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OBJECTIVE: The goals of this article are as follows. First, to investigate the possibility of detecting autism spectrum disorder (ASD) from text data using the latest generation of machine learning tools. Second, to compare model performance on two datasets of transcribed statements, collected using two different diagnostic tools. Third, to investigate the feasibility of knowledge transfer between models trained on both datasets and check if data augmentation can help alleviate the problem of a small number of observations. METHOD: We explore two techniques to detect ASD. The first one is based on fine-tuning HerBERT, a BERT-based, monolingual deep transformer neural network. The second one uses the newest, multipurpose text embeddings from OpenAI and a classifier. We apply the methods to two separate datasets of transcribed statements, collected using two different diagnostic tools: thought, language, and communication (TLC) and autism diagnosis observation schedule-2 (ADOS-2). We conducted several cross-dataset experiments in both a zero-shot setting and a setting where models are pretrained on one dataset and then training continues on another to test the possibility of knowledge transfer. RESULTS: Unlike previous studies, the models we tested obtained average results on ADOS-2 data but reached very good performance of the models in TLC. We did not observe any benefits from knowledge transfer between datasets. We observed relatively poor performance of models trained on augmented data and hypothesize that data augmentation by back translation obfuscates autism-specific signals. CONCLUSION: The quality of machine learning models that detect ASD from text data is improving, but model results are dependent on the type of input data or diagnostic tool.
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In this paper, we investigate the time evolution of the rank correlation coefficients of the prestige indicators of the journals (such as Scimago Journal Rank) over 21 years, for 9856 journals in various disciplines. The observed dependencies do not differ qualitatively from those observed for the time evolution of the ranking correlations in wealth rheology among the richest people recently found by Burda et al. [Entropy 23, 842 (2021)], but quantitatively the changes in rank correlations for human wealth are much stronger than in the coefficients measuring the prestige of journals. In terms of Kendall's rank correlation coefficients, disciplines "Agricultural and Biological Sciences" and "Earth and Planetary Science" are the most typical, meaning that the time evolution of their rank correlation coefficient based on Scimago Journal Rank is closest to the time evolution of an average over all disciplines. The time evolution of the mean value of the overlap ratio is closest to the time evolution of the overlap ratio for "Psychology" and "Physics and Astronomy" disciplines. The Kendall rank correlation coefficients and the overlap ratio decrease nearly linearly over time, except for the first year, where their decay is significantly faster. The analogy between human wealth and the prestige indicators of journals is strengthened by performing a Monte Carlo simulation of the time evolution of the probability distribution function of Scimago Journal Rank. The simulation is based on a simple model of economic systems. Due to the different coverage of the journals in Scimago Journal & Country Rank and Web of Science, the identically defined measures based on the data in these databases are different.
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Scientific cooperation on an international level has been well studied in the literature. However, much less is known about this cooperation on an intercontinental level. In this paper, we address this issue by creating a collection of approximately 13.8×106 publications around the papers by one of the highly cited authors working in complex networks and their applications. The obtained rank-frequency distribution of the probability of sequences describing continents and the number of countries-with which authors of papers are affiliated-follows the power law with an exponent -1.9108(15). Such dependence is known in the literature as Zipf's law, and it has been originally observed in linguistics; later, it turned out that it is very commonly observed in various fields. The number of distinct "continent (number of countries)" sequences in a function of the number of analyzed papers grows according to power law with exponent 0.527(14); i.e., it follows Heap's law.
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Extracellular vesicles (EVs) are nanoparticles containing various bioactive cargos-e.g., proteins, RNAs, and lipids-that are released into the environment by all cell types. They are involved in, amongst other functions, intercellular communication. This article presents studies on EVs produced by the probiotic yeast Saccharomyces boulardii CNCM I-745. The size distribution and concentration of EVs in the liquid culture of yeast were estimated. Moreover, the vesicles of S. boulardii were tested for their cytotoxicity against three model human intestinal cell lines. This study did not show any significant negative effect of yeast EVs on these cells under tested conditions. In addition, EVs of S. boulardii were verified for their ability to internalize in vitro with human cells and transfer their cargo. The yeast vesicles were loaded with doxorubicin, an anticancer agent, and added to the cellular cultures. Subsequently, microscopic observations revealed that these EVs transferred the compound to human intestinal cell lines. A cytotoxicity test confirmed the activity of the transferred doxorubicin. Detailed information about the proteins present in EVs might be important in terms of exploring yeast EVs as carriers of active molecules. Thus, proteomic analysis of the EV content was also conducted within the present study, and it allowed the identification of 541 proteins after matching them to the Saccharomyces Genome Database (SGD). Altogether, this study provides strong evidence that the EVs of the probiotic CNCM I-745 strain could be considered a drug delivery system.
