20260 research outputs found
Sort by
Impact of activity limitations due to fear of falling on changes in frailty in Korean older adults: a longitudinal study
No full textThis study investigated the frailty change patterns among Korean older adults during 2006–2020 and the effect of activity limitations induced by the fear of falling (FOF) on these patterns. We employed a descriptive longitudinal design utilizing data from Waves 1 to 8 of the Korean Longitudinal Study of Aging. The exclusion criteria were a baseline age < 65 years, frailty index (FI) captured only at baseline, and death or unknown survival status. Multilevel modeling, combining regression equations at two levels, was used to examine the effect of activity limitations due to FOF on frailty, adjusting for other confounding factors. An increase in FI (1.97; p <.001) was demonstrated in participants who had experienced falls versus those who had not in the past 2 years. Notably, those facing activity limitations due to FOF exhibited a more significant increase in FI (4.62; p <.001) compared with those without; frailty progression intensified over time in the former (0.54, p <.001). Activity limitations due to FOF had a more pronounced impact on frailty than falls; moreover, these activity limitations accelerated the progression of frailty. Healthcare providers must prioritize addressing FOF by employing both physical and psychological interventions to mitigate activity limitations and ultimately decelerate frailty
The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial
Get PDFBackground: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. Methods: Using a modified Dixon’s up-and-down allocation approach, we sequentially enrolled male and female patients aged 19–60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer’s Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. Results: We included 22 male and 22 female patients. Based on Dixon’s up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18–0.20) mg/kg in the male group and 0.29 (0.29–0.30) mg/kg in the female group. Conclusions: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. Trial registration: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022)
Comparison between low-volume local anesthetic with intravenous dexamethasone and conventional volume without dexamethasone for superior trunk block after arthroscopic shoulder surgery: a randomized controlled non-inferiority trial
No full textIntroduction This study aimed to investigate whether low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while maintaining the analgesic duration compared with conventional volume of local anesthetic without intravenous dexamethasone when performing ultrasound-guided superior trunk block in patients undergoing arthroscopic shoulder surgery. Methods Eighty-four adult patients undergoing arthroscopic shoulder surgery under general anesthesia were randomly assigned to receive ultrasound-guided superior trunk block using 7 mL of 0.5% ropivacaine with 0.15 mg/kg of intravenous dexamethasone (treatment group), or 15 mL of 0.5% ropivacaine with intravenous normal saline (control group). The co-primary outcomes were (1) the duration of analgesia (time between block completion and onset of surgical pain with a Numeric Rating Scale pain score of 4 or higher), which was compared against a non-inferiority margin of 3 hours, and (2) the incidence of diaphragmatic paresis evaluated using M-mode ultrasonography in the post-anesthesia care unit. Results The mean duration of analgesia was 12.4 (6.8) and 11.2 (4.6) hours in the treatment and control groups, respectively (mean difference: −1.2 hours; 95% CI −3.8 to 1.3]; p for non-inferiority<0.001), meeting the non-inferiority criteria. The incidence of diaphragmatic paresis was 45.2% and 85.4% in the treatment and control groups, respectively (relative risk: 0.53; 97.5% CI 0.35 to 0.80; p<0.001). Conclusions Superior trunk block using low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while providing non-inferior analgesic duration compared with the conventional volume of local anesthetic in patients undergoing arthroscopic shoulder surgery
Bevacizumab Alone Versus Bevacizumab Plus Irinotecan in Patients With Recurrent Glioblastoma: A Nationwide Population-Based Study
Get PDFBackground: For treating recurrent glioblastoma, for which there is no established treatment, the antiangiogenic antibody, bevacizumab, is used alone or with irinotecan. This study was aimed at comparing the survival of patients with recurrent glioblastoma receiving bevacizumab monotherapy and those receiving bevacizumab plus irinotecan combination therapy (B+I) by using a nationwide population-based dataset. Methods: Patients matching the International Classification of Diseases code C71.x were screened from the Health Insurance Review and Assessment Service database. From January 2008 to November 2021, patients who underwent surgery or biopsy and subsequent standard concurrent chemoradiation with temozolomide were included. Among them, those who received bevacizumab monotherapy or B+I were selected. Demographic characteristics, inpatient stay, prescription frequency, survival outcomes, and steroid prescription duration were compared between these two groups. Results: Eight hundred and forty-six patients who underwent surgery or biopsy and received concurrent chemoradiotherapy with temozolomide were included. Of these, 450 and 396 received bevacizumab monotherapy and B+I, respectively. The corresponding median overall survival from the initial surgery was 22.60 months (95% confidence interval [CI], 20.50–24.21) and 20.44 months (95% CI, 18.55–22.60; P = 0.508, log-rank test). The B+I group had significantly more bevacizumab prescriptions (median 5 times; BEV group: median 3 times). Cox analysis, based on the postsurgery period, revealed that male sex (hazard ratio [HR], 1.28; P = 0.002), older age (HR, 1.01; P = 0.042), and undergoing biopsy instead of surgery (HR, 1.79; P < 0.0001) were significantly associated with decreased survival. Fewer radiotherapy cycles correlated with improved survival outcomes (HR, 0.63; P = 0.001). Cox analysis, conducted from the start of chemotherapy including bevacizumab, showed that male sex was the only variable significantly associated with decreased survival (HR, 1.18; P = 0.044). Conclusion: We found no significant difference in overall survival between the bevacizumab monotherapy and B+I groups. Considering the additional potential toxicity associated with irinotecan, bevacizumab monotherapy could be a suitable treatment option for treating recurrent glioblastoma
HRP2 유전자 결실 돌연변이 열대열말라리아 항원 검출을 위한 신속진단키트의 개발 및 성능평가
No full textMasterⅠ. 서론 1
1. 말라리아(Malaria) 1
2. 말라리아 감염 경로와 생활사 (Life cycle and mode of infection) 3
3. 히스티딘 풍부 단백질 2(Histidine rich protein 2, HRP 2) 5
4. 본 연구의 목적 7
Ⅱ. 재료 및 방법 8
1. 신속진단키트의 연구 방법 및 이론 8
2. 말라리아 신속진단키트 개발 10
1) 항체 쌍 선별시험 (Antibody pairing test) 10
① 항체와 검체의 준비 10
② 나이트로셀룰로스 멤브레인 준비 11
③ 골드 나노파티클 콜로이드 용액 준비 11
④ 항체 쌍 선별시험 방법 12
2) 검출 항체 최적화 (Detector Ab optimization) 14
① 최적신호 결정시험(Peak signal test) 14
② 검출 항체-골드 축합 (Gold conjugation) 16
3) 포획 항체 최적화 (Capture Ab optimization) 17
4) 검체 전개액 최적화 (Assay buffer optimization) 19
3. 말라리아 신속진단키트 성능평가 20
1) 성능평가 개요 (Overview of performance evaluation) 20
2) 분석적 민감도(Analytical sensitivity) 22
① 최소 검출 한계 (Limit of Detection, LoD) 22
② 고역가 후크 효과(High-dose hook effect) 23
③ HRP2 결실 검체 시험 (HRP2 deleted panel test) 24
④ 검출 범위 (Measuring range) 24
3) 분석적 특이도(Analytical specificity) 25
① 간섭 반응 시험(Interference test) 25
② 교차 반응 시험(Cross-reactivity test) 26
4) 가속노화 안정성(Accelerated aging stability) 28
Ⅲ. 결과 29
1. 말라리아 신속진단키트 개발 29
1) 항체 쌍 선별시험 결과(Antibody pairing test result) 29
① HRP2 항체 쌍 선별시험(HRP2 antibody pairing test) 29
② LDH 항체 쌍 선별시험(LDH antibody pairing test) 31
2) 검출 항체 최적화 결과(Detector Ab optimization result) 33
3) 포획 항체 최적화 결과(Capture Ab optimization result) 35
4) 검체 전개액 최적화 결과(Assay buffer optimization result) 37
2. 말라리아 신속진단키트 성능평가 38
1) 분석적 민감도 시험 결과(Analytical sensitivity test result) 38
① 최소 검출 한계(Limit of Detection, LoD) 38
② 고역가 후크 효과(High-dose hook effect) 40
③ HRP2 결실 검체 시험(HRP2 deleted panel test) 41
2) 분석적 특이도 시험 결과(Analytical specificity test result) 42
① 간섭 반응 시험(Interference test) 44
② 교차 반응 시험(Cross-reactivity test) 45
3) 가속노화 안정성 시험 결과(Accelerated aging stability test result) 48
Ⅳ. 고 찰 50
Ⅴ. 결 론 54
참 고 문 헌 5
Functional insights into LINC01446 and its implications for hepatocellular carcinoma diagnosis and metastasis
No full textMasterⅠ. INTRODUCTION. 1
Ⅱ. MATERIALS AND METHODS. 3
1. Public dataset resources. 3
2. Patient sample collection and clinical terminology definitions. 3
3. Cell culture and transfection. 8
4. Isolation of RNA from pairs of HCC tissues and cell lines. 9
5. Prediction of LINC01446 derived in EVs. 10
6. Separation of blood samples. 10
7. Isolation of RNA from blood. 10
8. Identification of small EVs. 11
9. Quantitative real time-polymerase chain reaction (qRT-PCR). 11
10. Western blotting. 12
11. Immunofluorescence. 14
12. Inhibition of endocytosis. 14
13. Cell growth and viability. 14
14. Wound healing assay. 15
15. Transwell assay. 15
16. Mouse models. 16
17. Immunohistochemistry. 18
18. Statistical analysis. 18
Ⅲ. RESULTS. 20
1. Identify HCC-associated lncRNA and analysis of their clinical correlation. 20
2. LINC01446 as a non-invasive diagnosis marker for HCC. 24
3. LINC01446 knockdown inhibits in vitro metastasis of HCC. 30
4. LINC01446 knockdown suppresses in vivo metastasis of HCC. 34
Ⅳ. DISCUSSION. 38
Ⅴ. REFERENCES. 40
국문요약. 4
Urinary GADD45G Protein Excretion Is Associated with IgA Nephropathy Progression
