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1.
PLoS One ; 19(4): e0298740, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38669282

RESUMO

In this research, we employed functional magnetic resonance imaging (fMRI) to examine the neurological basis for understanding wh-questions in wh-in-situ languages such as Korean, where wh-elements maintain their original positions instead of moving explicitly within the sentence. Our hypothesis centered on the role of the salience and attention network in comprehending wh-questions in wh-in-situ languages, such as the discernment of wh-elements, the demarcation between interrogative types, and the allocation of cognitive resources towards essential constituents vis-à-vis subordinate elements in order to capture the speaker's communicative intent. We explored subject and object wh-questions and scrambled wh-questions, contrasting them with yes/no questions in Korean. Increased activation was observed in the left anterior insula and bilateral frontal operculum, irrespective of the wh-position or scrambling of wh-element. These results suggest the interaction between the salience and attentional system and the syntactic linguistic system, particularly the left anterior insula and bilateral frontal operculum, in comprehending wh-questions in wh-in-situ languages.


Assuntos
Compreensão , Idioma , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Compreensão/fisiologia , Adulto , Adulto Jovem , Mapeamento Encefálico , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , República da Coreia , Córtex Insular/fisiologia , Córtex Insular/diagnóstico por imagem
2.
Anticancer Res ; 42(10): 4945-4954, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191979

RESUMO

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Proteína BRCA1/genética , Carcinoma Epitelial do Ovário/genética , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Prognóstico
4.
Ultrasonography ; 41(3): 553-565, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35537817

RESUMO

PURPOSE: The aim of this study was to analyze the imaging findings and clinical characteristics of extratendinous migration of calcific tendinitis of the shoulder with temporal changes. METHODS: Seventy-six patients with extratendinous calcific tendinitis of the shoulder diagnosed by ultrasonography (US) or magnetic resonance imaging (MRI) were enrolled in this retrospective study. Clinical symptoms and imaging findings (on radiography, US, and MRI) of extratendinous calcific tendinitis during an acute painful attack were analyzed. Temporal changes were analyzed in 28 patients before an acute attack and 40 patients after an acute attack. For comparison, 65 patients with intratendinous calcific tendinitis were included. RESULTS: Patients with extratendinous calcific tendinitis had a significantly higher average visual analogue scale (VAS) score (8.8±1.6) than the intratendinous group (6.4±2.2) (P<0.001). The fragmented type (80.5%) was the most common shape on US; sonographic black hole appearance (14.6%) and echogenic fluid (9.8%) were characteristic findings of intrabursal calcifications. In 28 patients with previous radiographs, radiographic type III (78.6%) was dominant and the location of calcific deposits changed (82.1%) during the acute painful attack, which was also perceivable in 12 patients with previous US or MRI. In follow-up radiographs of 40 patients, calcifications shrunk by more than 50% or became invisible in 82.5% of patients, with symptom improvement (VAS score, 8.9±1.5 to 1.9±1.2). Follow-up US and MRI of 16 patients also showed decreased size (56.3%) or disappearance (43.7%) of calcific deposits. CONCLUSION: Extratendinous calcific tendinitis has distinctive imaging features, the temporal changes of which correlate well with clinical symptoms.

5.
Org Lett ; 24(8): 1652-1656, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35195421

RESUMO

A highly stereoselective asymmetric total synthesis of (-)-jimenezin (1), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.

6.
Molecules ; 26(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684673

RESUMO

A series of halogenated 1,5-diarylimidazole compounds were synthesized and their inhibitory effects on LPS-induced PGE2 production in RAW 264.7 cells were evaluated. A wide variety of 2,4-, 4-, and 2-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles were synthesized for SAR study via two different pathways. Overall, 4-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles, regardless of the species of halogen, exhibited very strong inhibitory activities of PGE2 production. Among them, 4-chloro-5-(4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole (3, IC50 3.3 nM ± 2.93), and 4-chloro-5-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)imidazole (13, IC50 5.3 nM ± 0.23) showed the best results.


