Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.

A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions.

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrPC) into a pathogenic form (PrPSc). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.

Reusable Colorimetric Biosensors on Sustainable Silk-Based Platforms.

In biosensor development, silk fibroin is advantageous for providing transparent, flexible, chemically/mechanically stable, biocompatible, and sustainable substrates, where the biorecognition element remains functional for long time periods. These properties are employed here in the production of point-of-care biosensors for resource-limited regions, which are able to display glucose levels without the need for external instrumentation. These biosensors are produced by photopatterning silk films doped with the enzymes glucose oxidase and peroxidase and photoelectrochromic molecules from the dithienylethene family acting as colorimetric mediators of the enzymatic reaction. The photopatterning results from the photoisomerization of dithienylethene molecules in the silk film from its initial uncolored opened form to its pink closed one. The photoisomerization is dose-dependent, and colored patterns with increasing color intensities are obtained by increasing either the irradiation time or the light intensity. In the presence of glucose, the enzymatic cascade reaction is activated, and peroxidase selectively returns closed dithienylethene molecules to their initial uncolored state. Color disappearance in the silk film is proportional to glucose concentration and used to distinguish between hypoglycemic (below 4 mM), normoglycemic (4-6 mM), and hyperglycemic levels (above 6 mM) by visual inspection. After the measurement, the biosensor can be regenerated by irradiation with UV light, enabling up to five measurement cycles. The coupling of peroxidase activity to other oxidoreductases opens the possibility to produce long-life reusable smart biosensors for other analytes such as lactate, cholesterol, or ethanol.

Mechanical thrombectomy with a new intermediate balloon catheter combining the BGC and DAC features: Initial clinical experience with the iNedit device.

INTRODUCTION: The iNedit balloon distal access catheter is a novel thrombectomy device. It has an inner diameter of 0.058″, proximal outer diameter of 2.13 mm, and distal outer diameter of 1.67mm. It is compatible with a 0.088″ guide catheter and includes a balloon located 5 cm from the catheter tip, enabling proximal flow restriction and combined therapy with stent retrievers. We investigate the appraisal of the use, safety, and efficacy of the iNedit catheter in the first-in-human study. METHODS: In the preliminary cases that demanded training on the product previous to a multicentric study, prospective data were collected on 22 consecutive patients treated with the iNedit catheter to perform thrombectomy for acute ischemic stroke due to large vessel occlusion within 24 h. The outcome measures consisted of several evaluations of user experience rated on a 5-point scale ranging from 1 (bad) to 5 (excellent), as well as assessments of procedural safety outcomes such as artery perforation and arterial occlusion, procedural efficacy outcomes including first-pass effect (Thrombolysis In Cerebral Infarction [TICI] 2c/3) and final recanalization (TICI 2b/3), and clinical efficacy outcomes such as a 3-month 0-2 modified Rankin Scale (mRS). RESULTS: The mean age was 72 ± 12 years old; median National Institute Health Stroke Scale was 17 (11-19). Sites of primary occlusion were: 2 internal carotid artery, 12 M1-MCA, 7 M2-MCA, and one P1. Median score evaluation of the appraisal of use was 4- IQR [4-5]. The median number of passes was 1 [IQR 1-2]. First pass complete recanalization rate was 50% and the final recanalization rate was 94.45%. No artery perforation and arterial occlusion. Good functional outcome mRS 0-2 was achieved in 50% of patients. CONCLUSIONS: In this initial clinical experience, iNedit device achieved a high rate of first-pass effect and final recanalization rate with no safety concerns, thus favoring a high percentage of good clinical outcomes.

Alternativas de reconstrucción mamaria inmediata

La mastectomía total por cáncer de mama produce una deformidad importante en las pacientes, con alteraciones severas de su autoestima, imagen corporal, sexualidad, y calidad de vida en general. El gold estándar en los países desarrollados es la reconstrucción mamaria inmediata y, actualmente existen pocas contraindicaciones absolutas para realizar alguna técnica de reconstrucción. Este artículo se describen las opciones reconstructivas (colgajos e implantes), tiempos de reconstrucción, ventajas y desventajas de ambas técnicas, potenciales complicaciones, y se propone un algoritmo de tratamiento. La elección de la técnica de reconstrucción debería ser decidida entre la paciente y su cirujano/a, considerando características físicas, factores relacionados con la enfermedad y tratamiento oncológico, y preferencias de las pacientes.

