Pub Date : 2022-06-21DOI: 10.1515/labmed-2022-0030
A. Bronkhorst, Vida Ungerer, Angela Oberhofer, S. Holdenrieder
Abstract Genomes of diverse origins are continuously shed into human body fluids in the form of fragmented cell-free DNA (cfDNA). These molecules maintain the genetic and epigenetic codes of their originating source, and often carry additional layers of unique information in newly discovered physico-chemical features. Characterization of cfDNA thus presents the opportunity to non-invasively reconstruct major parts of the host- and metagenome in silico. Data from a single specimen can be leveraged to detect a broad range of disease-specific signatures and has already enabled the development of many pioneering diagnostic tests. Moreover, data from serial sampling may allow unparalleled mapping of the scantily explored landscape of temporal genomic changes as it relates to various changes in different physiological and pathological states of individuals. In this review, we explore how this vast dimension of biological information accessible through cfDNA analysis is being tapped towards the development of increasingly powerful molecular assays and how it is shaping emerging technologies. We also discuss how this departure from traditional paradigms of snapshot genetic testing may pave the way for an onrush of new and exciting discoveries in human biology.
{"title":"The rising tide of cell-free DNA profiling: from snapshot to temporal genome analysis","authors":"A. Bronkhorst, Vida Ungerer, Angela Oberhofer, S. Holdenrieder","doi":"10.1515/labmed-2022-0030","DOIUrl":"https://doi.org/10.1515/labmed-2022-0030","url":null,"abstract":"Abstract Genomes of diverse origins are continuously shed into human body fluids in the form of fragmented cell-free DNA (cfDNA). These molecules maintain the genetic and epigenetic codes of their originating source, and often carry additional layers of unique information in newly discovered physico-chemical features. Characterization of cfDNA thus presents the opportunity to non-invasively reconstruct major parts of the host- and metagenome in silico. Data from a single specimen can be leveraged to detect a broad range of disease-specific signatures and has already enabled the development of many pioneering diagnostic tests. Moreover, data from serial sampling may allow unparalleled mapping of the scantily explored landscape of temporal genomic changes as it relates to various changes in different physiological and pathological states of individuals. In this review, we explore how this vast dimension of biological information accessible through cfDNA analysis is being tapped towards the development of increasingly powerful molecular assays and how it is shaping emerging technologies. We also discuss how this departure from traditional paradigms of snapshot genetic testing may pave the way for an onrush of new and exciting discoveries in human biology.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43388945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1515/labmed-2022-0027
E. Neuberger, P. Simon
Abstract Background Physical activity can have a strong impact on the concentration of several promising candidate biomarkers, including cell-free DNA (cfDNA). Content This narrative review describes the current understanding of how physical strain leads to increases of cfDNA and discusses how this interferes with attempts to standardize cfDNA analysis in clinical laboratory medicine. Summary In general, all cells of the human body can release DNA, whereas neutrophils are described as the major source releasing cfDNA under resting conditions. Event at low physical load, cfDNA is rapidly released by immune cells. We recently, identified neutrophils as the major cell-type contributing to cfDNA increases during acute exercise. Both, endurance and strength training can affect the signal-to-noise ratio of liquid biopsy (LB) analysis, affecting the clinical validity between minutes up to several days. Furthermore, we discuss why physical distress of various kinds in a perioperative cancer setting can improve or compromise signal-to-noise. Therefore, physiological events including, but not limited to, activation of blood cells can provoke pre-analytical challenges for ultra-sensitive detection of cfDNA in LB settings. Outlook We discuss why future attempts to standardize liquid biopsy may therefore profit from a deeper understanding of the physiological release mechanisms of cfDNA.