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Vesículas Extracelulares , Probióticos , Humanos , Saccharomyces cerevisiae , Proteômica , Vesículas Extracelulares/metabolismo , Probióticos/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/metabolismoRESUMO
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease that occurs predominantly in children. According to the guidelines, ADEM belongs to the myelin oligodendrocyte glycoprotein (MOG)-associated diseases and usually manifests after febrile infections (also after SARS-CoV-2) or postvaccinally. OBJECTIVES: Incidence, course and clinical, and as well, as radiological features and new developments and treatment of ADEM. METHODS: Analysis and review of the literature on ADEM and of notable cases and guidelines. RESULTS: The first signs of ADEM include fever, nausea and vomiting, headache and meningism as well as, by definition, encephalopathy, which usually manifests as drowsiness and confusion. The radiological diagnosis is made by magnetic resonance imaging (MRI). Here, the asymmetrically distributed, diffuse and tumefactive lesions can be located supra- and infratentorially. In the acute phase, the lesions usually show contrast enhancement and restricted diffusion. Spinal involvement of the gray matter with the typical Hpattern with myelitis transversa is not uncommon. ADEM has mostly a monophasic course, with a recurrent form ("relapsing ADEM") in 1-20% of cases. For treatment, steroids and in severe cases immunosuppressive drugs are used. CONCLUSIONS: ADEM is generally a monophasic disease whose symptoms usually last for a few weeks or months. It is crucial to differentiate ADEM from other demyelinating diseases, like for example multiple sclerosis, in order not to delay the proper treatment.
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Encefalomielite Aguda Disseminada , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/terapia , Humanos , Imageamento por Ressonância Magnética , Glicoproteína Mielina-Oligodendrócito/uso terapêuticoRESUMO
Inflammatory myofibroblastic tumor (IMT) is a rare borderline malignancy, usually treated with surgery only. Exceedingly rare cases of inoperable, recurrent, or metastatic IMTs pose a therapeutic challenge. We report successful treatment of a 7-year-old girl with an inoperable anaplastic lymphoma kinase (ALK)-negative IMT of the tongue. The patient underwent various anti-inflammatory (steroids, nonsteroidal anti-inflammatory drugs, clarithromycin) and antiproliferative (chemotherapy) therapies to enable tumor regression and complete resection. Ultimately, next-generation sequencing of the tumor revealed a TFG-ROS-1 translocation, allowing for an off-label targeted therapy with crizotinib. Crizotinib treatment caused slight tumor regression but evident change of its structure, allowing for complete non-mutilating resection. Two histopathology examinations revealed complete disappearance of neoplastic cells following therapy. The patient remains disease-free 22 months after the delayed surgery. In children with inoperable ALK-negative IMTs, molecular testing must be performed to identify other targetable oncogenic fusions, including TFG-ROS1.
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Antineoplásicos/uso terapêutico , Crizotinibe/uso terapêutico , Neoplasias de Tecido Muscular/tratamento farmacológico , Neoplasias da Língua/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Criança , Feminino , Humanos , Neoplasias de Tecido Muscular/genética , Neoplasias de Tecido Muscular/patologia , Neoplasias de Tecido Muscular/cirurgia , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias da Língua/genética , Neoplasias da Língua/cirurgiaRESUMO
Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project.
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Neoplasias Pancreáticas , Quimioterapia Adjuvante , Criança , Pré-Escolar , Humanos , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Doenças RarasRESUMO
Cutaneous melanoma is rare in children and, like other very rare pediatric tumors, it suffers from a shortage of knowledge and clinical expertise. The clinical management of pediatric melanoma is often challenging. Its clinical and pathological diagnosis may be difficult, and there is no standard treatment. In the absence of specific treatment guidelines, young patients are generally treated following the same principle as for adults, but concern remains about their access to clinical trials and new drugs, which have been shown to dramatically change the natural history of advanced melanoma. This paper presents the internationally recognized recommendations for the diagnosis and treatment of children and adolescents with cutaneous melanoma, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded project called PARTNER (Paediatric Rare Tumours Network - European Registry). Main recommendations for melanoma are to discuss pediatric patients in multidisciplinary teams that include both pediatric oncologists and specialists in adult melanoma; to enroll patients in prospective trials, if available; to collect data in national-international databases; and to develop an effective international collaboration between pediatric and adult melanoma groups in order to facilitate the transfer of potentially effective new agents from the adult to the pediatric setting.
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Melanoma , Neoplasias Cutâneas , Adolescente , Adulto , Criança , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Melanoma/terapia , Estudos Prospectivos , Sistema de Registros , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Melanoma Maligno CutâneoRESUMO
Protein kinase CK2 has been considered as an attractive drug target for anti-cancer therapy. The synthesis of N-hydroxypropyl TBBi and 2MeTBBi derivatives as well as their respective esters was carried out by using chemoenzymatic methods. Concomitantly with kinetic studies toward recombinant CK2, the influence of the obtained compounds on the viability of two human breast carcinoma cell lines (MCF-7 and MDA-MB-231) was evaluated using MTT assay. Additionally, an intracellular inhibition of CK2 as well as an induction of apoptosis in the examined cells after the treatment with the most active compounds were studied by Western blot analysis, phase-contrast microscopy and flow cytometry method. The results of the MTT test revealed potent cytotoxic activities for most of the newly synthesized compounds (EC50 4.90 to 32.77 µM), corresponding to their solubility in biological media. We concluded that derivatives with the methyl group decrease the viability of both cell lines more efficiently than their non-methylated analogs. Furthermore, inhibition of CK2 in breast cancer cells treated with the tested compounds at the concentrations equal to their EC50 values correlates well with their lipophilicity since derivatives with higher values of logP are more potent intracellular inhibitors of CK2 with better proapoptotic properties than their parental hydroxyl compounds.
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Antineoplásicos/farmacologia , Apoptose , Benzimidazóis/química , Neoplasias da Mama/tratamento farmacológico , Caseína Quinase II/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/síntese química , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos , Células MCF-7 , Relação Estrutura-AtividadeRESUMO
The concept of Heider balance, usually applied to interpersonal relations, is generalized here to opinions gathered in surveys. At first, we compare four algorithms, which drive a matrix dataset to a balanced state. The criterion is that the final state obtained with an algorithm should be as close as possible to the initial state. The result is that deterministic differential equations work better than their Monte Carlo counterparts. Next, we apply the winning algorithms to the matrix of correlations between opinions gathered in American states between 1974 and 1998. The results are interpreted in terms of the classic comfort hypothesis (E. Babbie, 2007).
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The main goal of our work is to show how ideas change in social networks. Our analysis is based on three concepts: (i) temporal networks, (ii) the Axelrod model of culture dissemination, (iii) the garbage can model of organizational choice. The use of the concept of temporal networks allows us to show the dynamics of ideas spreading processes in networks, thanks to the analysis of contacts between agents in networks. The Axelrod culture dissemination model allows us to use the importance of cooperative behavior for the dynamics of ideas disseminated in networks. In the third model decisions on solutions of problems are made as an outcome of sequences of pseudorandom numbers. The origin of this model is the Herbert Simon's view on bounded rationality. In the Axelrod model, ideas are conveyed by strings of symbols. The outcome of the model should be the diversity of evolving ideas as dependent on the chain length, on the number of possible values of symbols and on the threshold value of Hamming distance which enables the combination.
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We study wealth rank correlations in a simple model of macroeconomy. To quantify rank correlations between wealth rankings at different times, we use Kendall's τ and Spearman's ρ, Goodman-Kruskal's γ, and the lists' overlap ratio. We show that the dynamics of wealth flow and the speed of reshuffling in the ranking list depend on parameters of the model controlling the wealth exchange rate and the wealth growth volatility. As an example of the rheology of wealth in real data, we analyze the lists of the richest people in Poland, Germany, the USA and the world.
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Candida albicans CNB1 plays a role in the response in vitro and in vivo to stress generated by PB-WUT-01, namely 1,3-dimethyl-7-(2-((1-(3-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)propyl)-1H-purine-2,6(3H,7H)-dione. The antifungal mechanism involved the calcineurin pathway-regulated genes SAP9-10. Galleria mellonella treated with PB-WUT-01 (at 0.64 µg/mg) showed limited candidiasis and remained within the highest survival rates. The molecular mode of action of PB-WUT-01 was rationalized by in silico docking studies toward both human and C. albicans calcineurin A (CNA) and calcineurin B (CNB) complexes, respectively. PB-WUT-01 acting as a calcineurin inhibitor in the C. albicans cells enhances the cells' susceptibility. Therefore it could be a suitable alternative treatment in patients with candidiasis.