Assuntos
Dinoprostona/biossíntese , Imidazóis , Células RAW 264.7/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Halogenação , Imidazóis/síntese química , Imidazóis/farmacologia , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
7.
Ann Lab Med ; 41(5): 447-454, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33824232

RESUMO

BACKGROUND: Urine reagent strip test (URST) results are semi-quantitative; therefore, the precision of URSTs is evaluated as the proportion of categorical results from repeated measurements of a sample that are concordant with an expected result. However, URSTs have quantitative readout values before ordinal results challenging statistical monitoring for internal quality control (IQC) with control rules. This study aimed to determine the sigma metric of URSTs and derive appropriate control rules for IQC. METHODS: The URiSCAN Super Plus fully automated urine analyzer (YD Diagnostics, Yongin, Korea) was used for URSTs. Change in reflectance rate (change %R) data from IQC for URSTs performed between November 2018 and May 2020 were analyzed. Red blood cells, bilirubin, urobilinogen, ketones, protein, glucose, leukocytes, and pH were measured from 2-3 levels of control materials. The total allowable error (TEa) for a grade was the difference in midpoints of a predefined change %R range between two adjacent grades. The sigma metric was calculated as TEa/SD. Sigma metric-based control rules were determined with Westgard EZ Rules 3 software (Westgard QC, Madison, WI, USA). RESULTS: Seven out of the eight analytes had a sigma metric >4 in the control materials with a negative grade (-), which were closer to the cut-offs. Corresponding control rules ranged from 12.5s to 13.5s. CONCLUSIONS: Although the URST is a semi-quantitative test, statistical IQC can be performed using the readout values. According to the sigma metric, control rules recommended for URST IQC in routine clinical practice are 12.5s to 13.5s.


Assuntos
Fitas Reagentes , Gestão da Qualidade Total , Urinálise , Indicadores e Reagentes , Controle de Qualidade , Software
8.
Biomol Ther (Seoul) ; 29(4): 410-418, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653970

RESUMO

Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5- trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 µM, these compounds inhibited the production of active IL-1ß, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

9.
Taiwan J Obstet Gynecol ; 60(1): 36-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33495005

RESUMO

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.


Assuntos
Algoritmos , Carcinoma Epitelial do Ovário/diagnóstico , Detecção Precoce de Câncer/métodos , Doenças Ovarianas/diagnóstico , Neoplasias Ovarianas/diagnóstico , Tri-Iodotironina/sangue , Adulto , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Reações Falso-Positivas , Feminino , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise
10.
Bioorg Med Chem ; 29: 115861, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33214038

RESUMO

Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin's 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Triazóis/farmacologia , Inibidores da Dipeptidil Peptidase IV/síntese química , Inibidores da Dipeptidil Peptidase IV/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
11.
Front Chem ; 8: 494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714895

RESUMO

The cross-metathesis (CM) of methallyl halides catalyzed using four different ruthenium-based complexes-Grubbs catalyst, Grubbs second-generation catalyst, Hoveyda-Grubbs second-generation catalyst, and Stewart-Grubbs catalyst-was investigated. When methallyl chloride or bromide was reacted with a model substrate containing a benzyl ether group, the Grubbs catalyst, and Grubbs second-generation catalyst did not promote the reaction well. However, the Hoveyda-Grubbs second-generation catalyst and Stewart-Grubbs catalyst afforded the corresponding products in moderate to good yield with moderate E/Z selectivity. Accordingly, several functionalized methallyl halides were prepared by CM. Various functional groups were well-tolerated in this system when the Stewart-Grubbs catalyst was used. To demonstrate the practical utility of our method, methallyl halide CM was successfully employed for the formal total synthesis of a natural product (-)-presphaerene, in which the precursor of the key cyclopentanecarboxylate intermediate was efficiently prepared in three steps.

12.
Ann Clin Lab Sci ; 50(3): 417-422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32581038

RESUMO

OBJECTIVE: The carcinoembryonic antigen (CEA) is coupled with a diagnosis and prognosis for cancers METHODS: The analytical performance of CEA by chemiluminescent immunoassay (HISCL-5000, Sysmex, Kobe, Japan) was evaluated on the basis of precision, linearity, trueness, and method comparison. Clinical evaluation was performed by area under the receiver operating characteristic curve (AU-ROC) curve analysis for lung, stomach and colorectal cancers. RESULTS: Total coefficient of variation (CV) (5.039% to 5.632%), linearity (0.5 to 982 ng/mL) and the percentage bias by trueness verification were less than desirable specifications for imprecision (6.4%) and bias (14.3%). The regression equation was y=0.354+0.957x(r=0.968) from method comparison. AUROC for lung, stomach, and colorectal cancers compared with normal healthy control ranged from 0.908 to 0.967 (cut-off 4.50 to 4.71 ng/mL), and compared with non-malignant benign disease, ranged from 0.578 to 0.721 (cut-off 8 to 20.70 ng/mL). CONCLUSIONS: CEA by HISCL-5000 immunoassay provided reliable performance. Comorbidities should be considered for interpretation of CEA.