{"title":"Cell-free DNA in sports medicine: implications for clinical laboratory medicine","authors":"E. Neuberger, P. Simon","doi":"10.1515/labmed-2022-0027","DOIUrl":"https://doi.org/10.1515/labmed-2022-0027","url":null,"abstract":"Abstract Background Physical activity can have a strong impact on the concentration of several promising candidate biomarkers, including cell-free DNA (cfDNA). Content This narrative review describes the current understanding of how physical strain leads to increases of cfDNA and discusses how this interferes with attempts to standardize cfDNA analysis in clinical laboratory medicine. Summary In general, all cells of the human body can release DNA, whereas neutrophils are described as the major source releasing cfDNA under resting conditions. Event at low physical load, cfDNA is rapidly released by immune cells. We recently, identified neutrophils as the major cell-type contributing to cfDNA increases during acute exercise. Both, endurance and strength training can affect the signal-to-noise ratio of liquid biopsy (LB) analysis, affecting the clinical validity between minutes up to several days. Furthermore, we discuss why physical distress of various kinds in a perioperative cancer setting can improve or compromise signal-to-noise. Therefore, physiological events including, but not limited to, activation of blood cells can provoke pre-analytical challenges for ultra-sensitive detection of cfDNA in LB settings. Outlook We discuss why future attempts to standardize liquid biopsy may therefore profit from a deeper understanding of the physiological release mechanisms of cfDNA.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47113701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-27DOI: 10.1515/labmed-2022-0009
C. Keup, R. Kimmig, S. Kasimir-Bauer
Abstract The heterogeneity of each individual oncologic disease can be mirrored by molecular analysis of a simple blood draw in real time. Liquid biopsy testing has been shown useable for cancer detection, proof of minimal residual disease, therapy decision making and monitoring. However, an individual blood analyte does not present a comprehensive picture of the disease. It was recently shown that multi-modal/multi-parametric/multi-analyte liquid biopsy testing has the advantage of generating a high-resolution snapshot of the disease complexity. The different blood analytes such as circulating tumor cells, circulating immune cells, tumor-educated platelets, extracellular vesicles, cell-free DNA, cell-free RNA and circulating proteins complement each other and have additive value for clinical cancer management. We, here, like to review the studies leading to these promising conclusions and like to, at the end, mention that many challenges lie ahead before the translation into the clinic can be accomplished, including issues concerning clinical utility, method standardization, cost reimbursement and data management.
{"title":"Multimodality in liquid biopsy: does a combination uncover insights undetectable in individual blood analytes?","authors":"C. Keup, R. Kimmig, S. Kasimir-Bauer","doi":"10.1515/labmed-2022-0009","DOIUrl":"https://doi.org/10.1515/labmed-2022-0009","url":null,"abstract":"Abstract The heterogeneity of each individual oncologic disease can be mirrored by molecular analysis of a simple blood draw in real time. Liquid biopsy testing has been shown useable for cancer detection, proof of minimal residual disease, therapy decision making and monitoring. However, an individual blood analyte does not present a comprehensive picture of the disease. It was recently shown that multi-modal/multi-parametric/multi-analyte liquid biopsy testing has the advantage of generating a high-resolution snapshot of the disease complexity. The different blood analytes such as circulating tumor cells, circulating immune cells, tumor-educated platelets, extracellular vesicles, cell-free DNA, cell-free RNA and circulating proteins complement each other and have additive value for clinical cancer management. We, here, like to review the studies leading to these promising conclusions and like to, at the end, mention that many challenges lie ahead before the translation into the clinic can be accomplished, including issues concerning clinical utility, method standardization, cost reimbursement and data management.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49311686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-26DOI: 10.1515/labmed-2021-0189
Shan-Shan Li, Wen-hui Nan, Yue Yin, Li Qin, Mei Jia, Zhi-Hong Yue
Abstract Objectives To investigate the latest cutoff value of high-sensitivity cardiac troponin I for major adverse cardiac events (MACEs) during the perioperative period of coronary artery bypass grafting (CABG). Methods A total of 200 patients, into MACEs and non-MACEs groups according to the occurrence of MACEs over a 12 day postoperative period underwent a complete baseline history survey, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination during a preoperative cardiology consultation. Serum levels of hs-TnI, myohemoglobin, creatine kinase MB isoform (CK-MB), and B-type natriuretic peptide were assessed using a Beckman DXI800 automatic chemiluminescence immune analyzer. Results The 200 patients were classified into the MACEs (n=10) and non-MACEs (n=190) groups. Based on a receiver-operating characteristic analysis, the optimal 4–6 h postoperative hs-TnI, CK-MB, and MYO joint cut-off levels for predicting perioperative MACEs were 2,622.3 pg/mL, 17.9 ng/mL, and 190.2 ng/mL, respectively. The AUC was 0.779 (95% confidence interval: 0.622–0.937; p<0.05) with a sensitivity of 80.0% and a specificity of 74.0%. When the hs-TnI, CK-MB, and MYO levels exceeded the joint cut-off levels, the incidence of MACEs was significantly increased during the perioperative period (Log rank p<0.05). Cox regression analysis showed that dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG (p<0.05). Conclusion An hs-TnI level of 2,622.3 pg/mL, CK-MB level of 17.9 ng/mL, and MYO level of 190.2 ng/mL were the cutoff values for predicting MACEs. Dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG.
