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This study assessed the performance of the BioFire Blood Culture Identification 2 (BCID2) panel in identifying microorganisms and antimicrobial resistance (AMR) profiles in positive blood cultures (BCs) and its influence on turnaround time (TAT) compared with conventional culture methods. We obtained 117 positive BCs, of these, 102 (87.2%) were correctly identified using BCID2. The discordance was due to off-panel pathogens detected by culture (n = 13), and additional pathogens identified by BCID2 (n = 2). On-panel pathogen concordance between the conventional culture and BCID2 methods was 98.1% (102/104). The conventional method detected 19 carbapenemase-producing organisms, 14 extended-spectrum beta-lactamase-producing Enterobacterales, 18 methicillin-resistant Staphylococcus spp., and four vancomycin-resistant Enterococcus faecium. BCID2 correctly predicted 53 (96.4%) of 55 phenotypic resistance patterns by detecting AMR genes. The TAT for BCID2 was significantly lower than that for the conventional method. BCID2 rapidly identifies pathogens and AMR genes in positive BCs.
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Hemocultura , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase Multiplex/métodos , Humanos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , Proteínas de Bactérias/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterococcus faecium/genética , Enterococcus faecium/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/isolamento & purificação , Bacteriemia/microbiologia , Bacteriemia/diagnósticoRESUMO
BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.
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BACKGROUND: There is little data about the performance of multiplex rapid antigen tests (RATs) on the detection of SARS-CoV-2, influenza A (Flu A), and influenza B (Flu B). This study is to evaluate the performance of Panbio COVID-19/Flu A&B rapid panel (Abbott Diagnostics, Korea) and analyze the factors influencing its sensitivity. METHODS: Nasopharyngeal swabs were collected and stored at the Korea University Anam hospital. In total, 400 residual samples from nasopharyngeal swabs were examined. The diagnostic accuracy of RAT was compared to that of RT-qPCR using the Allplex SARS-CoV-2/FluA/FluB/RSV Assay (Seegene, Seoul, South Korea). RESULTS: Panbio COVID-19/Flu A&B rapid panel showed the sensitivities of 88.0%, 92.0%, and 100% for SARS-CoV-2, Flu A, and Flu B, respectively, and specificities of 100% for all. The agreements with previously licensed single-plex RATs were shown to be high. In the analysis of variables affecting sensitivity, inappropriate sampling time after symptom onset (STASO) and high cycle threshold (Ct value) were shown to negatively affect the sensi-tivity. CONCLUSIONS: In conclusion, the multiplex RAT is useful for diagnosing SARS-CoV-2 and Flu A/B, but more clinical studies are needed.
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COVID-19 , Vírus da Influenza A , Influenza Humana , Humanos , Influenza Humana/diagnóstico , SARS-CoV-2 , Vírus da Influenza B/genética , COVID-19/diagnóstico , Nasofaringe , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In consideration of the substantial occurrence rates of diabetes mellitus (DM) and depression, it is imperative to identify patients with DM who are at an elevated risk of developing depression. Accordingly, this study aimed to examine whether the risk of depression escalated proportionally with the severity of diabetes. METHODS: 2,067,017 adults diagnosed with type 2 DM, with the exception of those diagnosed with depression either before or within one year of the index date, were identified from a nationwide population-based cohort in Korea. Severity scores for DM were established based on various factors, including insulin use, DM duration of at least 5 years, use of three or more oral hypoglycemic agents, the presence of chronic kidney disease (CKD), cardiovascular diseases (CVD), or diabetic retinopathy. Each of these attributes was assigned a score of one point for diabetes severity, and their cumulative sum was defined as a diabetes severity score, ranging from 0 to 6. RESULTS: During a median follow-up of 6.2 years, 407,047 cases of major depression were identified. Each component contributing to the DM severity