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Purpose: This study aimed to validate the Geriatric Trauma Outcome Score (GTOS) for predicting mortality associated with trauma in older Korean adults and compare the GTOS with the Trauma and Injury Severity Score (TRISS). Methods: This study included patients aged ≥65 years who visited the Chungbuk National University Hospital Regional Trauma Center between January 2016 and December 2022. We used receiver operating characteristic (ROC) curves and calibration plots to assess the discrimination and calibration of the scoring systems. Results: Among 3053 patients, the median age was 77 years, and the mortality rate was 5.2%. The overall GTOS-predicted mortality and 1-TRISS were 5.4% (IQR [3.7-9.5]) and 4.7% (interquartile range [IQR] [4.7-4.7]), respectively. The areas under the curves (AUCs) of 1-TRISS and GTOS for the total population were 0.763 (95% confidence interval [CI], 0.719-0.806) and 0.794 (95%CI, 0.755-0.833), respectively. In the Glasgow Coma Scale (GCS) ≤12 group, the in-hospital mortality rate was 27.5% (79 deaths). The GTOS-predicted mortality and 1-TRISS in this group were 18.6% (IQR [7.5-34.7]) and 26.9% (IQR [11.9-73.1]), respectively. The AUCs of 1-TRISS and GTOS for the total population were 0.800 (95%CI, 0.776-0.854) and 0.744 (95%CI, 0.685-0.804), respectively. Conclusion: The GTOS and TRISS demonstrated comparable accuracy in predicting mortality, while the GTOS offered the advantage of simpler calculations. However, the GTOS tended to underestimate mortality in patients with GCS ≤12; thus, its application requires care in such cases.
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Senescence has been demonstrated to either inhibit or promote tumorigenesis. Resolving this paradox requires spatial mapping and functional characterization of senescent cells in the native tumor niche. Here, we identified senescent p16 Ink4a + cancer-associated fibroblasts with a secretory phenotype that promotes fatty acid uptake and utilization by aggressive lung adenocarcinoma driven by Kras and p53 mutations. Furthermore, rewiring of lung cancer metabolism by p16 Ink4a + cancer-associated fibroblasts also altered tumor cell identity to a highly plastic/dedifferentiated state associated with progression in murine and human LUAD. Our ex vivo senolytic screening platform identified XL888, a HSP90 inhibitor, that cleared p16 Ink4a + cancer-associated fibroblasts in vivo. XL888 administration after establishment of advanced lung adenocarcinoma significantly reduced tumor burden concurrent with the loss of plastic tumor cells. Our study identified a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype.
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BACKGROUND: Reactivation of the varicella zoster virus (VZV) results in herpes zoster (HZ), which is a painful unilateral rash with a typical dermatomal distribution. HZ may be followed by postherpetic neuralgia (PHN), vasculopathy, myelopathy, retinal necrosis, and cerebellitis. Vasculopathy can cause ischemic stroke, aneurysms, arterial dissection, transient ischemic attack, and rarely, peripheral arterial disease (PAD). The possible mechanism is that the VZV travels to the arteries through the sensory ganglia, leading to inflammation and pathological vascular remodeling, which result in vasculopathy. CASE DESCRIPTION: Here, we describe a rare case of femoral artery occlusion induced vasculopathy 5 years after HZ. A 65-year-old woman visited our pain clinic with persistent pain following HZ that occurred 3 months earlier. She had several rash scars on the right thigh along with a continuous throbbing, shooting, and sharp pain. The patient was diagnosed with PHN and prescribed with medications that relieved the leg pain. The symptoms remained stationary for almost 5 years. She presented again with complaints of a paroxysmal tingling sensation in the right thigh and claudication due to increased pain, which had begun 6 months prior. She reported leg pain after walking for 10 minutes. Lumbar spine magnetic resonance imaging (MRI) revealed foraminal stenosis at the level of right L2, with no abnormality below L2. Subsequently, the patient was evaluated for vascular diseases. Lower extremity ultrasonography and computed tomography (CT) angiography revealed stenosis and thrombotic occlusions in the right superficial femoral and tibial arteries as well as the left middle femoral and tibial arteries. Surgical revascularization via percutaneous angioplasty was performed bilaterally. The leg pain was relieved after the procedure and the claudication improved. CONCLUSIONS: Peripheral artery occlusion is a rare phenomenon following HZ. In cases involving changes in HZ symptoms, further evaluation is required for potential vasculopathy.