Total mastectomy for breast cancer treatment can be a cause of deformity and distress for patients, with severe impairment of self-esteem, body image, sexuality, and quality of life. In developing countries, immediate breast reconstruction is the gold standard, and there are only a few absolut contraindications for some technique of breast reconstruction. This article describes reconstructive options (flaps and allo-plastic material), reconstructive timing, pros and cons of both techniques, potential complications, and an algorithm of treatment is proposed. Choice of the reconstructive technique should be decided by the patient and her surgeon, considering physical characteristics, factors related with the disease and oncologic treatments, and patients' preferences.

Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation.

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.

Revisión de medicamentos sin receta con aspartamo: Indicación Farmacéutica segura en fenilcetonuria / Review of non-prescription medicines with aspartame: safe pharmaceutical indication in phenylketonuria

Introducción: La fenilcetonuria es el trastorno hereditario más frecuente del metabolismo de los aminoácidos y su abordaje suele centrarse en die-tas restringidas en fenilalanina, un aminoácido presente en el edulcorante aspartamo habitualmente usado como excipiente en tecnología farmacéutica. Objetivo: El objetivo principal es la revisión de los medicamentos sin receta comercializados en España hasta marzo de 2023 y que contienen aspartamo en su composición. Método: Se realizó una revisión en la base de datos BOT plus de todos los medicamentos comercializados en España que contienen aspartamo. Se seleccionaron solo los MSR. Se consultaron las fichas técnicas en el Centro de información online de medicamentos de la AEMPS (CIMA), y los datos obtenidos se registraron en una tabla. Resultados: Se obtuvieron 570 medicamentos; 58 eran MSR. Cuando exista petición de MSR con aspartamo en pacientes con fenilcetonuria, en el SIF, tras su evaluación, en el 100% de los casos, el farmacéutico aplicando el Servicio de Indicación Farmacéutica podría indicar un MSR alternativo, con el mismo principio activo pero sin aspartamo como excipiente. Conclusiones: La actuación del farmacéutico comunitario para aplicar el SIF es muy importante en pacientes con fenilcetonuria. Existen medicamentos que no requieren prescripción y se pueden indicar en estos pacientes. El farmacéutico debe tener a su disposición las herramientas necesarias que le faciliten el SIF con este tipo de enfermos. (AU)

Introduction: Phenylketonuria is the most common inherited disorder of amino acid metabolism and its management usually focuses on diets restricted in phenylalanine, an amino acid present in the sweet-ener aspartame commonly used as an excipient in pharmaceutical technology. Objective: The main objective is the review of non-prescription medicines marketed in Spain until March 2023 and that contain aspartame in their composition.Methods: A review of all medicines marketed in Spain containing aspartame was carried out in the BOT plus database. Only MSRs were selected. The data sheets were consulted at the AEMPS online medicines information centre (CIMA), and the data obtained were recorded in a table.Results: 570 medicines were obtained; 58 were MSRs. When there is a request for MSRs with aspartame in patients with phenylketonuria, in the SIF, after evaluation, in 100% of the cases, the pharmacist applying the Pharmaceutical Indication Service could indicate an alternative MSR, with the same active ingredient but without aspartame as an excipient.Conclusions: The action of the community phar-macist to apply the SIF is very important in patients with phenylketonuria. There are medicines that do not require a prescription and can be prescribed for these patients. Pharmacists should have the necessary tools at their disposal to facilitate the SIF with this type of patient. (AU)

Uterus infantilis: a novel phenotype associated with AARS2 new genetic variants. A case report.

Objectives: To report the first Mexican case with two novel AARS2 mutations causing primary ovarian failure, uterus infantilis, and early-onset dementia secondary to leukoencephalopathy. Methods: Detailed clinical, clinimetric, neuroimaging features, muscle biopsy with biochemical assays of the main oxidative phosphorylation complexes activities, and molecular studies were performed on samples from a Mexican female. Results: We present a 41-year-old female patient with learning difficulties since childhood and primary amenorrhea who developed severe cognitive, motor, and behavioral impairment in early adulthood. Neuroimaging studies revealed frontal leukoencephalopathy with hypometabolism at the fronto-cerebellar cortex and caudate nucleus. Uterus infantilis was detected on ultrasound study. Clinical exome sequencing identified two novel variants, NM_020745:c.2864G>A (p.W955*) and NM_020745:c.1036C>A (p.P346T, p.P346Wfs*18), in AARS2. Histopathological and biochemical studies on muscle biopsy revealed mitochondrial disorder with cytochrome C oxidase (COX) deficiency. Conclusions: Several adult-onset cases of leukoencephalopathy and ovarian failure associated with AARS2 variants have been reported. To our best knowledge, none of them showed uterus infantilis. Here we enlarge the genetic and phenotypic spectrum of AARS2-related dementia with leukoencephalopathy and ovarian failure and contribute with detailed clinical, clinometric, neuroimaging, and molecular studies to disease and novel molecular variants characterization.

