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Botulinum neurotoxins (BoNTs) are valuable tools to unveil molecular mechanisms of exocytosis in neuronal and non-neuronal cells due to their peptidase activity on exocytic isoforms of SNARE proteins. They are produced by Clostridia as single-chain polypeptides that are proteolytically cleaved into light, catalytic domains covalently linked via disulfide bonds to heavy, targeting domains. This format of two subunits linked by disulfide bonds is required for the full neurotoxicity of BoNTs. We have generated a recombinant version of BoNT/B that consists of the light chain of the toxin fused to the protein transduction domain of the human immunodeficiency virus-1 (TAT peptide) and a hexahistidine tag. His6-TAT-BoNT/B-LC, expressed in Escherichia coli and purified by affinity chromatography, penetrated membranes and exhibited strong enzymatic activity, as evidenced by cleavage of the SNARE synaptobrevin from rat brain synaptosomes and human sperm cells. Proteolytic attack of synaptobrevin hindered exocytosis triggered by a calcium ionophore in the latter. The novel tool reported herein disrupts the function of a SNARE protein within minutes in cells that may or may not express the receptors for the BoNT/B heavy chain, and without the need for transient transfection or permeabilization.
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Toxinas Botulínicas Tipo A , Exocitose , Animais , Humanos , Ratos , Toxinas Botulínicas Tipo A/metabolismo , Toxinas Botulínicas Tipo A/genética , Toxinas Botulínicas Tipo A/isolamento & purificação , Proteínas SNARE/metabolismo , Proteínas SNARE/genética , Masculino , Sinaptossomos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/genética , Permeabilidade da Membrana Celular/efeitos dos fármacos , Toxinas Botulínicas/metabolismo , Toxinas Botulínicas/genética , Toxinas Botulínicas/química , Toxinas Botulínicas/isolamento & purificaçãoRESUMO
This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.
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Capilares , Retinopatia Diabética , Oftalmoscopia , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/patologia , Feminino , Masculino , Oftalmoscopia/métodos , Pessoa de Meia-Idade , Capilares/diagnóstico por imagem , Capilares/patologia , Adulto , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Idoso , Angiofluoresceinografia/métodosRESUMO
Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C6 and cepham C7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b, which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.
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Antibacterianos , Cefalosporinas , Complexos de Coordenação , Antibacterianos/química , Antibacterianos/síntese química , Cefalosporinas/química , Cefalosporinas/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Penicilinas/química , Penicilinas/síntese química , Estrutura Molecular , Modelos Moleculares , beta-Lactamas/química , beta-Lactamas/síntese química , Antibióticos beta LactamRESUMO
Networks of coupled Kerr parametric oscillators (KPOs) are a leading physical platform for analog solving of complex optimization problems. These systems are colloquially known as "Ising machines." We experimentally and theoretically study such a network under the influence of an external force. The force breaks the collective phase-parity symmetry of the system and competes with the intrinsic coupling in ordering the network configuration, similar to how a magnetic field biases an interacting spin ensemble. Specifically, we demonstrate how the force can be used to control the system, and highlight the crucial role of the phase and symmetry of the force. Our Letter thereby provides a method to create Ising machines with arbitrary bias, extending even to exotic cases that are impossible to engineer in real spin systems.
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This review article focuses on amidinatotetrylenes that potentially can (or have already shown to) behave as bi- or tridentate ligands because they contain at least one amidinatotetrylene moiety (silylene, germylene or stannylene) and one (or more) additional coordinable fragment(s). Currently, they are being widely used as ligands in coordination chemistry, small molecule activation and catalysis. This review classifies those that have been isolated as transition metal-free compounds into five families that differ in the position(s) of the donor group(s) (D) on the amidinatotetrylene moiety, namely: ED{R1NC(R2)NR1}, EX{DNC(R2)NR1}, EX{R1NC(D)NR1}, EX{DNC(R2)ND} and E{R1NC(R2)ND}2 (E=Si, Ge or Sn). Those that do not exist as transition metal-free compounds but have been observed as ligands in transition metal complexes are cyclometallated and ring-opened amidinatotetrylene ligands. This article presents schematic descriptions of their structures, the approaches used for their syntheses and a quick overview of their involvement (as ligands) in transition metal-catalysed reactions. The literature is covered up to the end of 2023.
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Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
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Cicatriz , Colágeno , Fibroblastos , Cicatrização , Peixe-Zebra , Humanos , Animais , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Colágeno/metabolismo , Cicatrização/efeitos dos fármacos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/tratamento farmacológico , Pele/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Fibrose , Peptídeos/farmacologia , Peptídeos/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacosRESUMO
Active Learning (AL) has the potential to solve a major problem of digital pathology: the efficient acquisition of labeled data for machine learning algorithms. However, existing AL methods often struggle in realistic settings with artifacts, ambiguities, and class imbalances, as commonly seen in the medical field. The lack of precise uncertainty estimations leads to the acquisition of images with a low informative value. To address these challenges, we propose Focused Active Learning (FocAL), which combines a Bayesian Neural Network with Out-of-Distribution detection to estimate different uncertainties for the acquisition function. Specifically, the weighted epistemic uncertainty accounts for the class imbalance, aleatoric uncertainty for ambiguous images, and an OoD score for artifacts. We perform extensive experiments to validate our method on MNIST and the real-world Panda dataset for the classification of prostate cancer. The results confirm that other AL methods are 'distracted' by ambiguities and artifacts which harm the performance. FocAL effectively focuses on the most informative images, avoiding ambiguities and artifacts during acquisition. For both experiments, FocAL outperforms existing AL approaches, reaching a Cohen's kappa of 0.764 with only 0.69% of the labeled Panda data.
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Neoplasias da Próstata , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Masculino , Aprendizado de Máquina , Teorema de Bayes , Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Artefatos , Redes Neurais de ComputaçãoRESUMO
In brief: MEK signalling pathway is required for hypoblast differentiation in mouse embryos, but its role in ungulate embryos remains controversial. This paper demonstrates that MEK is required for hypoblast specification in the inner cell mass of the ovine blastocyst and that it plays a role during the hypoblast migration occurring following blastocyst hatching. Abstract: Early embryo development requires the differentiation of three cell lineages in two differentiation events. The second lineage specification differentiates the inner cell mass into epiblast, which will form the proper fetus, and hypoblast, which together with the trophectoderm will form the extraembryonic membranes and the fetal part of the placenta. MEK signalling pathway is required for hypoblast differentiation in mouse embryos, but its role in ungulate embryos remains controversial. The aim of this work was to analyse the role of MEK signalling on hypoblast specification at the blastocyst stage and on hypoblast migration during post-hatching stages in vitro in the ovine species. Using well-characterized and reliable lineage markers, and different MEK inhibitor concentrations, we demonstrate that MEK signalling pathway is required for hypoblast specification in the inner cell mass of the ovine blastocyst, and that it plays a role during the hypoblast migration occurring following blastocyst hatching. These results show that the role of MEK signalling pathway on hypoblast specification is conserved in phylogenetically distant mammals.