{"title":"The latest cutoff value of high-sensitivity cardiac troponin I (access hs-TnI) for major adverse cardiac events during the perioperative period of coronary artery bypass grafting: a retrospective study from a single heart center","authors":"Shan-Shan Li, Wen-hui Nan, Yue Yin, Li Qin, Mei Jia, Zhi-Hong Yue","doi":"10.1515/labmed-2021-0189","DOIUrl":"https://doi.org/10.1515/labmed-2021-0189","url":null,"abstract":"Abstract Objectives To investigate the latest cutoff value of high-sensitivity cardiac troponin I for major adverse cardiac events (MACEs) during the perioperative period of coronary artery bypass grafting (CABG). Methods A total of 200 patients, into MACEs and non-MACEs groups according to the occurrence of MACEs over a 12 day postoperative period underwent a complete baseline history survey, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination during a preoperative cardiology consultation. Serum levels of hs-TnI, myohemoglobin, creatine kinase MB isoform (CK-MB), and B-type natriuretic peptide were assessed using a Beckman DXI800 automatic chemiluminescence immune analyzer. Results The 200 patients were classified into the MACEs (n=10) and non-MACEs (n=190) groups. Based on a receiver-operating characteristic analysis, the optimal 4–6 h postoperative hs-TnI, CK-MB, and MYO joint cut-off levels for predicting perioperative MACEs were 2,622.3 pg/mL, 17.9 ng/mL, and 190.2 ng/mL, respectively. The AUC was 0.779 (95% confidence interval: 0.622–0.937; p<0.05) with a sensitivity of 80.0% and a specificity of 74.0%. When the hs-TnI, CK-MB, and MYO levels exceeded the joint cut-off levels, the incidence of MACEs was significantly increased during the perioperative period (Log rank p<0.05). Cox regression analysis showed that dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG (p<0.05). Conclusion An hs-TnI level of 2,622.3 pg/mL, CK-MB level of 17.9 ng/mL, and MYO level of 190.2 ng/mL were the cutoff values for predicting MACEs. Dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47858622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives Third dose of SARS-CoV-2 vaccination was started from December 1, 2021 in Japan. However, data on the precise analysis of the side effects after third vaccination, remain scarce. Here, we examined the side effects and the levels of SARS-CoV-2 IgG antibody in healthy volunteers who underwent BNT162b2 vaccination. Methods Forty-one healthy volunteers were assessed for the side effects of the vaccination for the third dose, and samples were used for the measurement of SARS-CoV-2 IgG antibody with chemiluminescent assays against the Receptor Binding Domain (RBD) of the virus. Results We analyzed the humoral responses and found that the IgG levels showed clear declining trends with age. Commonly reported side effects in the participants after the third dose were similar to those in second dose, such as, generalized weakness/fatigue (65.9%), headache (58.5%), and sore arm/pain (87.8%). The frequency of the fever was slightly less (39.0%), compared to the second dose (57.5%), but localized symptoms, such as itching (14.6%) and lymphadenopathy (14.6%) were not negligible, which were not seen at the second dose. The number of side effects were tended to be decreased with age. Conclusions The production of IgG after the third doses of BNT162b2 vaccination decreases age-dependently. The number of side effects were tended to be decreased with age. The high frequencies of generalized weakness/fatigue, fever, and sore arm/pain were not negligible, after the third dose.
