met inclusion criteria. We compared clinical parameters at eliglustat initiation (i.e., baseline) and follow-up in treatment-naïve patients and used linear mixed models to estimate annual change from baseline in parameters among patients who switched to eliglustat after ≥1 year on enzyme replacement therapy. Over 4 years of follow-up in non-splenectomized treatment-naïve patients, hemoglobin and platelet count increased, liver and spleen volume decreased, and total lumbar spine bone mineral density (BMD) Z-score decreased slightly. Among non-splenectomized switch patients, on average, hemoglobin decreased -0.030 (95% CI: -0.053, -0.008) g/dL (N = 272) and platelet count increased 2.229 (95% CI: 0.751, 3.706) × 103/mm3 (N = 262) annually up to 10 years; liver volume decreased (-0.009 [95% CI: -0.015, -0.003] MN) (N = 102) and spleen volume remained stable (-0.070 [95% CI: -0.150, 0.010] MN) (N = 106) annually up to 7 years; and total lumbar spine BMD Z-score increased 0.041 (95% CI: 0.015, 0.066) (N = 183) annually up to 8 years. Among splenectomized switch patients, clinical parameters were stable over time. These long-term, real-world outcomes are consistent with the eliglustat clinical trials and emerging real-world experience across the GD phenotypic spectrum.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Deciphering the irradiation induced fragmentation-rearrangement mechanisms in valence ionized CF3CH2F.

The increasing presence of 1,1,1,2-tetrafluoroethane (CF3CH2F) in the atmosphere has prompted detailed studies into its complex photodissociation behavior. Experiments focusing on CF3CH2F irradiation have unveiled an array of ions, with the persistent observation of the rearrangement product CHF2+ not yet fully understood. In this work, we combine density functional theory, coupled-cluster calculations with a complete basis set formalism, and atom-centered density matrix propagation molecular dynamics to investigate the energetics and dynamics of different potential pathways leading to CHF2+. We found that the two-body dissociation pathway involving an HF rearrangement, which was previously considered complex for CHF2+ formation, is actually straightforward but not likely due to the facile loss of HF. In contrast, our calculations reveal that the H elimination pathway, once thought of as a potential route to CHF2+, is not only comparably disadvantageous from both thermodynamic and kinetic points of view but also does not align with experimental data, particularly the lack of a rebound peak at m/z 101-102. We establish that the formation of CHF2+ is predominantly via the HF elimination channel, a conclusion experimentally corroborated by studies involving the trifluoroethylene cation CF2CHF+, a key intermediate in this process.

Symmetrical placement of bilateral percutaneous bone-anchored hearing systems via guide-marker.

Objectives: To investigate the use of a novel technique to estimate the symmetrical placement of percutaneous bone-anchored hearing systems (BAHS) with a guide-marker in patients undergoing bilateral surgery with this device. Study Design: Prospective cohort study. Methods: A guide-marker and anatomical landmarks were used to estimate the implant placement and transferred to the contralateral ear in 12 subjects eligible for bilateral BAHS surgery. To investigate the bilateral symmetry, preoperative tri-dimensional (3D) computed tomography (CT) image reconstruction was used to compare the distances between the mandibular condyle and implant placement estimation (mandible-implant distance) in both the right and left ears of the subjects. Results: The guide-marker could be used to estimate the bilateral implant placement in all subjects included in this study, simply and easily, including one subject with craniofacial malformation. The mean mandible-implant distances were 5.37 and 5.38 cm, in the right and left ears of the subjects, respectively, and no differences were observed between them, thereby indicating optimal bilateral symmetry. Conclusion: The use of the guide-marker proved to be an effective tool to provide symmetrical placement of bilateral BAHS. We propose a novel method employing a simple guide-marker and tracing based on symmetrical anatomical landmarks to achieve precise placement and optimal symmetry and which may be easily adopted in the surgical routine of BAHS. Level of Evidence: 3.

A comparative study of Lachancea thermotolerans fermentative performance under standardized wine production conditions.

