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Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer

  • Hyun Kyu Kim;Yena Song;Minji Kye;Byeongho Yu;Sang Beom Park;Ji Hyeon Kim;Sung-Hwan Moon;Hyungkyu Choi;Jong-Seok Moon;Jae Sang Oh;Man Ryul Lee
    • International Journal of Stem Cells
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    • v.17 no.2
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    • pp.194-203
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    • 2024
  • Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2~4 and 2~3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

Propofol Alone versus Propofol in Combination with Midazolam for Sedative Endoscopy in Patients with Paradoxical Reactions to Midazolam

  • Ji Hyung Nam;Dong Kee Jang;Jun Kyu Lee;Hyoun Woo Kang;Byung-Wook Kim;Byung Ik Jang;Committees of Quality Management and Conscious Sedation of Korean Society of Gastrointestinal Endoscopy
    • Clinical Endoscopy
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    • v.55 no.2
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    • pp.234-239
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    • 2022
  • Background/Aims: The efficacy of propofol in gastrointestinal endoscopy for patients with midazolam-induced paradoxical reactions remains unclarified. This study aimed to compare the efficacy and safety of propofol-based sedation in patients who previously experienced paradoxical reactions. Methods: This was a prospective, single-blinded, randomized controlled pilot study. Participants with a history of paradoxical reactions to midazolam during a previous esophagogastroduodenoscopy were recruited and randomly assigned to group I (propofol monosedation) or group II (combination of propofol and midazolam). The primary endpoint was the occurrence of a paradoxical reaction. Results: A total of 30 participants (mean age, 54.7±12.6 years; male, 19/30) were randomly assigned to group I (n=16) or group II (n=14). There were no paradoxical reactions in group I, but there were two in group II, without a significant difference (p=0.209). The mean dose of propofol was higher in group I than in group II (p=0.002). Meanwhile, the procedure and recovery times did not differ between groups. Conclusions: Propofol-based sedation was safe and effective for patients who experienced paradoxical reactions to midazolam. However, caution is needed because few cases of paradoxical reaction again can happen in group II in which midazolam was readministered.

Discriminative Power of Seoul Cognitive Status Test in Differentiating Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Dementia Based on CERAD-K Standards

  • Hasom Moon;Eek-Sung Lee;Seunghee Na;Dayeong An;Joon Soo Shin;Duk L. Na;Hyemin Jang
    • Dementia and Neurocognitive Disorders
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    • v.23 no.3
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    • pp.136-145
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    • 2024
  • Background and Purpose: We developed a new digital cognitive assessment called Seoul Cognitive Status Test (SCST), formerly called Inbrain Cognitive Screening Test. The purpose of this study was to validate the clinical utility of the SCST by comparing its scores of those with subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and dementia diagnosed by the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K). Methods: All participants (n=296) who completed the CERAD-K, SCST, and Instrumental Activities of Daily Living tests were included in this study. Total score, cognitive domain scores, and subtest scores of the SCST were compared among the 3 groups (SCD, aMCI, and dementia). Additionally, correlations between SCST and CERAD-K subtests were examined. Results: Cognitive domain scores and total score of the SCST showed significant differences among the three groups, with scores being the highest in the order of SCD, aMCI, and dementia (p<0.001). Most subtests of the SCST also showed higher scores in the order of SCD, aMCI, and dementia (p<0.001). However, SCD and aMCI groups showed no significant differences in scores of the Phonemic Word Fluency Test (p=0.083) or Korean Trail Making Test-Elderly version Part A (p=0.434). Additionally, there was no significant difference in the score of Place Recognition (p=0.274) of the Word-Place Association Test between aMCI and dementia groups. Conclusions: In conclusion, differences in total score, cognitive domain scores, and subtest scores of the SCST among the 3 groups of participants diagnosed using CERAD-K confirm the clinical utility of the SCST for cognitive assessment.

Executive Summary of the 2021 International Conference of Korean Dementia Association: A Report From the Academic Committee of the Korean Dementia Association

  • Kee Hyung Park;Jae-Won Jang;Jeewon Suh;SangHak Yi;Jae-Sung Bae;Jae-Sung Lim;Hyon Lee;Juhee Chin;Young Ho Park;Yun Jeong Hong;Geon Ha Kim;Academic Committee of the Korean Dementia Association
    • Dementia and Neurocognitive Disorders
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    • v.21 no.2
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    • pp.45-58
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    • 2022
  • Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer's dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD's diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

Clinical Application of Plasma Neurofilament Light Chain in a Memory Clinic: A Pilot Study

  • YongSoo Shim
    • Dementia and Neurocognitive Disorders
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    • v.21 no.2
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    • pp.59-70
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    • 2022
  • Background and Purpose: Neurofilament light chain (NfL) has been considered as a biomarker for neurodegenerative diseases including Alzheimer's disease (AD). We measured plasma NfL levels in older adults with cognitive complaints and evaluated their clinical usefulness in AD. Methods: Plasma levels of NfL, measured by using the single molecule array method, were acquired in a total of 113 subjects consisting of subjective cognitive decline (SCD; n=14), mild cognitive impairment (MCI; n=37), or dementia of Alzheimer type (DAT; n=62). Plasma NfL level was compared among three groups, and its association with cognitive and functional status was also analyzed. Results: After adjusting for age, plasma NfL level was higher in subjects with DAT (65.98±84.96 pg/mL), compared to in subjects with SCD (16.90±2.54 pg/mL) or MCI (25.53±10.42 pg/mL, p=0.004). NfL levels were correlated with scores of the mini-mental state examination (r=-0.242, p=0.021), clinical dementia rating (CDR) (r=0.291, p=0.005), or CDR-sum of boxes (r=0.276, p=0.008). Just for participants who performed amyloid positron emission tomography (PET), the levels were different between subjects with PET (-) (n=17, 25.95±13.25 pg/mL) and PET (+) (n=16, 63.65±81.90 pg/mL, p=0.010). Additionally, plasma NfL levels were different between vascular dementia and vascular MCI, and between Parkinson's disease- dementia and no dementia. Conclusions: This pilot study shows that in subjects with DAT, plasma NfL levels increase. Plasma NfL level correlated with cognitive and functional status. Further longitudinal studies may help to apply the plasma NfL levels to AD, as a potential biomarker for the diagnosis and predicting progression.

Enhancing ketamine anesthesia with midazolam and fentanyl for children's ear surgery: a prospective randomized study

  • Seong Min Han;So Young Kwon;Jang Hyeok In;Jin Deok Joo
    • Journal of Yeungnam Medical Science
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    • v.41 no.3
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    • pp.207-212
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    • 2024
  • Background: Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. Methods: This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 ㎍/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. Results: The MFK group exhibited significantly lower scores for patient movement (p<0.01) and emergence agitation (p<0.01) and markedly higher surgeon satisfaction scores (p<0.01) than the K group. Conclusion: Administering a midazolam-fentanyl-ketamine combination effectively reduced spontaneous movement during surgery and emergence agitation during recovery without prolonging discharge times in children undergoing MTI.

Lack of Association between Inhaled Corticosteroid Use Based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease

  • Bo-Guen Kim;Sun Hye Shin;Jung-Wan Yoo;Yong Suk Jo;Hye Yun Park
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.3
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    • pp.329-337
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    • 2024
  • Background: Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. Methods: We retrospectively analyzed 107 COPD patients without a history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion (ppb) were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. Results: The median FeNO value was 32 ppb (interquartile range, 19 to 45) and 34 (20.0%) patients were classified as high FeNO group (median 74 ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01 to 6.91; p=0.049). Conclusion: High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

Doctor's Attitudes toward Hospice and Palliative Care for Terminal Cancer Patients (말기 암 환자의 호스피스 완화의료에 대한 의사들의 태도)

  • Moon, Do-Ho;Lee, Myung-Ah;Koh, Su-Jin;Choi, Youn-Seon;Kim, Su-Hyun;Yeom, Chang-Hwan
    • Journal of Hospice and Palliative Care
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    • v.9 no.2
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    • pp.93-100
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    • 2006
  • Purpose: This study was designed to understand the doctor's attitude toward hospice and palliative care for terminal cancer patients. Methods: Specialists who work at general hospital were surveyed with questionnaires about hospice and palliative care for terminal cancer patients. The questionnaires comprise 17 items. The data were statistically analyzed. Results: Eighty one doctors responded. Their median age was 35 years old. Thirty six doctors (44.4%) were from internal medicine. The median of specialist's experience was 4 years. Forty three respondents (53.2%) have rarely examined and treated cancer patients even a week. Thirty seven respondents (45.6%) knew the exact definition of hospice and palliative care. Eighty respondents (98.8%) felt that hospice and palliative care is necessary, and 91.2% of them responded the necessity of palliative medicine specialist. As to the question 'Do you positively referred terminal cancer patient to hospice and palliative care?', 55 respondents (67.9%) responded 'Yes' and 22 (27.2%) 'No'. Among the 'Yes' respondents 17 (30.9%) had an experience of hesitation for referring patients to hospice and palliative care; the most common reason was the disagreement of family members (6, 35.3%). As for the reasons of responding 'No', 6 doctors (27.2%) did so because of their 'feeling of abandoning the patients' and the other f for the 'lack of information on the referral procedure for hospice and palliative care'. Thirty seven specialists (45.7%) thought it is most desirable for the patients to have hospice and palliative care for 3 months before death. Fifty eight specialists (71.6%) responded that hospice and palliative care help controlling the patient's psychological symptoms before all. Conclusion: While most doctors recognize the need of hospice and palliative care for patients with terminal ranter, their attitude toward hospice and palliative care was rather reserved. We suggest that continuing education, information and promotion for hospice and palliative care should be provided for doctors.

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Association between Spiritual Well-Being and Pain, Anxiety and Depression in Terminal Cancer Patients: A Pilot Study (말기암환자의 영적 안녕과 통증, 불안 및 우울과의 연관성: 예비 연구)

  • Lee, Yong Joo;Kim, Chul-Min;Linton, John A.;Lee, Duk Chul;Suh, Sang-Yeon;Seo, Ah-Ram;Ahn, Hong-Yup
    • Journal of Hospice and Palliative Care
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    • v.16 no.3
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    • pp.175-182
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    • 2013
  • Purpose: Spirituality is an important domain and is related with physical and psychological symptoms in terminal cancer patient. The aim of this study is to examine how patients' spirituality is associated with their physical and psychological symptoms as it has been explored by few studies. Methods: In this cross sectional study, 50 patients in the palliative ward of a tertiary hospital were interviewed. Spiritual well-being, depression, anxiety and pain is measured by Functional Assessment of Chronic-Illness Therapy-Spirituality (FACIT-Sp), hospital anxiety and depression scale (HADS) and the Korean version of the Brief Pain Inventory (BPI-K). The correlations between patients' spiritual well-being and anxiety, depression and pain were analysed. The association between spiritual well-being and age, gender, palliative performance scale (PPS), religion, mean pain intensity, anxiety, depression were assessed by univariate and multivariate regression analyses. Results: Spiritual well-being was negatively correlated with the mean pain intensity (r=-0.283, P<0.05), anxiety (r=-0.613, P<0.05) and depression (r=-0.526, P<0.05). In multivariate regression analysis, spiritual well-being showed negative association with anxiety (OR=-1.03, 95% CI=-1.657~-0.403, P=0.002) and positive association with the existence of religion (OR=9.193, 95% CI=4.158~14.229, P<0.001). Conclusion: In this study, patients' anxiety and existence of religion were significantly associated with spiritual well-being after adjusting age, gender, PPS, mean pain intensity, depression. Prospective studies are warranted.

Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

  • Lee, Chang Min;Yoo, Moon-Won;Son, Young-Gil;Oh, Sung Jin;Kim, Jong-Han;Kim, Hyoung-Il;Park, Joong-Min;Hur, Hoon;Jee, Ye Seob;Hwang, Sun-Hwi;Jin, Sung-Ho;Lee, Sang Eok;Park, Ji-Ho;Seo, Kyung Won;Park, Sungsoo;Kim, Chang Hyun;Jeong, In Ho;Lee, Han Hong;Choi, Sung Il;Lee, Sang-Il;Kim, Chan Young;Kim, In-Hwan;Son, Myoung-Won;Pak, Kyung Ho;Kim, Sungsoo;Lee, Moon-Soo;Min, Jae-Seok
    • Journal of Gastric Cancer
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    • v.20 no.2
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    • pp.152-164
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    • 2020
  • Purpose: To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). Materials and Methods: This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. Results: The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693-4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664-1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595-85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502-5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618-3.028; P<0.001) were determined as independent prognostic factors for DFS. Conclusions: S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.