Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Games Health J ; 13(2): 84-92, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37699207

RESUMO

Objective: Wordbot, a chatbot designed for gamified education, transforms the process of memorizing complex medical terminology into an engaging and enjoyable activity for medical students. Taking inspiration from the "guessing words" game, Wordbot aims to improve medical students' learning outcomes by making the vocabulary memorization process more memorable. Materials and Methods: Wordbot, which can be implemented on the LINE platform, was created for this research, specifically to improve medical terminology learning. Wordbot incorporated mobile devices and personal computer-compatible flashcard games with features such as user ranking and personalization to enhance motivation and optimize learning outcomes. In the experimental research setting, half of a total of 48 nursing students were randomly assigned to use Wordbot for 4 months, and the other half were assigned to a control group relying on self-study without the help of Wordbot. Both groups received pretest and post-test to assess their respective learning of medical terminology. In this study, a statistical t-test was used to analyze the results between the two groups. In addition, user usability testing was conducted to evaluate the usability of Wordbot and gather feedback on user experience. Results: The results of this study have demonstrated that Wordbot is effective in facilitating students learning of medical terminology. Students experienced a significant improvement in their knowledge of medical terminology. An average user usability test score of 83.25 indicated that users' satisfaction with Wordbot is high. Conclusion: Incorporating gamification and personalization elements in Wordbot can significantly improve the overall enjoyment of the learning process. By participating in diverse interactive activities, users can effectively enhance their proficiency in spelling, recognition, and speaking. Wordbot utilizes sophisticated algorithms to generate customized questions based on identified mistakes, which facilitate error identification and correction. The robust findings of this study overwhelmingly support Wordbot's role as a convenient and easily accessible tool for learning medical terminology. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Chang Gung Medical Foundation (Protocol code: 202201586B0, date of approval: 8 November 2022). We obtained informed consent from all of our study participants regarding their willingness to participate in this study.


Assuntos
Educação Médica , Estudantes de Medicina , Humanos , Aprendizagem , Motivação , Retroalimentação
2.
Med Educ ; 57(11): 1123, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37705226
3.
Artigo em Inglês | MEDLINE | ID: mdl-36901193

RESUMO

Medical terminology can be challenging for healthcare students due to its unfamiliar and lengthy terms. Traditional methods such as flashcards and memorization can be ineffective and require significant effort. To address this, an online chatbot-based learning model called Termbot was designed to provide an engaging and convenient method for enhancing medical terminology learning. Termbot, accessible through the LINE platform, offers crossword puzzles that turn boring medical terms into a fun learning experience. An experimental study was conducted, which showed that students who trained with Termbot made significant progress in learning medical terms, demonstrating the potential of chatbots to improve learning outcomes. Termbot's gamified approach to learning can also be applied to other fields, making it a useful tool for students to learn medical terminology conveniently and enjoyably.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Humanos , Aprendizagem , Estudantes
4.
Front Bioinform ; 2: 813599, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304301

RESUMO

Deciphering the genotypic diversity of within-individual pathogens and verifying the evolutionary model can help elucidate resistant genotypes, virulent subpopulations, and the mechanism of opportunistic pathogenicity. However, observed polymorphic mutations (PMs) are rare and difficult to be detected in the "dominant-lineage" model of bacterial infection due to the low frequency. The four pooled group B Streptococcus (GBS) samples were collected from the genital tracts of healthy pregnant women, and the pooled samples and the isogenic controls were genomically sequenced. Using the PMcalling program, we detected the PMs in samples and compared the results between two technical duplicates, GBS-M001T and GBS-M001C. Tested with simulated datasets, the PMcalling program showed high sensitivity especially in low-frequency PMs and reasonable specificity. The genomic sequence data from pooled samples of GBS colonizing carrier pregnant women were analyzed, and few high-frequency PMs and some low-frequency PMs were discovered, indicating a dominant-lineage evolution model. The PMs mainly were nonsynonymous and enriched in quorum sensing, glycolysis/gluconeogenesis, ATP-binding cassette (ABC) transporters, etc., suggesting antimicrobial or environmental selective pressure. The re-analysis of the published Burkholderia dolosa data showed a diverse-community model, and only a few low-frequency PMs were shared between different individuals. Genes of general control non-repressible 5-related N-acetyltransferases family, major facilitator superfamily (MFS) transporter, and ABC transporter were positive selection candidates. Our findings indicate an unreported nature of the dominant-lineage model of GBS colonization in healthy women, and a formerly not observed mutation pool in a colonized microbial community, possibly maintained by selection pressure.

5.
SAGE Open Nurs ; 8: 23779608221094538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509432

RESUMO

Introduction: It is estimated that mores nurses are needed in the future, nursing students' career preferences are important to contribute the shortage of nursing manpower in Macao. Little is known regarding the preferences for nursing students' career preferences and related factors among nursing students. Objective: To explore and investigate the career preferences and related factors among nursing students in Macao. Methods: A descriptive, cross-sectional survey study design was adopted to assess career preferences and related factors among nursing students in Macao. Results: In total, 217 nursing students completed surveys. The most favorite career preferences among nursing students were community health nursing, paediatric nursing, medical surgical nursing, and obstetric & gynecological nursing; while the least career preferences among nursing students were oncology and hospice nursing, mental health nursing, and ER nursing. Factors were related to "gender", "education", and "nursing is my first study preference" among Macao nursing students for career preferences. Conclusion: The senior nursing students prefer working in community health nursing and the junior and female nursing students prefer working in pediatric nursing and obstetric and gynecological nursing. The more understandings of nursing students' career preferences, the better nursing curriculum design and implication to promote nursing students' intention for working in the least career preferences work.

6.
Clin Infect Dis ; 75(12): 2153-2160, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-35486954

RESUMO

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of invasive neonatal infections. This study aimed to investigate the trend of GBS serotype and genotype change and their correlation with antimicrobial resistance before and after implementation of intrapartum antibiotic prophylaxis (IAP). METHODS: We performed serotyping, whole-genome sequencing, antimicrobial susceptibility testing, and single-nucleotide polymorphism (SNP)-based phylogenetic analysis on 238 invasive GBS isolates collected from October 1998 to February 2020 in Taiwan. RESULTS: There were 7 serotypes and 6 clonal complexes (CCs) among the 238 GBS isolates, and more than half of the isolates carried multiple antimicrobial resistance genes. The expansion of CC17 strains and the increase in late-onset disease occurred synchronously after the implementation of IAP. Analysis of the carriage isolates from pregnant women showed diverse serotype distribution in the IAP era. The antimicrobial susceptibility testing showed that all 238 strains were susceptible to ampicillin and penicillin, while the number of various resistance genes in GBS genomes was found increased with the expansion of CC17. Compared with reference genomes, 697 nonsynonymous SNPs in 443 protein-coding genes were CC17 specific. CONCLUSIONS: The study revealed the expansion of GBS CC17 and the increase of late-onset disease that occurred simultaneously with the implementation of IAP. Although the susceptibility of CC17 to antimicrobial agents is not different from that of other sequence types at present, GBS with phenotypic resistance to antimicrobials may emerge in the future, given the environmental selection pressure and the continued accumulation of SNP mutations.


Assuntos
Sepse Neonatal , Infecções Estreptocócicas , Recém-Nascido , Gravidez , Feminino , Humanos , Antibioticoprofilaxia , Virulência , Filogenia , Infecções Estreptocócicas/tratamento farmacológico , Antibacterianos/uso terapêutico , Genômica , Streptococcus agalactiae
7.
ACS Infect Dis ; 8(3): 626-634, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35171577

RESUMO

Streptococcus pneumoniae serotypes 6A and 6B are two of the common causes of invasive pneumococcal diseases. Although capsular polysaccharide conjugates of these two serotypes are included in the leading 13-valent pneumococcal conjugate vaccine, its low immunogenicity and high threshold for manufacturing technology indicated the need for vaccine improvement. Structurally defined synthetic immunogens have potential in dealing with these problems. To this end, we built a library of capsular polysaccharide fragments through convergent chemical synthesis in [2 + 2], [4 + 4], [4 + 3], [4 + 2], and [4 + 1] coupling manners. The library is comprised of 18 glycan antigens from trisaccharides to pseudo-octasaccharides, derived from the capsular repeating phosphorylated pseudo-tetrasaccharide with or without phosphate. Eight of them were selected for mouse immunization and further immunological studies. Four pseudo-tetrasaccharides with terminal or bridging phosphate elicited opsonic antibodies, which exhibited bactericidal activities and moderate cross-reactivities.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Animais , Anticorpos Antibacterianos , Camundongos , Oligossacarídeos , Infecções Pneumocócicas/prevenção & controle , Sorogrupo
10.
J Biomed Sci ; 27(1): 89, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831077

RESUMO

BACKGROUND: Salmonella enterica serotype Typhimurium is a nontyphoidal and common foodborne pathogen that causes serious threat to humans. There is no licensed vaccine to prevent the nontyphoid bacterial infection caused by S. Typhimurium. METHODS: To develop conjugate vaccines, the bacterial lipid-A free lipopolysaccharide (LFPS) is prepared as the immunogen and used to synthesize the LFPS-linker-protein conjugates 6a-9b. The designed bifunctional linkers 1-5 comprising either an o-phenylenediamine or amine moiety are specifically attached to the exposed 3-deoxy-D-manno-octulosonic acid (Kdo), an α-ketoacid saccharide of LFPS, via condensation reaction or decarboxylative amidation. In addition to bovine serum albumin and ovalbumin, the S. Typhimurium flagellin (FliC) is also used as a self-adjuvanting protein carrier. RESULTS: The synthesized conjugate vaccines are characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and fast performance liquid chromatography (FPLC), and their contents of polysaccharides and protein are determined by phenol-sulfuric acid assay and bicinchoninic acid assay, respectively. Enzyme-linked immunosorbent assay (ELISA) shows that immunization of mouse with the LFPS-linker-protein vaccines at a dosage of 2.5 µg is sufficient to elicit serum immunoglobulin G (IgG) specific to S. Typhimurium lipopolysaccharide (LPS). The straight-chain amide linkers in conjugates 7a-9b do not interfere with the desired immune response. Vaccines 7a and 7b derived from either unfractionated LFPS or the high-mass portion show equal efficacy in induction of IgG antibodies. The challenge experiments are performed by oral gavage of S. Typhimurium pathogen, and vaccine 7c having FliC as the self-adjuvanting protein carrier exhibits a high vaccine efficacy of 74% with 80% mice survival rate at day 28 post the pathogen challenge. CONCLUSIONS: This study demonstrates that lipid-A free lipopolysaccharide prepared from Gram-negative bacteria is an appropriate immunogen, in which the exposed Kdo is connected to bifunctional linkers to form conjugate vaccines. The decarboxylative amidation of Kdo is a novel and useful method to construct a relatively robust and low immunogenic straight-chain amide linkage. The vaccine efficacy is enhanced by using bacterial flagellin as the self-adjuvanting carrier protein.


Assuntos
Lipopolissacarídeos/química , Vacinas contra Salmonella/química , Vacinas Conjugadas/química , Animais , Lipídeo A , Camundongos , Camundongos Endogâmicos BALB C , Vacinas contra Salmonella/imunologia , Vacinas Conjugadas/imunologia
11.
Thorax ; 75(8): 689-692, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32444435

RESUMO

In 500 children aged ≤10 years after 13-valent pneumococcal conjugate vaccine (PCV)13 immunisation in different schedules, serotypes 19A-specific and 19F-specific immunoglobulin G (IgG) were predicted to persist above 0.35 µg/mL for ≥10 years in all groups, likely due to PCV13-induced memory with natural boosting from residual diseases and colonisation. Generally, serotype-specific IgG could persist above 0.35 µg/mL longer (≥5 years) in the catch-up group than in the 2+1 and 3+1 immunisation groups. 14.5% of the carriage isolates belonged to PCV13 serotypes; statistical analysis revealed that a high serum IgG level (>10.96 µg/mL) will be required to eliminate the point-prevalence nasopharyngeal carriage of serotype 19A.


Assuntos
Portador Sadio/prevenção & controle , Nasofaringe/microbiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae/isolamento & purificação , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Tempo
12.
Pediatr Neonatol ; 61(3): 338-342, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32156480

RESUMO

BACKGROUND: The most severe form of pneumococcal disease is invasive pneumococcal disease (IPD), including empyema, sepsis and meningitis. Thomsen-Friedenreich antigen (TA; Galß1-3GalNAc) activation is known to be a predictor of Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS). There have been limited data to correlate TA activation and overall disease severity of IPD in children. The study aimed to prove the positive correlation between TA activation and disease severity and to demonstrate the trend of TA level during the disease course. METHODS: We retrospectively reviewed the medical records from 38 pediatric patients aged from 0 to 18 years with microbiologically-confirmed IPD between 2010 and 2015 at a medical center in Taiwan. All cases underwent TA activation testing by the fluorescence-labeled peanut lectin agglutination method. Medical information including demographic data, laboratory findings, co-morbidities, and outcome was collected and reviewed. We compared the clinical manifestations and associated co-morbidities between TA-positive and TA-negative patients. RESULTS: Among the 38 patients, 25 (66%) showed TA activation. Compared to TA-negative patients, patients with TA activation had a statistically higher rate of prolonged anemia, thrombocytopenia, and acute kidney injury. TA-positive patients also had a longer intensive care unit stay and overall hospitalization days. The TA levels usually peaked 5-10 days after disease onset. Twenty-one pneumococcal isolates were recovered from the patients and serotyping was determined in 11 isolates: 10 serotype 19A and 1 serotype 3. CONCLUSIONS: TA determination not only helps to diagnose Sp-HUS but also is a predictor for IPD severity. Among hospitalized patients with severe pneumococcal disease, the peak of TA level usually appeared 5-10 days after disease onset.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Síndrome Hemolítico-Urêmica/diagnóstico , Infecções Pneumocócicas/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Pneumocócicas/imunologia , Estudos Retrospectivos
13.
J Microbiol Immunol Infect ; 53(1): 94-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29804657

RESUMO

BACKGROUND: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. METHODS: Clinical isolates of S.pneumoniae from January 2012 to December 2015 at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. RESULTS: During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p = 0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. CONCLUSIONS: A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone.


Assuntos
Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Portador Sadio , Criança , Pré-Escolar , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Estudos Prospectivos , Sistema Respiratório/microbiologia , Sorotipagem , Escarro/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Taiwan , Vacinas Conjugadas/administração & dosagem , Adulto Jovem
14.
Vaccine ; 37(36): 5147-5152, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31377076

RESUMO

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST6315A, ST8315B, and ST166/33823A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Penicilinas/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/imunologia , Estudos Prospectivos , Sorogrupo
15.
Nurse Educ Today ; 74: 85-90, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30611081

RESUMO

BACKGROUND: Nursing students' attitudes toward older people affect the quality of care provided to the aging population. Although gerontological nursing has been delivered as a stand-alone course in Macao since 2008, Macao nursing students' attitudes toward older people have not been investigated. OBJECTIVE: The purposes of this study were 1) to explore nursing students' background information and attitudes toward older people and 2) to examine the presence of relationships between these factors and gerontological nursing education in Macao, a special administrative region of China. METHODS: A cross-sectional survey design was adopted. Nursing students in Macao were invited to complete a questionnaire to record their demographic characteristics and gerontological nursing education and measure their attitudes toward older people using Kogan's Attitudes Toward Older People (KAOP) scale. RESULTS: Data from 377 (83.04%) nursing students who returned the questionnaire were analyzed. The students were found to have positive attitudes toward older people, with a mean KAOP score of 168.44 ±â€¯18.38 (mean ±â€¯standard deviation). In particular, the item with the lowest mean score was "older adults have excessive demands for love" (2.5 ±â€¯1.2), while the item with the highest mean score was "older adults need no more love than others" (6.0 ±â€¯1.0). The results also revealed that Macao nursing students' positive attitudes toward older people were associated with having "religion," "good experience in gerontological nursing taught course," and "good experience in clinical practice with older people," which were thus considered to be the predictors of their positive attitudes toward older people. CONCLUSION: Religion and gerontological nursing education are associated with Macao nursing students' attitudes toward older people. A longitudinal study is needed to evaluate the gradual changes in nursing students' attitudes. Nursing students' future career choices and perceptions of gerontological nursing education should be explored in a future study.


Assuntos
Atitude do Pessoal de Saúde , Enfermagem Geriátrica/educação , Estudantes de Enfermagem/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Macau , Masculino , Pesquisa em Educação em Enfermagem , Pesquisa em Avaliação de Enfermagem , Estudantes de Enfermagem/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
16.
J Med Microbiol ; 67(5): 709-723, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29557769

RESUMO

Purpose. Pneumococcal virulence protein-based vaccines can provide serotype-independent protection against pneumococcal infections. Many studies, including clinical observational studies on Thomsen-Friedenrich antigen exposure and haemolytic uremic syndrome, defined the role of neuraminidases NanA, NanB and NanC in host-pneumococcus interaction. Since neuraminidases are major virulence proteins, they are potential targets for both vaccines and small molecule inhibitors. Here we explored the utility of three neuraminidases as protein vaccine antigens to generate neutralizing antibodies and to increase survival following pneumococcal infections.Methodology. Rabbits and mice were immunized subcutaneously with enzymatically active recombinant NanA, NanB and NanC as individual or a combination of the three neuraminidases. Antisera titres were determined by ELISA. Neuraminidase activity inhibition by antiserum was tested by peanut lectin and flow cytometry. Clinical isolates with serotype 3, 6B, 14, 15B, 19A and 23F were used to infect immunized mice by tail vein injection.Results/Key findings. Presence of high levels of IgG antibodies in antisera against NanA, NanB and NanC indicates that all of the three neuraminidases are immunogenic vaccine antigens. To generate potent NanA neutralizing antibodies, both lectin and catalytic domains are essential, whereas for NanB and NanC a single lectin domain is sufficient. Immunization with triple neuraminidases increased the survival of mice when intravenously challenged with clinical isolates of serotype 3 (40 %), 6B (60 %), 15B (60 %), 19A (40 %) and 23F (30 %).Conclusion. We recommend the inclusion of three pneumococcal neuraminidases in future protein vaccine formulations to prevent invasive pneumococcal infection caused by various serotypes.

17.
Gene ; 597: 59-65, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27773726

RESUMO

Streptococcus agalactiae (GBS) causes serious infections in humans and other species. A total of 25 complete GBS genomes, including the first sequenced serotype VI genome (GBS-M002), were compared in this study. The power law model suggested that the pan-genome of GBS is open, with approximately 1300 genes in the core genome of GBS, accounting for approximately 60% of the average genome content. GBS-M002 has 73 specific genes and is one of the five strains containing >60 specific genes. Based on COG (Cluster of Orthologous Groups of proteins) functional classification, 24% of the genes related to defense mechanisms are specific among the strains. A phylogenetic tree shows that GBS-M002 is closely related to certain strains of serotypes III and V from humans and to isolates of unknown serotype from dog and bovine hosts, suggesting the universal infection potential of GBS from humans to other mammal and fish hosts.