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Antifúngicos/farmacologia , Inibidores de Calcineurina/farmacologia , Calcineurina/metabolismo , Candida albicans/efeitos dos fármacos , Teofilina/análogos & derivados , Animais , Antifúngicos/síntese química , Antifúngicos/metabolismo , Apoptose/efeitos dos fármacos , Ácido Aspártico Endopeptidases/metabolismo , Biofilmes/efeitos dos fármacos , Inibidores de Calcineurina/síntese química , Inibidores de Calcineurina/metabolismo , Candida albicans/fisiologia , Chlorocebus aethiops , Proteínas Fúngicas/metabolismo , Larva/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mariposas , Ligação Proteica , Teofilina/metabolismo , Teofilina/farmacologia , Células VeroRESUMO
A new approach for the sensitive, robust and rapid determination of idarubicin (IDA) in human plasma and urine samples based on liquid chromatography with fluorescence detection (LC-FL) was developed. Satisfactory chromatographic separation of the analyte after solid-phase extraction (SPE) was performed on a Discovery HS C18 analytical column using a mixture of acetonitrile and 0.1% formic acid in water as the mobile phase in isocratic mode. IDA and daunorubicin hydrochloride used as an internal standard (I.S.) were monitored at the excitation and emission wavelengths of 487 and 547 nm, respectively. The method was validated according to the FDA and ICH guidelines. The linearity was confirmed in the range of 0.1-50 ng/mL and 0.25-200 ng/mL, while the limit of detection (LOD) was 0.05 and 0.125 ng/mL in plasma and urine samples, respectively. The developed LC-FL method was successfully applied for drug determinations in human plasma and urine after oral administration of IDA at a dose of 10 mg to a patient with highly advanced alveolar rhabdomyosarcoma (RMA). Moreover, the potential exposure to IDA present in both fluids for healthcare workers and the caregivers of patients has been evaluated. The present LC-FL method can be a useful tool in pharmacokinetic and clinical investigations, in the monitoring of chemotherapy containing IDA, as well as for sensitive and reliable IDA quantitation in biological fluids.
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Monitoramento de Medicamentos/métodos , Idarubicina/sangue , Idarubicina/urina , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/normas , Antibióticos Antineoplásicos/urina , Cromatografia Líquida/métodos , Daunorrubicina/sangue , Daunorrubicina/normas , Daunorrubicina/urina , Monitoramento de Medicamentos/normas , Monitoramento de Medicamentos/estatística & dados numéricos , Fluorescência , Humanos , Idarubicina/normas , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase SólidaRESUMO
Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992-2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72-125.75; p = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.
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Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Anidrase Carbônica IX/genética , Transportador de Glucose Tipo 1/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Musculares/tratamento farmacológico , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Embrionário/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Adolescente , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia , Anidrase Carbônica IX/metabolismo , Carboplatina/uso terapêutico , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Dactinomicina/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Expressão Gênica , Transportador de Glucose Tipo 1/metabolismo , Humanos , Hipóxia/diagnóstico , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/mortalidade , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ifosfamida/uso terapêutico , Lactente , Recém-Nascido , Masculino , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/genética , Neoplasias Musculares/mortalidade , Terapia Neoadjuvante/métodos , Prognóstico , Estudos Prospectivos , Rabdomiossarcoma Alveolar/diagnóstico , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/mortalidade , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vincristina/uso terapêuticoRESUMO
The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA250-264, HPV-E743-57) to generate self-assembling peptide epitopes (SAPEs). The obtained results showed that the SAPEs were able to form nanostructures with a diameter from 20 to 200 nm. The SAPEs adjuvanted with CpG induced and expanded antigen-specific CD8+ T cells in mice. Furthermore, tumor-bearing mice vaccinated with SAPEs harboring the HPV E743-57 peptide showed a delayed tumor growth and an increased survival compared to sham-treated mice. In conclusion, self-assembling peptide based systems increase the immunogenicity of peptide epitope vaccines and therefore warrants further development toward clinical use.
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Epitopos de Linfócito T/metabolismo , Peptídeos/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/metabolismo , Células Cultivadas , Epitopos de Linfócito T/imunologia , Imunoterapia , Camundongos , Nanopartículas/química , Ovalbumina/química , Vacinação/métodosRESUMO
This study presents a framework for workflow optimisation of multimodal image-guided procedures (MIGP) based on discrete event simulation (DES). A case of a combined X-Ray and magnetic resonance image-guided transarterial chemoembolisation (TACE) is presented to illustrate the application of this method. We used a ranking and selection optimisation algorithm to measure the performance of a number of proposed alternatives to improve a current scenario. A DES model was implemented with detail data collected from 59 TACE procedures and durations of magnetic resonance imaging (MRI) diagnostic procedures usually performed in a common MRI suite. Fourteen alternatives were proposed and assessed to minimise the waiting times and improve workflow. Data analysis observed an average of 20.68 (7.68) min of waiting between angiography and MRI for TACE patients in 71.19% of the cases. Following the optimisation analysis, an alternative was identified to reduce waiting times in angiography suite up to 48.74%. The model helped to understand and detect 'bottlenecks' during multimodal TACE procedures, identifying a better alternative to the current workflow and reducing waiting times. Simulation-based workflow analysis provides a cost-effective way to face some of the challenges of introducing MIGP in clinical radiology, highligthed in this study.
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Quimioembolização Terapêutica/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Imagem Multimodal/métodos , Radiografia Intervencionista/métodos , Fluxo de Trabalho , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Fatores de TempoRESUMO
With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfanyl]-1,3-benzoxazole and Michael-type addition of aryltetrazole to phenyl vinyl sulfone. The chemical structures of the synthesized compounds were confirmed by means of 1H NMR, 13C NMR, IR and HRMS spectral data. The compounds were tested against the moulds: Fusarium sambucinum, Fusarium oxysporum, Colletotrichum coccodes, Aspergillus niger, and the yeast Candida albicans. The results showed that among the moulds only C. coccodes was significantly sensitive to all the structures examined. All the tetrazole derivatives acted at the same level against C. albicans and demonstrated a high cell growth inhibition (97-99%) at the concentrations ranging from 16 to 0.0313µg/mL. The mode of action of 2-({3-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5c) and 2-({3-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5d) was established by verifying fungal growth in the presence of osmotic protector-sorbitol. The effect of compound 5c or 5d combined with Fluconazole was determined using the checkerboard method. The calculated fractional inhibitory concentration index (FIC) indicated antagonism (FIC >1). Additionally, survival experiments with lepidopteran Galleria mellonella treated with compounds 5c and 5d were performed and demonstrated the lack of toxicity of these compounds.
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Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Tetrazóis/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Fungos/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tetrazóis/síntese química , Tetrazóis/químicaRESUMO
Although childhood rhabdomyosarcoma typically metastasizes to lungs, various processes may mimic metastatic etiology. Described herein is the case of an 8½-year-old boy with orbital embryonal rhabdomyosarcoma (RME) in whom three small foci were detected within both lungs on computed tomography. The lesion number and size, however, did not fulfil the Cooperative Weichteilsarkom Study Group 2006 protocol criteria for lung metastasis. Chemotherapy for localized RME produced primary tumor regression and vanishing of the left lung lesion. Two lesions in the right lung remained unchanged. On thoracoscopy multiple minute nodules disseminated in both lungs were detected. Histopathology excluded RME spread but indicated anthracosis in the lung parenchyma and intrapulmonary lymph nodes. Heavy smoking by parents and previous home furnace combustion appeared to be predisposing factors. Uncommon non-malignant intrapulmonary diseases, including anthracosis, should be considered when staging pediatric cancer.
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Antracose/complicações , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Neoplasias Orbitárias/complicações , Rabdomiossarcoma Embrionário/complicações , Antracose/diagnóstico , Biópsia , Criança , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Orbitárias/diagnóstico , Rabdomiossarcoma Embrionário/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Simple and sensitive liquid chromatography (LC) methods with fluorescence (FL) detection for the determination of bendamustine (BM) in human plasma and urine were developed and validated. The procedure of BM extraction from a plasma sample involved solid-phase extraction with a C18 SPE column, while liquid-liquid extraction with dichloromethane was applied for a urine sample. In both methods, cinoxacin was used as the internal standard. Chromatographic separations were performed on a Synergi Max-RP column, while FL detector was set at the excitation wavelength of 328 nm and the emission wavelength of 420 nm. The LC-FL methods were validated for accuracy, precision, selectivity, linearity, recovery, and stability. The detection limits for BM were 0.5 and 2.5 ng mL-1 in plasma and urine, respectively. The intra-day and inter-day precisions were less than 9.86 %, while the accuracies were higher than 92.63 and 94.29 % for BM in plasma and urine, respectively. The proposed LC-FL methods were sensitive, robust, and specific, allowing reliable drug quantification in plasma and urine samples. The methodologies were successfully applied to monitoring of BM in a child with cancer treated with BM.