{"title":"Assessment of antibody titer and side effects after third doses of COVID-19 mRNA vaccination in healthy volunteers","authors":"Rikei Kozakai, Susumu Suzuki, Kana Fukami, Kuniko Hoshi, Yoshihiko Izumi, Shin-ichiro Takahashi","doi":"10.1515/labmed-2022-0057","DOIUrl":"https://doi.org/10.1515/labmed-2022-0057","url":null,"abstract":"Abstract Objectives Third dose of SARS-CoV-2 vaccination was started from December 1, 2021 in Japan. However, data on the precise analysis of the side effects after third vaccination, remain scarce. Here, we examined the side effects and the levels of SARS-CoV-2 IgG antibody in healthy volunteers who underwent BNT162b2 vaccination. Methods Forty-one healthy volunteers were assessed for the side effects of the vaccination for the third dose, and samples were used for the measurement of SARS-CoV-2 IgG antibody with chemiluminescent assays against the Receptor Binding Domain (RBD) of the virus. Results We analyzed the humoral responses and found that the IgG levels showed clear declining trends with age. Commonly reported side effects in the participants after the third dose were similar to those in second dose, such as, generalized weakness/fatigue (65.9%), headache (58.5%), and sore arm/pain (87.8%). The frequency of the fever was slightly less (39.0%), compared to the second dose (57.5%), but localized symptoms, such as itching (14.6%) and lymphadenopathy (14.6%) were not negligible, which were not seen at the second dose. The number of side effects were tended to be decreased with age. Conclusions The production of IgG after the third doses of BNT162b2 vaccination decreases age-dependently. The number of side effects were tended to be decreased with age. The high frequencies of generalized weakness/fatigue, fever, and sore arm/pain were not negligible, after the third dose.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46421815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-25DOI: 10.1515/labmed-2021-0181
M. Atkins, P. McGuire, Bhirundra Balgobin, Sophie Williams, F. Ceesay, Neville Desouza, P. Patel, D. Taylor
Abstract Objectives Patients treated with clozapine are required to have regular venous blood samples taken to measure white blood cell (WBC) and neutrophil counts to reduce the risk of agranulocytosis. The need for regular venous blood sampling can deter patients and clinicians from treatment with clozapine. Finger prick sampling offers patients a simpler and less invasive technique that is likely to be more acceptable. We undertook to evaluate a novel point of care testing (POCT) device which measures WBC and neutrophil counts using a small volume of capillary blood from a finger prick sample. Methods A total of 215 patients who were being treated with clozapine and were having a venous blood sample taken for haematological monitoring also provided a fingerprick capillary blood sample. The capillary and venous samples were tested using the Sight OLO® POCT analyser, and the venous sample also tested using a standard laboratory method. Results For both the WBC and the neutrophil counts, there was a strong correlation between the results from the standard laboratory venous method and the POCT assay (R=0.94 and 0.95, respectively for capillary blood samples, and R=0.98 for both WBC and neutrophil counts for venous blood samples). Compared with the standard laboratory venous blood method, mean biases were −1.0×109/L for WBC and −0.5×109/L for neutrophils for the capillary blood POCT method, and −0.4×109/L for WBC and −0.4×109/L for neutrophils for the venous blood POCT method. Overall, 6 of 215 (2.8%) of patients had levels below clozapine monitoring thresholds (WBC <3.5×109/L and Neutrophils <1.5×109/L) by capillary blood, and 5 (2.3%) by venous blood by POCT. Of these, 2 had sub-threshold counts on the standard laboratory method. Conclusions The POCT analyser provided results for both WBC and neutrophil counts that were comparable with those from a standard venous blood laboratory method. Using POCT devices may make haematological monitoring easier in patients being treated with clozapine, and thereby increase the use of clozapine in the treatment of schizophrenia.
{"title":"Point-of-care haematological monitoring during treatment with clozapine","authors":"M. Atkins, P. McGuire, Bhirundra Balgobin, Sophie Williams, F. Ceesay, Neville Desouza, P. Patel, D. Taylor","doi":"10.1515/labmed-2021-0181","DOIUrl":"https://doi.org/10.1515/labmed-2021-0181","url":null,"abstract":"Abstract Objectives Patients treated with clozapine are required to have regular venous blood samples taken to measure white blood cell (WBC) and neutrophil counts to reduce the risk of agranulocytosis. The need for regular venous blood sampling can deter patients and clinicians from treatment with clozapine. Finger prick sampling offers patients a simpler and less invasive technique that is likely to be more acceptable. We undertook to evaluate a novel point of care testing (POCT) device which measures WBC and neutrophil counts using a small volume of capillary blood from a finger prick sample. Methods A total of 215 patients who were being treated with clozapine and were having a venous blood sample taken for haematological monitoring also provided a fingerprick capillary blood sample. The capillary and venous samples were tested using the Sight OLO® POCT analyser, and the venous sample also tested using a standard laboratory method. Results For both the WBC and the neutrophil counts, there was a strong correlation between the results from the standard laboratory venous method and the POCT assay (R=0.94 and 0.95, respectively for capillary blood samples, and R=0.98 for both WBC and neutrophil counts for venous blood samples). Compared with the standard laboratory venous blood method, mean biases were −1.0×109/L for WBC and −0.5×109/L for neutrophils for the capillary blood POCT method, and −0.4×109/L for WBC and −0.4×109/L for neutrophils for the venous blood POCT method. Overall, 6 of 215 (2.8%) of patients had levels below clozapine monitoring thresholds (WBC <3.5×109/L and Neutrophils <1.5×109/L) by capillary blood, and 5 (2.3%) by venous blood by POCT. Of these, 2 had sub-threshold counts on the standard laboratory method. Conclusions The POCT analyser provided results for both WBC and neutrophil counts that were comparable with those from a standard venous blood laboratory method. Using POCT devices may make haematological monitoring easier in patients being treated with clozapine, and thereby increase the use of clozapine in the treatment of schizophrenia.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49599905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-24DOI: 10.1515/labmed-2022-0054
T. Niedrist, S. Pailer, Renate Jahrbacher, H. Gruber, M. Herrmann, W. Renner
Abstract Objectives Exercise induces telomerase activity and regulates shelterin expression. These effects are believed to preserve telomeres. However, the impact of exercise intensity on telomerase and shelterins has not been studied systematically. This pilot study investigated the kinetics of leukocyte telomerase activity (LTA) and the expression of telomere-related genes in response to exercise at different intensities. Methods Seven healthy women completed three exercise sessions at low, moderate and high intensity on a stationary bicycle ergometer. Blood was collected before, 24 and 48 h after each session. LTA, leukocyte telomere length (LTL), expression of telomerase reverse transcriptase (TERT), telomeric repeat binding factor 1 (TERF-1), 2 (TERF-2) and the serum concentration of telomeric repeat binding factor-1 protein (TRF-1) were determined. Results LTA increased 24 h after moderate and high intensity exercise and returned to baseline levels after 48 h. TERF-2 expression showed a tendency to decrease 24 h after high-intensity exercise. Other markers (TERT, TERF-1, LTL, TRF-1) were not affected by any intensity. Conclusions From the present results it can be concluded that the telomeric effects of exercise are short-lived and depend on the intensity level. Future studies should confirm these results in a larger cohort focusing on the first 24 h post-exercise.
目的运动诱导端粒酶活性，调节庇护蛋白的表达。这些作用被认为可以保护端粒。然而，运动强度对端粒酶和庇护蛋白的影响尚未有系统的研究。本初步研究探讨了不同强度运动对白细胞端粒酶活性(LTA)和端粒相关基因表达的影响。方法7名健康女性在固定式自行车测力仪上完成低、中、高强度3组运动。每次治疗前、24小时和48小时采集血液。检测LTA、白细胞端粒长度(LTL)、端粒酶逆转录酶(TERT)、端粒重复结合因子1 (TERF-1)、2 (TERF-2)表达及血清端粒重复结合因子-1蛋白(TRF-1)浓度。结果中高强度运动后24 h LTA升高，48 h后恢复至基线水平，高强度运动后24 h TERF-2表达呈下降趋势。其他标志物(TERT, TERF-1, LTL, TRF-1)不受任何强度的影响。结论运动对端粒的影响是短暂的，且与运动强度有关。未来的研究应该在更大的队列中确认这些结果，重点关注运动后的第一个24小时。
{"title":"Intensity-dependent stimulation of leukocyte telomerase activity by endurance exercise – a pilot study","authors":"T. Niedrist, S. Pailer, Renate Jahrbacher, H. Gruber, M. Herrmann, W. Renner","doi":"10.1515/labmed-2022-0054","DOIUrl":"https://doi.org/10.1515/labmed-2022-0054","url":null,"abstract":"Abstract Objectives Exercise induces telomerase activity and regulates shelterin expression. These effects are believed to preserve telomeres. However, the impact of exercise intensity on telomerase and shelterins has not been studied systematically. This pilot study investigated the kinetics of leukocyte telomerase activity (LTA) and the expression of telomere-related genes in response to exercise at different intensities. Methods Seven healthy women completed three exercise sessions at low, moderate and high intensity on a stationary bicycle ergometer. Blood was collected before, 24 and 48 h after each session. LTA, leukocyte telomere length (LTL), expression of telomerase reverse transcriptase (TERT), telomeric repeat binding factor 1 (TERF-1), 2 (TERF-2) and the serum concentration of telomeric repeat binding factor-1 protein (TRF-1) were determined. Results LTA increased 24 h after moderate and high intensity exercise and returned to baseline levels after 48 h. TERF-2 expression showed a tendency to decrease 24 h after high-intensity exercise. Other markers (TERT, TERF-1, LTL, TRF-1) were not affected by any intensity. Conclusions From the present results it can be concluded that the telomeric effects of exercise are short-lived and depend on the intensity level. Future studies should confirm these results in a larger cohort focusing on the first 24 h post-exercise.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66983993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-20DOI: 10.1515/labmed-2021-0171
Qian Wang, Jin Du, Lingcong Chen, Yuying Du, W. Luo
Abstract Objectives Not many reports have covered large-scale point of care testing (POCT) blood glucose comparisons, and many interfering factors affect detection. This study aims to verify the performance of POCT blood glucose meters and discusses the factors that interfere with detection. Methods Accuracy and precision verification in five glucose concentration groups-high 1 (H1), High 2 (H2), medium 1 (M1), medium 2 (M2), and low (L); comparison of different test methods and specimens; and also the influence of iodophor was investigated in a dilution experiment. Results A total of 58 out of 64 Accu-Chek Inform II POCT blood glucose meters (ACI II) qualified for testing. A proportional significant difference in the relative bias was observed with the POCT instruments in the intermediate and high glucose concentration groups (H=15.364, p=0.02). There were significant differences among the five groups with compliance rates (χ2=21.03, p=0.00); Group L showed higher values than groups H1 and H2. The precision verification met the requirements issued by the Consensus. Significant differences were found between the three detection methods. The measurement of the Glucose Oxidase Method (Cobas B 123) was lower than that of the HITACHI Plasma Hexokinase Method and the Glucose Dehydrogenase Method on the ACI II (p=0.005 and 0.003) in the preliminary study. No differences were seen among the three types of specimens (p>0.05). The glucose results were incorrect in the presence of iodophor interference. Conclusions The ACI II and Cobas B123 (with a slightly negative bias) provide sufficiently accurate measurements, and all types of blood specimens can be applied. Iodophor, a disinfectant, interferes with glucose measurement.
摘要目的没有多少报道涉及大规模的护理点检测（POCT）血糖比较，并且许多干扰因素影响检测。本研究旨在验证POCT血糖仪的性能，并讨论干扰检测的因素。方法对高1（H1）、高2（H2）、中1（M1）、中2（M2）和低（L）五个葡萄糖浓度组的准确度和精密度进行验证；不同试验方法和试样的比较；并在稀释实验中研究了碘伏的影响。结果64台Accu-Chek Inform II POCT血糖仪（ACI II）中，共有58台合格。在中、高糖浓度组中，POCT仪器的相对偏倚存在比例显著差异（H=15.364，p=0.02）。五组之间的依从性差异有显著性（χ2=21.03，p=0.00）；L组的数值高于H1和H2组。精度验证符合《共识》提出的要求。三种检测方法之间存在显著差异。在初步研究中，葡萄糖氧化酶法（Cobas B123）的测量值低于日立血浆己糖激酶法和葡萄糖脱氢酶法对ACI II的测量值（p=0.005和0.003）。三种类型的标本之间没有差异（p>0.05）。在存在碘伏干扰的情况下，葡萄糖结果是不正确的。结论ACI II和Cobas B123（有轻微的负偏差）提供了足够准确的测量，并且可以应用所有类型的血液样本。碘伏是一种消毒剂，会干扰葡萄糖的测量。
{"title":"Comparison of POCT glucose meters and analysis of the interference factor","authors":"Qian Wang, Jin Du, Lingcong Chen, Yuying Du, W. Luo","doi":"10.1515/labmed-2021-0171","DOIUrl":"https://doi.org/10.1515/labmed-2021-0171","url":null,"abstract":"Abstract Objectives Not many reports have covered large-scale point of care testing (POCT) blood glucose comparisons, and many interfering factors affect detection. This study aims to verify the performance of POCT blood glucose meters and discusses the factors that interfere with detection. Methods Accuracy and precision verification in five glucose concentration groups-high 1 (H1), High 2 (H2), medium 1 (M1), medium 2 (M2), and low (L); comparison of different test methods and specimens; and also the influence of iodophor was investigated in a dilution experiment. Results A total of 58 out of 64 Accu-Chek Inform II POCT blood glucose meters (ACI II) qualified for testing. A proportional significant difference in the relative bias was observed with the POCT instruments in the intermediate and high glucose concentration groups (H=15.364, p=0.02). There were significant differences among the five groups with compliance rates (χ2=21.03, p=0.00); Group L showed higher values than groups H1 and H2. The precision verification met the requirements issued by the Consensus. Significant differences were found between the three detection methods. The measurement of the Glucose Oxidase Method (Cobas B 123) was lower than that of the HITACHI Plasma Hexokinase Method and the Glucose Dehydrogenase Method on the ACI II (p=0.005 and 0.003) in the preliminary study. No differences were seen among the three types of specimens (p>0.05). The glucose results were incorrect in the presence of iodophor interference. Conclusions The ACI II and Cobas B123 (with a slightly negative bias) provide sufficiently accurate measurements, and all types of blood specimens can be applied. Iodophor, a disinfectant, interferes with glucose measurement.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45602940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Innate immune receptors detect nucleic acids, such as viruses, and initiate an immune response by secreting interferon (IFN) and regulating IFN-stimulated genes (ISG). in autoimmune conditions, expression of ISGs funded, show the activation of nucleic acid sensory pathways. However, the nucleus-localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. to sustain immune hemostasis, these innate immune sensors develop different strategies for discriminating between self or non-self-nucleic acid. We reviewed all the sensors involved in the innate immune system in the present study. A better understanding of these sensors can lead to new treatments for infections, cancer, and autoimmune and inflammatory disorders.
{"title":"Innate immune sensors for detecting nucleic acids during infection","authors":"Zohreh-Al-Sadat Ghoreshi, Mohsen Nakhaee, M. Samie, Mohsen Sharif Zak, Nasir Arefinia","doi":"10.1515/labmed-2021-0173","DOIUrl":"https://doi.org/10.1515/labmed-2021-0173","url":null,"abstract":"Abstract Innate immune receptors detect nucleic acids, such as viruses, and initiate an immune response by secreting interferon (IFN) and regulating IFN-stimulated genes (ISG). in autoimmune conditions, expression of ISGs funded, show the activation of nucleic acid sensory pathways. However, the nucleus-localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. to sustain immune hemostasis, these innate immune sensors develop different strategies for discriminating between self or non-self-nucleic acid. We reviewed all the sensors involved in the innate immune system in the present study. A better understanding of these sensors can lead to new treatments for infections, cancer, and autoimmune and inflammatory disorders.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45797732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As of the end of January 2022, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 351 million individuals worldwide and caused more than 5.6 million deaths. In the year of 2021, numerous groups, including us, have been reported about humoral responses and side effects after two doses of BNT162b2 vaccinations [1–4]. Subsequently, third dose of SARS-CoV-2 vaccination have just started from December 1, 2021 in Japan. Currently, several groups have started to report humoral responses after third doses of vaccinations, indicating an efficacy of a third dose [5–7]. However, further studies are warranted to verify these findings. Our group have recently reported antibody titers and side effects after two doses of BNT162b2 vaccination [4], and subsequent study of antibody decline 6 months after first vaccination [8]. In the current study, we examined levels of SARS-CoV-2 antibodies among healthy volunteers at Tohoku Medical and Pharmaceutical University Hospital, before and after vaccination with the Pfizer/BioNTechBNT162b2mRNAvaccine for the third time. Antibody titers were evaluated using a newly established, highly sensitive, fully automated chemiluminescent enzyme immunoassay (CLEIA) designed to specifically detect IgG and IgM against the SARS-CoV-2 spike protein receptor-binding domain (RBD) as described [4, 8]. Of 41 volunteers who received two doses of BNT162b2 at our hospital, all completed 9 months of follow-up after the first dose. At the time of writing, all 41 participants have completed this period, and none experienced SARS-CoV-2 infections prior to third vaccination or during post-third vaccination follow-up. Serum samples were obtained on average 279.5 days (SD 5.5 days) after the first dose of BNT162b2 (Figure 1A). 264.4 days (SD 5.8 days) after the first dose of BNT162b2, mean anti-RBD IgM was 0.3 C.O.I. (SD 0.3), which was baseline level and equal to day 0 and 180 days after first vaccination [4] (Figure 1B). Additionally, mean anti-RBD IgG antibodies was 17.3 AU/mL (SD 13.1) at 264.4 days after vaccination (Figure 1C),whichwas 6.36%of the antibody after the second dose. At 15 days after the third vaccination (day 279.5), anti-SARS-CoV-2 IgM was modestly but significantly increased (average, 1.7 C.O.I. [SD 3.9], 5.7-fold increase) (Figure 1B), while anti-SARS-CoV-2 IgG was more markedly increased (average, 702.9 AU/mL [SD 402.9], 40.6-fold increase) (Figure 1C). Quite recently, the antibody titers before and after a third dose of the SARS-Cov-2 BNT162b2 vaccine in adults agedmore that 60 years (n=97) have been published [7]. In their study, median IgG titer was increased from 440 to 25,468 (AU/mL), with no major adverse events. From the retrospective cohort study, Saciuk et al. [9], concluded that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago. Barda et al. [10], recently demonstrated that using data from mandatory health-care coverage for over half of
{"title":"Assessment of antibody titer after third doses of COVID-19 mRNA vaccination in healthy volunteers","authors":"Rikei Kozakai, Kuniko Hoshi, Yoshihiko Izumi, Shinichirou Takahashi","doi":"10.1515/labmed-2022-0008","DOIUrl":"https://doi.org/10.1515/labmed-2022-0008","url":null,"abstract":"As of the end of January 2022, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 351 million individuals worldwide and caused more than 5.6 million deaths. In the year of 2021, numerous groups, including us, have been reported about humoral responses and side effects after two doses of BNT162b2 vaccinations [1–4]. Subsequently, third dose of SARS-CoV-2 vaccination have just started from December 1, 2021 in Japan. Currently, several groups have started to report humoral responses after third doses of vaccinations, indicating an efficacy of a third dose [5–7]. However, further studies are warranted to verify these findings. Our group have recently reported antibody titers and side effects after two doses of BNT162b2 vaccination [4], and subsequent study of antibody decline 6 months after first vaccination [8]. In the current study, we examined levels of SARS-CoV-2 antibodies among healthy volunteers at Tohoku Medical and Pharmaceutical University Hospital, before and after vaccination with the Pfizer/BioNTechBNT162b2mRNAvaccine for the third time. Antibody titers were evaluated using a newly established, highly sensitive, fully automated chemiluminescent enzyme immunoassay (CLEIA) designed to specifically detect IgG and IgM against the SARS-CoV-2 spike protein receptor-binding domain (RBD) as described [4, 8]. Of 41 volunteers who received two doses of BNT162b2 at our hospital, all completed 9 months of follow-up after the first dose. At the time of writing, all 41 participants have completed this period, and none experienced SARS-CoV-2 infections prior to third vaccination or during post-third vaccination follow-up. Serum samples were obtained on average 279.5 days (SD 5.5 days) after the first dose of BNT162b2 (Figure 1A). 264.4 days (SD 5.8 days) after the first dose of BNT162b2, mean anti-RBD IgM was 0.3 C.O.I. (SD 0.3), which was baseline level and equal to day 0 and 180 days after first vaccination [4] (Figure 1B). Additionally, mean anti-RBD IgG antibodies was 17.3 AU/mL (SD 13.1) at 264.4 days after vaccination (Figure 1C),whichwas 6.36%of the antibody after the second dose. At 15 days after the third vaccination (day 279.5), anti-SARS-CoV-2 IgM was modestly but significantly increased (average, 1.7 C.O.I. [SD 3.9], 5.7-fold increase) (Figure 1B), while anti-SARS-CoV-2 IgG was more markedly increased (average, 702.9 AU/mL [SD 402.9], 40.6-fold increase) (Figure 1C). Quite recently, the antibody titers before and after a third dose of the SARS-Cov-2 BNT162b2 vaccine in adults agedmore that 60 years (n=97) have been published [7]. In their study, median IgG titer was increased from 440 to 25,468 (AU/mL), with no major adverse events. From the retrospective cohort study, Saciuk et al. [9], concluded that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago. Barda et al. [10], recently demonstrated that using data from mandatory health-care coverage for over half of","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66983663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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