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Diferenciação Celular , Movimento Celular , Desenvolvimento Embrionário , Sistema de Sinalização das MAP Quinases , Animais , Feminino , Gravidez , Blastocisto/metabolismo , Blastocisto/citologia , Massa Celular Interna do Blastocisto/metabolismo , Massa Celular Interna do Blastocisto/citologia , Linhagem da Célula , Ovinos , Transdução de Sinais , CamundongosRESUMO
Background: Prolonged hospitalization in severe COVID-19 cases can lead to substantial muscle loss and functional deterioration. While rehabilitation is essential, conventional approaches face capacity challenges. Therefore, evaluating the effectiveness of robotic-assisted rehabilitation for patients with post-COVID-19 fatigue syndrome to enhance both motor function and overall recovery holds paramount significance. Our objective is to assess the effectiveness of rehabilitation in post-COVID-19 patients with upper extremity impairment through the utilization of a hand exoskeleton-based robotic system. Methods: A total of 13 participants experiencing acute or limited functional or strength impairment in an upper extremity due to COVID-19 were enrolled in the study. A structured intervention consisted of 45 min therapy sessions, conducted four times per week over a six-week period, utilizing a hand exoskeleton. The research employed standardized health assessments, motion analysis, and semi-structured interviews for pre-intervention and follow-up evaluations. Paired sample t-tests were employed to statistically analyze the outcomes. Results: The outcomes showed a reduction in overall dependence levels across participants, positive changes in various quality of life-related measurements, and an average increase of 60.4 ± 25.7% and 28.7 ± 11.2% for passive and active flexion, respectively. Conclusions: Our data suggest that hand exoskeleton-based robotic systems hold promise to optimize the rehabilitation outcomes following severe COVID-19. Trial registration: ID NCT06137716 at ClinicalTrials.gov.
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The extreme low humidity and temperatures in Antarctica make it one of the harsher areas for life on our planet. In a global change context, environmental barriers that prevented the arrival of alien species in Antarctica are weakening. Deception Island, one of the four active volcanoes of Antarctica, is especially vulnerable to the impacts of alien species. Geothermal areas (GA) in this Island offer unique microclimatic conditions that could differentially affect native and alien soil arthropods. Here we explore the desiccation tolerance of a native (Cryptopygus antarcticus) and an alien (Proisotoma minuta) springtail (Collembola) species to these extreme environmental conditions. GA and non-geothermal areas (NGA) were selected to evaluate intra- and interspecific variation in desiccation tolerance. Populations of P. minuta from GA had greater desiccation tolerance than populations from NGA. However, desiccation tolerance of C. antarcticus did not differ between GA and NGA. This native species had greater desiccation tolerance than the alien P. minuta, but also greater body size. Our findings show that the alien P. minuta responds differently to environmental conditions than the native C. antarcticus. Furthermore, body size may influence desiccation tolerance in these two springtail species.
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Artrópodes , Dessecação , Animais , Regiões Antárticas , Artrópodes/fisiologia , TemperaturaRESUMO
Background: Incomplete species inventories for Antarctica represent a key challenge for comprehensive ecological research and conservation in the region. Additionally, data required to understand population dynamics, rates of evolution, spatial ranges, functional traits, physiological tolerances and species interactions, all of which are fundamental to disentangle the different functional elements of Antarctic biodiversity, are mostly missing. However, much of the fauna, flora and microbiota in the emerged ice-free land of the continent have an uncertain presence and/or unresolved status, with entire biodiversity compendia of prokaryotic groups (e.g. bacteria) being missing. All the available biodiversity information requires consolidation, cross-validation, re-assessment and steady systematic inclusion in order to create a robust catalogue of biodiversity for the continent. New information: We compiled, completed and revised eukaryotic species inventories present in terrestrial and freshwater ecosystems in Antarctica in a new living database: terrANTALife (version 1.0). The database includes the first integration in a compendium for many groups of eukaryotic microorganisms. We also introduce a first catalogue of amplicon sequence variants (ASVs) of prokaryotic biodiversity. Available compendia and literature to date were searched for Antarctic terrestrial and freshwater species, integrated, taxonomically harmonised and curated by experts to create comprehensive checklists of Antarctic organisms. The final inventories comprises 470 animal species (including vertebrates, free-living invertebrates and parasites), 306 plants (including all Viridiplantae: embryophytes and green algae), 997 fungal species and 434 protists (sensu lato). We also provide a first account for many groups of microorganisms, including non-lichenised fungi and multiple groups of eukaryotic unicellular species (Stramenophila, Alveolata and Rhizaria (SAR), Chromists and Amoeba), jointly referred to as "protists". In addition, we identify 1753 bacterial (obtained from 348117 ASVs) and 34 archaeal genera (from 1848 ASVs), as well as, at least, 14 virus families. We formulate a basic tree of life in Antarctica with the main lineages listed in the region and their "known-accepted-species" numbers.
