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Gut permeability and its correlation with patient's traits and blood inflammatory markers in severe asthma: Real-world assessment from the Korean severe asthma registry-2 (KoSAR-2)
Challenge of Precautionary Allergen Labeling for Ensuring the Safety of Children With Food Allergies
Background: Precautionary allergen labeling (PAL) is mandatory and legally regulated in Korea. This study aims to investigate the frequency of PAL use in food products, evaluate its competence, and seek direction for improvement. Methods: Cow’s milk (CM) and hen’s egg white (EW) protein concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The results validated PAL using the Voluntary Incidental Trace Allergen Labeling® 3.0 program. A survey was conducted on guardians to compare preferences and understanding of the current and the arbitrarily revised PAL. Results: PAL was used in 91.8% (280/305) of baby food products. ELISA results using randomly selected baby food products showed that only 16.7% (5/30; No PAL with no contamination, n = 4; PAL with real-contamination risk, n = 1) were validated to PAL. A detectable CM was found in two products (2/26, 7.7%), with one product exceeding the reference dose (10.3 ± 0.17 ppm). EW was not detected at all (0/16). A total of 207 surveys from guardians were collected and categorized into three groups: food allergy (FA, n = 103), diseases other than food allergies (Others, n = 52), and no disease (Control, n = 52). The FA group exhibited the highest frequency of checking food allergen labeling (“always”: 78.6%, “often”: 9.7%), with a similar PAL adherence (“always”: 58.3%, “often”: 10.4%). None of the groups were satisfied with the current PAL. The ‘allergen-free’ statement was mostly preferred across all groups. The FA group notably preferred PAL with concentration statements. Conclusion: PAL is excessively prevalent and insufficient in ensuring the safety of children with FAs, necessitating a revision towards a more patient-friendly, evidence-based system for affected individuals and their families
Distribution and impact of p16INK4A+ senescent cells in elderly tissues: a focus on senescent immune cell and epithelial dysfunction
Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population
Soft tissue paradigm based Treatment planning in skeletal class III
Objectives: This study aimed to propose guidelines for the indications of non-extraction, extraction camouflage treatment, and orthognathic surgery by comparing the degree of soft tissue improvement effects. This comparison focused on changes in CKHA, a soft tissue indicator corresponding to the major hard tissue indicator, ANB. Materials and methods: Sixty-six patients, 25 males and 41 females, aged between 18 and 50 years and diagnosed with skeletal Class III malocclusion (ANB < 0°), were enrolled in the study. Participants were categorized into three groups based on the treatment approach: G1, non-extraction (n = 20); G2, extraction (n = 20); and G3, orthognathic surgery (n = 26). To assess variations in treatment outcomes, measurements derived from lateral cephalometric radiographs obtained before and after treatment were analyzed and compared across the different treatment methods. Results: Significant differences were observed in the ANB between the G1 and G2/G3 groups. However, no significant differences were observed in CKHA levels after treatment. Furthermore, in G2, the CKHA approached the normal range at -1.8° (normal range: -2.0°), suggesting that soft tissue responses can normalize despite minimal changes in the skeletal structure. Conclusions: Although surgery resulted in the most significant skeletal changes, both camouflage groups demonstrated distinct advantages in the soft tissue paradigm. In G2, a noticeable posterior movement of the lower lip was observed along with a corresponding posterior shift in the soft tissue B point. Clinical relevance: This study provides guidelines for non-extraction, extraction and surgical treatment selection aimed at achieving soft tissue objectives
Burden of disease scenarios by state in the USA, 2022–50: a forecasting analysis for the Global Burden of Disease Study 2021
Background: The capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informed public. Through the integration of new data sources, the refinement of methodologies, and the inclusion of additional causes, we have improved our previous forecasting efforts within the scope of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to produce forecasts at the state and national levels for the USA under various possible scenarios. Methods: We developed a comprehensive framework for forecasting life expectancy, healthy life expectancy (HALE), cause-specific mortality, and disability-adjusted life-years (DALYs) due to 359 causes of disease and injury burden from 2022 to 2050 for the USA and all 50 states and Washington, DC. Using the GBD 2021 Future Health Scenarios modelling framework, we forecasted drivers of disease, demographic drivers, risk factors, temperature and particulate matter, mortality and years of life lost (YLL), population, and non-fatal burden. In addition to a reference scenario (representing the most probable future trajectory), we explored various future scenarios and their potential impacts over the next several decades on human health. These alternative scenarios comprised four risk elimination scenarios (including safer environment, improved behavioural and metabolic risks, improved childhood nutrition and vaccination, and a combined scenario) and three USA-specific scenarios based on risk exposure or attributable burden in the best-performing US states (improved high adult BMI and high fasting plasma glucose [FPG], improved smoking, and improved drug use [encompassing opioids, cocaine, amphetamine, and others]). Findings: Life expectancy in the USA is projected to increase from 78·3 years (95% uncertainty interval 78·1–78·5) in 2022 to 79·9 years (79·5–80·2) in 2035, and to 80·4 years (79·8–81·0) in 2050 for all sexes combined. This increase is forecasted to be modest compared with that in other countries around the world, resulting in the USA declining in global rank over the 2022–50 forecasted period among the 204 countries and territories in GBD, from 49th to 66th. There is projected to be a decline in female life expectancy in West Virginia between 1990 and 2050, and little change in Arkansas and Oklahoma. Additionally, after 2023, we projected almost no change in female life expectancy in many states, notably in Oklahoma, South Dakota, Utah, Iowa, Maine, and Wisconsin. Female HALE is projected to decline between 1990 and 2050 in 20 states and to remain unchanged in three others. Drug use disorders and low back pain are projected to be the leading Level 3 causes of age-standardised DALYs in 2050. The age-standardised DALY rate due to drug use disorders is projected to increase considerably between 2022 and 2050 (19·5% [6·9–34·1]). Our combined risk elimination scenario shows that the USA could gain 3·8 additional years (3·6–4·0) of life expectancy and 4·1 additional years (3·9–4·3) of HALE in 2050 versus the reference scenario. Using our USA-specific scenarios, we forecasted that the USA could gain 0·4 additional years (0·3–0·6) of life expectancy and 0·6 additional years (0·5–0·8) of HALE in 2050 under the improved drug use scenario relative to the reference scenario. Life expectancy and HALE are likewise projected to be 0·4–0·5 years higher in 2050 under the improved adult BMI and FPG and improved smoking scenarios compared with the reference scenario. However, the increases in these scenarios would not substantially improve the USA's global ranking in 2050 (from 66th of 204 in life expectancy in the reference scenario to 63rd–64th in each of the three USA-specific scenarios), indicating that the USA's best-performing states are still lagging behind other countries in their rank throughout the forecasted period. Regardless, an estimated 12·4 million (11·3–13·5) deaths could be averted between 2022 and 2050 if the USA were to follow the combined scenario trajectory rather than the reference scenario. There would also be 1·4 million (0·7–2·2) fewer deaths over the 28-year forecasted period with improved adult BMI and FPG, 2·1 million (1·3–2·9) fewer deaths with improved exposure to smoking, and 1·2 million (0·9–1·5) fewer deaths with lower rates of drug use deaths. Interpretation: Our findings highlight the alarming trajectory of health challenges in the USA, which, if left unaddressed, could lead to a reversal of the health progress made over the past three decades for some US states and a decline in global health standing for all states. The evidence from our alternative scenarios along with other published studies suggests that through collaborative, evidence-based strategies, there are opportunities to change the trajectory of health outcomes in the USA, such as by investing in scientific innovation, health-care access, preventive health care, risk exposure reduction, and education. Our forecasts clearly show that the time to act is now, as the future of the country's health and wellbeing—as well as its prosperity and leadership position in science and innovation—are at stake. Funding: Bill & Melinda Gates Foundation
MZ세대 임상 간호사의 재직의도 영향요인
MasterⅠ. 서론 1
A. 연구의 필요성 1
B. 연구의 목적 5
C. 용어의 정의 6
Ⅱ. 문헌고찰 8
A. MZ세대 간호사의 재직의도 8
B. 간호사의 재직의도 관련 요인 12
1. 간호조직문화 14
2. 전문직 자아개념 16
3. 일반적 특성에 따른 관련 요인 17
Ⅲ. 연구방법 19
A. 연구설계 19
B. 연구대상자 및 표집방법 19
C. 연구도구 21
D. 자료수집방법 및 절차 24
E. 자료분석방법 25
F. 윤리적 고려 26
Ⅳ. 연구결과 27
A. 대상자의 일반적 특성 27
B. 대상자의 간호조직문화, 전문직 자아개념, 재직의도 정도 30
C. 대상자의 일반적 특성에 따른 재직의도 차이 32
D. 대상자의 간호조직문화, 전문직 자아개념, 재직의도 간 상관관계 35
E. 대상자의 재직의도에 미치는 영향요인 37
Ⅴ. 논의 39
Ⅵ. 결론 및 제언 44
A. 결론 44
B. 제언 46
참고문헌 47
부록 60
ABSTRACT 7
Prognosis prediction and immunotherapy optimisation for cryptogenic new-onset refractory status epilepticus
Background: Cryptogenic new-onset refractory status epilepticus (cNORSE) currently lacks comprehensive knowledge regarding its clinical dynamics, prognostic factors and treatment guidance. Here we present the longitudinal clinical profiles, predictive factors for outcomes and the optimal duration of immunotherapy in patients with cNORSE.