Assuntos
Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/imunologia , Imunoensaio/métodos , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/imunologia , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/imunologia , Confiabilidade dos Dados , Feminino , Proteínas Ligadas por GPI/imunologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Curva ROC
13.
PLoS One ; 15(4): e0230837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271789

RESUMO

Interrogation elicits anxiety in individuals under scrutiny regardless of their innocence, and thus, anxious responses to interrogation should be differentiated from deceptive behavior in practical lie detection settings. Despite its importance, not many empirical studies have yet been done to separate the effects of interrogation from the acts of lying or guilt state. The present fMRI study attempted to identify neural substrates of anxious responses under interrogation in either innocent or guilt contexts by developing a modified "Doubt" game. Participants in the guilt condition showed higher brain activations in the right central-executive network and bilateral basal ganglia. Regardless of the person's innocence, we observed higher activation of the salience, theory of mind and sensory-motor networks-areas associated with anxiety-related responses in the interrogative condition, compared to the waived conditions. We further explored two different types of anxious responses under interrogation-true detection anxiety in the guilty (true positive) and false detection anxiety in the innocent (false positive). Differential neural responses across these two conditions were captured at the caudate, thalamus, ventral anterior cingulate and ventromedial prefrontal cortex. We conclude that anxiety is a common neural response to interrogation, regardless of an individual's innocence, and that there are detectable differences in neural responses for true positive and false positive anxious responses under interrogation. The results of our study highlight a need to isolate complex cognitive processes involved in the deceptive acts from the emotional and regulatory responses to interrogation in lie detection schemes.


Assuntos
Ansiedade , Encéfalo/diagnóstico por imagem , Culpa , Detecção de Mentiras/psicologia , Adulto , Análise de Variância , Ansiedade/psicologia , Encéfalo/fisiologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Aplicação da Lei , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia
14.
Scand J Clin Lab Invest ; 79(5): 347-353, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31210062

RESUMO

The analytical performance and clinical application of measuring insulin and connecting peptide (C-peptide) by point of care (POC) assay were evaluated. A POC assay system (SelexOn, Osang Healthcare Inc., Anyang-si, Korea) was evaluated for precision, linearity, limit of blank (LOB), and limit of detection (LOD). Method comparison was performed with the Cobas Elecsys insulin and C-peptide assay (Roche Diagnostics GmbH, Mannheim, Germany) using 215 and 201 patient specimens for insulin and C-peptide, respectively. For clinical application, insulin resistance indices were studied. Homeostasis model assessment (HOMA) 1 and 2, Quantitative insulin sensitivity check index (QUIKI), fasting insulin resistance index (FIRI), and other indices were evaluated. The coefficient of variation (CV) of imprecision for low, medium, and high concentrations was 10.8%1, 15.99%, and 12.05%, respectively, for insulin and 9.21%, 13.51%, and 13.77%, respectively, for C-peptide. The linearity was validated to 839.78 pmol/L for insulin and to 17.30 nmol/L for C-peptide. LOB and LOD were 8.05 and 9.72 pmol/L for insulin and 0.05 and 0.08 nmol/L for C-peptide, respectively. For the method comparison, the regression equation was y = 1.259x - 8.818 (r = 0.957) for insulin and y = 1.163x - 0.088 (r = 0.985) for C-peptide. The ROC value and overall accuracy were as follows: HOMA2 (C-peptide), 0.809, 79.7%; TyG, 0.788, 73.6%; CPR, 0.775, 74.8%; HOMA1, 0.725, 70.3%; QUIKI, 0.720, 70.3%; FIRI, 0.715, 70.1%; McAuley, 0.658, 65.1%; HOMA2 (Insulin), 0.645, 64.7%; Raynaud, 0.611, 61.4%, respectively. The POC assay system for insulin and C-peptide provided reliable results through a rapid and simple test that could be applied to clinical settings.