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A method has been developed for synthesizing [FeFe]-H2ase mimics with diverse structures and properties, employing cross-metathesis of olefins. Vinylmetallocenes (5 and 6) and vinyl half-sandwich complexes (10 and 11) have been used as cross-metathesis partners with [FeFe]-H2ase mimics (4, 8, and 9) bearing a double bond in the moiety attached to the ADT-bridge nitrogen. Electrochemical studies of these complexes, encompassing metallocene-type (7a-b, 12a-b, and 13a-b) as well as half-sandwich derivatives (12c and 13c-d), have demonstrated that the introduction of a redox unit has a marginal impact on the reduction potential of these [FeFe]-H2ase mimics. The application of this cross-metathesis approach has allowed the synthesis of [FeFe]-H2ase mimics featuring an Ir(III) electrochemical antenna (16-18) as well as systems having an electron-donor-photosensitizer structure (ED-PS) (23). The electrocatalytic properties of these complexes have been elucidated through electrochemical studies.
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Automated semantic segmentation of histopathological images is an essential task in Computational Pathology (CPATH). The main limitation of Deep Learning (DL) to address this task is the scarcity of expert annotations. Crowdsourcing (CR) has emerged as a promising solution to reduce the individual (expert) annotation cost by distributing the labeling effort among a group of (non-expert) annotators. Extracting knowledge in this scenario is challenging, as it involves noisy annotations. Jointly learning the underlying (expert) segmentation and the annotators' expertise is currently a commonly used approach. Unfortunately, this approach is frequently carried out by learning a different neural network for each annotator, which scales poorly when the number of annotators grows. For this reason, this strategy cannot be easily applied to real-world CPATH segmentation. This paper proposes a new family of methods for CR segmentation of histopathological images. Our approach consists of two coupled networks: a segmentation network (for learning the expert segmentation) and an annotator network (for learning the annotators' expertise). We propose to estimate the annotators' behavior with only one network that receives the annotator ID as input, achieving scalability on the number of annotators. Our family is composed of three different models for the annotator network. Within this family, we propose a novel modeling of the annotator network in the CR segmentation literature, which considers the global features of the image. We validate our methods on a real-world dataset of Triple Negative Breast Cancer images labeled by several medical students. Our new CR modeling achieves a Dice coefficient of 0.7827, outperforming the well-known STAPLE (0.7039) and being competitive with the supervised method with expert labels (0.7723). The code is available at https://github.com/wizmik12/CRowd_Seg.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , HumanosRESUMO
As part of a long-term research project aiming at generating a biomechanical model of a fossil human tongue from a carefully designed 3D Finite Element mesh of a living human tongue, we present a computer-based method that optimally registers 3D CT images of the head and neck of the living human into similar images of another primate. We quantitatively evaluate the method on a baboon. The method generates a geometric deformation field which is used to build up a 3D Finite Element mesh of the baboon tongue. In order to assess the method's ability to generate a realistic tongue from bony structure information alone, as would be the case for fossil humans, its performance is evaluated and compared under two conditions in which different anatomical information is available: (1) combined information from soft-tissue and bony structures; (2) information from bony structures alone. An Uncertainty Quantification method is used to evaluate the sensitivity of the transformation to two crucial parameters, namely the resolution of the transformation grid and the weight of a smoothness constraint applied to the transformation, and to determine the best possible meshes. In both conditions the baboon tongue morphology is realistically predicted, evidencing that bony structures alone provide enough relevant information to generate soft tissue.
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Hominidae , Animais , Humanos , Fósseis , Crânio/diagnóstico por imagem , Língua/diagnóstico por imagem , Papio , Análise de Elementos Finitos , Simulação por ComputadorRESUMO
E(hmds)(bqfam) (E = Ge (1a), Sn (1b); hmds = N(SiMe3)2, bqfam = N,N'-bis(quinol-8-yl)formamidinate), which are amidinatotetrylenes equipped with quinol-8-yl fragments on the amidinate N atoms, have been synthesized from the formamidine Hbqfam and Ge(hmds)2 or SnCl(hmds). Both 1a and 1b are fluxional in solution at room temperature, as the E atom oscillates from being attached to the two amidinate N atoms to being chelated by an amidinate N atom and its closest quinolyl N atom (both situations are similarly stable according to density functional theory calculations). The hmds group of 1a and 1b is still reactive and the deprotonation of another equivalent of Hbqfam can be achieved, allowing the formation of the homoleptic derivatives E(bqfam)2 (E = Ge, Sn). The reactions of 1a and 1b with [AuCl(tht)] (tht = tetrahydrothiophene), [PdCl2(MeCN)2], [PtCl2(cod)] (cod = cycloocta-1,5-diene), [Ru3(CO)12] and [Co2(CO)8] have been investigated. The gold(I) complexes [AuCl{κE-E(hmds)(bqfam)}] (E = Ge, Sn) have a monodentate κE-tetrylene ligand and display fluxional behavior in solution the same as that of 1a and 1b. However, the palladium(II) and platinum(II) complexes [MCl{κ3E,N,N'-ECl(hmds)(bqfam)}] (M = Pd, Pt; E = Ge, Sn) contain a κ3E,N,N'-chloridotetryl ligand that arises from the insertion of the tetrylene E atom into an M-Cl bond and the coordination of an amidinate N atom and its closest quinolyl N atom to the metal center. Finally, the binuclear ruthenium(0) and cobalt(0) complexes [Ru2{µE-κ3E,N,N'-E(hmds)(bqfam)}(CO)6] and [Co2{µE-κ3E,N,N'-E(hmds)(bqfam)}(µ-CO)(CO)4] (E = Ge, Sn) have a related κ3E,N,N'-tetrylene ligand that bridges two metal atoms through the E atom. For the κ3E,N,N'-metal complexes, the quinolyl fragment not attached to the metal is pendant in all the germanium compounds but, for the tin derivatives, is attached to (in the Pd and Pt complexes) or may interact with (in the Ru2 and Co2 complexes) the tin atom.
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Numerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistent Salmonella Typhimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages, Salmonella persists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages showed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistent Salmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.
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Interações Hospedeiro-Patógeno , Peixe-Zebra , Animais , Macrófagos/microbiologia , Salmonella typhimurium , FenótipoRESUMO
El osteocondroma es el tumor óseo benigno más frecuente, representa el 35% de los tumores óseos benignos y el 8% de los tumores óseos. Está formado por una exostosis de hueso trabecular recubierta de cartílago que afecta la región metafisaria de los huesos largos, a partir del cartílago de crecimiento, alrededor de la rodilla, en el hombro o la muñeca, y es extremadamente raro en las falanges de la mano o el pie. Crece durante la niñez y la adolescencia hasta alcanzar la madurez esquelética; por lo tanto, su crecimiento en un adulto sugiere la transformación maligna en condrosarcoma, aunque también existen reportes sin malignización. Además, el calcáneo es un hueso corto, por lo que, desde el punto de vista fisiopatológico, sería inesperada la aparición de este tipo de lesión. El objetivo de este artículo es presentar un caso de osteocondroma de calcáneo solitario con crecimiento después de la madurez esquelética, su diagnóstico y tratamiento, así como una revisión bibliográfica. Esta presentación de caso es importante, dados la localización infrecuente y el potencial de transformación maligna del osteocondroma, y la escasa bibliografía sobre el tema. Nivel de Evidencia: IV