Methods: This retrospective secondary endpoint analysis investigated patients with cNORSE identified from a prospective autoimmune encephalitis cohort at a national referral centre in Korea. The main outcomes included longitudinal functional scales, seizure frequency and the number of antiseizure medications. Measures encompassed NORSE-related clinical parameters such as the duration of unconsciousness, immunotherapy profiles, cytokine/chemokine analysis, and serial MRI scans.
Results: A total of 74 patients with cNORSE were finally analysed (mean age: 38.0±18.2; 36 (48.6%) male). All patients received first-line immunotherapy, and 91.9% (68/74) received second-line immunotherapy. A total of 83.8% (62/74) regained consciousness within a median duration of 30 days (14-56), and 50% (31/62) achieved good outcome (mRS ≤2) at 2 years. Poor 1-year outcomes (mRS ≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at 3-month MRI, and prolonged unconsciousness (≥60 days). Those with mTL atrophy exhibited a higher seizure burden post-NORSE. The optimal duration of immunotherapy appeared to be between 18 weeks and 1-year post-NORSE onset.
Conclusions: This study elucidates longitudinal clinical dynamics, functional outcomes, prognostic factors and immunotherapy response in patients with cNORSE. These findings might contribute to a more standardised understanding and clinical decision-making for cNORSE
Celastrol에 의한 항암 효과에 있어 mTORC2/Akt axis의 역할과 기전 연구
MasterI. INTRODUCTION 1
II. MATERIALS AND METHODS 9
A. Chemicals and antibodies 9
B. Cell culture 9
C. Cell viability assay 10
D. Live-cell imaging 10
E. Morphological examination of the ER and mitochondria 11
F. Measurement of mitochondrial Ca2+ levels 11
G. Measurement of acidic lysosome levels 11
H. Small interfering RNA-mediated knockdown 12
I. Immunoblot analysis 12
J. Statistical analysis 13
III. RESULTS 14
1. A transient activation of mTOR and Akt may be critical for celastrol-induced cell death 14
2. mTORC2, but not mTORC1, is critical for celastrol-induced paraptosis 29
3. Inhibition of mTOR or Akt delays mitochondrial calcium overload 33
4. Activation of mTOR/Akt axis contributes to celastrol-induced proteotoxic stress and paraptosis 38
5. Inhibition of mTOR, but not Akt inhibited JNK 42
6. Celastrol is not cytotoxic to MCF10A cells 47
7. mTOR-mediated autophagy is not critically involved in celastrol-induced cell death 50
IV. DISCUSSION 59
V. REFERENCES 71
VI. 국문요약 8
Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases
Automated Measurement of Effective Radiation Dose by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Background/Objectives: Calculating the radiation dose from CT in 18F-PET/CT examinations poses a significant challenge. The objective of this study is to develop a deep learning-based automated program that standardizes the measurement of radiation doses. Methods: The torso CT was segmented into six distinct regions using TotalSegmentator. An automated program was employed to extract the necessary information and calculate the effective dose (ED) of PET/CT. The accuracy of our automated program was verified by comparing the EDs calculated by the program with those determined by a nuclear medicine physician (n = 30). Additionally, we compared the EDs obtained from an older PET/CT scanner with those from a newer PET/CT scanner (n = 42). Results: The CT ED calculated by the automated program was not significantly different from that calculated by the nuclear medicine physician (3.67 ± 0.61 mSv and 3.62 ± 0.60 mSv, respectively, p = 0.7623). Similarly, the total ED showed no significant difference between the two calculation methods (8.10 ± 1.40 mSv and 8.05 ± 1.39 mSv, respectively, p = 0.8957). A very strong correlation was observed in both the CT ED and total ED between the two measurements (r2 = 0.9981 and 0.9996, respectively). The automated program showed excellent repeatability and reproducibility. When comparing the older and newer PET/CT scanners, the PET ED was significantly lower in the newer scanner than in the older scanner (4.39 ± 0.91 mSv and 6.00 ± 1.17 mSv, respectively, p < 0.0001). Consequently, the total ED was significantly lower in the newer scanner than in the older scanner (8.22 ± 1.53 mSv and 9.65 ± 1.34 mSv, respectively, p < 0.0001). Conclusions: We successfully developed an automated program for calculating the ED of torso 18F-PET/CT. By integrating a deep learning model, the program effectively eliminated inter-operator variability