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Liposomal formulations of antibiotics for inhalation offer the potential for the delivery of high drug doses, controlled drug release kinetics in the lung, and an excellent safety profile. In this study, we evaluated the in vivo performance of a liposomal formulation for the poorly soluble, antituberculosis agent, bedaquiline. Bedaquiline was encapsulated within monodisperse liposomes of â¼70 nm at a relatively high drug concentration (â¼3.6 mg/mL). Formulations with or without fucose residues, which bind to C-type lectin receptors and mediate a preferential binding to macrophage mannose receptor, were prepared, and efficacy was assessed in an in vivo C3HeB/FeJ mouse model of tuberculosis infection (H37Rv strain). Seven intranasal instillations of 5 mg/kg bedaquiline formulations administered every second day resulted in a significant reduction in lung burden (â¼0.4-0.6 Δlog10 CFU), although no differences between fucosylated and nonfucosylated formulations were observed. A pharmacokinetic study in healthy, noninfected Balb/c mice demonstrated that intranasal administration of a single dose of 2.5 mg/kg bedaquiline liposomal formulation (fucosylated) improved the lung bioavailability 6-fold compared to intravenous administration of the same formulation at the same dose. Importantly, intranasal administration reduced systemic concentrations of the primary metabolite, N-desmethyl-bedaquiline (M2), compared with both intravenous and oral administration. This is a clinically relevant finding as the M2 metabolite is associated with a higher risk of QT-prolongation in predisposed patients. The results clearly demonstrate that a bedaquiline liposomal inhalation suspension may show enhanced antitubercular activity in the lung while reducing systemic side effects, thus meriting further nonclinical investigation.
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TA2Viewer is an open-access, web-based application and database for browsing anatomical terms and associated medical information on a computer or mobile device (https://ta2viewer.openanatomy.org/). It incorporates the official digital version of the second edition of Terminologia Anatomica (TA2) as published by the Federative International Programme for Anatomical Terminology (FIPAT), and adopted by the International Federation of Associations of Anatomists (IFAA) and other associations. It provides a dynamic and interactive view of the Latin and English nomenclatures. The organizational hierarchy of the terminology can be navigated by using a scrollable, expandable, and collapsible structured listing. Interactive search includes the official TA2 terms, synonyms, and related terms. TA2Viewer also uses TA2 term information to provide convenient access to other online resources, including Google web and image searches, PubMed, and Radiopaedia. Using cross-references from Wikidata, which were provided by the Wikipedia community, TA2Viewer offers links to Wikipedia, UBERON, UMLS, FMA, MeSH, NeuroNames, the public domain 20th edition of Gray's Anatomy, and other data sources. In addition, it can optionally use unofficial synonyms from Wikidata to provide multilingual term searches in hundreds of languages. By leveraging TA2, TA2Viewer provides free access to a curated anatomical nomenclature and serves as an index of online anatomical knowledge.
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Anatomia , Terminologia como Assunto , Anatomia/educação , Humanos , Internet , Navegador , Bases de Dados FactuaisRESUMO
Almost 20% of the Latin nouns (193/993) in Terminologia Histologica (TH), the international standard nomenclature for human histology and cytology, display linguistic problems, particularly in the areas of orthography, gender, and declension. Some anatomists have opposed efforts to restore the quality of the Latin nomenclature as pedantry, preferring to create or modify Latin words so that they resemble words in English and other modern languages. A Latin microanatomical nomenclature is vulnerable to the criticism of anachronism, so the requirement for the use of authentic Latin, including derivation of new words from Greek and Latin words rather than from modern languages, if possible, may be even greater than it is for the anatomical nomenclature. The most common problem identified here appears to have been caused by derivation of Latin nouns by addition of -us and -um second declension endings to English words. Many Latin nouns (128) in TH contain one of six morphemes that have been treated this way even though the original Greek words are either first declension masculine or third declension neuter nouns. Ironically, deriving Latin nouns directly from Greek morphemes often results in words that look more familiar to speakers of Romance and Germanic languages than those derived indirectly through modern languages (e.g., astrocyte, collagene, dendrita, lipochroma, osteoclasta and telomere instead of astrocytus, collagenum, dendritum, lipochromum, osteoclastus, and telomerus).