score was significantly associated with an increased risk of depression (all P-values <0.001), with insulin use and the presence of CVD demonstrating the most significant correlation with depression risk. As the DM severity score increased, the risk of depression was observed to significantly escalate (P for trend <0.001). After adjusting for potential confounding variables, the hazard ratios (95% confidence intervals) of depression were 1.15 (1.14-1.16) in 1 point, 1.28 (1.27-1.29) in 2 points, 1.45 (1.43-1.47) in 3 points, 1.70 (1.67-1.73) in 4 points, 1.91 (1.84-1.98) in 5 points, and 2.01 (1.79-2.26) in 6 points, respectively. CONCLUSION: The results of this study indicate that diabetes severity is positively associated with an elevated risk of developing major depression. Based on these findings, it is feasible to consider targeting depression screening efforts towards individuals with higher diabetes severity scores.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Insulinas , Insuficiência Renal Crônica , Adulto , Humanos , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Diabetes Mellitus/epidemiologiaRESUMO
We evaluated the performance of SARS-CoV-2 assays in the vaccinated group using receptor-binding domain antibody assays (RBD Ab assay), neutralizing antibody assay (nAb assay), and interferon-gamma release assay (IGR assay). We also compared the performance of the SARS-CoV-2 assays based on vaccine type in a large population. We collected 1851 samples from vaccinated individuals with vector, mix-and-match (MM), and mRNA vaccines. The performance of the RBD Ab assays was assessed by SARS-CoV-2 IgG II Quant (Abbott Laboratories, Sligo, Ireland), SARS-CoV-2 IgG (Beckman Coulter, CA, USA), and anti-SARS-CoV-2 S (Roche Diagnostics GmbH, Mannheim, Germany). The nAb assay was assessed by cPass SARS-CoV-2 neutralization antibody detection kits (GenScript, NJ, USA). The IGR assay was assessed by QuantiFERON (Qiagen, Venlo, The Netherlands). Median values of the RBD Ab assays and nAb assay sequentially increased after the first and second vaccinations. RBD Ab assays and nAb assay showed very strong correlations. The median values of the RBD Ab, nAb, and IGR were higher in the mRNA vaccine group than in the vector and MM vaccine groups. The agreement and correlation among the RBD Ab assays, nAb assay, and IGR assay were higher in the mRNA vaccine group than in the vector and MM vaccine groups. We compared the performance of the RBD Ab assay, nAb assay, and IGR assay based on the vaccine types using the RBD Ab, nAb, and IGR assays. This study provides a better understanding of the assessment of humoral and cellular immune responses after vaccination.
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BACKGROUND: Therapeutic drug monitoring (TDM) of antifungal drugs is recommended. LC-MS/MS outperforms bioassay and high-performance liquid chromatography (HPLC) for TDM. In this study, we validated TDM for voriconazole, posaconazole, and itraconazole using HPLC-MS/MS with the multiple reaction monitoring (MRM) method. METHODS: For the validation of LC-MS/MS for antifungal TDM, accuracy, precision, linearity, carryover, lower limit of quantitation (LLOQ), ion suppression, and sample stability tests were performed according to the guidelines of the United States Food and Drug Administration (FDA) and the Clinical and Laboratory Standards Institute (CLSI). RESULTS: The LC-MS/MS triazole method showed that all analytes had biases less than 8.9% and coefficients of variation (CV) less than 7.7%. The linearity was validated over the ranges of 0.20 to 5.86 mg/L for voriconazole, 0.12 to 4.96 mg/L for posaconazole, 0.09 to 1.85 mg/L for itraconazole, and 0.12 to 2.38 mg/L for OH-itraconazole. Ion suppression and carryover were negligible. The lower limits of quantitation (LLOQs) for voriconazole, posaconazole, itraconazole, and OH-itraconazole were 0.114 mg/L, 0.206 mg/L, 0.118 mg/L, and 0.065 mg/L, respectively. Voriconazole, posaconazole, itraconazole, and OH-itraconazole can be stored at 4â for 4 - 7 days, according to sample stability. Sample preparation took < 15 minutes per batch, and analytical run time was 5 minutes per sample. CONCLUSIONS: We developed and validated a simple, reliable, and quick LC-MS/MS method for triazole antifungal agents TDM suitable for routine hospital practice.