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Arteriopatías Oclusivas , Arteria Femoral , Herpes Zóster , Humanos , Femenino , Anciano , Herpes Zóster/complicaciones , Arteriopatías Oclusivas/etiologíaAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Sirtuina 1 , Sirtuina 2 , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Sirtuina 1/metabolismo , Sirtuina 2/antagonistas & inhibidores , Sirtuina 2/metabolismo , Metabolismo Energético , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , RatonesRESUMEN
Abnormalities in glucose metabolism that precede the onset of type 2 diabetes (T2D) activate immune cells, leading to elevated inflammatory factors and chronic inflammation. However, no single-cell RNA sequencing (scRNA-seq) studies have characterized the properties and networks of individual immune cells in T2D. Here, we analyzed peripheral blood mononuclear cells (PBMCs) from non-diabetes and T2D patients by scRNA-seq. We found that CD14 monocytes in T2D patients were in a pro-inflammatory state and intermediate monocytes expressed more MHC class II genes. In T2D patients, cytotoxic CD4 T cells, effector memory CD8 T cells, and γδ T cells have increased cytotoxicity and clonal expansion. B cells were characterized by increased differentiation into intermediate B cells, plasma cells, and isotype class switching with increased expression of soluble antibody genes. These results suggest that monocytes, T cells, and B cells could interact to induce chronic inflammation in T2D patients with pro-inflammatory characteristics.
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Diabetes Mellitus Tipo 2 , Leucocitos Mononucleares , Análisis de la Célula Individual , Humanos , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Análisis de la Célula Individual/métodos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Femenino , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Adulto , Inflamación/inmunología , Estudios de Casos y ControlesRESUMEN
Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.
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In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and proso millet, with eight different blending ratios were investigated. The total phenolic compounds and flavonoid contents ranged from 14.43-16.53 mg gallic acid equivalent/g extract and 1.22-5.37 mg catechin equivalent/g extract, respectively, depending on the blending ratio. The DI-8 blend (30% oats, 30% sorghum, 15% finger millet, 15% adzuki bean, and 10% proso millet) exhibited relatively higher antioxidant and anti-diabetic effects than other blending samples. The levels of twelve amino acids and eight organic acids in the grain mixes were measured. Among the twenty metabolites, malonic acid, asparagine, oxalic acid, tartaric acid, and proline were identified as key metabolites across the blending samples. Moreover, the levels of lactic acid, oxalic acid, and malonic acid, which are positively correlated with α-glucosidase inhibition activity, were considerably higher in the DI-blending samples. The results of this study suggest that the DI-8 blend could be used as a functional ingredient as it has several bioactive compounds and biological activities, including anti-diabetic activity.
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Antioxidantes , Grano Comestible , Antioxidantes/farmacología , Antioxidantes/química , Grano Comestible/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Flavonoides/análisis , Flavonoides/química , Flavonoides/farmacología , Fenoles/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Aminoácidos/metabolismo , Aminoácidos/análisisRESUMEN
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.
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Antirreumáticos , Artritis Reumatoide , Sinoviocitos , Pez Cebra , Animales , Humanos , Ratones , Artritis Reumatoide/tratamiento farmacológico , Células RAW 264.7 , Sinoviocitos/efectos de los fármacos , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Ratas , Masculino , Citocinas/metabolismo , Células THP-1 , Indoles/farmacología , Indoles/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratas Sprague-DawleyRESUMEN
The utilization of multi-omics research has gained popularity in clinical investigations. However, effectively managing and merging extensive and diverse datasets presents a challenge due to its intricacy. This research introduces a Multi-Omics Analysis Sandbox Toolkit, an online platform designed to facilitate the exploration, integration, and visualization of datasets ranging from single-omics to multi-omics. This platform establishes connections between clinical data and omics information, allowing for versatile analysis and storage of both single and multi-omics data. Additionally, users can repeatedly utilize and exchange their findings within the platform. This toolkit offers diverse alternatives for data selection and gene set analysis. It also presents visualization outputs, potential candidates, and annotations. Furthermore, this platform empowers users to collaborate by sharing their datasets, analyses, and conclusions with others, thus enhancing its utility as a collaborative research tool. This Multi-Omics Analysis Sandbox Toolkit stands as a valuable asset in comprehensively grasping the influence of diverse factors in diseases and pinpointing potential biomarkers.
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BACKGROUND: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence. METHODS: Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD+ and NADH levels, ATP production rate by Seahorse analyzer, and intracellular ATP content. Mitochondrial fitness was estimated by measurements of mitochondrial membrane potential, ROS, and calcium accumulation by flow cytometry, and morphology was visualized by TEM. Bioinformatic analysis, real-time qPCR, western blotting, chemical reaction prediction, and molecular docking were utilized to identify the drug target. The immunogenic potential was assessed by high mobility group box (HMGB)1 ELISA assay, luciferase-based extracellular ATP assay, ectopic calreticulin expression by flow cytometry, and validated by phagocytosis assay, and in vivo vaccination assay using syngeneic C57BL/6 mice. RESULTS: Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients' stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities. CONCLUSIONS: Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.
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Highly selective etching of silicon nitride (Si3N4) and silicon dioxide (SiO2) has received considerable attention from the semiconductor community owing to its precise patterning and cost efficiency. We investigated the etching selectivity of Si3N4 and SiO2 in an NF3/O2 radio-frequency glow discharge. The etch rate linearly depended on the source and bias powers, whereas the etch selectivity was affected by the power and ratio of the gas mixture. We found that the selectivity can be controlled by lowering the power with a suitable gas ratio, which affects the surface reaction during the etching process. X-ray photoelectron spectroscopy of the Si3N4 and QMS measurements support the effect of surface reaction on the selectivity change by surface oxidation and nitrogen reduction with the increasing flow of O2. We suggest that the creation of SiOxNy bonds on the surface by NO oxidation is the key mechanism to change the etch selectivity of Si3N4 over SiO2.
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Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.
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Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Eleusine , Simulación del Acoplamiento Molecular , Extractos Vegetales , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Eleusine/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antihipertensivos/farmacología , Antihipertensivos/química , Cromatografía Líquida de Alta Presión , Peptidil-Dipeptidasa A/metabolismo , Hipertensión/tratamiento farmacológico , Espectroscopía de Resonancia MagnéticaRESUMEN
We present the case of a victim of a motor vehicle accident in his late 60s who suffered from severe torso injuries. He initially presented with abdominal and chest pain, and underwent emergency laparotomy for hemoperitoneum. After surgery, the patient developed pneumonia and septicemia, which were responsive to antibiotics. The patient was treated with mechanical ventilation in the intensive care unit for approximately 10 days and experienced a severe weight loss of approximately 30%, but slowly recovered without dyspnea. Notably, on hospital day 24, he experienced sudden respiratory distress and flail motion of the chest wall in a general ward. This late presentation of flail chest was attributed to non-union at rib fracture sites, and was likely exacerbated by malnutrition and osteomyelitis. Surgical stabilization of rib fractures and excision of the infected rib were successfully performed. The findings from this case highlight the complexity of managing delayed onset of flail chest. The findings from this case suggest the importance of vigilance for late emerging complications in patients with trauma, even when initial symptoms are absent.
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Tórax Paradójico , Desnutrición , Osteomielitis , Fracturas de las Costillas , Traumatismos Torácicos , Heridas no Penetrantes , Humanos , Masculino , Tórax Paradójico/cirugía , Tórax Paradójico/complicaciones , Fijación Interna de Fracturas , Osteomielitis/complicaciones , Fracturas de las Costillas/complicaciones , Fracturas de las Costillas/cirugía , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/cirugía , AncianoRESUMEN
The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.
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Senescencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Fibroblastos , Fibrosis Pulmonar Idiopática , Animales , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Ratones , Humanos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/genética , Senoterapéuticos/farmacología , Masculino , Pulmón/patología , Pulmón/metabolismo , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/genéticaRESUMEN
We investigated the clinical implications of the mean corpuscular volume (MCV) in patients with major trauma. This single-center retrospective review included 2021 trauma patients admitted to the intensive care unit between January 2016 and June 2020. We included 1218 patients aged [Formula: see text] 18 years with an injury severity score [Formula: see text] 16 in the final analysis. The clinical and laboratory variables were compared between macrocytosis (defined as MCV [Formula: see text] 100 fL) and non-macrocytosis groups. Cox regression analysis was performed to calculate the hazard ratios (HRs) of variables for 30-day mortality, with adjustment for other potential confounding factors. The initial mean value of MCV was 102.7 fL in the macrocytosis group (n = 199) and 93.7 fL in the non-macrocytosis group (n = 1019). The macrocytosis group showed a significantly higher proportion of initial hypotension, transfusion within 4 and 24 h, and 30-day mortality than the non-macrocytosis group. Age ([Formula: see text] 65 years), hypotension (systolic blood pressure [Formula: see text] 90 mmHg), transfusion (within 4 h), anemia (Hb < 12 g/day in women, < 13 g/day in men), and macrocytosis were significantly associated with 30-day mortality (adjusted HR = 1.4; 95% confidence interval 1.01-1.94; p = 0.046) in major trauma patients. Thus, initial macrocytosis independently predicted 30-day mortality in patients with major trauma at a Level I trauma center.
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Anemia Macrocítica , Anemia , Deficiencia de Ácido Fólico , Hipotensión , Masculino , Humanos , Femenino , Anciano , Índices de Eritrocitos , Estudios Retrospectivos , PronósticoRESUMEN
Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.
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Neoplasias Colorrectales , Perfilación de la Expresión Génica , Humanos , Perfilación de la Expresión Génica/métodos , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodos , ARNRESUMEN
Uranyl ammonium carbonate (AUC), with the chemical formula UO2CO3·2(NH4)2CO3, plays a crucial role in the wet conversion of uranium hexafluoride (UF6) into uranium dioxide (UO2) or triuranium octaoxide (U3O8) for nuclear fuel production, and is used in commercial and research reactors. In this study, the precipitation of AUC from uranyl fluoride (UO2F2) solution and its subsequent conversion into U3O8 powder were investigated. AUC precipitation was performed at uranium concentrations in UO2F2 solution of 80-120 gL-1, ammonium carbonate (NH4)2CO3 concentrations of 200-400 gL-1, and (NH4)2CO3 to U (C/U) ratios of 5-9. The conversion of AUC into U3O8 powder was studied and sintering of the U3O8 nuclear material derived from ammonium uranyl carbonate (ex-AUC U3O8) was conducted at temperatures of 1000-1800 °C. The kinetics of AUC precipitation from the UO2F2 solution were studied using fundamental kinetic equations, and the kinetics of AUC conversion into UO3 were examined using an isoconversion method based on the thermogravimetric analysis of AUC. The final product of U3O8 nuclear material was characterized using typical techniques, such as thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. This study provides valuable insights into the production and characterization of AUC and U3O8 nuclear materials, which are key materials in the nuclear fuel industry.
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BACKGROUND: The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. METHODS: This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. RESULTS: e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. CONCLUSIONS: In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.
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Anestésicos por Inhalación , Diástole , Sevoflurano , Función Ventricular Izquierda , Humanos , Sevoflurano/administración & dosificación , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anestésicos por Inhalación/administración & dosificación , Diástole/efectos de los fármacos , Masculino , Anciano , Función Ventricular Izquierda/efectos de los fármacos , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Éteres Metílicos/administración & dosificación , Colecistectomía Laparoscópica , AdultoRESUMEN
Background: Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC). Methods: This retrospective cohort study included 11 420 participants aged ≥40â years with forced expiratory volume in 1â s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted, were further divided by low FVC (FVC <80% predicted). We estimated the 5-year progression rates of CAC by comparing participants with and without PRISm at baseline using mixed linear models. Results: Of the 11 420 participants, 8536 (75%), 811 (7%) and 2073 (18%) had normal spirometry, PRISm with normal FVC and PRISm with low FVC, respectively. During the mean (range) follow-up of 6.0 (0.5-17.2)â years, the multivariable adjusted ratio of 5-year CAC progression rates comparing participants with PRISm to those with normal spirometry was 1.08 (95% CI 1.04-1.13). This rate was higher in participants with PRISm with low FVC (1.21 (95% CI 1.12-1.30)) than in those with normal FVC. Conclusion: In this longitudinal cohort study of subjects without a history of CVD, PRISm was significantly associated with CAC progression, which was more evident in the group with PRISm and low FVC.
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OBJECTIVE: This study evaluated protective behaviors against coronavirus disease-2019 (COVID-19) and related factors in individuals with depressive symptoms. METHODS: This cross-sectional study included data from the 2020 Korean Community Health Survey. Depressive symptoms, COVID- 19 protection behaviors, and related factors were investigated in 228,485 people. Chi-square test and logistic regression analysis were used to analyze categorical variables. Statistical analysis was performed using SPSS software (version 27.0). RESULTS: In the study, 3.9% (n=8,970) had depressive symptoms. The prevalence of depressive symptoms was higher in individuals in their 19-39 years , and ≥60s than in those in their 40-59 years (p<0.001). Lower education level and household income were associated with a higher prevalence of depression (p<0.001). Among the various occupations, service workers had the highest prevalence of depressive symptoms (p<0.001). Individuals with depressive symptoms were less likely to adopt protective behaviors against COVID-19 (p<0.001) or exhibit concerns regarding death and economic damage (p<0.001) compared to individuals without depressive symptoms. Individuals with depressive symptoms were more likely to have unhealthy behaviors than those without depressive symptoms (p<0.001). Individuals with depressive symptoms considered that the COVID-19 response by the government and other organizations was inadequate (p<0.001). CONCLUSION: During the COVID-19 pandemic, individuals with depressive symptoms faced greater challenges in adopting protective behaviors. Therefore, it is crucial to develop strategies to protect people with depressive symptoms during another pandemic in the future.