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Anatomistas , Vocabulário , Humanos , Idioma , LinguísticaRESUMO
The purpose of a standard terminology is to facilitate communication. Thus, changing the name of an anatomical structure or the meaning of an anatomical term undermines that aspiration and cuts connections with anatomy's long history. Two types of anatomical terms are the most vulnerable to logical arguments for revision-ones that are descriptive, but viewed, at least by some, as inaccurate, and ones that contain words that are polysemic or vague. A half dozen examples of each type are discussed, including ductus deferens, glandula seminalis, articulationes costochondrales, vulva and fascia. In general, traditional terms should be preserved, but judgments about which terms are traditional should be based on five centuries of modern anatomy, not just the past several decades.
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Anatomia , Glândulas Seminais , Masculino , Feminino , Humanos , Fáscia/anatomia & histologia , Comunicação , Costelas , Vulva , Anatomia/históriaRESUMO
In a previous essay, we wrote about the shortcomings of the four basic tissue dogma of histology - miscellaneous tissues lumped under the ill-fitting name "connective tissues" and the existence of human tissues that are not recognized as subtypes of any of the four "basic types". A provisional reclassification of human tissues was constructed to improve the precision and completeness of the tissue taxonomy. Here, we address criticisms from a recent paper that claims that the four basic tissue dogma is more useful than that revised classification in medical education and in clinical practice. Some of the criticism appears to arise from the common misconception of a tissue as simply an array of similar cells.
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Tecido Conjuntivo , Técnicas Histológicas , HumanosRESUMO
Acupuncture point names written in Chinese Han characters often provide clinically useful information in both their literal and figurative meanings about location and therapeutic use. The World Health Organization (WHO) standard acupuncture nomenclature includes these names in Han characters in an unusual array that includes both "original" forms and, in parentheses, simplified forms. Construction of a multilingual table of acupuncture point names during development of a database revealed that the assumption that the "original" form in the WHO nomenclature was the traditional Chinese character was frequently false. The Han character forms in the pdf of the 2009 reprint of WHO Standard Acupuncture Point Locations were carefully compared with Han characters used in traditional and simplified Chinese, Japanese and Korean writing systems. This work utilized three online tools: UnicodePlus, Unihan Database Lookup, and Wiktionary. Only 48% of the "original" character forms were traditional Chinese characters. The Unicode number was correct in 99%, but in most cases the East Asian font used was not a traditional Chinese one. The issue about Han character forms was also found in all earlier versions of the WHO standard acupuncture nomenclature. Other detected problems included the use of wrong characters for an "original" character form in one name and for a simplified character form in another name. The WHO standard acupuncture nomenclature should be revised with a focus on accuracy in the usage of Han characters.
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Pontos de Acupuntura , Idioma , Humanos , Terapia por Acupuntura , Multilinguismo , Terminologia como AssuntoRESUMO
Substantivation, the use of an adjective or participle as a noun, is commonly used informally to shorten Latin anatomical terms. Dozens of substantives also appear in the international standard anatomical terminology. Most of these are venerable and familiar as nouns in Latin anatomical terms. Examples of Latin nouns derived directly or indirectly from Greek and Latin adjectives and participles are presented here. Although neologisms are said to enrich languages, careful consideration is required before adding to a technical vocabulary. Terms consisting of a substantive or displaying a substantive as the head noun may be vague to learners and nonspecialists.
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Anatomia , Idioma , HumanosRESUMO
The Hazard Quotient (HQ) compares field application rate to intrinsic toxicity assessed with sensitive indicator species. As a hazard indicator for risk assessment, the HQ must be calibrated against measured effects under field conditions. Because protection goals may be context specific, we analyse how choice of acceptance criteria affects setting of the HQ and calibrate HQ for various scenarios under the strict condition that no false negative conclusions may be reached. We use Non-Target Arthropod toxicity data from laboratory studies on inert (Tier 1) and on natural substrates (Tier 2) and calibrate the HQ using application rates and arthropod abundance counts from field studies in orchards, arable fields, and hay meadows in 34 locations in Western Europe. With 21 formulations (17 active substances) tested in mostly multi-rate field studies, our reference data base has 120/121 values at Tier 1/Tier 2, respectively. We use the Proportion of Affected Taxa and Duration of Effect to jointly define acceptance criteria, starting with No Observed Effects. Absence of field effects is correctly predicted with HQ < 1.3 at Tier 1 and HQ < 0.48 at Tier 2, but these settings result in a high proportion of false positive outcomes. Increasing accepted duration of effect from 0 to 4 to 8 weeks results in HQ-threshold changes from 1.3 to 6.4 to 250 for Tier 1 studies and from 0.48 to 1.1 to 5.7 for Tier 2 studies. This coincides with a clear decrease in false positive outcomes. Recovery within a year is correctly concluded for 73% of the products passing the corresponding Tier 1 HQ < 2600 and for 92% of products at Tier 2 (HQ <230). Our analysis shows that the calibration is appropriate for a broad geographical range, for in-field and off-field situations and for phytophagous and non-phytophagous species alike.
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Artrópodes , Animais , Calibragem , Europa (Continente) , Medição de Risco/métodosRESUMO
The eponymous term torcular Herophili has been used for the confluence of sinuses. Although no original writings of Herophilus are extant, his accomplishments and descriptions live on in the writings of such authors as Galen. However, in regard to the torcular Herophili, there are some inconsistencies in the secondary sources and their translations regarding what was actually originally described by Herophilus. Herein, we review the history of the term torcular Herophili, which is so often used in clinical medicine.
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Cavidades Cranianas , HumanosRESUMO
The central dogma of systematic anatomy is the well-known hierarchy of anatomical structures: body-systems-organs-tissues-cells. This schema omits extracellular matrix and extracellular fluids, which account for a significant proportion of body mass, and distorts the meanings of the terms system, organ and tissue in anatomy. These faults are partially due to oversimplification, presumably intended for educational purposes, and confusion of anatomy's organ systems with physiological systems. A revised schema of the hierarchy of systematic anatomy is presented that is more complete and more consistent with the long history of anatomy.
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The concept of source-sink dynamics as a potentially important component of metapopulation dynamics was introduced in the 1980s. The objective of the present review was to review the considerable body of work that has been developed, to consider its theoretical implications as well as to understand how source-sink dynamics may manifest under field conditions in the specific case of nontarget arthropods in the agricultural environment. Our review concludes that metapopulation dynamics based on field observations are often far more complex than existing theoretical source-sink models would indicate, because they are dependent on numerous population processes and influencing factors. The difficulty in identifying and measuring these factors likely explains why empirical studies assessing source-sink dynamics are scarce. Furthermore, we highlight the importance of considering the spatial and temporal heterogeneity of agricultural landscapes when assessing the population dynamics of nontarget arthropods in the context of the risk from the use of plant protection products. A need is identified to further develop and thoroughly validate predictive population models, which can incorporate all factors relevant to a specific system. Once reliable predictive models for a number of representative nontarget arthropod species are available, they could provide a meaningful tool for refined risk evaluations (higher tier level risk assessment), addressing specific concerns identified at the initial evaluation stages (lower tier level risk assessment). Environ Toxicol Chem 2021;40:2667-2679. © 2021 ERM, FMC, Syngenta, Bayer AG, BASF SE, Corteva agriscience. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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Artrópodes , Agricultura , Animais , Ecotoxicologia , Dinâmica Populacional , Medição de RiscoRESUMO
Tuberculosis remains a leading cause of death, therapeutic failure being mainly due to non-compliance with prolonged treatments, often associated with severe side-effects. New therapeutic strategies are demanded and, considering that the lung is the primary site of infection, direct lung delivery of antibiotics is possibly an effective approach. Therapeutic success in this context depends on suitable carriers that reach the alveoli where Mycobacterium hosts (macrophages) reside, as well as on their ability to promote macrophage capture and intracellular accumulation of drugs. In this work, we propose inhalable polymeric microparticles produced from chondroitin sulfate, a polymer composed by moieties recognized by macrophage receptors. Spray-drying of chondroitin sulfate in combination with two first-line antitubercular drugs (isoniazid and rifabutin) yielded respirable microparticles that evidenced no cytotoxic effects on lung epithelial cells (A549) and macrophages (dTHP1 and J744A.1). The microparticles exhibited tendency for macrophage capture in a dose-dependent manner, which was validated through imaging. High content image analysis revealed that rifabutin induced a dose-dependent increase in phospholipid content of macrophages, which could be prevented by formulation in chondroitin sulfate microparticles. This work provides indications on the potential of chondroitin sulfate carriers to interact with macrophages, thus providing a platform for drug delivery in the context of macrophage intracellular diseases, namely tuberculosis.
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Antituberculosos/administração & dosagem , Sulfatos de Condroitina/química , Portadores de Fármacos/química , Macrófagos Alveolares/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Administração por Inalação , Animais , Linhagem Celular , Humanos , Isoniazida/administração & dosagem , Macrófagos Alveolares/microbiologia , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifabutina/administração & dosagem , Tuberculose Pulmonar/microbiologiaRESUMO
The modern view that the human body is composed of tissues and body fluids, and that there are four basic tissue types, may be a more significant departure from Artistotle's homoeomeres, and from Bichat's membranes and tissues, than commonly appreciated. The older concepts described these body parts as structural and functional parts of organs, whereas it is now commonplace to consider a tissue to be a grouping of similar cells with a variable amount of extracellular matrix. The development of the microscope as a useful tool in human anatomy shifted focus from tissues to cells and led to changes in the definition of tissue and the classification of tissues. Not all of these changes have been consistent with observable facts: many tissues contain diverse cell types, not all "connective tissues" are proper connective tissues, and some specialized tissues are not easily classified as subtypes of one of the four basic types. Here we propose corrective measures, including re-recognition of compound tissues, cataloging all adult human tissue types, and increasing the emphasis on function during the construction of a complete taxonomy of human adult tissues. Specific problems in the current scheme and a preliminary reclassification of human adult tissues are discussed.
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Anatomia/história , Técnicas Histológicas/história , História do Século XIX , História do Século XX , História do Século XXI , HumanosRESUMO
The π-conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b0]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) with deep-red/near-infrared (NIR) absorption and emission has been investigated as a contrast agent for in vivo optical and photoacoustic imaging. PCPDTBT is encapsulated within poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG2kDa -PLGA4kDa or PEG5kDa -PLGA55kDa ) micelles or enveloped by the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG2kDa -DPPE), to investigate the formulation effect on imaging performance, biodistribution, and biocompatibility. Nanoparticles that meet the quality requirements for parenteral administration are generated with similar physicochemical properties. Optical phantom imaging reveals that both PEG-PLGA systems exhibit a 30% higher signal-to-background ratio (SBR) than PEG2kDa -DPPE. This trend cannot be observed in a murine HeLa xenograft model following intravenous administration since dramatic differences in biodistribution are observed. PEG2kDa -PLGA4kDa systems accumulate more rapidly in the liver compared to other formulations and PEG2kDa -DPPE demonstrates a higher tumor localization. Protein content in the "hard" corona differs between formulations (PEG2kDa -DPPE < PEG2kDa -PLGA4kDa < PEG5kDa -PLGA55kDa ), although this observation alone does not explain biodistribution patterns. PEG2kDa -PLGA4kDa systems show the highest photoacoustic amplitude in a phantom, but also a lower signal in the tumor due to differences in biodistribution. This study demonstrates that formulations for conjugated polymer contrast agents can have significant impact on both imaging performance and biodistribution.
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Nanopartículas , Técnicas Fotoacústicas , Animais , Meios de Contraste , Camundongos , Poliésteres , Polietilenoglicóis , Polímeros , Distribuição TecidualRESUMO
Most of the terms in Terminologia Anatomica are arranged by organ systems (systemata); however, the names for these systems are often used by physiologists and other biomedical scientists for related functional systems. These functional systems may differ in their composition from the anatomist's organ systems. In addition, many functional systems have been described that do not correspond to organ systems. Similarly, the non-standard anatomical terms alimentary tract, respiratory tract, urinary tract and reproductive tract lack a consistent meaning in the biomedical sciences. For clear communication, one should be cautious when using terms that may have other meanings in other disciplines. This appears to be particularly true for high level terms in the nomenclature of systematic anatomy.
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Anatomia/educação , Terminologia como Assunto , HumanosRESUMO
Regular anatomical (RA) terminology rules were developed to simplify and clarify Latin anatomical terms in a systematic manner. These rules, which prohibit conjunctions, prepositions, and appositions, and define a consistent word order pattern, are extensions of the original 1895 rule of anatomical nomenclature that anatomical terms should be as short and simple as possible. It is not coincidental that most terms in Terminologia Anatomica (TA), and many traditional terms that were not used in TA, are consistent with RA term rules, and that the RA term rules are also consistent with the guidelines for expanding short form terms to full, unique terms. The consistent form of RA terms facilitates learning and translation, and is easier for humans and machines to manipulate than terms that are not compliant with RA term rules. Despite assertions to the contrary, RA terms are proper Latin terms that simplify the anatomical terminology and, in many cases, restore traditional terms.