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Antifúngicos , Itraconazol , Estados Unidos , Humanos , Cromatografia Líquida de Alta Pressão , Voriconazol , Cromatografia Líquida , Espectrometria de Massas em Tandem , TriazóisRESUMO
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections and hospitalization in infants and young children. Here, we analyzed the genetic diversity of RSV using partial G gene sequences in 84 RSV-A and 78 RSV- B positive samples collected in Seoul, South Korea, for 10 consecutive years, from 2010 to 2019. Our phylogenetic analysis revealed that RSV-A strains were classified into either the ON1 (80.9%) or NA1 (19.0%) genotypes. On the other hand, RSV-B strains demonstrated diversified clusters within the BA genotype. Notably, some sequences designated as BA-SE, BA-SE1, and BA-DIS did not cluster with previously identified BA genotypes in the phylogenetic trees. Despite this, they did not meet the criteria for the assignment of a new genotype based on recent classification methods. Selection pressure analysis identified three positive selection sites (amino acid positions 273, 274, and 298) in RSV-A, and one possible positive selection site (amino acid position 296) in RSV-B, respectively. The mean evolutionary rates of Korean RSV-A from 1999 to 2019 and RSV-B strains from 1991 and 2019 were estimated at 3.51 × 10-3 nucleotides (nt) substitutions/site/year and 3.32 × 10-3 nt substitutions/site/year, respectively. The population dynamics in the Bayesian skyline plot revealed fluctuations corresponding to the emergence of dominant strains, including a switch of the dominant genotype from NA1 to ON1. Our study on time-scaled cumulative evolutionary analysis contributes to a better understanding of RSV epidemiology at the local level in South Korea.
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Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Criança , Humanos , Pré-Escolar , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Filogenia , Seul , Teorema de Bayes , República da Coreia/epidemiologia , Genótipo , Epidemiologia MolecularRESUMO
This study aimed to assess the performance of our in-house method for rapid direct bacterial identification (ID) and antimicrobial susceptibility testing (AST) using a positive blood culture (BC) broth. For Gram-negative bacteria, 4 mL of BC broth was aspirated and passed through a Sartorius Minisart syringe filter with a pore size of 5 µm. The filtrate was then centrifuged and washed. A small volume of the pellet was used for ID, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and for AST, using automated broth microdilution. For Gram-positive cocci, 4 mL of BC broth was passed through the Minisart syringe filter. Then, 4 mL of sterile distilled water was injected in the direction opposite to that of the filtration to collect the bacterial residue trapped in the filter. Compared with the conventional method performed with pure colonies on agar plates, 94.0% (234/249) were correctly identified using the in-house method, with rates of 91.4% (127/139) and 97.3% (107/110) for Gram-positive and Gram-negative isolates, respectively. Of 234 correctly identified isolates, 230 were assessed by AST. Categorical agreement and essential agreement were 93.3% and 94.5%, respectively, with a minor error rate of 3.8%, a major error rate of 3.4%, and a very major error rate of 1.6%. Our in-house preparation method showed good performance in rapid direct ID and AST using positive BC broths compared to the conventional method. This simple method can shorten the conventional turnaround time for ID and AST by at least 1 day, potentially contributing to better patient management.
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Antibacterianos , Bacteriemia , Humanos , Antibacterianos/farmacologia , Hemocultura/métodos , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bactérias , Bactérias Gram-Negativas , Bacteriemia/diagnóstico , Bacteriemia/microbiologiaRESUMO
BACKGROUND: This study aimed to develop and validate a U-HPLC-MS/MS method for simultaneous determination of four immunosuppressants in human whole blood. METHODS: The method was based on the injection of 20 µL of calibrators and controls pretreated with the liquid phase extraction method for chromatography separation and mass spectrometry determination. LPE offline was performed by adding 0.1 mol/L ZnSO4 and acetonitrile, while separation of target compounds was achieved within 2.5 minutes by a Zorbax Eclipse XDB-C8 column using ammonium acetate and ACN mixed with formic acid as solvents. RESULTS: The assay offers ng/mL detection limits (from 1.1 to 12.4 ng/mL), accuracy (% deviation from -4.4% to 5.6%), precision (CV less than 15% at all QC levels), and linearity (from 23.4 to 948 ng/mL for CsA, from 2.11 to 45.5 ng/mL for TAC, SIR and EVR). The recovery and matrix results were acceptable, and the carryover was less than 1%. The results of method comparison show that IA-based methods overestimated the concentration of drugs compared with the MS-based method. Comparing our MS-based method with external LC-MS/MS showed that the results were within 2 SDs. CONCLUSIONS: We have developed a reliable assay for the analysis of CsA, TAC, SIR and EVR in whole blood using U-HPLC-MS/MS.
