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1.
ACS Catal ; 14(19): 14974-15013, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39386919

ABSTRACT

Solar-driven thermochemical hydrogen (STCH) production represents a sustainable approach for converting solar energy into hydrogen (H2) as a clean fuel. This technology serves as a crucial feedstock for synthetic fuel production, aligning with the principles of sustainable energy. The efficiency of the conversion process relies on the meticulous tuning of the properties of active materials, mostly commonly perovskite and fluorite oxides. This Review conducts a comprehensive review encompassing experimental, computational, and thermodynamic and kinetic property studies, primarily assessing the utilization of perovskite oxides in two-step thermochemical reactions and identifying essential attributes for future research endeavors. Furthermore, this Review delves into the application of machine learning (ML) and density functional theory (DFT) for predicting and classifying the thermochemical properties of perovskite materials. Through the integration of experimental investigations, computational modeling, and ML methodologies, this Review aspires to expedite the screening and optimization of perovskite oxides, thus enhancing the efficiency of STCH processes. The overarching objective is to propel the advancement and practical integration of STCH systems, contributing significantly to the realization of a sustainable and carbon-neutral energy landscape.

2.
BMC Nurs ; 23(1): 712, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363171

ABSTRACT

BACKGROUND: The use of appropriate personal protective equipment (PPE) in healthcare settings is a very important factor of infection control activities to prevent transmission of infection. In this study, we aimed to develop a non-face-to-face method that can reduce transmission of infection and an educational method that allows self-learning and self-training, and verify the effectiveness of a donning and doffing PPE education using video debriefing on third-year nursing students in clinical train. METHODS: The researcher assigned groups through random sampling using a random number table from the list of research subjects who agreed to participate. Therefore, 35 subjects in the experimental group with an education on donning and doffing PPE using video debriefing and 34 subjects in the control group with video-based training (VBT) were participated in April 2023 at a university in Incheon, South Korea. The evaluation phase involved verifying effects of the education on observer evaluation donningand doffing PPE performance and self-evaluation donningand doffing PPE performance. Satisfaction with the education also assessed immediately after intervention by the experimental group. RESULTS: The experimental group had significantly higher scores for observer evaluationdonning (t = 7.84, p < .001) and observer evaluation doffing (t = 6.52, p < .001) PPE performances than the control group. However, there was no significant difference in self-evaluation donning (t = 0.98, p < .330) or doffing PPE performance (t = 0.17, p < .869) between the two groups. In the experimental group that applied video debriefing, learning satisfaction was 4.33 ± 0.82 points out of 5 points. CONCLUSIONS: The education on donning and doffing PPE applying video debriefing was effective. If the education developed in this study is used as a self-learning method to improve the infection control capacity necessary to respond to a disaster crisis caused by infectious diseases, it is considered to be useful for preventing the transmission of infectious diseases in the future.

3.
Intern Emerg Med ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235708

ABSTRACT

We investigated the risk of cardiovascular events, all-cause mortality, and liver-related mortality according to the presence of metabolic syndrome (MetS) and fatty liver index (FLI). In this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2009 to 2012. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥ 60. Risk of all-cause mortality, liver-related mortality, and major adverse cardiovascular events (MACE) including myocardial infarction (MI), stroke, heart failure (HF), and cardiovascular disease (CVD)-related mortality was assessed according to the presence of MetS and FLI among adults (aged 40 to 80 years) who underwent health examinations (n = 769,422). During a median 8.59 years of follow up, 44,356 (5.8%) cases of MACE, 24,429 (3.2%) cases of all-cause mortality, and 1114 (0.1%) cases of liver-related mortality were detected in the entire cohort. When the FLI < 30 without MetS group was set as a reference, the FLI ≥ 60 with MetS group had the highest risk of MACE (adjusted hazard ratio [aHR] 2.05, 95% confidence interval [CI] 1.98-2.13) and all-cause mortality (aHR 1.96, 95% CI 1.86-2.07). The risk of liver-related mortality (aHR 10.71, 95% CI 8.05-14.25) was highest in the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group had a higher risk of MACE (aHR 1.39, 95%CI 1.28-1.51), a lower risk of liver-related mortality (aHR 0.44, 95%CI 0.33-0.59), and no significant difference in all-cause mortality compared with the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group was associated with the highest risk of MACE and the FLI ≥ 60 without MetS group had the highest risk liver-related mortality, but there was no significant difference in all-cause mortality between two groups. In conclusion, as FLI levels increase, the risk of MACE increases, and the risk increases additively in the presence of MetS. The risk of liver-related mortality increases with higher FLI levels, the effect of high FLI on increased risk is more significant in groups without MetS compared to those with MetS.