Funnel Shaped Anterior Communicating Artery Fenestration Mistaken for an Aneurysm: A Cautionary Tale.

This report portrays a case of a funnel shaped anterior communicating artery (ACoA) fenestration which was mistaken as a small A1 aneurysm in a subarachnoid hemorrhage case. Although tridimensional rotational digital subtraction angiography improves aneurysm diagnosis specially at the ACoA complex, current spatial resolution might leave behind a considerable percentage of ACoA fenestrations. This may lead to diagnostic errors and unnecessary treatments risking iatrogenic complications. Luckily for our patient, a concomitant aneurysm warranted clipping and subsequent surgical exploration of the ACoA complex revealed the pitfall, thus preventing further action. Interestingly, another group of authors who reported similar misdiagnosis with ACoA aneurysms were able to prevent a third error, thanks to the experience acquired with 2 prior cases. Therefore, this clinical image aims to raise wider awareness of the need for very cautious consideration of imaging depicting small and/or atypical aneurysms in the ACoA complex.

Effectiveness of Computerized Cognitive Training by VIRTRAEL on Memory and Executive Function in Older People: A Pilot Study.

The prevalence of people over 60 years of age with cognitive impairment has increased in recent decades. As a consequence, numerous computerized cognitive trainings (CCT) have been developed. This pilot study aimed to determine the effectiveness of the CCT with VIRTRAEL in improving older adults' cognition. Fifty-five participants (x¯ = 72.7 years; SD = 6.5) underwent CCT, and twenty participants (x¯ = 76.1 years; SD = 7.6) received face-to-face cognitive stimulation with a paper-and-pencil methodology. Both trainings were conducted in nine sessions (45-60 min each). Participants completed a pre-post training neuropsychological assessment. ANCOVAs and the standardized clinical change were performed. VIRTRAEL's group showed a significant and greater improvement in verbal learning (p < 0.006) and delayed recall (p ≤ 0.001), working memory (p < 0.005), abstract (p < 0.002) and semantic reasoning (p < 0.015), and planning (p < 0.021). Additionally, more large clinical changes (d > 0.8) were found in the VIRTRAEL condition (in verbal learning and delayed free and cued recall) than in the standard group. Here we show that the CCT with VIRTRAEL is effective in improving cognitive function in older adults and is superior to the standard format. These preliminary findings indicate that CCT is a useful tool potentially applicable in the fight against cognitive symptomatology associated with aging and neurodegenerative diseases. VIRTRAEL represents a breakthrough in this field as it is inexpensive and easily accessible to any older person, regardless of whether they live far from health care resources.

Full-mouth rehabilitation in a completely digital workflow using partially adhesive monolithic zirconia restorations.

OBJECTIVE: This clinical case describes a completely digital workflow using current digital technologies for a full-mouth adhesive rehabilitation with ultra-translucent multilayer zirconia restorations. CLINICAL CONSIDERATIONS: A healthy 60-year-old man with abfractions on all upper and lower molars and severe tooth wear underwent a full-mouth rehabilitation with laminate veneers and partial adhesive restorations. A proper zirconia bonding protocol was realized to provide a durable bond between the ultra-translucent zirconia and the resin cement. Furthermore, the implementation of a digital workflow enables the clinician to have an effective communication during treatment planning and simplify the clinical and laboratory procedures, providing the patient with long-term esthetic treatment and functional results. CONCLUSION: The implementation of a completely digital workflow and the use of ultra-translucent multilayer zirconia for indirect adhesive restorations can be an alternative with simplified and predictable procedures for patients with dental wear and teeth discolorations. CLINICAL SIGNIFICANCE: The digital workflow described is intended to facilitate the planning and execution of a full-mouth adhesive rehabilitation and demonstrates to clinicians a reliable zirconia bonding concept for minimally invasive anterior and posterior restorations.