Osteochondroma is the most common benign bone tumor, accounting for 35% of benign bone tumors and 8% of bone tumors. It is formed by an exostosis of trabecular bone covered with cartilage that affects the metaphyseal region of long bones, from the growth plate, around the knee, in the shoulder or wrist, and it is extremely rare in the phalanges of the hand or foot. It grows during childhood and adolescence until skeletal maturity. Therefore, its growth in an adult suggests a malignant transformation into chondrosarcoma, although there are also reports without malignancy. Furthermore, the calcaneus is a short bone, so the appearance of this type of injury would be pathophysiologically unexpected. Our objective is to present a case of solitary calcaneal osteochondroma with growth after skeletal maturity, its diagnosis and treatment, as well as a review of the literature. Its relevance stems from the scarcity of literature, its uncommon location, and the possibility of malignancy. Level of Evidence: IV
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Adulto , Neoplasias Ósseas , Calcâneo , OsteocondromaRESUMO
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Introduction: Sleep-disordered breathing (SDB) are highly prevalent in patients with heart failure (HF). The presence of obstructive sleep apnea syndrome (OSA) determines a worse prognosis in these patients. There are questionnaires aimed at evaluating the probability of OSA, although none have been validated in patients with HF. The primary objective of this study was to establish the prevalence of SDB in a cohort of patients with HF and reduced ejection fraction (HFrEF) from the Multidisciplinary HF Unit (UMIC). As a secondary objective, to evaluate the usefulness of the Stop-Bang, Berlin, and 2ABN3M questionnaires for TRS screening in these patients. Methodology: Cross-sectional, observational study, including the active cohort of the UMIC, over 18 years with HFrEF, clinically stable and informed consent. Patients with cognitive, neurological or hearing impairment with limitations when conducting the interview were excluded. Patients with other limiting or uncontrolled sleep disorders, continuous home oxygen therapy requirements, did not enter the study. Berlin, Stop-Bang, and 2ABN3M questionnaires were administered, classifying the population into high-risk, intermediate-risk, and low-risk groups of presenting SDB. All patients underwent outpatient respiratory polygraphy (RP). Descriptive statistics were used to characterize demographic variables, measures of central tendency and dispersion. SPSS statistical software was used. Results: 387 patients were included, 248 men (64.1%), mean age was 63.5 ± 0.6 years. The etiology of HF was ischemic in 41.6% of patients. The body mass index was 29.3 ± 0.3 kg/m2. LVEF was 34.2 ± 0.5, pro-BNP 1233.8 ± 137.6 pg/ml. The results of the questionnaires showed that 52.1% (198) presented a high risk of SDB according to the Berlin questionnaire. With Stop-Bang, 35.9% (139) were high risk, 42.1% (163) intermediate risk, and the remaining 22% (85) low risk. With the 2ABN3M score, 62% (240) were high risk. A total of 156 respiratory polygraphs (40.3% of the population) were performed. The cut-off point to define the presence of sleep apnea was considered to be an AHI >15. 58.3% (91) of the patients presented TRS. Of these, 95% presented obstructive apnea and 5% central apnea with periodic Cheyne-Stokes breathing. A high percentage (26%) presented AHI greater than 30. The sensitivity of the Berlin and Stop-Bang questionnaires was 75.8% and 91.2%, respectively, with a specificity of 53.8% and 24.6%. Regarding the 2ABN3M score, a sensitivity of 71.4% and a specificity of 44.6% were observed. Conclusions: The prevalence of sleep-disordered breathing in patients with HFrEF was high in our cohort and obstructive apnea predominated. Given the high sensitivity (91.2%) of the Stop-Bang questionnaire found in our study, it could be useful as a screening tool for TRS in this type of patient. The importance of investigating this pathology whose clinical presentation can be non-specific and remain underdiagnosed is highlighted.
Introdução: Os distúrbios respiratórios do sono (DRS) são altamente prevalentes em pacientes com insuficiência cardíaca (IC). A presença da síndrome da apneia obstrutiva do sono (SAOS) determina pior prognóstico nesses pacientes. Existem questionários destinados a avaliar a probabilidade de AOS, porém nenhum foi validado em pacientes com IC. O objetivo primário deste estudo foi estabelecer a prevalência de DRS em uma coorte de pacientes com IC e fração de ejeção reduzida (ICFEr) da Unidade Multidisciplinar de IC (UMIC). Como objetivo secundário, avaliar a utilidade dos questionários Stop-Bang, Berlin e 2ABN3M para triagem de SRT nesses pacientes. Metodologia: Estudo transversal, observacional, inclui a coorte ativa da UMIC, maiores de 18 anos com ICFEr, clinicamente estável e consentimento informado. Foram excluídos pacientes com deficiência cognitiva, neurológica ou auditiva com limitações na realização da entrevista. Pacientes com outros distúrbios do sono limitantes ou descontrolados, requisitos de oxigenoterapia domiciliar contínua, não entraram no estudo. Os questionários Berlin, Stop-Bang e 2ABN3M foram aplicados, classificando a população em grupos de alto risco, risco intermediário e baixo risco de apresentar DRS. Todos os pacientes foram submetidos à poligrafia respiratória (PR) ambulatorial. A estatística descritiva foi utilizada para caracterizar as variáveis ââdemográficas, medidas de tendência central e dispersão. Foi utilizado o software estatístico SPSS. Resultados: foram incluídos 387 pacientes, 248 homens (64,1%), com idade média de 63,5 ± 0,6 anos. A etiologia da IC foi isquêmica em 41,6% dos pacientes. O índice de massa corporal foi de 29,3 ± 0,3 kg/m2. FEVE foi de 34,2 ± 0,5, pro-BNP 1233,8 ± 137,6 pg/ml. Os resultados dos questionários mostraram que 52,1% (198) apresentaram alto risco de DRS de acordo com o questionário de Berlim. Com Stop-Bang, 35,9% (139) eram de alto risco, 42,1% (163) de risco intermediário e os restantes 22% (85) de baixo risco. Com a pontuação 2ABN3M, 62% (240) eram de alto risco. Foram realizados 156 polígrafos respiratórios (40,3% da população). O ponto de corte para definir a presença de apneia do sono foi considerado um IAH >15. 58,3% (91) dos pacientes apresentaram SRT. Destes, 95% apresentavam apnéia obstrutiva e 5% apnéia central com respiração Cheyne-Stokes periódica. Uma alta porcentagem (26%) apresentou IAH maior que 30. A sensibilidade dos questionários Berlin e Stop-Bang foi de 75,8% e 91,2%, respectivamente, com especificidade de 53,8% e 24,6%. Em relação ao escore 2ABN3M, observou-se sensibilidade de 71,4% e especificidade de 44,6%. Conclusões: A prevalência de distúrbios respiratórios do sono em pacientes com ICFEr foi alta em nossa coorte, com predominância de apneias obstrutivas. Dada a alta sensibilidade (91,2%) do questionário Stop-Bang encontrado em nosso estudo, ele pode ser útil como uma ferramenta de triagem para ERT nesse tipo de paciente. Ressalta-se a importância da investigação dessa patologia cuja apresentação clínica pode ser inespecífica e permanecer subdiagnosticada.
RESUMO
We present a combination of light-sheet excitation and two-dimensional fluorescence intensity ratio (FIR) measurements as a simple and promising technique for three-dimensional temperature mapping. The feasibility of this approach is demonstrated with samples fabricated with sodium yttrium fluoride nanoparticles co-doped with rare-earth ytterbium and erbium ions (NaYF4:Yb3+/Er3+) incorporated into polydimethylsiloxane (PDMS) as a host material. In addition, we also evaluate the technique using lipid-coated NaYF4:Yb3+/Er3+ nanoparticles immersed in agar. The composite materials show upconverted (UC) fluorescence bands when excited by a 980 nm near-infrared laser light-sheet. Using a single CMOS camera and a pair of interferometric optical filters to specifically image the two thermally-coupled bands (at 525 and 550 nm), the two-dimensional FIR and, hence, the temperature map can be readily obtained. The proposed method can take optically sectioned (confocal-like) images with good optical resolution over relatively large samples (up to the millimetric scale) for further 3D temperature reconstruction.
RESUMO
[This corrects the article DOI: 10.1039/D3SC02709K.].