The study explores diverse strains of Lachancea thermotolerans in single-inoculum wine fermentation conditions using synthetic grape must. It aims to analyze the role of the species without external influences like other microorganisms or natural grape must variability. Commercial strains and selected vineyard isolates, untested together previously, are assessed. The research evaluates volatile and non-volatile chemical compounds in final wine, revealing significant strain-based variations. L. thermotolerans notably produces lactic acid and consumes malic acid, exhibiting moderate ethanol levels. The volatile profile displays strain-specific impacts, affecting higher alcohol and ester concentrations compared to S. cerevisiae. These effects vary based on the specific compounds. Using a uniform synthetic must enables direct strain comparisons, eliminating grape-related, environmental, or timing variables in the experiment, facilitating clearer insights into the behavior of L. thermotolerans in wine fermentation. The study compares for the first time all available commercial strains of L. thermotolerans.

Improvement of thrombosis management in patients with cancer: a practical consensus document of recommendations for cancer-associated thrombosis patients' healthcare in Spain.

Cancer patients are at risk of venous thromboembolism (VTE), its recurrence, but also at risk of bleeding while anticoagulated. In addition, cancer therapies have been associated to increased VTE risk. Guidelines for VTE treatment in cancer patients recommend low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) for the initial treatment, DOAC for VTE short-term treatment, and LMWH or DOAC for VTE long-term treatment. This consensus article arises from a collaboration between different Spanish experts on cancer-associated thrombosis. It aims to reach an agreement on a practical document of recommendations for action allowing the healthcare homogenization of cancer-associated thrombosis (CAT) patients in Spain considering not only what is known about VTE management in cancer patients but also what is done in Spanish hospitals in the clinical practice. The text summarizes the current knowledge and available evidence on the subject in Spain and provides a series of practical recommendations for CAT management and treatment algorithms to help clinicians to manage CAT over time.

Evaluation of clinical and microbiological factors related to mortality in patients with Gram-negative bacterial infections treated with ceftazidime-avibactam: A prospective multicentric cohort study.

OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Epigenetic control of adamantinomatous craniopharyngiomas.

INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 ACP patients (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multi-dimensional scaling. Statistical associations between clusters and clinical features were achieved using Fisher's test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = 0.0006), hypomethylated in CpG Island (CGI), non-CGI sites, and globally (P < 0.001), and associated with greater tumor size (24.1 vs 9.5cm3, P = 0.04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell-adhesion, cytoskeleton organization, and cytokine binding, and also cell-type specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of ACP patients were consistently revealed by unsupervised machine learning methods, being one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.

Antecedents to and outcomes associated with teacher-child relationship perceptions in early childhood: Further evidence for child-driven effects.

Preschool teachers' perceptions about relationships with students (teacher-child relationships [TCRs]) predict children's subsequent social competence (SC) and academic progress. Why this is so remains unclear. Do TCRs shape children's development, or do child attributes influence both TCRs and subsequent development? Relations between TCRs and other measures were examined for 185 preschoolers (107 girls, 89 longitudinal, and ~75% European American). Teachers rated TCRs and child social/affective behaviors. Teacher-child interactions (TCIs) and children's affect expressiveness were observed. Child SC and receptive vocabulary were assessed. TCRs were significantly correlated with each type of outcome. TCIs, SC, expressed affect, and teacher-rated behaviors also predicted TCRs longitudinally. Results suggest that TCR ratings predict subsequent adaptation because they summarize children's behavioral profiles rather than on TCR quality per se.

The Important Role of Hemispherotomy for Rasmussen Encephalitis: Clinical and Functional Outcomes.

BACKGROUND: Rasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes. METHODS: All patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes. RESULTS: Forty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS. CONCLUSIONS: Considering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life.

Incommensurate Spiral Spin Order in CaMn2Bi2 Observed via High-Pressure Neutron Diffraction.

High-pressure neutron diffraction is employed to investigate the magnetic behavior of CaMn2Bi2 in extreme conditions. In contrast to antiferromagnetic ordering on Mn atoms reported at ambient pressure, our results reveal that at high pressure, incommensurate spiral spin order emerges due to the interplay between magnetism on the Mn atoms and strong spin-orbit coupling on the Bi atoms: sinusoidal spin order is observed at pressures as high as 7.4 GPa. First-principles calculations with a noncollinear spin orientation demonstrate band crossing behavior near the Fermi level as a result of strong hybridization between the d orbitals of Mn and the p orbitals of Bi atoms. Competing antiferromagnetic order is observed at different temperatures in the partially frustrated lattice. Theoretical models have been developed to investigate spin dynamics. This research provides a unique toolbox for conducting experimental and theoretical magnetic and spin dynamics studies of magnetic quantum materials via high-pressure neutron diffraction.

A Genetic Lab-on-Phone Test for Point-of-Care Diagnostic of Lactose Intolerance near Patient and in less than 90 Minutes.

BACKGROUND: The -13910 C/T single nucleotide polymorphism located within the MCM6 gene, an enhancer region located upstream of the lactase-phlorizin hydrolase gene, is associated with lactase persistence/non-persistence traits among the Caucasian population. The performance of a new point-of-care CE-IVD (In Vitro Diagnostic) marked isothermal lab-on-phone lactose intolerance assay, using crude samples, was assessed in comparison with Sanger sequencing using purified DNA, as reference method. METHODS: The study was conducted following a non-probability sampling using direct buccal swab (n = 63) and capillary blood (n = 43) clinical samples from a total of 63 volunteers. A 3 × 3 confusion matrix/contingency table was used to evaluate the performance of the isothermal lab-on-phone lactose intolerance assay. RESULTS: The isothermal lab-on-phone lactose intolerance assay successfully detected the -13910 C/T variant with a limit of detection of 5 cells/assay and demonstrated an overall accuracy of 98.41% (95% CI, 91.47%-99.96%) for buccal swab samples and 100% (95% CI, 91.19%-100%) for capillary blood, taking just 90 min from sample to result, with only 2 min hands-on. CONCLUSIONS: The lab-on-phone pocket-sized assay displayed good performance when using direct buccal swab and capillary blood samples, enabling a low-cost, real-time, and accurate genotyping of the -13910 C/T region for the rapid diagnosis of primary lactose intolerance at point-of-care, which enables a prompt implementation of appropriate diet habits and/or intolerance therapies. To our knowledge, this is the first point-of-care genetic test for lactose intolerance to be made available on the market.

Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of Crotalus durissus collilineatus venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet. Methods: We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP+ (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models. Results: Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP+ on cell viability and differentiation. Conclusion: These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models.

Aplicação do programa shuttle time no ensino do badminton na escola: refletindo relações de gênero / Application of the shuttle time program in teaching badminton at school: reflecting gender relations / Aplicación del programa shuttle time en la enseñanza del bádminton en la escuela: reflejando las relaciones de género

O objetivo deste estudo é descrever sobre a questão de gênero nas aulas de badminton na Educação Física escolar. O estudo trata-se de um relato de experiência de abordagem qualitativa e de natureza descritiva. Participaram do estudo duas turmas de 7º anos de uma escola pública. Os instrumentos de coleta de dados foram dois questionários e observação participante. Construímos uma sequência didática, contendo dez aulas com momentos dialógicos e vivenciais. Os dados revelam que a questão de gênero foi refletida e compreendida pelos e pelas estudantes nas aulas de badminton. Consideramos que os objetivos propostos na sequência didática foram alcançados, tendo em vista que as relações de gênero foram potencializadas por meio das vivências e das reflexões.

The objective of this study is to describe the gender issue in badminton classes in school Physical Education. The study is an experience report with a qualitative approach and descriptive nature. Two 7th grade classes from a public school participated in the study. The data collection instruments were two questionnaires and participant observation. We built a didactic sequence, containing ten classes with dialogical and experiential moments. The data reveal that the gender issue was reflected and understood by students in badminton classes. We consider that the objectives proposed in the didactic sequence were achieved, considering that gender relations were enhanced through experiences and reflections.

El objetivo de este estudio es describir la problemática de género en las clases de bádminton en la Educación Física escolar. El estudio es un relato de experiencia con enfoque cualitativo y carácter descriptivo. En el estudio participaron dos clases de séptimo grado de una escuela pública. Los instrumentos de recolección de datos fueron dos cuestionarios y la observación participante. Construimos una secuencia didáctica que contiene diez clases con momentos dialógicos y vivenciales. Los datos revelan que la cuestión de género fue reflejada y comprendida por los estudiantes en las clases de bádminton. Consideramos que se lograron los objetivos propuestos en la secuencia didáctica, considerando que las relaciones de género se potenciaron a través de experiencias y reflexiones.