Adsorption of lanthanide double-decker phthalocyanines on single-walled carbon nanotubes: structural changes and electronic properties as studied by density functional theory.

CONTEXT: Molecular modeling of carbon nanotubes and lanthanide double-decker phthalocyanines hybrids is challenging due to the presence of 4f-electrons. In this paper, we analyzed the trends in structural changes and electronic properties when a lanthanide (La, Gd, and Lu) bisphthalocyanine molecule is adsorbed on the surface of two single-walled carbon nanotubes (SWCNTs) models: armchair and zigzag. The density functional theory (DFT) computations showed that the height of bisphthalocyanines complexes (LnPc2) when adsorbed on a nanotube (LnPc2+SWCNT) is the structural feature which is most affected by the nanotube model. The formation energy of the LnPc2+SWCNT hybrid depends on the metal atom and the nanotube chirality. LaPc2 and LuPc2 bind stronger to the zigzag nanotube, while for GdPc2, bonding to the armchair nanotube is the stronger one. The HOMO-LUMO gap energy (Egap) shows a correlation between the nature of lanthanide and the nanotube chirality. In the case of adsorption on armchair nanotube, Egap tends to match the gap of isolated LnPc2, whereas for adsorption on the zigzag nanotube, it is closer to the value for the isolated nanotube model. The spin density is localized on the phthalocyanines ligands (plus on Gd in the case of GdPc2), when the bisphthalocyanine is adsorbed on the surface of the armchair nanotube. For bonding to zigzag nanotube (ZNT), it extends over both components, except for LaPc2+ZNT, where spin density is found on the nanotube only. METHOD: All DFT calculations were carried out using the DMol3 module of Material Studio 8.0 software package from Accelrys Inc. The computational technique chosen was the general gradient approximation functional PBE in combination with a long-range dispersion correction developed by Grimme (PBE-D2), the double numerical basis set DN, and the DFT semi-core pseudopotentials.

Technical note: A mobile collaborative workspace to assist forensic experts in disaster victim identification scenarios.

Integrated approaches to disaster victim identification (DVI) management have led to a need for technologies to improve interaction among parties involved in post-mortem (PM) and ante-mortem (AM) data collection through better communication and coordination. Mobile Forensic Workspace© (MFW) is a collaborative mobile system that not only facilitates the systematic collection of high-quality data, but also allows DVI professionals to coordinate activities and exchange data through secure real-time communication at major disaster scenarios in accordance with security, privacy and legal protocols. MFW is adaptable to any communication format (text, voice calls, photographs, etc.) and is dynamically self-reconfigurable when connectivity problems arise. It also allows data integration and backup through secure communication channels between local and remote servers. The feasibility of the system has been demonstrated through implementation of MFW on the iOS platform for iPhone, iPod Touch and iPad terminals. A further strength of MFW is that it provides out-of-the-box support for INTERPOL DVI forms. The application of information and communication technologies for DVI was shown to be useful in improving DVI management by enhancing the quality of data collection and enabling non-Internet dependent real-time data sharing and communication.

Agile Methodologies Applied to the Development of Internet of Things (IoT)-Based Systems: A Review.

Throughout the evolution of software systems, empirical methodologies have been used in their development process, even in the Internet of Things (IoT) paradigm, to develop IoT-based systems (IoTS). In this paper, we review the fundamentals included in the manifesto for agile software development, especially in the Scrum methodology, to determine its use and role in IoTS development. Initially, 4303 documents were retrieved, a number that was reduced to 186 after applying automatic filters and by the relevance of their titles. After analysing their contents, only 60 documents were considered. Of these, 38 documents present the development of an IoTS using some methodology, 8 present methodologies focused on the construction of IoTS software, and 14 present methodologies close to the systems life cycle (SLC). Finally, only one methodology can be considered SLC-compliant. Out of 38 papers presenting the development of some IoTS following a methodology for traditional information systems (ISs), 42.1% have used Scrum as the only methodology, while 10.5% have used Scrum combined with other methodologies, such as eXtreme Programming (XP), Kanban and Rapid Prototyping. In the analysis presented herein, the existing methodologies for developing IoTSs have been grouped according to the different approaches on which they are based, such as agile, modelling, and service oriented. This study also analyses whether the different proposals consider the standard stages of the development process or not: planning and requirements gathering, solution analysis, solution design, solution coding and unit testing (construction), integration and testing (implementation), and operation and maintenance. In addition, we include a review of the automated frameworks, platforms, and tools used in the methodologies analysed to improve the development of IoTSs and the design of their underlying architectures. To conclude, the main contribution of this work is a review for IoTS researchers and developers regarding existing methodologies, frameworks, platforms, tools, and guidelines for the development of IoTSs, with a deep analysis framed within international standards dictated for this purpose.

