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1.
Clin Radiol ; 79(1): e73-e79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37914602

RESUMO

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigação sanguínea , Estudos Prospectivos , Meios de Contraste , Ultrassonografia/métodos , Imageamento por Ressonância Magnética
2.
Rhinology ; 61(2): 153-160, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375133

RESUMO

BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus. METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated. RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted. CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.


Assuntos
Sinusite , Seio Esfenoidal , Humanos , Seio Esfenoidal/diagnóstico por imagem , Estudos Retrospectivos , Nomogramas , Sinusite/cirurgia , Endoscopia
3.
Rhinology ; 61(1): 47-53, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306524

RESUMO

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Obstrução Nasal , Doenças Nasais , Humanos , Doenças Nasais/complicações , Doenças Nasais/cirurgia , Doenças Nasais/diagnóstico , Qualidade de Vida , Sonolência , Obstrução Nasal/etiologia , Obstrução Nasal/cirurgia , Obstrução Nasal/psicologia , Síndrome , Nariz
4.
Rhinology ; 60(3): 177-187, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233583

RESUMO

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.


Assuntos
Transtornos do Olfato , Olfato , Humanos , Transtornos do Olfato/etiologia , Resultado do Tratamento , Endoscopia/métodos , Retalhos Cirúrgicos
5.
Int J Oral Maxillofac Surg ; 50(9): 1203-1209, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33658151

RESUMO

The purpose of this study was to assess skeletal stability and predictors of relapse in patients undergoing an isolated Le Fort I osteotomy. A retrospective cohort study of 92 subjects undergoing Le Fort I osteotomy for Class III malocclusion was implemented. Predictor variables were demographic and perioperative factors. The primary outcome variable was postoperative skeletal position with relapse defined as >2mm sagittal and/or vertical change at A-point on serial lateral cephalograms at immediate postoperative, 1 year, and latest follow-up time points. Mean advancement at A-point was 6.28±2.63mm and mean lengthening was 0.92±1.76mm. Eight subjects (8.70%) had relapse (>2mm) in the sagittal plane, and two subjects (2.17%) in the vertical plane. No subjects required reoperation for relapse as overbite and overjet remained in an acceptable range due to dental compensation. In regression analysis, magnitude of maxillary advancement was an independent predictor of relapse in the sagittal plane (P=0.008). There were no significant predictors of relapse in the vertical plane. This study suggests that isolated Le Fort I osteotomy for correction of skeletal Class III malocclusion is a stable procedure and that greater advancement is an independent risk factor for sagittal relapse.


Assuntos
Má Oclusão Classe III de Angle , Osteotomia de Le Fort , Cefalometria , Seguimentos , Humanos , Má Oclusão Classe III de Angle/cirurgia , Mandíbula , Maxila/diagnóstico por imagem , Maxila/cirurgia , Recidiva , Estudos Retrospectivos
6.
Oncogene ; 39(4): 946-949, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31537904

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7.
Clin Microbiol Infect ; 24(10): 1055-1063, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29208560

RESUMO

OBJECTIVES: To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)-BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays-on the detection of viral respiratory infections. METHODS: A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay. RESULTS: Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848-0.949), 0.949 (95% confidence interval, 0.882-0.979) and 0.954 (95% confidence interval, 0.871-0.985), respectively. The three mPCRs were comparable in terms of detection of FluA. CONCLUSIONS: Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.


Assuntos
Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/diagnóstico , Viroses/diagnóstico , Vírus/genética , Humanos , Infecções Respiratórias/virologia , Viroses/virologia
8.
Clin Otolaryngol ; 42(2): 425-432, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27960043

RESUMO

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Metástase Linfática/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taiwan/epidemiologia
9.
J Laryngol Otol ; 130(6): 565-70, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27160281

RESUMO

BACKGROUND: A nationwide population-based cohort was used to examine the severity of liver cirrhosis and risk of mortality from oral cancer. METHODS: The cohort consisted of 3583 patients with oral cancer treated by surgery between 2008 and 2011 in Taiwan. They were grouped on the basis of normal liver function (n = 3471), cirrhosis without decompensation (n = 72) and cirrhosis with decompensation (n = 40). The primary endpoint was mortality. Hazard ratios of death were also determined. RESULTS: The mortality rates in the respective groups were 14.8 per cent, 20.8 per cent and 37.5 per cent at one year (p < 0.001). The adjusted hazard ratios of death at one year for each group compared to the normal group were 2.01 (p = 0.021) for cirrhotic patients without decompensation, 4.84 (p < 0.001) for those with decompensation and 2.65 (p < 0.001) for those receiving chemotherapy. CONCLUSION: Liver cirrhosis can be used to predict one-year mortality in oral cancer patients. Chemotherapy should be used with caution and underlying co-morbidities should be managed in cirrhotic patients to reduce mortality risk.


Assuntos
Cirrose Hepática/epidemiologia , Neoplasias Bucais/mortalidade , Adulto , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan/epidemiologia
10.
Oncogene ; 35(12): 1517-28, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-26119938

RESUMO

Heat-shock protein 5 (HSPA5) is a marker for poor prognosis in breast cancer patients and has an important role in cancer progression, including promoting drug resistance and metastasis. In this study, we identify that the specific lysine residue 447 (K447) of HSPA5 could be modified with polyubiquitin for subsequent degradation through the ubiquitin proteasomal system, leading to the suppression of cell migration and invasion of breast cancer. We further found that GP78, an E3 ubiquitin ligase, interacted with the C-terminal region of HSPA5 and mediated HSPA5 ubiquitination and degradation. Knock down of GP78 significantly increased the expression of HSPA5 and enhanced migration/invasive ability of breast cancer cells. Knock down of histone deacetylase-6 (HDAC6) increased the acetylation of HSPA5 at lysine residues 353 (K353) and reduced GP78-mediated ubiquitination of HSPA5 at K447 and then increased cell migration/invasion. In addition, we demonstrate that E3 ubiquitin ligase GP78 preferentially binds to deacetylated HSPA5. Notably, the expression levels of GP78 inversely correlated with HSPA5 levels in breast cancer patients. Patients with low GP78 expression significantly correlated with invasiveness of breast cancer, advanced tumor stages and poor clinical outcome. Taken together, our results provide new mechanistic insights into the understanding that deacetylation of HSPA5 by HDAC6 facilitates GP78-mediated HSPA5 ubiquitination and suggest that post-translational regulation of HSPA5 protein is critical for HSPA5-mediated metastatic properties of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Choque Térmico/metabolismo , Histona Desacetilases/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Desacetilase 6 de Histona , Histona Desacetilases/genética , Humanos , Camundongos SCID , Dados de Sequência Molecular , Invasividade Neoplásica , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma/metabolismo , Homologia de Sequência de Aminoácidos , Ubiquitinação
11.
Australas Phys Eng Sci Med ; 38(3): 493-501, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26346030

RESUMO

It was the aim of this work to assess and track the workload, working conditions and professional recognition of radiation oncology medical physicists (ROMPs) in the Asia Pacific region over time. In this third survey since 2008, a structured questionnaire was mailed in 2014 to 22 senior medical physicists representing 23 countries. As in previous surveys the questionnaire covered seven themes: 1 education, training and professional certification, 2 staffing, 3 typical tasks, 4 professional organisations, 5 resources, 6 research and teaching, and 7 job satisfaction. The response rate of 100% is a result of performing a survey through a network, which allows easy follow-up. The replies cover 4841 ROMPs in 23 countries. Compared to 2008, the number of medical physicists in many countries has doubled. However, the number of experienced ROMPs compared to the overall workforce is still small, especially in low and middle income countries. The increase in staff is matched by a similar increase in the number of treatment units over the years. Furthermore, the number of countries using complex techniques (IMRT, IGRT) or installing high end equipment (tomotherapy, robotic linear accelerators) is increasing. Overall, ROMPs still feel generally overworked and the professional recognition, while varying widely, appears to be improving only slightly. Radiation oncology medical physics practice has not changed significantly over the last 6 years in the Asia Pacific Region even if the number of physicists and the number and complexity of treatment techniques and technologies have increased dramatically.