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Imunossupressores , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodosRESUMO
Nasopharyngeal swabs (NPS) or washings have traditionally been used to diagnose respiratory tract infections. Reverse transcriptase PCR (RT-PCR) is widely used for rapid viral detection using samples from the upper respiratory tract. However, RT-PCR is rarely applied to sputum samples, mainly due to the viscosity of sputum. Thus, we assessed the detection rates of respiratory viruses from NPS, sputum samples, and combined NPS and sputum samples using multiplex RT-PCR (Allplex respiratory panels I, II, and III; Seegene, Seoul, South Korea). Paired NPS and sputum samples were collected from 219 patients admitted to the hospital with acute respiratory illnesses from October to December 2019. RT-PCR was performed on each sample for virus detection. Combined samples for virus detection were produced using remnant NPS and sputum samples with a positive virus signal. Respiratory viral nucleic acid was identified in 92 (42%) of 219 patients. Among the 92 viral detections, 61 (28%) were detected by both NPS and sputum samples. Twenty-four (11%) were sputum positive/NPS negative, and seven (3%) were sputum negative/NPS positive. For the combined NPS-sputum samples (n = 92), all paired samples positive in both specimens (n = 61) were also positive in the combined NPS-sputum sample. Twenty-seven (87%) of the 31 discordant paired samples were positive in the combined samples. Out of the total of 103 viruses identified before combining the samples, the detection rate of the combined samples was 94% (97/103), which was higher than the detection rates of sputum (88%; 91/103) and NPS (71%; 73/103). Because additional tests incur additional costs, our findings suggest that combining samples instead of testing separate samples using RT-PCR is likely the most cost-effective method of viral testing for patients with acute respiratory illnesses. IMPORTANCE This study reveals that RT-PCR utilizing sputum significantly increased the detection rate for respiratory viral nucleic acids among adult patients admitted to the hospital, compared to nasopharyngeal swabs (NPS). Notably, combined samples of sputum and NPS maintained the majority of the improved sputum detection rate with only a few positive signal losses from NPS samples. In order to detect respiratory viruses in adult patients with acute respiratory illness, it is important to choose the optimal respiratory samples. This study helped to improve our understanding of this process.
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Infecções Respiratórias , Vírus , Humanos , Adulto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escarro , Nasofaringe , Vírus/genética , Nariz , Infecções Respiratórias/diagnósticoRESUMO
We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.
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COVID-19 , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Feminino , Humanos , Imunidade Celular , Masculino , RNA Mensageiro , SARS-CoV-2/genética , Vacinação , Vacinas Sintéticas , Vacinas de mRNARESUMO
The CDC73/HRPT2 gene, a defect which causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, encodes CDC73/parafibromin. We aimed to investigate whether CDC73 would be a target for ubiquitin-proteasome degradation. We cloned full-length cDNAs encoding a family of 58 ubiquitin-specific deubiquitinating enzymes (DUBs), also known as ubiquitin-specific proteases (USPs). Use of the yeast two-hybrid system then enabled us to identify USP37 as interacting with CDC73. The biochemical interaction between the USP37 and CDC73 and their reciprocal binding domains were studied. Co-localization of CDC73 and USP37 was observed in cells. CDC73 was found to be polyubiquitinated, and polyubiquitination of CDC73 was prominent in mutants. CDC73 was deubiquitinated via K48-specific ubiquitin chains by USP37, but not by the catalytically inactive USP37C350S mutant. Observation of the binding between deletion mutants of CDC73 and USP37 revealed that the ß-catenin binding site of CDC73 and the ubiquitin-interacting motifs 2 and 3 (UIM2 and 3) of USP37 were responsible for the interaction between the two proteins. Moreover, these two enzymes co-existed within the nucleus of COS7 cells. We conclude that USP37 is a DUB for CDC73 and that the two proteins interact through specific domains, suggesting that USP37 is responsible for the stability of CDC73 in HPT-JT syndrome.
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Endopeptidases/metabolismo , Hiperparatireoidismo , Neoplasias Maxilomandibulares , Adenoma , Fibroma , Humanos , Hiperparatireoidismo/genética , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/patologia , Fatores de Transcrição , Proteínas Supressoras de Tumor/metabolismo , UbiquitinasRESUMO
BACKGROUND: This study aimed to evaluate whether our equation model developed from the Sysmex hematology analyzer can discriminate patients with Plasmodium vivax (P. vivax) infection from those with acute febrile illness (AFI) and healthy controls. Besides, we compared our model with the previously studied models. METHODS: A total of 312 blood samples were collected from the P. vivax, AFI, and healthy control groups. All samples were tested for routine complete blood count conducted by using a Sysmex XE-2100 or XE-5000 analyzer. We compared the reportable and research parameters generated from the Sysmex analyzer among the three groups. The selected parameters that showed a significant difference between the P. vivax and the other group were included in the logistic regression analysis to develop our model (N-OIpv model). Moreover, we analyzed the CBC data according to the previous models, such as the presence of abnormal blue coded events in the WBC/BASO scattergram called the observer-interpretation (OIpv) model, and the previous equation model (N-OD1pv model) developed by Campuzano-Zuluaga et al. Results: The N-OIpv model, which consists of three parameters, such as mean cell volume, plateletcrit, and Lymph-X, showed the best performance for detection of malaria (97.4% accuracy). Also, this model can increase the sensitivity by about 11.9% to 18.1% compared with the OIpv and N-OD1pv models, respectively. CONCLUSIONS: We concluded that the N-OIpv model using the Sysmex hematology analyzer is a useful diagnostic tool in the routine laboratory workup for malaria.
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Hematologia , Malária Vivax , Humanos , Contagem de Leucócitos , Malária Vivax/diagnóstico , Plasmodium vivax , República da CoreiaRESUMO
The new allele C*08:228 showed one nucleotide difference from C*08:01:01 in codon 36 (TTC -> TTG).
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Genes MHC Classe I , Antígenos HLA-C , Alelos , Sequência de Bases , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Humanos , República da Coreia , Análise de Sequência de DNARESUMO
BACKGROUND: Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia. METHODS: Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model. RESULTS: Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer's disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer's disease. CONCLUSION: More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.
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Doença de Alzheimer , Síndrome Metabólica , Adulto , Estudos de Coortes , Humanos , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
BACKGROUND: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers. METHODS: We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death. RESULTS: We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes. CONCLUSIONS: Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.
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COVID-19 is spreading rapidly around the world, and the number of related deaths is also increasing. In particular, diabetes patients have shown more severe conditions and a higher mortality rate related to COVID-19, and as no effective treatment or vaccine has been developed yet, efforts to prevent infection are very important. The most important steps to prevent infection are social distancing, wearing a mask and performing proper hand hygiene, and also telemedicine can be used to resolve the physical and psychological barriers to access to medical institutions for diabetes patients.
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COVID-19/epidemiologia , COVID-19/prevenção & controle , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Automonitorização da Glicemia/métodos , COVID-19/sangue , Diabetes Mellitus/sangue , Higiene das Mãos/métodos , Humanos , Pandemias/prevenção & controle , Distanciamento FísicoRESUMO
BACKGROUND: The measurement of glycemic control among patients with diabetes mellitus is important for predicting the risk of diabetic complications. Glycated hemoglobin (HbA1c) measurements have been used for long-term glycemic control in clinical practice. However, glycated albumin (GA) or glycated serum protein (GSP) is a more reliable indicator of glycemic control in the short term (2 - 4 weeks) and an alternative marker of HbA1c in clinical situations with changing red blood cell (RBC) lifespan. Here, we evaluated an analytical performance of the two enzymatic assays commercially available, Lucica GA-L and Autolab GA, for the determination of GA (%). METHODS: For each assay, the imprecision was evaluated based on CLSI EP05-A2. In total, serum samples of 283 subjects were simultaneously tested using the two enzymatic assays for method comparison according to CLSI EP09-A3. Some subjects collected the laboratory data for HbA1c. RESULTS: The GA (%) value of the Lucica GA-L assay showed highly reproducible results with within-run, between-run, and total coefficient of variations (CVs) below 2.4%. The Autolab GA assay also showed reliable results with within-run, between-run, and total CVs below 3.9%. The Lucica GA-L assay showed a very high correlation with the Autolab GA assay (r = 0.9993). However, at the median decision point (MDP, 14.3%), the estimated bias of the Autolab GA assay was 4.5%, exceeding the allowable bias (2.9%) accounting for the biological variation. For the correlation analysis between HbA1c and GA (%), the two assays demonstrated the same pattern, with no statistical differences between the two independent correlation coefficients. CONCLUSIONS: Both GA assays evaluated in this study showed good precision and excellent correlation, but the comparability at MDP did not meet the acceptance criteria.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Glicemia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Produtos Finais de Glicação Avançada , Humanos , Albumina Sérica , Albumina Sérica GlicadaRESUMO
Background Radiogenomic investigations for breast cancer provide an understanding of tumor heterogeneity and discover image phenotypes of genetic variation. However, there is little research on the correlations between US features of breast cancer and whole-transcriptome profiling. Purpose To explore US phenotypes reflecting genetic alteration relevant to breast cancer treatment and prognosis by comparing US images of tumor with their RNA sequencing results. Materials and Methods From January to October 2016, B-mode and vascular US images in 31 women (mean age, 49 years ± 9 [standard deviation]) with breast cancer were prospectively analyzed. B-mode features included size, shape, echo pattern, orientation, margin, and calcifications. Vascular features were evaluated by using microvascular US and contrast agent-enhanced US: vascular index, vessel morphologic features, distribution, penetrating vessels, enhancement degree, order, margin, internal homogeneity, and perfusion defect. RNA sequencing was conducted with total RNA obtained from a surgical specimen by using next-generation sequencing. US features were compared with gene expression profiles, and ingenuity pathway analysis was used to analyze gene networks, enriched functions, and canonical pathways associated with breast cancer. The P value for differential expression was extracted by using a parametric F test comparing nested linear models. Results Thirteen US features were associated with various patterns of 340 genes (P < .05). Nonparallel orientation at B-mode US was associated with upregulation of TFF1 (log twofold change [log2FC] = 4.0; P < .001), TFF3 (log2FC = 2.5; P < .001), AREG (log2FC = 2.6; P = .005), and AGR3 (log2FC = 2.6; P = .003). Complex vessel morphologic structure was associated with upregulation of FZD8 (log2FC = 2.0; P = .01) and downregulation of IGF1R (log2FC = -2.0; P = .006) and CRIPAK (log2FC = -2.4; P = .01). The top networks with regard to orientation or vessel morphologic structure were associated with cell cycle, death, and proliferation. Conclusion Compared with RNA sequencing, B-mode and vascular US features reflected genomic alterations associated with hormone receptor status, angiogenesis, or prognosis in breast cancer. © RSNA, 2020 Online supplemental material is available for this article.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Genômica , Análise de Sequência de RNA , Ultrassonografia de Intervenção , Adulto , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Genetic variations associated with major depressive disorder (MDD) may affect the structural aspects of neural networks mediated by the molecular pathways involved in neuronal survival and synaptic plasticity. However, few studies have applied a novel approach such as whole-exome sequencing (WES) analysis to investigate the genetic contribution to the neurostructural changes in MDD. METHODS: In the first part of the study, we investigated rare variants of selected genes from previous WES studies using a WES analysis in 184 patients with MDD and 82 healthy controls. In the second part of the study, we explored the association between the common genetic variants from the WES analysis and cortical thickness in 91 patients with MDD and 75 healthy controls. The gray-matter thickness of each cortical region was measured using FreeSurfer. RESULTS: We identified recurrent non-silent variants in 24 MDD-related genes including FASN, MYH13, UNC13D, LILRA1, CACNA1B, TRIO, HOMER3, and BCAR3, and observed eleven recurrently altered copy number alternations where a gain on 15q11.2 and losses on 7q34 and 15q11.1-q11.2 in MDD genomes. We also found that rs11592462 in CDH23, a calcium-dependent cell-adhesion molecule encoding gene, was significantly associated with thinning in the right anterior cingulate cortex. LIMITATION: The small sample size may lead our findings to be underpowered regarding rare variants. CONCLUSION: The present study identified that non-synonymous rare variants were significantly associated with risk of MDD and found that genetic contributions to the development of MDD may be mediated by alterations in cortical thickness of emotion-processing neural circuits.