Assuntos
Bioensaio/métodos , Peptídeo C/sangue , Insulina/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Curva ROC
15.
Ann Lab Med ; 39(6): 566-571, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31240885

RESUMO

ELISAs and rapid diagnostic tests (RDTs) are widely used for diagnosing dengue virus (DENV) infection. Using 138 single blood samples, we compared the ability to detect non-structural (NS)-1 antigen and anti-DENV IgM/IgG antibodies among (1) DENV Detect NS1 ELISA, DENV Detect IgM capture ELISA and DENV Detect IgG ELISA (InBios International, Inc.); (2) Anti-Dengue virus IgM Human ELISA and Anti-Dengue virus IgG Human ELISA (Abcam); (3) Dengue virus NS1 ELISA, Anti-Dengue virus ELISA (IgM) and Anti-Dengue virus ELISA (IgG) (Euroimmun); (4) Asan Easy Test Dengue NS1 Ag 100 and Asan Easy Test Dengue IgG/IgM (Asan Pharm); (5) SD BIOLINE Dengue Duo (Standard Diagnostics); and (6) Ichroma Dengue NS1 and Ichroma Dengue IgG/IgM (Boditech Med). For NS1 antigen detection, InBios and Euroimmun showed higher sensitivities (100%) than the RDTs (42.9-64.3%). All tests demonstrated variable sensitivities for IgM (38.1-90.5%) and IgG (65.7-100.0%). InBios and Boditech Med demonstrated higher sensitivity (95.6% and 88.2%, respectively) than the other tests for combined NS1 antigen and IgM antibody. Five NS1 antigen tests had good agreement (92.8-98.6%) without showing positivity for chikungunya. However, all IgG tests demonstrated potential false-positivity with variable ranges. Clinical laboratories should note performance variations across tests and potential cross-reactivity.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/metabolismo , Dengue/diagnóstico , Reações Cruzadas , Dengue/virologia , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/análise
16.
Ann Lab Med ; 39(3): 252-262, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30623617

RESUMO

BACKGROUND: The risk of ovarian malignancy algorithm (ROMA) is used for assessing ovarian cancer risk in women with a pelvic mass. Its diagnostic accuracy is variable. We investigated whether the clinically acceptable minimal sensitivity of >80.0% could be obtained with the suggested cutoff of 7.4%/25.3% for pre/postmenopausal women and with adjusted cutoffs set to a specificity of ≥75.0% or a sensitivity of 95.0%, in a hospital with a lower ovarian cancer (OC) prevalence than previously reported. METHODS: ROMA scores were calculated from measurements of human epididymis protein 4 and cancer antigen 125 in blood specimens from 443 patients with a pelvic mass. The ROMA-based risk group was compared against biopsy (N=309) or clinical follow-up with imaging (N=134) results. The ROMA sensitivity and specificity for predicting epithelial OC (EOC) and borderline ovarian tumor (BOT) were calculated for the suggested and adjusted cutoff values. RESULTS: When targeting BOT and EOC, the prevalence was 7.4% and sensitivity and specificity at the suggested cutoff were 63.6% and 90.7%, respectively. Sensitivity was 81.8% at the 4.65%/13.71% cutoff set to a specificity of 75.0%. When targeting only EOC, the prevalence was 4.1% and sensitivity and specificity at the suggested cutoff were 77.8% and 89.4%, respectively. Sensitivity was 88.9% at the 4.78%/14.35% cutoff set to a specificity of 75.0%. CONCLUSIONS: The sensitivity of ROMA was lower than expected when using the suggested cutoff. When using the adjusted cutoff, its sensitivity reached 80.0%.


Assuntos
Algoritmos , Neoplasias Ovarianas/diagnóstico , Adulto , Área Sob a Curva , Antígeno Ca-125/sangue , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Prevalência , Proteínas/análise , Curva ROC , República da Coreia/epidemiologia , Sensibilidade e Especificidade , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos
18.
Org Lett ; 20(20): 6398-6402, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30295489

RESUMO

A stereoselective protection-free asymmetric total synthesis of (+)-chamuvarinin (1), a potent anticancer and antitrypanosomal agent, has been accomplished. The adjacently linked [bis(tetrahydrofuran)]tetrahydropyran (THF-THF-THP) core of this natural product with seven stereogenic centers was constructed in a completely substrate-controlled fashion. The inter-ring stereochemistry ( threo,threo,threo) of the oxatricyclic core was established in a stereoselective fashion by a chelation-controlled Keck allylation, whereas the intraring cis or trans relative stereochemistry was controlled by a stereoselective internal alkylation.