Assuntos
Pessoal de Saúde/estatística & dados numéricos , Medicina Nuclear/estatística & dados numéricos , Radioterapia (Especialidade)/estatística & dados numéricos , Ásia , Humanos , Inquéritos e Questionários , Carga de Trabalho
12.
Gene Ther ; 22(11): 923-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333349

RESUMO

Achieving persistent expression is a prerequisite for effective genetic therapies for inherited disorders. These proof-of-concept studies focused on adeno-associated virus (AAV) administration to newborn monkeys. Serotype rh10 AAV expressing ovalbumin and green fluorescent protein (GFP) was administered intravenously at birth and compared with vehicle controls. At 4 months postnatal age, a second injection was administered intramuscularly, followed by vaccination at 1 year of age with ovalbumin and GFP. Ovalbumin was highest 2 weeks post administration in the treated monkey, which declined but remained detectable thereafter; controls demonstrated no expression. Long-term AAV genome copies were present in myocytes. At 4 weeks, neutralizing antibodies to rh10 were present in the experimental animal only. With AAV9 administration at 4 months, controls showed transient ovalbumin expression that disappeared with the development of strong anti-ovalbumin and anti-GFP antibodies. In contrast, increased and maintained ovalbumin expression was noted in the monkey administered AAV at birth, without antibody development. After vaccination, the experimental monkey maintained levels of ovalbumin without antibodies, whereas controls demonstrated high levels of antibodies. These preliminary studies suggest that newborn AAV administration expressing secreted and intracellular xenogenic proteins may result in persistent expression in muscle, and subsequent vector administration can result in augmented expression without humoral immune responses.


Assuntos
Anticorpos Neutralizantes/imunologia , Técnicas de Transferência de Genes , Tolerância Imunológica/genética , Animais , Animais Recém-Nascidos , Anticorpos Heterófilos , Anticorpos Neutralizantes/genética , Dependovirus/genética , Feminino , Terapia Genética , Vetores Genéticos/imunologia , Imunidade Humoral/genética , Imunidade Humoral/imunologia , Macaca mulatta , Ovalbumina/sangue , Ovalbumina/genética , Projetos Piloto
13.
N Engl J Med ; 371(6): 507-518, 2014 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-25029335

RESUMO

BACKGROUND: The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS: We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-ß, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS: We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. CONCLUSIONS: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).


Assuntos
Inflamação/genética , Proteínas de Membrana/genética , Mutação , Dermatopatias Vasculares/genética , Idade de Início , Citocinas/genética , Citocinas/metabolismo , Feminino , Fibroblastos/metabolismo , Genes Dominantes , Humanos , Lactente , Recém-Nascido , Inflamação/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Janus Quinases/antagonistas & inibidores , Pneumopatias/genética , Masculino , Linhagem , Fosforilação , Fator de Transcrição STAT1/metabolismo , Análise de Sequência de DNA , Dermatopatias Vasculares/metabolismo , Síndrome , Transcrição Gênica , Regulação para Cima
14.
Cell Death Dis ; 5: e1158, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24722283

RESUMO

Human diseases of impaired ribosome biogenesis resulting from disruption of rRNA biosynthesis or loss of ribosomal components are collectively described as 'ribosomopathies'. Treacher Collins syndrome (TCS), a representative human ribosomopathy with craniofacial abnormalities, is attributed to mutations in the tcof1 gene that has a homologous gene called nopp140. Previous studies demonstrated that the dao-5 (dauer and aged animal overexpression gene 5) of Caenorhabditis elegans is a member of nopp140 gene family and plays a role in nucleogenesis in the early embryo. Here, we established a C. elegans model for studying Nopp140-associated ribosomopathy. A null dao-5 mutant ok542 with a semi-infertile phenotype showed a delay in gonadogenesis, as well as a higher incidence of germline apoptosis. These phenotypes in dao-5(ok542) are likely resulted from inefficient rDNA transcription that was observed by run-on analyses and chromatin immunoprecipitation (ChIP) assays measuring the RNA Pol I occupancy on the rDNA promoter. ChIP assays further showed that the modifications of acetylated histone 4 (H4Ac) and dimethylation at the lysine 9 of histone 3 (H3K9me2) around the rDNA promoter were altered in dao-5 mutants compared with the N2 wild type. In addition, activated CEP-1 (a C. elegans p53 homolog) activity was also linked to the loss of DAO-5 in terms of the transcriptional upregulation of two CEP-1 downstream effectors, EGL-1 and CED-13. We propose that the dao-5 mutant of C. elegans can be a valuable model for studying human Nopp140-associated ribosomopathy at the cellular and molecular levels.


Assuntos
Apoptose , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , DNA Ribossômico/genética , Proteínas de Ligação a DNA/genética , Células Germinativas/citologia , Mutação/genética , Transcrição Gênica , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/citologia , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Nucléolo Celular/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Sequência Conservada , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Genes de Helmintos , Células Germinativas/metabolismo , Gônadas/anormalidades , Gônadas/metabolismo , Histonas/metabolismo , Humanos , Modelos Biológicos , Dados de Sequência Molecular , Regiões Promotoras Genéticas/genética , Estrutura Terciária de Proteína , RNA Polimerase I/metabolismo , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo
15.
J Perinatol ; 34(4): 268-74, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24457256

RESUMO

OBJECTIVE: To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS). STUDY DESIGN: We searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. RESULT: Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS. CONCLUSION: For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.


Assuntos
Sangue Fetal/química , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Sepse/diagnóstico , Proteína C-Reativa/análise , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Diagnóstico Precoce , Humanos , Recém-Nascido , Precursores de Proteínas/sangue , Sepse/epidemiologia
16.
Oncogene ; 33(11): 1375-84, 2014 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23624915

RESUMO

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Receptores ErbB/metabolismo , Matriz Extracelular/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Glicoproteínas de Membrana/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Glicoproteínas de Membrana/genética
17.
Osteoporos Int ; 25(3): 1131-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24343364

RESUMO

SUMMARY: We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients. INTRODUCTION: PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012. METHODS: Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use. RESULTS: We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Viés de Publicação , Projetos de Pesquisa , Medição de Risco/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-25570005

RESUMO

The purpose of this study is to build a cost-effective and easy-to-popularize laparoscopic training system based on improving traditional training box. The system has the capability of objective skills assessment and the function of automatic recording of training process and results, as well as 3-dimensional coordinate tracking of instruments. The results of pilot experiment in laparoscopic-assisted grip skill assessment had been shown the system can assess the different grip ability level between the senior surgeons and junior residents. Regarding to the evaluation of training effectiveness, five subjects without laparoscopic surgery experiences were asked to perform grip training for five days to observe their training curves. According to the experimental results, the total time taken for subject 1 to subject 5 are improved by 54.9%, 52.0%, 60.6%, 23.3%, and 63.5% separately.


Assuntos
Instrução por Computador , Laparoscopia/educação , Feminino , Humanos , Treinamento por Simulação
19.
Indian J Cancer ; 50(1): 14-20, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23713039

RESUMO

BACKGROUND AND PURPOSE: To evaluate the relationship of emotional status and health-related quality of life (HRQOL) in disease-free head and neck cancer (HNC) patients post treatment and to explore their predictive factors. MATERIALS AND METHODS: Seventy-three HNC patients, post treatment at least 1 year, were recruited to complete three questionnaires, EORTC QLQ-C30, EORTC-H&N35 cancer module, and the Beck Depression Inventory-II (BDI-II). RESULTS: Patients with depression demonstrated significantly poor global health status/QoL (score 41.7 vs. 71.9, P<0.001) and almost all functioning, except for role functioning. Besides, depressive patients presented statistically significant worse symptoms in all QLQ-C30 items, except constipation and financial problems, and in all QLQ-H&N35 symptoms except for teeth and coughing problems. Depression was significantly negative correlated with all functional scales and global health status/QoL (r = -0.341 to -0.750, all P<0.05), and was significantly positive correlated with symptom scales (r = 0.348 to 0.793, all P<0.05), except for constipation. Stepwise multiple linear regression analyses showed that physical functioning and physical distressful symptoms play an important role in the perception of HRQOL (total 46% explained). Global health status and impaired social functioning could explain depression in addition to emotional functioning (total 64% explained). CONCLUSIONS: HNC patients with depression were noted to have poorer HRQOL in almost every functioning symptom. HNC patients may get benefit from early interventions to improve HRQOL, emotional status, or both by a more rapid and friendly questionnaire to earlier identify patients with poor HRQOL or depressive status.


Assuntos
Depressão/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/psicologia , Qualidade de Vida , Adulto , Estudos Transversais , Depressão/epidemiologia , Intervalo Livre de Doença , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Inquéritos e Questionários
20.
Eur J Neurol ; 20(4): 616-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22672698

RESUMO

BACKGROUND AND PURPOSE: To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. METHODS AND MATERIALS: Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. RESULTS: Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. CONCLUSIONS: Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis.


Assuntos
Paralisia de Bell/complicações , Paralisia de Bell/tratamento farmacológico , Esteroides/uso terapêutico , Acidente Vascular Cerebral/complicações , Adulto , Paralisia de Bell/epidemiologia , Diabetes Mellitus/epidemiologia , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Classificação Internacional de Doenças , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Programas Nacionais de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida , Taiwan/epidemiologia
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