No full textBackground: Growth arrest and DNA damage 45G (GADD45G) is a family of proteins involved in DNA damage response and cell growth arrest. In this study, we show evidence that urinary GADD45G protein is associated with the progression of IgA nephropathy. Methods: Patients diagnosed with IgA nephropathy without reversible acute kidney injury at study initiation and with at least one subsequent serum creatinine (SCr) measurement were included. A 50% or greater increase in SCr level was used as an endpoint for the deterioration of renal function. Enzyme-linked immunosorbent assay (ELISA) was performed using a Human GADD45G ELISA kit. Renal biopsy tissues were stained with a monoclonal mouse anti-GADD45G antibody. Results: Forty-five patients whose renal biopsy revealed IgA nephropathy were enrolled. Urinary GADD45G and urinary protein concentrations were 1.26 [0.69–2.20] μg/g creatinine and 0.65 [0.24–1.60] g/g creatinine, respectively. Urinary GADD45G showed significant positive correlations with SCr-slopes and urinary protein. The SCr-slope of the highest tertile group of urinary GADD45G (above 1.95 μg/g creatinine) was significantly higher than that of the lowest tertile group (below 0.90 μg/g). Univariate Cox regression analysis showed that urinary GADD45G was significantly associated with deterioration of renal function. A Kaplan–Meier test showed a significant difference in event-free survival for deterioration of renal function between the highest urinary GADD45G tertile group and other tertile groups. The area under the receiver operating characteristics (ROC) curve indicated urinary GADD45G had a good performance in predicting renal outcome (cut-off point 1.67 μg/g, positive predictive value 36.8%, negative predictive value 100%). Immunohistochemistry showed that GADD45G was expressed across all pathologic grades of IgA nephropathy and mainly detected in the cytoplasm of renal tubules, whereas no staining was noted in normal tissues. Conclusions: Urinary GADD45G excretion was significantly associated with kidney disease progression in patients with IgA nephropathy
Interleukin (IL)-1/IL-6-Inhibitor–Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses
No full textBackground: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. Methods: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. Results: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10−35 and P = 1.1 × 10−24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6–inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. Conclusions: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor–associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes
Salivary microbiota reflecting changes in subgingival microbiota
Get PDFThe purpose of this study was to determine whether subgingival microbial changes according to the severity of periodontal disease and following the nonsurgical periodontal treatment of periodontitis are reflected in the saliva microbiota. Subgingival and saliva samples were collected from 7 periodontally healthy controls, 14 patients with gingivitis, 12 with moderate periodontitis, and 18 with severe periodontitis. Among subjects who received treatment, seven moderate and seven severe periodontitis patients were selected for post-treatment microbial analysis, and their samples were analyzed at baseline and 6 months after treatment. The V3 and V4 regions of the 16S rRNA gene were sequenced, and correlations of the relative abundance of phyla and health- or periodontitis-dominant species between subgingival plaque and saliva samples were analyzed using Spearman signed-rank tests. Alpha diversity was higher in saliva than subgingival plaque samples, and beta diversity was significantly different between the two samples. However, levels of phyla and most health- or periodontitis-dominant species in salivary microbiota were significantly correlated with those in subgingival plaque. The improvement in clinical parameters following treatment was accompanied by a microbial shift not only in subgingival plaque but also in saliva. The abundance of 2 phyla including Bacteroidetes, 6 genera including Porphyromonas and Treponema, and 11 species including Porphyromonas gingivalis, Tannerella forsythia, and Filifactor alocis was significantly reduced in saliva following treatment. These results indicate that the salivary microbiota can reflect changes in the subgingival microbiota, suggesting that saliva can be used as a diagnostic tool to monitor the periodontal health status of individuals. IMPORTANCE The salivary microbiota has attracted increasing attention as a promising method for monitoring periodontal disease. With regard to the pathogenesis of periodontal disease, however, subgingival plaque microbiota is the dominant etiological factor. Although it has been established that periodontopathogenic bacteria exist in saliva and their distribution differs, depending on the severity of the disease, it is necessary to analyze the extent to which the salivary microbiota reflects the subgingival microbiota. This study explored whether subgingival microbial changes according to the severity of periodontal disease and following the non-surgical periodontal treatment of periodontitis are reflected in the saliva microbiota and concluded that the salivary microbiota can reflect changes in the subgingival microbiota. Saliva can be used as a diagnostic tool to monitor the periodontal health status of individuals
Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability
Get PDFRecently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing