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In this study, lignin nanoparticles (LN) and octadecylamine-modified LN (LN-ODA) were utilized as coating materials to enhance the hydrophobic, antioxidant, and ultraviolet radiation-shielding (UV-shielding) properties of a TEMPO-oxidized nanocellulose film (TOCNF). The water contact angle (WCA) of the TOCNF was approximately 53° and remained stable for 1 min, while the modified LN-ODA-coated TOCNF reached over 130° and maintained approximately 85° for an hour. Pure TOCNF exhibited low antioxidant properties (4.7 %), which were significantly enhanced in TOCNF-LN (81.6 %) and modified LN-ODA (10.3 % to 27.5 %). Modified LN-ODA-coated TOCNF exhibited antioxidant properties two to six times higher than those of pure TOCNF. Modified LN-ODA exhibited thermal degradation max (Tmax) at 421 °C, while pure LN showed the main degradation temperature at approximately Tmax 330 °C. The thermal stability of TOCNF-LN-ODA-coated materials remained consistent with that of pure TOCNF, while the crystallinity index of the sample showed a slight decrease due to the amorphous nature of the lignin structure. The tensile strength of TOCNF was approximately 114.1 MPa and decreased to 80.1, 51.3, and 30.3 MPa for LN-ODA coating at 5, 10, and 15 g/m2, respectively.
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OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.
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In this study, we detected signatures of selection in Hanwoo and Angus beef cattle using allele frequency and haplotype-based methods based on imputed whole genome sequence variants. Our dataset included 13,202 Angus animals with 10,057,633 imputed SNPs and 10,437 Hanwoo animals with 13,241,550 imputed SNPs. The dataset was subset down to 6,873,624 SNPs in common between the two populations to identify within population (runs of homozygosity, extended haplotype homozygosity) and between population signals of selection (allele fixation index, extended haplotype homozygosity). Assuming these selection signals were complementary to each other, they were combined into a decorrelated composite of multiple signals to identify regions under selection for each of the breeds. 27 genomic regions spanning 25.15 Mb and harboring 360 genes were identified in Angus on chromosomes 1,3, 4, 5, 6, 7, 8, 12, 13, 14, 16, 20, 21 and 28. Similarly, in Hanwoo, 59 genes and 17 genomic regions spanning 5.21 Mb on chromosomes 2, 4, 5, 6, 7, 8, 9, 10, 13, 17, 20 and 24 were identified. Apart from a small region on chromosome 13, there was no major overlap of selection signals between the two breeds reflecting their largely different selection histories, environmental challenges, breeding objectives and breed characteristics. Positional candidate genes identified in selected genomic regions in Angus have been previously associated with growth, immunity, reproductive development, feed efficiency and adaptation to environment while the candidate genes identified in Hanwoo included important genes regulating meat quality, fat deposition, cholesterol metabolism, lipid synthesis, neuronal development, and olfactory reception.
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Brain electrical stimulation, particularly non-invasive brain stimulation (NIBS) techniques such as transcranial electrical stimulation (tES), have emerged as a promising treatment for various psychiatric disorders, including depression, anxiety, and post-traumatic stress disorder. tES techniques, such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), are cost-effective and safe interventions that are designed to affect neuronal circuits in the brain using various modalities. Although tES has shown effectiveness in the treatment of psychiatric disorders, there is a lack of comprehensive papers that consider its clinical implications. Therefore, this review aims to evaluate the clinical implications of tES and provide practical guidance for the treatment of psychiatric illnesses. Moreover, this review provides an overview of tES techniques and their mechanisms of action and summarizes recent clinical studies that have examined the use of tES for psychiatric disorders.
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Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.
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OBJECTIVES: Hearing loss causes numerous functional deficits. However, few studies have been conducted to assess the association between hearing loss and physical inactivity. This study aimed to evaluate the physical activity and sedentary behavior of hearing loss patients and their relation with the use of hearing aids. MATERIALS AND METHODS: We extracted participants over 60 years of age with information on hearing status and physical activities from the eighth Korea National Health and Nutritional Examination Survey conducted from 2019 to 2020. We classified them into four groups: a normal hearing group (≤25 dB), a mild hearing loss group (>25 dB and ≤40 dB), a moderate hearing loss group (>40 dB and ≤50 dB), and a non-serviceable hearing group (>50 dB). Additionally, we extracted hearing aid users with hearing levels exceeding 50 dB. RESULTS: After adjusting other factors, the non-serviceable hearing group walked less frequently than the moderate (p = 0.004) and mild hearing loss group (p < 0.001) and walked less and sat more than the normal hearing group (walking frequency: p < 0.001; walking time: p = 0.020; and sitting time: p = 0.034). Also, the hearing aid users walked more frequently (p = 0.003) and for longer (p = 0.045) than the non-serviceable hearing group. CONCLUSION: Hearing loss is associated with reduced walking and a sedentary lifestyle. The use of hearing aids is associated with improved physical activity. Appropriate interventions, including hearing aids, should be provided to hearing loss patients. LEVEL OF EVIDENCE: 3 (individual cross-sectional study) Laryngoscope, 2024.
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2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary α-carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation.
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BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.
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Néphrocarcinome , Interventions chirurgicales de cytoréduction , Tumeurs du rein , Études multicentriques comme sujet , Néphrectomie , Essais contrôlés randomisés comme sujet , Humains , Néphrocarcinome/chirurgie , Néphrocarcinome/traitement médicamenteux , Néphrocarcinome/secondaire , Tumeurs du rein/anatomopathologie , Tumeurs du rein/traitement médicamenteux , Tumeurs du rein/chirurgie , Néphrectomie/effets indésirables , Néphrectomie/méthodes , Études prospectives , Interventions chirurgicales de cytoréduction/effets indésirables , Nivolumab/usage thérapeutique , Nivolumab/effets indésirables , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/effets indésirables , Ipilimumab/usage thérapeutique , Ipilimumab/effets indésirables , Résultat thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Facteurs temps , Femelle , AdulteRÉSUMÉ
Background/Objective: In patients with severe trauma, intraosseous (IO) access is an alternative when intravenous (IV) access proves challenging. However, detailed insights into its utilization patterns and effectiveness are lacking. This study aims to evaluate the use and efficacy of IO access in hemodynamically unstable patients with trauma at level-1 trauma centers in South Korea. Methods: Data from six centers over 12 months were analyzed, focusing on patients with traumatic cardiac arrest or shock. Overall, 206 patients were included in the study: 94 in the IO group and 112 in the IV group. Results: The first-attempt success rate was higher in the IO group than in the IV group (90.4% vs. 75.5%). The procedure time in the IO group was also shorter than that in the IV group. The fluid infusion rate was lower in the IO group than in the IV group; however, the use of a pressure bag with IO access significantly increased the rate, making it comparable to the IV infusion rate. Further, regarding IO access, a humeral site provided a higher infusion rate than a tibial site. Conclusions: IO access offers a viable alternative to IV access for the initial resuscitation in patients with trauma, providing advantages in terms of procedure time and first-attempt success rate. The use of a pressure bag and a humeral site for IO access afforded infusion rates comparable to those associated with IV access.
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Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro. The assay was evaluated based on common analytical parameters setforth by regulatory guidelines, including specificity, selectivity,accuracy, precision, linearity, range and stability. Our results revealed that this resazurin-based cell viability potency assay reliably and reproducibly measured a dose-response of NK-EVs' cytotoxic activity against both cancer models. The assay showed precision with 5% and 20% variation for intra-run and inter-run variability. The assay signal showed specificity and selectivity of NK-EVs against cancer target cells, as evidenced by the diminished viability of cancer cells following a 5-hour treatment with NK-EVs, without any detectable interference or background. The linearity analysis of target cancer cells revealed strong linearity for densities of 5000 K562 and 1000 MDA-MB-231 cells per test with a consistent range. Importantly, NK-EVs' dose-response for cytotoxicity showed a strong correlation (|ρ| â¼ 0.8) with the levels of known cytotoxic factors associated with the NK-EVs' corona (FasL, GNLY, GzmB, PFN and IFN-γ), thereby validating the accuracy of the assay. The assay also distinguished cytotoxicity changes in degraded NK-EVs, indicating the ability of the assay to detect the potential loss of sample integrity. Compared to other commonly reported bioassays (i.e., flow cytometry, cell counting, lactate dehydrogenase release assay, DNA-binding reporter assay and confluence assay), our results support this highly sensitive resazurin-based viability potency assay as a high-throughput and quantitative method for assessing NK-EVs' cytotoxicity against both suspension and adherent cancer models for evaluating NK-EVs' biotherapeutics.
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BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSIONS: The ONFH risk increased rapidly when cumulative prednisolone use was ≥1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.
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BACKGROUND: Studies that use nonlinear methods to identify abnormal brain dynamics in patients with psychiatric disorders are limited. This study investigated brain dynamics based on EEG using multiscale entropy (MSE) analysis in patients with schizophrenia (SZ) and bipolar disorder (BD). METHODS: The eyes-closed resting-state EEG data were collected from 51 patients with SZ, 51 patients with BD, and 51 healthy controls (HCs). Patients with BD were further categorized into type I (n = 23) and type II (n = 16), and then compared with patients with SZ. A sample entropy-based MSE was evaluated from the bilateral frontal, central, and parieto-occipital regions using 30-s artifact-free EEG data for each individual. Correlation analyses of MSE values and psychiatric symptoms were performed. RESULTS: For patients with SZ, higher MSE values were observed at higher-scale factors (i.e., 41-70) across all regions compared with both HCs and patients with BD. Furthermore, there were positive correlations between the MSE values in the left frontal and parieto-occipital regions and PANSS scores. For patients with BD, higher MSE values were observed at middle-scale factors (i.e., 13-40) in the bilateral frontal and central regions compared with HCs. Patients with BD type I exhibited higher MSE values at higher-scale factors across all regions compared with those with BD type II. In BD type I, positive correlations were found between MSE values in all left regions and YMRS scores. CONCLUSIONS: Patients with psychiatric disorders exhibited group-dependent MSE characteristics. These results suggest that MSE features may be useful biomarkers that reflect pathophysiological characteristics.
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Trouble bipolaire , Électroencéphalographie , Entropie , Repos , Schizophrénie , Humains , Trouble bipolaire/physiopathologie , Schizophrénie/physiopathologie , Mâle , Femelle , Adulte , Électroencéphalographie/méthodes , Repos/physiologie , Adulte d'âge moyen , Encéphale/physiopathologie , Jeune adulte , Échelles d'évaluation en psychiatrieRÉSUMÉ
BACKGROUND: Bacteria within biofilms are thousand times more resistant to antibiotics. Neuraminidase is a crucial enzyme for bacterial adhesion and biofilm formation, it hydrolyzes glycosidic residue of glycoproteins, glycolipids, and oligosaccharides. Coreopsis lanceolata L. flowers may have a significant potential of bacterial neuraminidase (BNA) inhibition because of high natural abundance of chalcones. PURPOSE: The investigation of bacterial biofilm inhibitors has emerged as a novel therapeutic strategy against antibiotic resistance. Therefore, individual chalcones were isolated from C. lanceolata and their capacity to inhibit BNA and formation of Escherichia coli biofilm were evaluated. METHODS: Different chromatographic techniques were used to isolate the compounds (1-12). Enzyme inhibition and detailed kinetic behavior of compounds was determined by estimation of kinetic parameters (Michaelis-Menten constants (Km), maximum velocity (Vmax), dissociation constant for binding with the free enzyme (KI) and enzyme-substate complex (KIS)). Binding affinities (KSV) and binding modes of inhibitors were elucidated by fluorescence quenching and molecular docking, respectively. The natural abundance of chalcones was established through UPLC-Q-TOF/MS. The most potent inhibitor (1) was tested for its ability to inhibit the formation of E. coli biofilm, which was examined by crystal violet assay, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM). RESULTS: A series of eight chalcones (1-8) and four chalcone glucosides (9-12), inhibited BNA in a dose-dependent manner with IC50 of 8.3 â¼ 77.0 µM. The most potent chalcones were butein (1, IC50 = 8.3 µM) and its glucoside 9 (IC50 = 13.8 µM). The aglycones (1-8) showed non-competitive inhibition, while chalcone glucosides (9-12) displayed a mixed type I (KI < KIS). Inhibitory behaviors were doubly confirmed by KSV and matched with tendency of IC50. The functional group responsible for BNA inhibition were disclosed as 4'-hydroxyl group on B-ring by structure activity relationship (SAR) and molecular docking experiments. Butein (1) suppressed E. coli biofilm formation by > 50 % at 100 µM according to crystal violet assay, which was confirmed by SEM and CLSM imaging. CONCLUSION: The results showed that chalcones (1-8) and chalcone glucosides (9-12), metabolites isolated from the flowers of C. lanceolata, had BNA inhibitory and antibiofilm formation effect on E. coli.
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Antibactériens , Biofilms , Chalcones , Coreopsis , Escherichia coli , Fleurs , Sialidase , Antibactériens/pharmacologie , Antibactériens/composition chimique , Biofilms/effets des médicaments et des substances chimiques , Chalcones/pharmacologie , Chalcones/composition chimique , Coreopsis/composition chimique , Antienzymes/pharmacologie , Antienzymes/composition chimique , Escherichia coli/effets des médicaments et des substances chimiques , Fleurs/composition chimique , Cinétique , Tests de sensibilité microbienne , Simulation de docking moléculaire , Sialidase/antagonistes et inhibiteurs , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimiqueRÉSUMÉ
BACKGROUND: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa. METHODS: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up. RESULTS: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related. CONCLUSIONS: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful.
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Émotions , Tumeurs de la prostate , Humains , Mâle , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/diagnostic , Tumeurs de la prostate/psychologie , Sujet âgé , République de Corée , Adulte d'âge moyen , Biopsie , Enquêtes et questionnaires , Prise de décision , Études de cohortes , Prostate/anatomopathologieRÉSUMÉ
One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.
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The recently developed CRISPR activator (CRISPRa) system uses a CRISPR-Cas effector-based transcriptional activator to effectively control the expression of target genes without causing DNA damage. However, existing CRISPRa systems based on Cas9/Cas12a necessitate improvement in terms of efficacy and accuracy due to limitations associated with the CRISPR-Cas module itself. To overcome these limitations and effectively and accurately regulate gene expression, we developed an efficient CRISPRa system based on the small CRISPR-Cas effector Candidatus Woesearchaeota Cas12f (CWCas12f). By engineering the CRISPR-Cas module, linking activation domains, and using various combinations of linkers and nuclear localization signal sequences, the optimized eCWCas12f-VPR system enabled effective and target-specific regulation of gene expression compared with that using the existing CRISPRa system. The eCWCas12f-VPR system developed in this study has substantial potential for controlling the transcription of endogenous genes in living organisms and serves as a foundation for future gene therapy and biological research.
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Systèmes CRISPR-Cas , Humains , Régulation de l'expression des gènes , Édition de gène/méthodes , Cellules HEK293 , Protéines bactériennes/génétique , Protéines bactériennes/métabolismeRÉSUMÉ
Exposure and damage caused by noise have been reported in many countries around the world. However, few nationwide studies explored the association of residential environmental noise with depressive symptoms, this study aims to examine this association. The Korean Community Health Survey at the individual-level and the Korean Environmental Noise Measurement Database at the regional-level were used. A total of 30,630 individuals were eligible for the analysis. Multilevel model framework was applied to account for the clustered structure of the regional-level data in which individual-level data containing demographic characteristics and health information were nested. As a result of the analysis, Individuals living in the highest environmental noise area had a 1.55 times higher likelihood of experiencing depressive symptoms than those living in the lowest environmental noise area (95% CI, 1.04-2.31). After stratified analysis according to depressive symptom severity, individuals residing in areas with the highest environmental noise exposure had significantly higher odds of mild (aOR, 1.46; 95% CI, 1.02-2.07) and moderate symptoms (aOR, 1.70; 95% CI, 1.00-2.91). In conclusion, the higher the residential environmental noise, the higher the possibility of mild-to-moderate depressive symptoms. Our findings suggest the need for continued attention to and management of noise pollution, which has the potential to adversely affect individual's mental health.
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Dépression , Exposition environnementale , Analyse multiniveaux , Bruit , Humains , Femelle , Mâle , Dépression/épidémiologie , Dépression/étiologie , Adulte d'âge moyen , Exposition environnementale/effets indésirables , Bruit/effets indésirables , Adulte , République de Corée/épidémiologie , Sujet âgé , Enquêtes de santé , Jeune adulteRÉSUMÉ
Analyzing the concentration of ions in aqueous solutions in real-time plays an important role in the fields of chemistry and biology. Traditional methods for measuring ion concentrations, such as concentration analysis by measuring electrical conductivity, inductively coupled plasma mass spectrometry, and ion chromatography, have been used in many research fields. However, these methods are limited in determining ion concentrations instantaneously. Fourier-transform infrared-attenuated total reflectance (ATR-FTIR) spectroscopy provides a new approach for determining ion concentrations in aqueous solutions. This allows for fast analysis without pretreatment and is scalable for real-time measurements. In this study, we present a method for measuring ion concentrations by examining ion-water interactions in the O-H stretching band of aqueous solutions using ATR-FTIR spectroscopy. Five aqueous solutions, namely LiCl + HCl, LiOH + HCl, LiOH, Li3PO4, and NaCl were used in the experiments and prepared at concentrations between 0.5-2 M. The ion concentrations in the prepared aqueous solutions were measured using ATR-FTIR spectroscopy. We observed that the difference in absorbance increased and decreased linearly with changes in concentration. The concentration of ions in the aqueous solution could be measured by validating the designed linear regression analysis function model. In this study, we proposed five linear regression analysis function models, all of which showed high coefficients of determination above 0.9, with the highest coefficient of determination reaching 0.9969. These results show that ATR-FTIR spectroscopy has the potential to be applied as a rapid and simple concentration analysis system.
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BACKGROUND/AIMS: Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. METHODS: This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. RESULTS: The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity. CONCLUSION: In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.
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Marqueurs biologiques , Creatine kinase , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase , Glande thyroide , Thyréostimuline , Humains , Études rétrospectives , Mâle , Femelle , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/effets indésirables , Adulte d'âge moyen , Thyréostimuline/sang , Sujet âgé , Glande thyroide/effets des médicaments et des substances chimiques , Marqueurs biologiques/sang , Creatine kinase/sang , Facteurs temps , Adulte , Dyslipidémies/traitement médicamenteux , Dyslipidémies/sang , Dyslipidémies/diagnostic , Résultat thérapeutiqueRÉSUMÉ
Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.