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Anatomia , Terminologia como Assunto , HumanosRESUMO
Chemical recycling provides a promising solution to utilize plastic waste. Here, a catalytic hydrogenative depolymerization of polyamide 66 (PA 66) and polyurethane (PU) was developed. The system employed Ru pincer complexes at high temperature (200 °C) in THF solution, and even technical-grade polymers could be hydrogenated with satisfactory yields under these conditions. A comparison of the system with some known heterogeneous catalysts as well as catalyst poisoning tests supported the homogeneity of the system. These results demonstrate the potential of chemical recycling to regain building blocks for polymers and will be interesting for the further development of polymer hydrogenation.
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The rules of the anatomical nomenclature are sometimes in conflict with the principles of revision of the nomenclature. This is possibly most obvious is the debate about the use of the Latin words pudendus ("shameful") and sacer ("holy") in the anatomical nomenclature. The principles of revision stress preservation of traditional terms even if there are etymological concerns. On the other hand, the nomenclature rules state that anatomical names should, preferably, have informative or descriptive value and that the official Latin terms are the basis for translations of the international standard terminology into modern, vernacular languages. This issue of Clinical Anatomy contains responses to the removal of the noun pudendum and the replacement of the adjective pudendus with pudendalis in the second edition of Terminologia Anatomica.
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Anatomia , Genitália/anatomia & histologia , Publicações , Terminologia como Assunto , Tradução , HumanosRESUMO
INTRODUCTION: Communication in the biomedical sciences and clinical practice would be clearer if everyone used the same set of technical terms. Technical vocabularies, such as international standard terminologies, are attempts to avoid common linguistic problems, such as synonymy (many names for a single entity) and polysemy (many meanings for a single term). MATERIALS AND METHODS: Efforts made in human anatomical nomenclature since the late 19th century to deal with these issues were reviewed. RESULTS: The new designations official term, equivalent term, synonym and related term are defined, and current challenges (e.g., eponyms) are identified. DISCUSSION: The addition of synonyms and related terms to the international standard anatomical terminology allows indexing of these terms to the official terms and evaluation of the relationships between terms.
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Anatomia/história , Terminologia como Assunto , História do Século XIX , História do Século XX , História do Século XXI , HumanosRESUMO
The aim of this study was to investigate the potential of human serum albumin (HSA) as a solubilising agent/drug delivery vehicle for pulmonary administration of antimycobacterial benzothiazinone (BTZ) compounds. The solubility of four novel BTZ compounds (IR 20, IF 274, FG 2, AR 112) was enhanced 2 to 140-fold by incubation with albumin (0.38-134 µg/mL). Tryptophan 213 residue quenching studies indicated moderate binding strength to Sudlow's site I. Nanoparticle manufacture achieved 37-60% encapsulation efficiency in HSA particles (169 nm, zeta potential -31 mV). Drug release was triggered by proteases with >50% released in 4 h. The antimycobacterial activity of IR 20 and FG 2 loaded in HSA nanoparticles was enhanced compared to DMSO/phosphate buffered saline (PBS) or albumin/PBS solutions in an in vitro M. tuberculosis-infected macrophage model. Intranasal instillation was used to achieve pulmonary delivery daily over 10 days to M. tuberculosis infected mice for FG2 HSA nanoparticles (0.4 mg/kg), FG 2 DMSO/saline (0.4 and 8 mg/kg) and a reference compound, BTZ043, DMSO/saline (0.4 and 8 mg/kg). A lower lung M. tuberculosis burden was apparent for all BTZ cohorts, but only significant for BTZ043 at both doses. In conclusion, mechanisms of HSA nanoparticle loading and release of BTZ compounds were demonstrated, enhanced antimycobacterial activity of the nanoparticle formulations was demonstrated in a biorelevant in vitro bioassay and the effectiveness of BTZ by pulmonary delivery in vivo was established with pilot evidence for effectiveness when delivered by HSA nanoparticles. Finally, the feasibility of developing an inhaled nanoparticle-in-microparticle powder formulation was ascertained.