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1.
Sci Rep ; 14(1): 15323, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961252

ABSTRACT

Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. This study aimed to demonstrate the ultrasonographic (US) features of TERT promoter-mutated follicular thyroid cancer (FTC) and evaluate their predictive performance. A total of 63 patients with surgically confirmed FTC between August 1995 and April 2021 were included. All data were available for analysis of preoperative US findings and TERT promoter mutation results. Genomic DNA was extracted from the archived surgical specimens to identify TERT promoter mutations. Logistic regression analysis was performed to compare US findings between TERT promoter-mutated and wild-type FTCs. Of the 63 patients with FTC, 10 (15.9%) had TERT promoter mutations. TERT promoter-mutated FTCs demonstrated significantly different US suspicion categories compared to wild-type FTCs (Ps = 0.0054 for K-TIRADS and 0.0208 for ACR-TIRADS), with a trend toward an increasing prevalence of the high suspicion category (40.0% for both K-TIRADS and ACR-TIRADS; Ps for trend = 0.0030 for K-TIRADS and 0.0032 for ACR-TIRADS). Microlobulated margins and punctate echogenic foci were independent risk factors associated with TERT promoter mutation in FTC (odds ratio = 9.693, 95% confidence interval = 1.666-56.401, p = 0.0115 for margins; odds ratio = 8.033, 95% confidence interval = 1.424-45.309, p = 0.0182 for punctate echogenic foci). There were no significant differences in the composition and echogenicity of the TERT promoter-mutated and wild-type FTCs. TERT promoter-mutated FTCs were categorized more frequently as high suspicion by the K-TIRADS and ACR-TIRADS. Based on US findings, the independent risk factors for TERT promoter mutations in FTC are microlobulated margins and punctate echogenic foci.


Subject(s)
Adenocarcinoma, Follicular , Mutation , Promoter Regions, Genetic , Telomerase , Thyroid Neoplasms , Ultrasonography , Humans , Telomerase/genetics , Female , Male , Middle Aged , Ultrasonography/methods , Adenocarcinoma, Follicular/genetics , Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Follicular/pathology , Adult , Thyroid Neoplasms/genetics , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Aged , Retrospective Studies
2.
Bioorg Chem ; 150: 107586, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38955001

ABSTRACT

Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC50 values of 0.02-0.83 µM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders.

3.
Korean Circ J ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38956940

ABSTRACT

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

4.
J Microbiol Biotechnol ; 34(7): 1491-1500, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38960876

ABSTRACT

Inflammation is a biodefense mechanism that provides protection against painful conditions such as inflammatory bowel disease, other gastrointestinal problems, and irritable bowel syndrome. Paraprobiotics have probiotic characteristics of intestinal modulation along with merits of safety and stability. In this study, heat-killed Lactiplantibacillus plantarum KU15122 (KU15122) was investigated for its anti-inflammatory properties. KU15122 was subjected to heat-killed treatment for enhancement of its safety, and its concentration was set at 8 log CFU/mL for conducting different experiments. Nitric oxide production was most remarkably reduced in the KU15122 group, whereas it was increased in the LPS-treated group. In RAW 264.7 cells, KU15122 inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. ELISA revealed that among the tested strains, KU15122 exhibited the most significant reduction in PGE2, IL-1ß, and IL-6. Moreover, KU15122 inhibited various factors involved in the nuclear factor-kappa B, activator protein-1, and mitogen-activated protein kinase pathways. In addition, KU15122 reduced the generation of reactive oxygen species. The anti-inflammatory effect of KU15122 was likely attributable to the bacterial exopolysaccharides. Conclusively, KU15122 exhibits anti-inflammatory potential against inflammatory diseases.

5.
Article in English | MEDLINE | ID: mdl-38990729

ABSTRACT

IMPORTANCE: This study identifies key risk factors for pelvic organ prolapse (POP) in Korean women, providing valuable insights for prevention and personalized care. OBJECTIVES: The aim of this study was to identify risk factors for POP in Korean women. STUDY DESIGN: This retrospective case-control study analyzed 2003-2011 Korean health checkup data in postmenopausal women diagnosed with POP (cases) and age-matched controls without POP (1:4 ratio) to identify risk factors. RESULTS: Of 2,506,271 participants, 34,648 patients were selected for the POP group and 138,592 patients were selected for the control group. The risk of POP was found to be increased with overweight (body mass index, 23-24.9: odds ratio [OR], 1.146; 95% confidence interval [CI], 1.1-1.196; body mass index, 25-29.9: OR, 1.142; 95% CI, 1.097-1.189) and multiple childbirths (2 times: OR, 1.52; 95% CI, 1.39-1.653; ≥3: OR, 1.639; 95% CI, 1.493-1.8). The risk of POP was found to be decreased with smoking (OR, 0.769; 95% CI, 0.688-0.861), alcohol drinking (3-6/week: OR, 0.65; 95% CI, 0.557-0.758), and exercise (1-2/week: OR, 0.904; 95% CI, 0.862-0.947; 3-4/week: OR, 0.896; 95% CI, 0.844-0.951; 5-6/week: OR, 0.87; 95% CI, 0.788-0.96). CONCLUSIONS: This study found that overweight and multiple childbirths were associated with an increased risk of POP. Smoking, alcohol drinking, and exercise reduced the risk of POP, but socioeconomic status, age at menarche, and age at menopause were not found to be associated with POP.

6.
J Med Internet Res ; 26: e48535, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995678

ABSTRACT

BACKGROUND: With the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. OBJECTIVE: The aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. METHODS: The models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network-recurrent neural network model from images of the vertebral bone and paravertebral muscles. RESULTS: The mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P<.001). The AUROCs of these image models were higher than those of the fracture risk assessment models (0.810 for major osteoporotic risk, 0.780 for hip fracture risk). For the clinical model using age, sex, BMI, use of steroids, smoking, possible secondary osteoporosis, type 2 diabetes mellitus, HIV, hepatitis C, and renal failure, the AUROC value in the external validation cohort was 0.749 (95% CI 0.736-0.762), which was lower than that of the image model using vertebral bones and muscles (P<.001). CONCLUSIONS: The model using the images of the vertebral bone and paravertebral muscle showed better performance than that using the images of the bone-only or clinical variables. Opportunistic CT screening may contribute to identifying patients with a high fracture risk in the future.


Subject(s)
Deep Learning , Spinal Fractures , Tomography, X-Ray Computed , Humans , Female , Male , Tomography, X-Ray Computed/methods , Aged , Spinal Fractures/diagnostic imaging , Retrospective Studies , Middle Aged , Longitudinal Studies , Spine/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/injuries
8.
Bioorg Med Chem ; 110: 117832, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39002182

ABSTRACT

Tyrosinase is a metalloenzyme that contains copper(II) ions. We designed and synthesized eight known low-molecular-weight 2-mercaptobenzoxazole (2-MBO) analogs as tyrosinase inhibitors. Our focus was on the mercapto functional group, which interacts with copper ions. Analogs 1-3 exhibited mushroom tyrosinase inhibitory activity at the nanomolar level and demonstrated strong potency with extremely low half-maximal inhibitory concentration (IC50) values of 80-90 nM for l-dopa and 100-240 nM for l-tyrosine. Analogs 2, 4, and 5 showed the most potent anti-melanogenic effects in B16F10 cells, and their mode of action was demonstrated by kinetic analysis. Their anti-melanogenic effects were similar to the tyrosinase inhibition results, suggesting that their anti-melanogenic effects could be attributed to their tyrosinase inhibitory ability. Experiments using copper-chelating activity assays and changes in tyrosinase inhibitory activity with and without CuSO4 demonstrated that 2-MBO analogs inhibit tyrosinase activity by chelating the copper ions of tyrosinase. In conclusion, the 2-MBO analogs show potential as anti-melanogenic agents with potent tyrosinase inhibitory activity.

9.
Mycobiology ; 52(3): 201-206, 2024.
Article in English | MEDLINE | ID: mdl-38948449

ABSTRACT

The species within the family Cunninghamellaceae during an investigation of soil microfungi in Korea, in which three strains were isolated from Gangwon, Chungbuk, and Gyeongbuk provinces, designated as KNUF-22-121A, KNUF-22-126A, and KNUF-22-316, respectively. Because the morphological and molecular analyses of these three strains were identical, KNUF-22-316 underwent further detailed study. Phylogenetic analyses based on the concatenated nucleotide sequences of the internal transcribed spacer region and the large subunit 28S rRNA gene revealed that the strain belonged to the genus Absidia, but occupied a distinct phylogenetic position. The strain KNUF-22-316 was compared with closely related species Absidia radiata CGMCC 3.16257T and Absidia yunnanensis CGMCC 3.16259T, morphologically different with shorter sporangiophores, smaller sporangia and columellae, and the consistent presence of collars. Here, we provide a detailed description and images of this proposed new species, which we have named Absidia microsporangia sp. nov.

10.
Molecules ; 29(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38930952

ABSTRACT

Based on the fact that substances with a ß-phenyl-α,ß-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.


Subject(s)
Agaricales , Antioxidants , Enzyme Inhibitors , Melanins , Molecular Docking Simulation , Monophenol Monooxygenase , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Agaricales/enzymology , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Mice , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Thiazolidines/chemistry , Thiazolidines/pharmacology , Cell Line, Tumor , Kinetics , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Benzylidene Compounds/pharmacology , Benzylidene Compounds/chemistry , Pyrones
11.
Trauma Surg Acute Care Open ; 9(1): e001303, 2024.
Article in English | MEDLINE | ID: mdl-38835635

ABSTRACT

The evaluation and workup of fever and the use of antibiotics to treat infections is part of daily practice in the surgical intensive care unit (ICU). Fever can be infectious or non-infectious; it is important to distinguish between the two entities wherever possible. The evidence is growing for shortening the duration of antibiotic treatment of common infections. The purpose of this clinical consensus document, created by the American Association for the Surgery of Trauma Critical Care Committee, is to synthesize the available evidence, and to provide practical recommendations. We discuss the evaluation of fever, the indications to obtain cultures including urine, blood, and respiratory specimens for diagnosis of infections, the use of procalcitonin, and the decision to initiate empiric antibiotics. We then describe the treatment of common infections, specifically ventilator-associated pneumonia, catheter-associated urinary infection, catheter-related bloodstream infection, bacteremia, surgical site infection, intra-abdominal infection, ventriculitis, and necrotizing soft tissue infection.

12.
Infect Chemother ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38859715

ABSTRACT

BACKGROUND: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. MATERIALS AND METHODS: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. RESULTS: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes. CONCLUSION: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

13.
Neuropsychiatr Dis Treat ; 20: 1331-1344, 2024.
Article in English | MEDLINE | ID: mdl-38919562

ABSTRACT

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.


This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia.

14.
Article in English | MEDLINE | ID: mdl-38918903

ABSTRACT

Background: To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with acromegaly. Methods: We prospectively enrolled adults with acromegaly scheduled for endoscopic transsphenoidal surgery. All measurements were conducted when participants were admitted for a baseline work-up for acromegaly before surgery and surveillance approximately 3 to 6 months after surgery. Respiratory event index (REI) was used as a surrogate for apnea-hypopnea index (Trial Registration: NCT03526016). Results: Of the 35 patients with acromegaly (median age, 47 years; 40% men; median body mass index, 24.4 kg/m2), 24 (68.6%) had OSA (REI ≥5/hour), 15 (42.9%) had moderate-to-severe OSA (REI ≥15/hour). At baseline, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with the REI (ρ=0.53, P=0.001). The sensitivity and negative predictive value of a Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, age, Neck circumference, and Gender (STOP-Bang) score ≥ 3 were 93.3% and 87.5%, respectively, detecting moderate-to-severe OSA. Biochemical acromegaly remission was achieved in 32 (91.4%) patients. The median difference in the REI was -9.5/hour (95% confidence interval, -13.3 to -5.3). Half of the 24 patients diagnosed with OSA preoperatively had REI <5/hour postoperatively. In a linear mixed-effects model, changes in the REI across surgery were related to changes in IGF-1 levels. Conclusion: The STOP-Bang questionnaire is a reliable tool for OSA among patients with acromegaly. Improvement in OSA severity after surgery is related to decreased IGF-1 levels.

15.
Front Public Health ; 12: 1386394, 2024.
Article in English | MEDLINE | ID: mdl-38887256

ABSTRACT

Objectives: To investigate the factor structure and verify the validity and reliability of the Korean version of the Digital Burnout Scale (DBS) among Generation Z university students. Methodology: The World Health Organization guidelines were employed in the forward and back translation, synthesis, cross-cultural adaptation, and pre-survey phases to result in the Korean version of the DBS. The Korean version was then used to collect data from 330 university students online. Construct, convergent, discriminant, and concurrent validity, and internal consistency were assessed. Findings: The Korean version of the DBS had three subscales (digital aging, digital deprivation, and emotional exhaustion) and included 24 items. The results of the confirmatory factor analysis indicated adequate model fit indices. Convergent, discriminant, and concurrent validity were satisfactory. The Cronbach's ⍺ for the overall scale was 0.95. Conclusion: The Korean version of the DBS has good reliability and validity and can be used as a tool to assess the level of risk of digital burnout and provide appropriate support and intervention. Implications: The Korean version of the DBS will serve as a framework for developing healthy digital education by grasping individual characteristics. Longitudinal research is recommended to identify factors that cause digital usage and burnout for various age groups.


Subject(s)
Psychometrics , Students , Humans , Republic of Korea , Female , Male , Reproducibility of Results , Surveys and Questionnaires , Students/psychology , Young Adult , Universities , Adult , Burnout, Professional/psychology , Factor Analysis, Statistical , Burnout, Psychological
16.
Br J Pharmacol ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38852992

ABSTRACT

BACKGROUND AND PURPOSE: Only limited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH). Glabridin, a promising anti-obesity candidate, has only limited druggability due to its low in vivo chemical stability and bioavailability. Therefore, we developed vutiglabridin (VUTI), which is based on a glabridin backbone, and investigated its mechanism of action in treating NASH in animal models. EXPERIMENTAL APPROACH: Anti-NASH effects of VUTI were determined in in vitro fatty liver models, spheroids of primary human hepatocytes and L02 normal liver cell lines. To identify VUTI possible cellular target/s, biotin-labelled VUTI was synthesized and underwent chemical proteomic analysis. Further, the evaluation of VUTI therapeutic efficacy was carried out using an amylin-NASH and high-fat (HF) diet-induced obese (DIO) mouse models. This was carried out using transcriptomic, lipidomic and proteomic analyses of the livers from the amylin-NASH mouse model. KEY RESULTS: VUTI treatment markedly reduces hepatic steatosis, fibrosis and inflammation by promoting lipid catabolism, activating autophagy and improving mitochondrial dysfunction, all of which are hallmarks of effective NASH treatment. The cellular target of VUTI was identified as paraoxonase 2 (PON2), a newly proposed protein target for the treatment of NASH, VUTI enhanced PON2 activity. The results using PON2 knockdown cells demonstrated that PON2 is important for VUTI- activation of autophagy, promoting mitochondrial function, decreasing oxidative stress and alleviating lipid accumulation under lipotoxic condition. CONCLUSION AND IMPLICATIONS: Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH.

17.
Chemosphere ; 361: 142554, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851502

ABSTRACT

Increasing multidrug-resistant pathogenic microbial around the world become a global problem, making it imperative to develop effective methods for bacterial inactivation in wastewater. In this study, we propose a multifunctional photoelectrochemical (PEC) system to successfully disinfect microbial cells and degrade orange (II) dyes. CoOx NP were synthesized by spin-coating onto hydrothermally synthesized TiO2 nanorod arrays followed by electrodeposited NiFe-LDH to develop the NiFe-LDH/CoOx NP-TiO2 NRs. Interestingly, spin-coated CoOx NP-TiO2 NRs exhibited a 1.5-fold enhancement in photocurrent (1.384 mA/cm2) than pristine TiO2 NRs (0.92 mA/cm2). A NiFe-layered double hydroxide (LDH) cocatalysts layer further exhibits the maximum photocurrent density of 1.64 mA/cm2 with IPCE of 84.5% at 1.0 VAg/AgCl at 380 nm. Furthermore, NiFe-LDH/CoOx-TiO2 NR photoanodes were effectually employed for photoelectrochemical bacteria disinfection and organic pollutant removals. With NiFe-LDH/CoOx-TiO2 NR, 99% (120 min) bacterial inactivation and 99% (60 min) orange II dye decomposition efficiency was achieved. Superoxide radicals (-O2•), hydroxyl radicals (HO•), and holes (h+) played a critical role in the PEC degradation systems. Due to the synergy between NiFe-LDH cocatalyst and CoOx interlayer, surface water oxidation reactions were accelerated over NiFe-LDH/CoOx NP-TiO2 NRs. The charge transport process in NiFe-LDH/CoOx NP-TiO2 NRs photoanode-based PEC system was proposed in detail.


Subject(s)
Electrodes , Titanium , Wastewater , Titanium/chemistry , Wastewater/chemistry , Catalysis , Electrochemical Techniques/methods , Water Pollutants, Chemical/chemistry , Hydroxides/chemistry , Waste Disposal, Fluid/methods , Photochemical Processes , Nanotubes/chemistry , Coloring Agents/chemistry , Azo Compounds/chemistry , Water Purification/methods , Disinfection/methods
18.
J ECT ; 2024 06 10.
Article in English | MEDLINE | ID: mdl-38857335

ABSTRACT

OBJECTIVES: To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate. METHODS: A total of 49 patients who underwent 405 ECT treatment sessions under general anesthesia were retrospectively analyzed. Remimazolam, propofol, and etomidate were used for 93, 138, and 174 ECT sessions, respectively. The primary outcome was durations of motor and electroencephalogram (EEG) seizure activity, whereas secondary outcomes included hemodynamics (ie, mean arterial pressure [MAP] and heart rate [HR] at various time points from induction to postanesthesia care unit [PACU] discharge), antihypertensive drugs administration after electrical stimulus, and recovery profiles (ie, length of PACU stay and incidence of postictal confusion). RESULTS: Durations of motor and EEG seizures were shorter for remimazolam than etomidate (motor, P < 0.001; EEG, P = 0.003) but similar compared with propofol (motor, P = 0.191; EEG, P = 0.850). During seizure, remimazolam showed a comparable MAP and HR to etomidate (MAP: P = 0.806; HR: P = 0.116). The antihypertensive drug use was lowest for remimazolam (6.8%), followed by propofol (35.6%) and etomidate (65.6%), and the mean length of PACU stay was comparable for remimazolam (19.7 min), propofol (22.8 min), and etomidate (24.5 min). The occurrence of postictal confusion did not differ among the 3 agents (P > 0.050). CONCLUSIONS: Remimazolam is a promising anesthetic option for ECT because of its comparable seizure profiles, stable hemodynamics, and comparable PACU stay when compared with propofol and etomidate without additional adverse events.

19.
Nurse Educ Pract ; 78: 104029, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38943761

ABSTRACT

AIM: This study aimed to identify the best available evidence of the effects of synchronous e-learning in nursing education through a meta-analysis and to compare mean effect sizes between study subgroups. BACKGROUND: With the rapid development of synchronous e-learning, adequate preparation is essential, as the formulation of effective educational strategies is crucial for learners' success. However, rather than focusing solely on using technology to implement e-learning, instructors should design education programs that meet learning objectives while considering appropriate technologies and types of interactions. DESIGN: A meta-analysis and a subgroup analysis were conducted. METHODS: English and Chinese databases including PubMed, Embase, CINAHL, Web of Science, Cochrane Library and China National Knowledge Infrastructure were searched for relevant articles published between the inception of these databases through May 2023. The search included the establishment of these databases up until May 2023. Using a search strategy, we identified 3273 potentially relevant articles. Ten primary studies were included in the final analysis. We used random effect models to synthesize effect size (ES) and accommodate heterogeneity for the main effect. Sub-group analyses were conducted to analyze the variations in effect size to investigate possible causes of heterogeneity. RESULTS: We found synchronous e-learning to be more effective compared with the control groups, with a pooled random-effects standardized mean difference of 0.51, which is a medium effect size. Regarding learning outcomes, the effect size of reactions to learning (ES = 0.91, confidence interval [CI] = 0.14, 1.67) was higher than that of the psychomotor domain (ES = 0.57, CI = 0.17, 0.98), cognitive domain (ES = 0.63, CI = 0.11, 1.15) and affective domain (ES = 0.40, CI = 0.03, 0.76). In terms of interaction types and study characteristics were more effective if the studies included learner-learner interaction (ES = 0.83, CI = 0.36, 1.29), developed regions (ES = 0.55, CI = 0.17, 0.94), undergraduate nursing students (ES = 0.56, CI = 0.32, 0.80), no randomization (ES = 0.75, CI = 0.40, 1.10) and funding support (ES = 0.78, CI = 0.41, 1.16). CONCLUSIONS: Well-designed synchronous e-learning courses should consider learners' motivations and self-directed learning abilities by providing diverse learning resources and environments. Nurse educators should develop synchronous e-learning teaching strategies that include peer interaction. The affective domain of learning in synchronous e-learning needs to be developed and considered in future research.


Subject(s)
Education, Nursing , Humans , Education, Nursing/methods , Education, Distance , Computer-Assisted Instruction/methods , Students, Nursing/psychology
20.
Sci Rep ; 14(1): 14209, 2024 06 20.
Article in English | MEDLINE | ID: mdl-38902319

ABSTRACT

Accurate prediction of difficult direct laryngoscopy (DDL) is essential to ensure optimal airway management and patient safety. The present study proposed an AI model that would accurately predict DDL using a small number of bedside pictures of the patient's face and neck taken simply with a smartphone. In this prospective single-center study, adult patients scheduled for endotracheal intubation under general anesthesia were included. Patient pictures were obtained in frontal, lateral, frontal-neck extension, and open mouth views. DDL prediction was performed using a deep learning model based on the EfficientNet-B5 architecture, incorporating picture view information through multitask learning. We collected 18,163 pictures from 3053 patients. After under-sampling to achieve a 1:1 image ratio of DDL to non-DDL, the model was trained and validated with a dataset of 6616 pictures from 1283 patients. The deep learning model achieved a receiver operating characteristic area under the curve of 0.81-0.88 and an F1-score of 0.72-0.81 for DDL prediction. Including picture view information improved the model's performance. Gradient-weighted class activation mapping revealed that neck and chin characteristics in frontal and lateral views are important factors in DDL prediction. The deep learning model we developed effectively predicts DDL and requires only a small set of patient pictures taken with a smartphone. The method is practical and easy to implement.


Subject(s)
Deep Learning , Intubation, Intratracheal , Laryngoscopy , Humans , Laryngoscopy/methods , Prospective Studies , Female , Male , Middle Aged , Adult , Intubation, Intratracheal/methods , Aged , Image Processing, Computer-Assisted/methods , Smartphone , ROC Curve
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