What Makes a Beautiful Buttock Beautiful? A Case-Control Study Comparing Buttocks Models versus Normal Women by Magnetic Resonance Imaging, Photography and Anthropometry.

OBJECTIVES: To describe characteristics of women with aesthetically ideal buttocks and differentiate them from women with normal buttocks. METHODS: Case-control study comparing anatomy of women with ideal buttocks (buttocks models) to women with normal buttocks using magnetic resonance images, anthropometric measurements and photography. RESULTS: Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker gluteus maximus muscle (GMM). A bigger GMM adds more projection to the C point, point of maximum projection in the lateral view is 2.7 cm higher than the pubic bone. The amount of subcutaneous fat was equal in models and controls. CONCLUSIONS: Our study provides new knowledge regarding the tridimensional aspects of the beauty of the buttocks area. A beautiful buttock is a conjunction of adequate bony shape, muscle development, subcutaneous fat layer, and tight skin. Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker Gluteus Maximus Muscle. Accurate understanding of the aesthetic goals in a given patient can guide surgical technique. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bioactive Attributes and Analysis of Electronic Nose Feature Signals of Colombian Stingless Bees Propolis.

The volatile and non-volatile chemical composition and bioactivity of propolis from the species Apis mellifera has been widely studied, but there is very little knowledge regarding propolis of other bee species, which ultimately hinders their differentiation and potential use. In this work, 53 propolis samples of A. mellifera and four stingless bee species (Frieseomielitta sp., Melipona eburnea, Melipona sp., and Trigona sp.) were collected in Colombia. An electronic nose with 10 metal oxide semiconductor sensors (MOS) was used to generate a pattern of the representative volatile compounds of the samples. Ethanolic extracts were obtained to assess their antioxidant activity towards DPPH radical and ABTS radical cation, total phenolics, and color (CIELAB space). The results showed an overall similarity of the aromatic profiles between species. The antioxidant activity of Frieseomielitta sp. propolis was higher than that of A. mellifera and the other species, in correspondence with a higher phenolic content. CIELAB color parameter b* was the most differentiating variable among samples, indicating a variation of propolis colors between red and yellow. By combining the data from physico-chemical analysis and aromatic profile, it was possible to differentiate the propolis from each bee species, with the exception of those from Melipona sp. and Trigona sp., indicating their similarity. These results have practical significance since they are a starting point to recognizing and valuing native stingless bee propolis and their bioactive potential, which, in addition to geographical differentiation and further quality parameters evaluation, will enhance their commercial exploitation.

Hemangioma intramuscular con flebolitos de lengua. Reporte de un caso clínico-patológico

Se presenta un caso de hemangioma intramuscular con flebolitos de lengua en una mujer de 60 años. Clínicamente correspondía a una tumefacción de dos años de evolución, sin signos que sugirieran su origen vascular. Luego de su evaluación inicial se realizó biopsia excéresis de la lesión para su estudio histopatológico. En el estudio histológico se pudo observar una formación tisular redondeada y circunscripta constituida por tejido conjuntivo fibroso con abundantes capilares congestivos que desplazaban el tejido muscular, destacándose la presencia de trombos con calcificaciones dispuestas en capas concéntricas (flebolitos). En base a estos hallazgos morfológicos, el diagnóstico definitivo fue de hemangioma capilar intramuscular con flebolitos de lengua. Para confirmar la naturaleza neoplásica vascular de la lesión se realizó inmunomarcación con el anticuerpo GLUT1. Es de destacar, de acuerdo a la revisión bibliográfica realizada en PubMed, que esta entidad patológica es rara, particularmente en la lengua.