19.
Toxicol Appl Pharmacol ; 355: 93-102, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29960001

RESUMO

NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome is a component of innate immunity, and is responsible for producing mature IL-1ß and -18. Several flavonoids were found to affect inflammasome pathway, but the mechanism of action is still obscure. To elucidate the effects on NLRP3 inflammasome pathway and to determine the structure-activity relationships, NLRP3 inflammasome in differentiated THP-1 cells was activated via treatment with monosodium urate (MSU) crystals. Levels of mature IL-1ß, NLRP3 inflammasome components and apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC) oligomerization were investigated and the mechanisms of action were also elucidated. Among the 56 flavonoids initially tested, only flavone, 2',4'-dihhydroxyflavone, 3',4'-dichloroflavone, 4',5,7-trihydroxyflavone (apigenin), 3,4',5,7-tetrahydroxyflavone (kaempferol) and 3,3',4',5,7-pentahydroxyflavone (quercetin) significantly inhibited IL-1ß production at 10 µM. Apigenin, kaempferol and 3',4'-dichloroflavone inhibited ASC oligomerization without affecting the ASC level in cell lysates. Apigenin also inhibited absent in melanoma 2 (AIM2) inflammasome-related pathway, but not NLR family CARD domain-containing protein 4 (NLRC4) inflammasome activation. The action of apigenin on NLRP3 inflammasome activation is mediated partly via inhibition of phosphorylation of spleen tyrosine kinase/protein tyrosine kinase 2 (Syk/Pyk2) pathway. Furthermore, orally administered apigenin (100 mg/kg) strongly reduced the number of neutrophils and monocytes in MSU-induced peritonitis in mice. The present study, for the first time, demonstrated the structure-activity profiles of flavonoids in NLRP3 inflammasome activation and mechanisms of cellular action. Certain flavonoids including apigenin are expected to ameliorate the inflammatory symptoms in autoinflammatory diseases associated with NLRP3 inflammasome activation.


Assuntos
Flavonoides/farmacologia , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Animais , Caspase 1/efeitos dos fármacos , Linhagem Celular , Quinase 2 de Adesão Focal/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Monócitos/efeitos dos fármacos , Peritonite/induzido quimicamente , Peritonite/prevenção & controle , Relação Estrutura-Atividade , Quinase Syk/efeitos dos fármacos , Ácido Úrico
20.
Eur J Radiol ; 100: 147-153, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496074

RESUMO

OBJECTIVES: To determine what computed tomographic (CT) dimensions can predict obstructive lung disease on routine chest CT scans by comparing morphological and densitometric CT findings with pulmonary function test (PFT) in normal subjects and patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Consecutive patients (n = 646; 260 females and 386 males; mean age 54.9 years, ranged 20-90 years) who received chest CT scans with densitometry during a 3-month period were retrospectively analyzed in single center. PFT was undertaken in 235 patients (152 males, 83 females) at same times of CT scanning. The patients were grouped by age (<30 years, 31-45 years, 46-60 years, and >61 years). CT parameters including tracheal, azygoesophageal, thoracic vertical, anterior-posterior (AP), transverse diameters, transverse cardiac diameter, diameters of main, right, and left pulmonary arteries, and CT densitometric values including lung volume and density (-900 to -1000 Hounsfield Units, HU), low attenuation value cluster (default threshold: -950 HU) were compared with PFT values. Spearman correlation coefficients was used to evaluate the relationship between the CT indices and PFT. RESULTS: Ninety of 235 patients with PFT were smokers (76 males, 14 females). Obstructive PFT was detected in 65 patients (27.7%: 46 males, 19 females). Male smokers with obstructive PFT displayed significantly larger thoracic anterior-posterior (mean: normal, 172.3 cm versus COPD, 185.9 cm, p = 0.0001) and smaller transverse diameters (mean: normal, 247.0 cm vs. COPD, 235.8 cm, p = 0.01), and increased right pulmonary artery diameter (mean: normal, 20.3 cm v s. COPD, 22.1 cm, p < 0.001), and increased left pulmonary artery diameter (mean: normal, 19.7 cm vs. COPD, 20.6 cm, p < 0.025). The lung parenchyma density (-1000 to -900 HU) and greater concentration of largest cluster on densitometry were significantly different between normal and obstructive PFT pattern in male smoker. Residual volume and total lung capacity are positively correlated with lung volume and lung density (-1000 to -800) of densitometry. CONCLUSIONS: CT findings of the overexpansion of the lungs, such as increases in the vertical diameter of the lung and decreases in the transverse diameter of the heart, can be significant as indirect findings of early chronic obstructive diseases. However, despite the significant CT findings in male smokers, particularly those in their 40s, most lung function parameters were not decidedly abnormal.


Assuntos
Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Volume de Ventilação Pulmonar , Tomografia Computadorizada Espiral/métodos , Capacidade Pulmonar Total , Adulto Jovem
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