4.
World J Microbiol Biotechnol ; 40(10): 307, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162916

ABSTRACT

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.


Subject(s)
Anti-Bacterial Agents , Bacteriocins , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteriocins/pharmacology , Bacteriocins/chemistry , Humans , Structure-Activity Relationship , Molecular Dynamics Simulation , Peptides/pharmacology , Peptides/chemistry , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Clostridioides difficile/drug effects
5.
PLoS One ; 19(8): e0309044, 2024.
Article in English | MEDLINE | ID: mdl-39150944

ABSTRACT

This study aimed to determine the possibility of COVID-19 transmission through in-flight contact during flights for many patients with confirmed COVID-19 during the COVID-19 pandemic and explore infection prevention and control (IPC) methods for overseas infectious diseases. A retrospective cohort study was conducted on flight with a large number of confirmed case among. Delhi- Incheon flights in 2020. This flight was selected to confirm transmission through close contact with the cabin, with a total of 14 confirmed cases out of 190 passengers (including 10 flight attendants). After confirming COVID-19 test results for those entering Korea, we conducted an epidemiological investigation on confirmed patients to determine their general characteristics and epidemiological relevance. We analyzed the epidemiological relevance, occupational information, incubation period, and COVID-19 variation and genotype among confirmed patients who were in close contact with confirmed cases, and analyzed the possibility of transmission according to the distance of close contact in the flight. One confirmed patient was found to be highly likely to be infected due to close contact with the cabin. However, it occurred within two rows, not within 1 meter. In addition, considering the aerodynamics in the cabin and local incidence rate, infection in an unspecified number of local people could not be excluded. It was analyzed that the reason for reducing infection from close contact on board for a long time in a flight with a large number of confirmed cases was the effective IPC method. In order to prevent overseas infectious diseases caused by flights, autonomous IPC management of airlines and passengers is necessary in addition to national quarantine management such as symptom screening before boarding, wearing passenger masks while boarding, food and beverage restrictions, disinfection of public spaces, distancing between passengers, close contact management after boarding, and self-quarantine.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/transmission , COVID-19/epidemiology , COVID-19/prevention & control , Male , Female , Retrospective Studies , Adult , Middle Aged , Republic of Korea/epidemiology , SARS-CoV-2/isolation & purification , Pandemics/prevention & control , Aircraft , Aged
6.
Clin Nucl Med ; 49(9): e473-e475, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38968542

ABSTRACT

ABSTRACT: We report temporal changes in 18 F-FDG PET/CT in neuronal intranuclear inclusion disease (NIID). In a patient with encephalitis-like episodes, PET showed hypermetabolism correlating with EEG alterations. Affected sites later became hypometabolic and showed diffusion changes on MRI. In another patient, hypermetabolic regions correlated well with the EEG, whereas MRI showed changes after only 1 month. One chronic patient had diffuse hypometabolism, which correlated with atrophy on MRI and cerebral dysfunction on EEG. This is the first report of temporal changes in PET in NIID and suggests that it reflects the disease activity of NIID while correlating well with EEG.


Subject(s)
Fluorodeoxyglucose F18 , Intranuclear Inclusion Bodies , Neurodegenerative Diseases , Positron Emission Tomography Computed Tomography , Humans , Neurodegenerative Diseases/diagnostic imaging , Female , Male , Time Factors , Middle Aged , Tomography, X-Ray Computed , Electroencephalography , Multimodal Imaging , Positron-Emission Tomography
7.
BMC Med ; 22(1): 251, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886720

ABSTRACT

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.


Subject(s)
Diabetes Mellitus, Type 2 , Exercise , Thyroid Neoplasms , Thyroidectomy , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Male , Female , Middle Aged , Exercise/physiology , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Incidence , Adult , Republic of Korea/epidemiology , Thyroidectomy/adverse effects , Aged , Cohort Studies
8.
EBioMedicine ; 105: 105198, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38889480

ABSTRACT

BACKGROUND: Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model. METHODS: We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction. FINDINGS: Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression. INTERPRETATION: Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection. FUNDING: This research was funded by the National Research Foundation of Korea, the Korea Research Institute of Bioscience and Biotechnology, and the Korea National Institute of Health.


Subject(s)
Disease Models, Animal , Disease Progression , Lipid Metabolism , Mycobacterium avium-intracellulare Infection , Animals , Female , Mice , Mycobacterium avium-intracellulare Infection/microbiology , Mycobacterium avium-intracellulare Infection/metabolism , CD36 Antigens/metabolism , CD36 Antigens/genetics , Macrophages/metabolism , Humans , Mycobacterium avium Complex , Lung/metabolism , Lung/microbiology , Lung/pathology , Fatty Acids/metabolism , Mycobacterium avium , Disease Susceptibility
10.
Chem Mater ; 36(10): 4990-5001, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38828189

ABSTRACT

Mixing multiple cations can result in a significant configurational entropy, offer a new compositional space with vast tunability, and introduce new computational challenges. For applications such as the two-step solar thermochemical hydrogen (STCH) generation techniques, we demonstrate that using density functional theory (DFT) combined with Metropolis Monte Carlo method (DFT-MC) can efficiently sample the possible cation configurations in compositionally complex perovskite oxide (CCPO) materials, with (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 as an example. In the presence of oxygen vacancies (VO), DFT-MC simulations reveal a significant increase of the local site preference of the cations (short-range ordering), compared to a more random mixing without VO. Co is found to be the redox-active element and the VO is the preferentially generated next to Co due to the stretched Co-O bonds. A clear definition of the vacancy formation energy (Evf) is proposed for CCPO in an ensemble of structures evolved in parallel from independent DFT-MC paths. By combining the distribution of Evf with VO interactions into a statistical model, the oxygen nonstoichiometry (δ), under the STCH thermal reduction and oxidation conditions, is predicted and compared with the experiments. Similar to the experiments, the predicted δ can be used to extract the enthalpy and entropy of reduction using the van't Hoff method, providing direct comparisons with the experimental results. This procedure provides a full predictive workflow for using DFT-MC to obtain possible local ordering or fully random structures, understand the redox activity of each element, and predict the thermodynamic properties of CCPOs, for computational screening and design of these CCPO materials at STCH conditions.

11.
Brain Behav ; 14(2): e3389, 2024 02.
Article in English | MEDLINE | ID: mdl-38391108

ABSTRACT

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.


Subject(s)
Dizziness , Vestibular Diseases , Humans , Dizziness/diagnosis , Dizziness/epidemiology , Cross-Sectional Studies , Vertigo , Vestibular Diseases/diagnosis , Vestibular Diseases/epidemiology , Republic of Korea/epidemiology
12.
Diabetes Metab J ; 48(2): 290-301, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38171143

ABSTRACT

BACKGRUOUND: We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). METHODS: For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). RESULTS: During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. CONCLUSION: Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Retrospective Studies , Depression/epidemiology , Insulin
13.
J Glob Antimicrob Resist ; 36: 45-49, 2024 03.
Article in English | MEDLINE | ID: mdl-38128724

ABSTRACT

OBJECTIVES: Genetic changes in Mycobacterium abscessus during antibiotic treatment are not fully understood. This study aimed to investigate the genetic changes in M. abscessus in patients receiving antibiotic treatment, and their clinical implications. METHODS: Pretreatment and 12-month post-treatment M. abscessus isolates were obtained from patients with M. abscessus pulmonary disease. Isolates from each time point were separated into six groups based on their distinctive morphological characteristics. Twenty-four isolates, comprising 12 from patient A exhibiting progressive disease and 12 from patient B demonstrating stable disease, underwent sequencing. Subsequently, minimal inhibitory concentrations (MICs) for the administered antibiotics were measured. RESULTS: Persistent infection with a single strain was observed in patients A and B. During 12 months of treatment, MICs for administered drugs did not generally change over time in either patient and single nucleotide variations (SNV) associated with antimicrobial resistance (rrl, rrs, erm(41), gyrA, gyrB, whiB7 and hflX) were not mutated. Although not significant, 47 and 52 non-synonymous SNVs occurred in M. abscessus from patients A and B, respectively, and the accumulation of these SNVs differed in patients A and B, except for five SNVs. The most variable positions were within a probable NADH-dependent glutamate synthase gene and a putative YrbE family protein gene in patients A and B, respectively. CONCLUSIONS: Persistent infections by a single strain of M. abscessus were observed in two patients with different clinical courses. Genetic changes in M. abscessus during antibiotic treatment were relatively stable in these patients. CLINICAL TRIALS IDENTIFIER: NCT01616745 (ClinicalTrials.gov ID).


Subject(s)
Lung Diseases , Mycobacterium abscessus , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , Mycobacterium abscessus/genetics
14.
Microbiol Spectr ; : e0182523, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37594284

ABSTRACT

Unsatisfactory outcomes following long-term multidrug treatment in patients with Mycobacterium avium complex (MAC) pulmonary disease have urged us to develop novel antibiotics. Thiopeptides, a class of peptide antibiotics derived from natural products, have potential as drug candidates that target bacterial ribosomes, but drug development has been hampered due to their extremely poor solubility. Here, we evaluated three new compounds (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2 with enhanced aqueous solubility; the derivatives were generated based on structure-activity relationship analysis. We conducted in vitro drug susceptibility and intracellular antimycobacterial activity testing of the three thiopeptide derivatives against various MAC strains, including macrolide-resistant MAC clinical isolates. These compounds showed low MICs against MAC, similar to that of clarithromycin (CLR). In particular, two compounds, AJ-037 and AJ-206, had intracellular antimycobacterial activities, along with synergistic effects with CLR, and inhibited the growth of MAC inside macrophages. Moreover, these two compounds showed in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing cross-resistance with CLR. Taken together, the results of the current study suggest that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infection, including for macrolide-resistant MAC strains. IMPORTANCE Novel antibiotics for the treatment of MAC infection are urgently needed because the treatment outcomes using the standard regimen for Mycobacterium avium complex (MAC) pulmonary disease remain unsatisfactory. Here, we evaluated three novel thiopeptide derivatives (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2, and they were confirmed to be effective against macrolide-susceptible and macrolide-resistant MAC. Our thiopeptide derivatives have enhanced aqueous solubility through structural modifications of poorly soluble thiopeptides. The thiopeptide derivatives showed minimal inhibitory concentrations against MAC that were comparable to clarithromycin (CLR). Notably, two compounds, AJ-037 and AJ-206, exhibited intracellular antimycobacterial activities and acted synergistically with CLR to hinder the growth of MAC within macrophages. Additionally, these compounds demonstrated in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing any cross-resistance with CLR. We believe that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infections, including macrolide-resistant MAC strains.

15.
Endocrinol Metab (Seoul) ; 38(4): 445-454, 2023 08.
Article in English | MEDLINE | ID: mdl-37461149

ABSTRACT

BACKGRUOUND: Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. METHODS: We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. RESULTS: Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. CONCLUSION: The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Proto-Oncogene Proteins B-raf/genetics , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Mutation , Phenotype , Tumor Microenvironment/genetics
16.
Front Neurol ; 14: 1223996, 2023.
Article in English | MEDLINE | ID: mdl-37475735

ABSTRACT

Objectives: This study aimed to determine the pathophysiology of recurrent benign paroxysmal positional vertigo (BPPV) in young patients using gene expression profiling combined with bioinformatics analysis. Methods: Total RNA was extracted from the whole blood of four young patients with recurrent BPPV and four controls. The differentially expressed genes (DEGs) between the groups were screened using a microarray analysis based on the cutoff criteria of |log2 fold change| > 1 and an adjusted p-value of < 0.05. Functional enrichment analysis of DEGs was performed using Gene Ontology analysis, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of the Interacting Genes database. Results: A total of 39 DEGs were detected between the BPPV and control samples, comprising 33 upregulated DEGs and six downregulated DEGs in the BPPV group. Functional enrichment analysis indicated that the upregulated DEGs were significantly enriched in terms related to metabolic processes and the immune system. Two main pathways were extracted from the PPI network: one was associated with oxidative phosphorylation and stress and the other with the adaptive immune system and extracellular matrix degradation. Conclusion: The findings of our bioinformatics analysis indicated that oxidative stress or extracellular matrix degradation due to immune-mediated inflammatory responses may contribute to the development of recurrent BPPV in young patients.

17.
Sci Rep ; 13(1): 10677, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37393407

ABSTRACT

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4-8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.


Subject(s)
Diabetes Mellitus , Hepatitis B , Hepatitis C , Non-alcoholic Fatty Liver Disease , Adult , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Longitudinal Studies , Retrospective Studies , Diabetes Mellitus/epidemiology , Hepatitis B virus
18.
Diabetes Metab J ; 47(5): 682-692, 2023 09.
Article in English | MEDLINE | ID: mdl-37349081

ABSTRACT

BACKGRUOUND: We explored the risk of death from pneumonia according to cumulative duration in low household income state (LHIS) among adults with type 2 diabetes mellitus (T2DM). METHODS: Using Korean National Health Insurance Service data (2002 to 2018), the hazards of mortality from pneumonia were analyzed according to duration in LHIS (being registered to Medical Aid) during the 5 years before baseline (0, 1-4, and 5 years) among adults with T2DM who underwent health examinations between 2009 and 2012 (n=2,503,581). Hazards of outcomes were also compared in six groups categorized by insulin use and duration in LHIS. RESULTS: During a median 7.18 years, 12,245 deaths from pneumonia occurred. Individuals who had been exposed to LHIS had higher hazards of death from pneumonia in a dose-response manner (hazard ratio [HR], 1.726; 95% confidence interval [CI], 1.568 to 1.899 and HR, 4.686; 95% CI, 3.948 to 5.562 in those exposed for 1-4 and 5 years, respectively) compared to the non-exposed reference. Insulin users exposed for 5 years to LHIS exhibited the highest outcome hazard among six groups categorized by insulin use and duration in LHIS. CONCLUSION: Among adults with T2DM, cumulative duration in LHIS may predict increased risks of mortality from pneumonia in a graded dose-response manner. Insulin users with the longest duration in LHIS might be the group most vulnerable to death from pneumonia among adults with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Pneumonia , Adult , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Insulin/therapeutic use , Socioeconomic Factors , Pneumonia/epidemiology
19.
Front Neurol ; 14: 1157931, 2023.
Article in English | MEDLINE | ID: mdl-37064188

ABSTRACT

Object: To study multimodal neuroimaging study including resting state functional MRI (rs-fMRI), anatomical connectivity and brain morphology in patients with bilateral vestibulopathy (BVP) and relationship with clinical correlation. Methods: Thirteen patients with BVP (7 women; mean age ± SD = 63.5 ± 14.7 years, 22-80 years) and eighteen age and gender-matched controls were compared rs-fMRI and anatomical MRI. Also, we analyzed the relationship between multimodal neuroimaging and Dizziness Handicap Inventory score (DHI), Vestibular Disorders Activities of Daily Living Scale (VDRL), Geriatric Depression Scale (GDS) and Hospital Anxiety and Depression Scale (HADS). Results: Compared with controls, BVP patients showed decreased functional connectivity among the key nodes of the salience network, auditory (including vestibular) network, bilateral posterior parahippocampal gyri, bilateral paracingulate gyri, and right frontoparietal network, and the anatomical connectivity in the right cerebellum, corpus callosum tapetum, and left fornix. BVP patients showed decreased gray matter volume in the bilateral parahippocampal gyri, right precentral gyrus, anterior cingulate gyrus, and right middle temporal gyrus and increased gray matter volume in the right superior frontal gyrus compared with controls. Correlation analyses showed rs-fMRI and clinical variables showed no significant result. DHI correlated negatively with anatomical connectivity in the bilateral frontal parahippocampal cingulum, corpus callosum, right inferior fronto-occipital fasciculus, bilateral fornix, and gray matter volumes in the bilateral middle occipital gyri, right superior occipital gyrus, left angular gyrus, and right cuneus in BVP. VADL correlated negatively with Anatomical connectivity in the corpus callosum, bilateral fornix, bilateral cerebellum, bilateral superior and anterior thalamic radiation, right inferior fronto-occipital fasciculus, bilateral fronto-parietal cingulum, right dentatoruburothalamic tract and gray matter volumes in the right angular gyri, bilateral parahippocampal gyri, right middle temporal gyrus, right cuneus, bilateral inferior occipital gyri, left middle occipital gyrus, right superior frontal gyrus, left fusiform gyrus, bilateral caudate, left cerebellar crus, and bilateral calcarine gyri in BVP. Conclusions: This study identified reductions in the volume of the hippocampus and alterations in functional and anatomical connectivity that concurs with previously established characteristics of BVP. The degree of disability can be inferred from the change in the connectivity and volume between vestibular cortical areas and their network.

20.
Diabetes Res Clin Pract ; 199: 110666, 2023 May.
Article in English | MEDLINE | ID: mdl-37031890

ABSTRACT

AIMS: Weight gain and loss increase the risk of all-cause mortality. This study explored the association of short-term weight change with all-cause and cause-specific mortality in middle-aged to older people. METHODS: This was a 8.4-year retrospective cohort study of 645,260 adults aged 40 to 80 who underwent health checkups twice within a 2-year interval between January 2009 and December 2012. Cox analyses were used to analyze the association between short-term weight change and all-cause and cause-specific mortality. RESULTS: Weight gain and loss were associated with an increased risk of all-cause mortality: the hazard ratios were 2.05 (95% confidence interval [CI], 1.93-2.16), 1.21 (95% CI, 1.16-1.25), 1.12 (95% CI 1.08-1.17), and 1.60 (95% CI, 1.49-1.70) for the severe weight loss, moderate weight loss, moderate weight gain, and severe weight gain groups, respectively. This U-shaped association was also seen between weight change and cause-specific mortality. Within the weight loss group, those who regained weight after two years had a reduced mortality risk. CONCLUSIONS: In a middle-aged and elderly population, weight gain or loss of more than 3% during a 2-year interval was related to an elevated risk of all-cause and cause-specific mortality.


Subject(s)
Weight Gain , Weight Loss , Adult , Middle Aged , Humans , Aged , Cause of Death , Retrospective Studies , Body Mass Index , Body Weight , Risk Factors
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