Assuntos
Genoma Bacteriano , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bovinos , Cães , Ilhas Genômicas/genética , Humanos , Filogenia , Análise de Sequência de DNA , Streptococcus agalactiae/isolamento & purificação
18.
Medicine (Baltimore) ; 95(13): e3221, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27043691

RESUMO

Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS. We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ±â€Š80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ±â€Š190 mg/L) as well as the healthy controls (630 ±â€Š250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5-98.7%) and specificity of 71.9% (95% CI: 54.6-84.4%). This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children.


Assuntos
Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/etiologia , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/complicações , alfa-2-Glicoproteína-HS/metabolismo , Apolipoproteínas/metabolismo , Biomarcadores , Criança , Pré-Escolar , Cromatografia Líquida , Proteínas do Sistema Complemento/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulinas/metabolismo , Lactente , Recém-Nascido , Queratinas/metabolismo , Masculino , Neuraminidase/metabolismo , Pneumonia Pneumocócica/classificação , Curva ROC , Índice de Gravidade de Doença , Sialoglicoproteínas/metabolismo , Espectrometria de Massas em Tandem
19.
Bioorg Med Chem Lett ; 25(18): 3873-7, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26235951

RESUMO

In our previous studies on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesised numerous substituted carbazole and α-carboline derivatives, which exhibited anticancer activity. In this study, we designed and synthesised a series of 3,9-substituted ß-carbolines, by replacing the tricyclic rings of carbazole and α-carboline derivatives with isosteric ß-carboline, and evaluated anticancer activity. We observed that 9-(2-methoxybenzyl)-ß-carboline-3-carboxylic acid (11a) inhibited the growth of HL-60 cells by inducing apoptosis, with a half maximal inhibitory concentration of 4.0 µM. Our findings indicate that ß-carboline derivatives can be used as lead compounds for developing novel antitumor agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Carbolinas/química , Carbolinas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carbolinas/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
20.
Br J Pharmacol ; 172(5): 1195-221, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25363404

RESUMO

BACKGROUND AND PURPOSE: 4-Phenylquinolin-2(1H)-one (4-PQ) derivatives can induce cancer cell apoptosis. Additional new 4-PQ analogs were investigated as more effective, less toxic antitumour agents. EXPERIMENTAL APPROACH: Forty-five 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives were synthesized. Antiproliferative activities were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliun bromide assay and structure-activity relationship correlations were established. Compounds 9b, 9c, 9e and 11e were also evaluated against the National Cancer Institute-60 human cancer cell line panel. Hoechst 33258 and Annexin V-FITC/PI staining assays were used to detect apoptosis, while inhibition of microtubule polymerization was assayed by fluorescence microscopy. Effects on the cell cycle were assessed by flow cytometry and on apoptosis-related proteins (active caspase-3, -8 and -9, procaspase-3, -8, -9, PARP, Bid, Bcl-xL and Bcl-2) by Western blotting. KEY RESULTS: Nine 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives (7e, 8e, 9b, 9c, 9e, 10c, 10e, 11c and 11e) displayed high potency against HL-60, Hep3B, H460, and COLO 205 cancer cells (IC50 < 1 µM) without affecting Detroit 551 normal human cells (IC50 > 50 µM). Particularly, compound 11e exhibited nanomolar potency against COLO 205 cancer cells. Mechanistic studies indicated that compound 11e disrupted microtubule assembly and induced G2/M arrest, polyploidy and apoptosis via the intrinsic and extrinsic signalling pathways. Activation of JNK could play a role in TRAIL-induced COLO 205 apoptosis. CONCLUSION AND IMPLICATIONS: New quinolone derivatives were identified as potential pro-apoptotic agents. Compound 11e could be a promising lead compound for future antitumour agent development.


Assuntos
Antineoplásicos/farmacologia , Quinolonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA