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1.
Artículo en Inglés | MEDLINE | ID: mdl-38743333

RESUMEN

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (ß2-MG), N-acetyl-ß-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for ß2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.

2.
Biomater Sci ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712883

RESUMEN

Various strategies at the microscale/nanoscale have been developed to improve oral absorption of therapeutics. Among them, gastrointestinal (GI)-transporter/receptor-mediated nanosized drug delivery systems (NDDSs) have drawn attention due to their many benefits, such as improved water solubility, improved chemical/physical stability, improved oral absorption, and improved targetability of their payloads. Their therapeutic potential in disease animal models (e.g., solid tumors, virus-infected lungs, metastasis, diabetes, and so on) has been investigated, and could be expanded to disease targeting after systemic/lymphatic circulation, although the detailed paths and mechanisms of endocytosis, endosomal escape, intracellular trafficking, and exocytosis through the epithelial cell lining in the GI tract are still unclear. Thus, this review summarizes and discusses potential GI transporters/receptors, their absorption and distribution, in vivo studies, and potential sequential targeting (e.g., oral absorption and disease targeting in organs/tissues).

3.
Environ Int ; 187: 108709, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38723457

RESUMEN

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure.

4.
BMC Biol ; 22(1): 105, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702628

RESUMEN

BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.


Asunto(s)
N-Metiltransferasa de Histona-Lisina , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Histonas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética
5.
J Hosp Infect ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740304

RESUMEN

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. RESULTS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P=0.018), abbreviated burn severity index score ≥9 (P=0.012), and mechanical ventilation (P<0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P=0.048). CONCLUSIONS: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

6.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38610526

RESUMEN

Gold nanoparticles (AuNPs) are good candidates for donor material in energy transfer systems and can easily be functionalized with various ligands on the surface with Au-S bonding. Cyclodextrin (CD) forms inclusion complexes with fluorophores due to its unique structure for host-guest interaction. In this study, we fabricated ßCD-functionalized AuNPs using different lengths of thiol ligands and recognized cholesterol to confirm the energy-transfer-based turn-on fluorescence mechanism. AuNP-ßCD conjugated with various thiol ligands and quenched the fluorescein (Fl) dye, forming ßCD-Fl inclusion complexes. As the distance between AuNPs and ßCD decreased, the quenching efficiency became higher. The quenched fluorescence was recovered when the cholesterol replaced the Fl because of the stronger binding affinity of the cholesterol with ßCD. The efficiency of cholesterol recognition was also affected by the energy transfer effect because the shorter ßCD ligand had a higher fluorescence recovery. Furthermore, we fabricated a liposome with cholesterol embedded in the lipid bilayer membrane to mimic the cholesterol coexisting with lipids in human serum. These cellular cholesterols accelerated the replacement of the Fl molecules, resulting in a fluorescence recovery higher than that of pure lipid. These discoveries are expected to give guidance towards cholesterol sensors or energy-transfer-based biosensors using AuNPs.


Asunto(s)
Oro , Nanopartículas del Metal , Humanos , Colesterol , Transferencia de Energía , Fluoresceína , Compuestos de Sulfhidrilo
7.
Clin Shoulder Elb ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38556910

RESUMEN

For most shoulder surgeons, addressing massive rotator cuff tears that have retracted ends poses a significant challenge. This study introduces a technique, termed the "sandwich augmentation technique," which incorporates the long head of the biceps tendon (LHBT) into a single-row rotator cuff repair. The procedure, performed arthroscopically with the patient in the lateral decubitus position, involves attaching the LHBT and rotator cuff tissues together to the greater tuberosity. This effectively sandwiches them within the rotator cuff footprint. The goal of this technique is to enhance the thickness of the fully interposed cuff margin, thereby providing better support for the repair. The sandwich augmentation technique, which integrates the biceps into the rotator cuff repair, has demonstrated positive clinical outcomes and moderate anatomical results. It also prevents superior migration of the humeral head in cases of large or massive rotator cuff tears. Further research is required to assess the long-term effectiveness of this procedure.

8.
BMJ Neurol Open ; 6(1): e000578, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38618152

RESUMEN

Background: The landscape of stroke care has shifted from stand-alone hospitals to cooperative networks among hospitals. Despite the importance of these networks, limited information exists on their characteristics and functional attributes. Methods: We extracted patient-level data on acute stroke care and hospital connectivity by integrating national stroke audit data with reimbursement claims data. We then used this information to transform interhospital transfers into a network framework, where hospitals were designated as nodes and transfers as edges. Using the Louvain algorithm, we grouped densely connected hospitals into distinct stroke care communities. The quality and characteristics in given stroke communities were analysed, and their distinct types were derived using network parameters. The clinical implications of this network model were also explored. Results: Over 6 months, 19 113 patients with acute ischaemic stroke initially presented to 1009 hospitals, with 3114 (16.3%) transferred to 246 stroke care hospitals. These connected hospitals formed 93 communities, with a median of 9 hospitals treating a median of 201 patients. Derived communities demonstrated a modularity of 0.904, indicating a strong community structure, highly centralised around one or two hubs. Three distinct types of structures were identified: single-hub (n=60), double-hub (n=22) and hubless systems (n=11). The endovascular treatment rate was highest in double-hub systems, followed by single-hub systems, and was almost zero in hubless systems. The hubless communities were characterised by lower patient volumes, fewer hospitals, no hub hospital and no stroke unit. Conclusions: This network analysis could quantify the national stroke care system and point out areas where the organisation and functionality of acute stroke care could be improved.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38650430

RESUMEN

Objective: Spinal intramedullary hemangioblastoma is a rare and highly vascularized benign tumor. The characteristics of the tumor, its corresponding location, and surgical outcomes remain unknown. The purpose of this study was to identify risk factors and strategies for neurologic deterioration following hemangioblastoma surgery. Methods: A comprehensive retrospective analysis was undertaken to evaluate patients who underwent surgical intervention for intramedullary hemangioblastoma at our institution from 1993 to 2022. Patients with at least one year of follow-up data were included. The analysis covered patient demographics, pre- and post-operative Modified McCormick Scale (MMCS), tumor location, and tumor size. Results: This study included 25 cases. One-year after surgery, neurological deterioration was observed in 5 (20.0%) cases, and neurological improvement was found in 9 (36.0%) cases. Five cases were ventrally located, and twelve cases were dorsally located. Ventrally located cases were larger in tumor axial size (p = 0.029) than dorsal location tumors, resulting in poorer follow-up MMCS and a higher prevalence of von Hippel-Lindau syndrome (VHL) (p = 0.042). Three of them were confirmed to be supplied by the anterior spinal artery. In the case of dorsally located cases, there was no neurologic deterioration. Conclusion: In intramedullary spinal cord hemangioblastomas, cases located ventrally had a higher incidence of neurological deterioration following surgery than those located dorsally or in intramedullary extramedullary cases. Ventrally located hemangioblastomas were larger than those in other locations. They were mainly supplied by the anterior spinal artery in VHL patients.

10.
Sci Rep ; 14(1): 9081, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643187

RESUMEN

In this study, as part of basic research aimed at enhancing the accuracy of load and resistance coefficients to ensure their suitability for practical design and promoting the application of underutilized reliability-based design in Korea, the author conducts optimal design based on the reliability analysis of a vertical-type breakwater in the seas off of Haeundae, Yeosu, Mokpo, Gunsan, and Incheon-representative ports in Korea. In doing so, the author utilized the double-loop approach, which simultaneously addresses a reliability problem nested within an optimization process, employing the Polak-He optimization algorithm. To mitigate the substantial numerical effort required by the double-loop approach based on the Polak-He optimization algorithm, which necessitates the gradients of both cost and constraint functions, the subset simulation method was employed. In this process, the author deliberately refrained from using design waves of a specific return period and linear probabilistic models such as the Gaussian distribution, especially concerning wave and lift forces, often viewed as barriers to the widespread application of reliability-based design in Korea. Instead, the author focused on characterizing the uncertainties associated with the wave force, lift force, and overturning moment-variables that significantly impact the integrity of vertical-type breakwaters-by developing probabilistic models for these random variables directly from long-term in situ wave data. These models capture the varied characteristics of the Korean marine environment from sea to sea. In this way, the need for additional assumptions concerning the interrelationship between significant wave and maximum wave heights, along with the wave period, can be eliminated. Following Occam's razor principle, which suggests that explanations constructed with the smallest possible set of assumptions are superior, the reliability-based design optimization of a vertical-type breakwater presented in this study demonstrates promise in terms of simplicity and practicality. The limit state of the vertical-type breakwater was defined to encompass sliding, overturning, and collapse failures, and the strong interrelations between the wave force, lift force, and overturning moment were described using the Nataf joint distribution. As anticipated, simulation results show that solely considering sliding failure, as in the current reliability-based design platform in Korea, leads to an underestimated failure probability. Furthermore, ensuring a consistent failure probability for vertical-type breakwaters using design waves with a specific return period, as in past studies, is not feasible. In contrast, this study demonstrated that breakwaters optimally designed to meet the reliability index requirement of ß = 3.5-4 consistently maintain a target failure probability in all sea areas.

11.
Eur J Surg Oncol ; 50(6): 108361, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38657375

RESUMEN

BACKGROUND: Locally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection. METHODS: In this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival. RESULTS: A total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015). CONCLUSION: In conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients.

12.
Nat Commun ; 15(1): 3117, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600081

RESUMEN

Solute structure and its evolution in supersaturated aqueous solutions are key clues to understand Ostwald's step rule. Here, we measure the structural evolution of solute molecules in highly supersaturated solutions of KH2PO4 (KDP) and NH4H2PO4 (ADP) using a combination of electrostatic levitation and synchrotron X-ray scattering. The measurement reveals the existence of a solution-solution transition in KDP solution, caused by changing molecular symmetries and structural evolution of the solution with supersaturation. Moreover, we find that the molecular symmetry of H2PO4- impacts on phase selection. These findings manifest that molecular symmetry and its structural evolution can govern the crystallization pathways in aqueous solutions, explaining the microscopic origin of Ostwald's step rule.

13.
Opt Lett ; 49(8): 1945-1948, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621047

RESUMEN

Group III-nitride semiconductors with tubular structures offer significant potential across various applications, including optics, electronics, and chemical sensors. However, achieving tailored fabrication of these structures remains a challenge. In this study, we present a novel, to the best of our knowledge, method to fabricate micro-sized tubular structures by rolling the layered membrane of group III-nitride alloys utilizing the photoelectrochemical (PEC) etching. To customize the geometry of the tubular structure, we conducted an analytic calculation to predict the strain and deformation for the layered membrane. Based on the calculations, we designed and fabricated an AlGaN/GaN/InGaN/n-GaN/ sapphire structure using metal-organic chemical vapor deposition (MOCVD). Photolithography and PEC etching were employed to selectively etch the sacrificial InGaN layer. We investigated the changes of optical properties of the rolled-up structure by utilizing micro-photoluminescence (µ-PL) and micro-Raman spectroscopy.

14.
Psychiatry Investig ; 21(3): 284-293, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38569586

RESUMEN

OBJECTIVE: The impact of the government-initiated senior employment program (GSEP) on geriatric depressive symptoms is underexplored. Unearthing this connection could facilitate the planning of future senior employment programs and geriatric depression interventions. In the present study, we aimed to elucidate the possible association between geriatric depressive symptoms and GSEP in older adults. METHODS: This study employed data from 9,287 participants aged 65 or older, obtained from the 2020 Living Profiles of Older People Survey. We measured depressive symptoms using the Korean version of the 15-item Geriatric Depression Scale. The principal exposure of interest was employment status and GSEP involvement. Data analysis involved multiple linear regression. RESULTS: Employment, independent of income level, showed association with decreased depressive symptoms compared to unemployment (p<0.001). After adjustments for confounding variables, participation in GSEP jobs showed more significant reduction in depressive symptoms than non-GSEP jobs (ß=-0.968, 95% confidence interval [CI]=-1.197 to -0.739, p<0.001 for GSEP jobs, ß=-0.541, 95% CI=-0.681 to -0.401, p<0.001 for non-GSEP jobs). Notably, the lower income tertile in GSEP jobs showed a substantial reduction in depressive symptoms compared to all income tertiles in non-GSEP jobs. CONCLUSION: The lower-income GSEP group experienced lower depressive symptoms and life dissatisfaction compared to non-GSEP groups regardless of income. These findings may provide essential insights for the implementation of government policies and community-based interventions.

15.
Clin Genitourin Cancer ; : 102069, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38580522

RESUMEN

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

16.
Sci Rep ; 14(1): 9440, 2024 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658799

RESUMEN

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.


Asunto(s)
Melaninas , Pteridinas , Proteínas Quinasas S6 Ribosómicas 90-kDa , Transducción de Señal , alfa-MSH , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Melaninas/biosíntesis , Melaninas/metabolismo , Animales , alfa-MSH/metabolismo , alfa-MSH/farmacología , Ratones , Línea Celular Tumoral , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Rayos Ultravioleta , Morfolinas/farmacología , Cromonas/farmacología , Nitrilos/farmacología , Butadienos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Melanoma Experimental/metabolismo , Melanogénesis
17.
J Korean Med Sci ; 39(13): e104, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38599596

RESUMEN

BACKGROUND: The hollow-fiber infection model (HFIM) is a valuable tool for evaluating pharmacokinetics/pharmacodynamics relationships and determining the optimal antibiotic dose in monotherapy or combination therapy, but the application for personalized precision medicine in tuberculosis treatment remains limited. This study aimed to evaluate the efficacy of adjusted antibiotic doses for a tuberculosis patient using HFIM. METHODS: Model-based Bayesian forecasting was utilized to assess the proposed reduction of the isoniazid dose from 300 mg daily to 150 mg daily in a patient with an ultra-slow-acetylation phenotype. The efficacy of the adjusted 150-mg dose was evaluated in a time-to-kill assay performed using the bacterial isolate Mycobacterium tuberculosis (Mtb) H37Ra in a HFIM that mimicked the individual pharmacokinetic profile of the patient. RESULTS: The isoniazid concentration observed in the HFIM adequately reflected the target drug exposures simulated by the model. After 7 days of repeated dose administration, isoniazid killed 4 log10 Mtb CFU/mL in the treatment arm, while the control arm without isoniazid increased 1.6 log10 CFU/mL. CONCLUSION: Our results provide an example of the utility of the HFIM for predicting the efficacy of specific recommended doses of anti-tuberculosis drugs in real clinical setting.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Teorema de Bayes , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología
18.
Environ Res ; 252(Pt 1): 118869, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38580000

RESUMEN

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

19.
Clin Spine Surg ; 37(4): 131-137, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38637933

RESUMEN

STUDY DESIGN: Single-center retrospective study. OBJECTIVE: The objective of this study is to identify the factors leading to repeat surgery in patients with cervical ossification of the longitudinal ligament (OPLL) during a minimal 8-year follow-up after the initial surgery. SUMMARY OF BACKGROUND DATA: The long-term effects of cervical OPLL are well known, but it's not always clear how many patients need to have surgery again because their neurological symptoms get worse. METHODS: This study is included 117 patients who underwent surgery for cervical OPLL and had a follow-up of at least 8 years. OPLL type, surgical extent, surgical method, and sagittal radiological parameters were measured, and OPLL characteristics were analyzed. RESULTS: The average age of patients at the time of surgery was 53.2 years, with a male-to-female ratio of 78:39. The median follow-up duration was 122 months (96-170 mo). Out of the total, 20 cases (17.1%) necessitated repeat surgery, among which 8 cases required surgery at the same site as the initial operation. The highest rate of repeat surgery was observed in patients who underwent total laminectomy without fusion (TL), where 6 out of 21 patients (29%) needed a second surgery, and 5 of these (23%) involved the same surgical site. Patients who underwent repeat surgery at the same site exhibited a greater range of motion (ROM) one year postsurgery (16.4 ± 8.5° vs. 23.1 ± 12.7°, P =0.041). In addition, the ROM at 1 year was higher in patients who underwent TL compared with those who had laminoplasty. Furthermore, the recurrence rate for hill-shape OPLL was higher at 30.8% compared to 10% for plateau-shape OPLL ( P = 0.05). CONCLUSION: Larger cervical ROM 1 year after surgery is related to repeat surgery at the same level as previous surgery, especially in laminectomy without fusion surgery.


Asunto(s)
Vértebras Cervicales , Osificación del Ligamento Longitudinal Posterior , Reoperación , Humanos , Osificación del Ligamento Longitudinal Posterior/cirugía , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Estudios de Seguimiento , Anciano , Laminectomía , Adulto , Estudios Retrospectivos , Resultado del Tratamiento
20.
J Occup Health ; 66(1)2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38569527

RESUMEN

OBJECTIVES: Work from home (WFH) can increase sleep disturbances. However, only few studies have examined the connection between WFH and sleep disturbance while considering work-family conflict (WFC) and the changes brought about by the COVID-19 pandemic. This study aimed to examine the association between WFH and sleep disturbance, considering WFC, and assess how this association changed during the COVID-19 pandemic. METHODS: We used data from the fifth and sixth Korean Working Conditions Survey. WFH workers and a control group were selected using propensity score matching. Conditional logistic regression analysis was used to estimate the odds ratios (ORs) with 95% CIs for sleep disturbance in the WFH and control groups. RESULTS: The workers working from home showed significantly higher ORs for sleep disturbance before (4.26; 95% CI, 3.59-5.05) and during (1.52; 95% CI, 1.26-1.83) the COVID-19 pandemic. When stratified by WFC, the association was significant only in the workers with WFC before COVID-19. However, the association was not significant during COVID-19 among the workers with WFC. CONCLUSIONS: WFH was significantly associated with sleep disturbance among workers before COVID-19, but this association was not observed during the COVID-19 pandemic. Considering the significant role that WFC plays in this association, companies should provide a family-friendly WFH environment when adopting WFH practices.


Asunto(s)
COVID-19 , Trastornos del Sueño-Vigilia , Humanos , COVID-19/psicología , COVID-19/epidemiología , Masculino , Femenino , Adulto , República de Corea/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/psicología , Persona de Mediana Edad , Teletrabajo , SARS-CoV-2 , Encuestas y Cuestionarios , Pandemias
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