Apresentamos um caso de hemangioma intramuscular com flebólitos de língua em uma mulher de 60 anos. Clinicamente, correspondia a um inchaço com duração de dois anos, sem sinais que sugerissem sua origem vascular. Após sua avaliação inicial, foi realizada biópsia excisional da lesão para estudo histopatológico. No estudo histológico pôde-se observar uma formação tecidual arredondada e circunscrita constituída por tecido conjuntivo fibroso com abundantes capilares congestivos que deslocavam o tecido muscular, destacando a presença de trombos com calcificações dispostos em camadas concêntricas (flebólitos). Com base nesses achados morfológicos, o diagnóstico definitivo foi de hemangioma capilar intramuscular com flebólitos de língua. Para confirmar a natureza neoplásica vascular da lesão, foi realizada imunocoloração com o anticorpo GLUT1. Ressalta-se, de acordo com a revisão bibliográfica realizada no PubMed, que esta entidade patológica é rara, principalmente na língua.

Summary We present a case of intramuscular hemangioma with tongue phleboliths in a 60-year-old woman. Clinically it corresponded to a swelling of two years of evolution, without signs that suggested its vascular origin. After her initial evaluation, an excisional biopsy of the lesion was performed for histopathological study. In the histological study it was possible to observe a rounded and circumscribed tissue formation made up of fibrous connective tissue with abundant congestive capillaries that displaced the muscle tissue, highlighting the presence of thrombi with calcifications arranged in concentric layers (phleboliths). Based on these morphological findings, the definitive diagnosis was intramuscular capillary hemangioma with tongue phleboliths. To confirm the vascular neoplastic nature of the lesion, histochemical immunostaining was performed with the GLUT1 antibody. It is noteworthy, according to the bibliographic review carried out in PubMed, that this pathological entity is rare, particularly in the tongue.

Bona fide atypical scrapie faithfully reproduced for the first time in a rodent model.

Atypical Scrapie, which is not linked to epidemics, is assumed to be an idiopathic spontaneous prion disease in small ruminants. Therefore, its occurrence is unlikely to be controlled through selective breeding or other strategies as it is done for classical scrapie outbreaks. Its spontaneous nature and its sporadic incidence worldwide is reminiscent of the incidence of idiopathic spontaneous prion diseases in humans, which account for more than 85% of the cases in humans. Hence, developing animal models that consistently reproduce this phenomenon of spontaneous PrP misfolding, is of importance to study the pathobiology of idiopathic spontaneous prion disorders. Transgenic mice overexpressing sheep PrPC with I112 polymorphism (TgShI112, 1-2 × PrP levels compared to sheep brain) manifest clinical signs of a spongiform encephalopathy spontaneously as early as 380 days of age. The brains of these animals show the neuropathological hallmarks of prion disease and biochemical analyses of the misfolded prion protein show a ladder-like PrPres pattern with a predominant 7-10 kDa band. Brain homogenates from spontaneously diseased transgenic mice were inoculated in several models to assess their transmissibility and characterize the prion strain generated: TgShI112 (ovine I112 ARQ PrPC), Tg338 (ovine VRQ PrPC), Tg501 (ovine ARQ PrPC), Tg340 (human M129 PrPC), Tg361 (human V129 PrPC), TgVole (bank vole I109 PrPC), bank vole (I109I PrPC), and sheep (AHQ/ARR and AHQ/AHQ churra-tensina breeds). Our analysis of the results of these bioassays concludes that the strain generated in this model is indistinguishable to that causing atypical scrapie (Nor98). Thus, we present the first faithful model for a bona fide, transmissible, ovine, atypical scrapie prion disease.

Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon.

A subgroup of congenital disorders of glycosylation (CDGs) includes inherited GPI-anchor deficiencies (IGDs) that affect the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, including the first reaction catalyzed by the X-linked PIGA. Here, we show the first PIGA-CDG case reported in Mexico in a male child with a moderate-to-severe phenotype characterized by neurological and gastrointestinal symptoms, including megacolon. Exome sequencing identified the hemizygous variant PIGA c.145G>A (p.Val49Met), confirmed by Sanger sequencing and characterized as de novo. The pathogenicity of this variant was characterized by flow cytometry and complementation assays in PIGA knockout (KO) cells.

Glycans are not necessary to maintain the pathobiological features of bovine spongiform encephalopathy.

The role of the glycosylation status of PrPC in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrPC. Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrPC-expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrPC is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties.