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BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/etiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Factores de Transcripción Forkhead/metabolismo , Longevidad/genética , Chaperonas Moleculares/metabolismo , Factores de Transcripción/metabolismo , Animales , Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Intestinos/fisiología , Chaperonas Moleculares/genética , Unión Proteica , Transducción de Señal/genética , Tejido Subcutáneo/fisiología , Activación Transcripcional/genéticaRESUMEN
Aging is associated with changes in a variety of biological processes at the transcriptomic level, including gene expression. Two types of aging occur during a lifetime: chronological and physiological aging. However, dissecting the difference between chronological and physiological ages at the transcriptomic level has been a challenge because of its complexity. We analyzed the transcriptomic features associated with physiological and chronological aging using Caenorhabditis elegans as a model. Many structural and functional transcript elements, such as noncoding RNAs and intron-derived transcripts, were up-regulated with chronological aging. In contrast, mRNAs with many biological functions, including RNA processing, were down-regulated with physiological aging. We also identified an age-dependent increase in the usage of distal 3' splice sites in mRNA transcripts as a biomarker of physiological aging. Our study provides crucial information for dissecting chronological and physiological aging at the transcriptomic level.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , Perfilación de la Expresión Génica , Proteínas de Caenorhabditis elegans/genética , TranscriptomaRESUMEN
Circular RNA (circRNA) is a closed, single-stranded transcript widely detected in eukaryotes. Recent studies indicate that the levels of circRNAs change with age in various tissues in multiple species, ranging from nematodes to mammals. Here we discuss the functional roles of circRNAs in animal aging and longevity. We review studies regarding the differential expression of circRNAs that contributes to cellular senescence and the pathogenesis of aging-associated diseases. We explore the features of aging-associated circRNAs by discussing their potential as biomarkers of aging, tissue specificity, physiological roles, action mechanisms, and evolutionarily conserved characteristics. Our review provides insights into current progress in circRNA research and their significant functions in the aging process.
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Envejecimiento/genética , ARN Circular/fisiología , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Marcadores Genéticos , Humanos , Mamíferos/genética , Mamíferos/fisiologíaRESUMEN
BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.
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Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo , Humanos , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodos , Corteza Prefrontal , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/terapia , Giro del Cíngulo/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
INTRODUCTION: The long-term cognitive outcomes after transient global amnesia (TGA) have been contradictory in the literature. Our study aimed to longitudinally investigate the association between TGA and incident dementia using long-term data from a nationwide population-based cohort in South Korea. METHODS: The study population was recruited between 2002 and 2020 using the International Classification of Diseases (Tenth Revision; ICD-10) codes from the Korean National Health Insurance Service database. The cumulative incidence curve was plotted to compare the incidence of dementia between the TGA (ICD-10 code G45.4; n = 10,276) and non-TGA (n = 27,389) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression models, we obtained crude and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident dementia in patients with TGA compared to non-TGA controls. To examine independent variables determining dementia in the TGA group, logistic regression analysis was performed, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of dementia than the non-TGA group (p < 0.001, log-rank test). TGA was significantly associated with incident dementia in the univariate and multivariate Cox models (HR 1.34, 95% CI 1.28-1.39 and aHR 1.40, 95% CI 1.34-1.46, respectively). The adjusted logistic regression for incident dementia in the TGA group showed that age (per 1 year, aOR 1.09, 95% CI 1.09-1.10), female sex (aOR 1.31, 95% CI 1.18-1.45), diabetes (aOR 1.21, 95% CI 1.08-1.35), stroke (aOR 1.30, 95% CI 1.16-1.46), depression (aOR 1.53, 95% CI 1.33-1.76), anxiety (aOR 1.24, 95% CI 1.01-1.39), and rural residence (aOR 1.24, 95% CI 1.10-1.41) were independently associated with incident dementia. CONCLUSION: Our results suggest a longitudinal association of TGA with incident dementia.
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Amnesia Global Transitoria , Demencia , Humanos , Masculino , Femenino , Demencia/epidemiología , República de Corea/epidemiología , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Amnesia Global Transitoria/epidemiología , Estudios de Seguimiento , Incidencia , Factores de Riesgo , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization. METHODS: The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation. RESULTS: BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, ß-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels. CONCLUSION: BKC could be a drug candidate for the treatment of allergic asthma.
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Asma , Macrófagos , Ratones Endogámicos BALB C , Ovalbúmina , Animales , Asma/tratamiento farmacológico , Asma/inducido químicamente , Asma/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Femenino , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Células Th2/inmunología , Células Th2/efectos de los fármacos , Lipopolisacáridos , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community. METHOD: This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes. RESULTS: 7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate. CONCLUSION: In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.
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Células 3T3-L1 , Adipocitos , Adipogénesis , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Obesidad , Animales , Dieta Alta en Grasa/efectos adversos , Adipogénesis/efectos de los fármacos , Obesidad/metabolismo , Ratones , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Masculino , PPAR gamma/metabolismo , PPAR gamma/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Estearoil-CoA Desaturasa/metabolismo , Estearoil-CoA Desaturasa/genética , Ratones Obesos , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Adipoquinas/metabolismo , Fármacos Antiobesidad/farmacología , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Proteínas Potenciadoras de Unión a CCAATRESUMEN
BACKGROUND: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. METHODS: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1-9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7-9 (agreement) and fewer than 15% scored 1-3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall's coefficient of concordance were evaluated. RESULTS: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one's quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere's disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, "There are no reliable biomarkers for sensory or emotional factors of tinnitus." reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. CONCLUSION: We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.
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Consenso , Técnica Delphi , Acúfeno , Acúfeno/diagnóstico , Humanos , República de Corea , Encuestas y Cuestionarios , Calidad de Vida , Femenino , MasculinoRESUMEN
Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs.
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Proteínas de Caenorhabditis elegans/genética , Alimentos , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica , Insulina/genética , Longevidad/genética , Hormonas Peptídicas/genética , Proteínas de Caenorhabditis elegans/metabolismo , Señales (Psicología) , Ambiente , Factores de Transcripción Forkhead/metabolismo , Insulina/metabolismo , Optogenética , Hormonas Peptídicas/metabolismo , Células Receptoras Sensoriales/fisiología , Transducción de SeñalRESUMEN
Methane is a major greenhouse gas, and methanotrophs regulate the methane level in the carbon cycle. Soluble methane monooxygenase (sMMO) is expressed in various methanotroph genera, including Alphaproteobacteria and Gammaproteobacteria, and catalyzes the hydroxylation of methane to methanol. It has been proposed that MmoR regulates the expression of sMMO as an enhancer-binding protein under copper-limited conditions; however, details on this transcriptional regulation remain limited. Herein, we elucidate the transcriptional pathway of sMMO depending on copper ion concentration, which affects the interaction of MmoR and sigma factor. MmoR and sigma-54 (σ54) from Methylosinus sporium 5 were successfully overexpressed in Escherichia coli and purified to investigate sMMO transcription in methanotrophs. The results indicated that σ54 binds to a promoter positioned -24 (GG) and -12 (TGC) upstream between mmoG and mmoX1. The binding affinity and selectivity are lower (Kd = 184.6 ± 6.2 nM) than those of MmoR. MmoR interacts with the upstream activator sequence (UAS) with a strong binding affinity (Kd = 12.5 ± 0.5 nM). Mutational studies demonstrated that MmoR has high selectivity to its binding partner (ACA-xx-TGT). Titration assays have demonstrated that MmoR does not coordinate with copper ions directly; however, its binding affinity to UAS decreases in a low-copper-containing medium. MmoR strongly interacts with adenosine triphosphate (Kd = 62.8 ± 0.5 nM) to generate RNA polymerase complex. This study demonstrated that the binding events of both MmoR and σ54 that regulate transcription in M. sporium 5 depend on the copper ion concentration. IMPORTANCE This study provides biochemical evidence of transcriptional regulation of soluble methane monooxygenase (sMMO) in methanotrophs that control methane levels in ecological systems. Previous studies have proposed transcriptional regulation of MMOs, including sMMO and pMMO, while we provide further evidence to elucidate its mechanism using a purified enhancer-binding protein (MmoR) and transcription factor (σ54). The characterization studies of σ54 and MmoR identified the promoter binding sites and enhancer-binding sequences essential for sMMO expression. Our findings also demonstrate that MmoR functions as a trigger for sMMO expression due to the high specificity and selectivity for enhancer-binding sequences. The UV-visible spectrum of purified MmoR suggested an iron coordination like other GAF domain, and that ATP is essential for the initiation of enhancer elements. Binding assays indicated that these interactions are blocked by the copper ion. These results provide novel insights into gene regulation of methanotrophs.
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Cobre , Regulación Bacteriana de la Expresión Génica , Cobre/metabolismo , Oxigenasas/metabolismo , Proteínas de Unión al ADN/genética , Metano/metabolismoRESUMEN
Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T Citotóxicos , Linfocitos BRESUMEN
Metastatic cancer cells can develop anoikis resistance in the absence of substrate attachment and survive to fight tumors. Anoikis is mediated by endogenous mitochondria-dependent and exogenous death receptor pathways, and studies have shown that caspase-8-dependent external pathways appear to be more important than the activity of the intrinsic pathways. This paper reviews the regulation of anoikis by external pathways mediated by death receptors. Different death receptors bind to different ligands to activate downstream caspases. The possible mechanisms of Fas-associated death domain (FADD) recruitment by Fas and TNF receptor 1 associated-death domain (TRADD) recruitment by tumor necrosis factor receptor 1 (TNFR1), and DR4- and DR5-associated FADD to induce downstream caspase activation and regulate anoikis were reviewed. This review highlights the possible mechanism of the death receptor pathway mediation of anoikis and provides new insights and research directions for studying tumor metastasis mechanisms. Video Abstract.
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Anoicis , Caspasas , Proteolisis , Mitocondrias , Procesamiento Proteico-PostraduccionalRESUMEN
BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established. METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis. RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3. CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.
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Colecistectomía Laparoscópica , Colecistitis Aguda , Neoplasias de la Vesícula Biliar , Humanos , Adulto , Femenino , Anciano de 80 o más Años , Persona de Mediana Edad , Masculino , Colecistectomía Laparoscópica/efectos adversos , Neoplasias de la Vesícula Biliar/etiología , Estudios Retrospectivos , Colecistitis Aguda/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: To compare the short-term outcomes of robotic single-site cholecystectomy (RSSC) with single-incision laparoscopic cholecystectomy (SILC) and conventional multiport laparoscopic cholecystectomy (CMLC), focusing on postoperative pain outcomes. METHODS: This single-center retrospective study included consecutive patients with benign gallbladder disease who underwent cholecystectomy by a single surgeon between June 2019 and December 2021. Exclusion criteria were acute cholecystitis (AC) and other combined surgeries. One-to-one propensity score matching was performed between the RSSC and SILC or CMLC. RESULTS: Of the 157 patients included, 39 (24.8%) underwent RSSC, 32 (20.4%) underwent SILC, and 86 (54.8%) underwent CMLC. In a propensity score-matched cohort between RSSC and SILC (32 patients in each group), the number of additional analgesic injections was significantly lower in the RSSC group than in the SILC group (0.7 vs. 1.3, p = 0.002), and postoperative pain scores were also significantly lower at 6 h (2.8 vs. 3.6, p = 0.004) and 24 h (2.6 vs. 3.3, p = 0.021) after surgery in the RSSC group than in the SILC group. In a propensity score-matched cohort between RSSC and CMLC (23 patients in each group), the number of additional analgesic injections was significantly lower in the RSSC group than in the CMLC group (0.7 vs. 1.3, p = 0.005), and postoperative pain scores were also significantly lower at 6 h after surgery (2.9 vs. 3.7, p = 0.025) in the RSSC group than in the CMLC group. CONCLUSION: This study demonstrated that RSSC is helpful in reducing postoperative pain and the use of additional analgesics compared to both SILC and CMLC.
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Colecistectomía Laparoscópica , Procedimientos Quirúrgicos Robotizados , Humanos , Colecistectomía Laparoscópica/efectos adversos , Estudios Retrospectivos , Colecistectomía , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & controlRESUMEN
The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Retículo Endoplásmico/metabolismo , Proteostasis/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Hexosiltransferasas/metabolismo , Inmunidad Innata/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas de la Membrana/metabolismo , Pseudomonas aeruginosa/metabolismo , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Respuesta de Proteína Desplegada/fisiología , Regulación hacia Arriba/fisiología , Vitelogeninas/metabolismoRESUMEN
BACKGROUND: Although previous studies have reported differences of blood pressure (BP) according to BP measurement methods, studies in Korean population were scarce. This study aimed to compare BP differences according to different BP measurement methods and assess hypertension phenotype. METHODS: This prospective study recruited 183 individuals (mean 55.9 years; 51.4% males). The BP measurements included office BP (auscultatory attended office BP [ausAOBP], automated attended office BP [aAOBP], and automated unattended office BP [aUAOBP]) and out-of-office BP (home BP [HBP] and ambulatory BP [ABP]) measurements taken within one week of each other. RESULTS: The mean systolic/diastolic BP differences between ausAOBP and other BPs according to different BP measurement methods were 3.5/2.3 mmHg for aAOBP; 6.1/2.9 mmHg for aUAOBP; 15.0/7.3 mmHg for daytime ABP; and 10.6/3.4 mmHg for average HBP. The increasing disparity between ausAOBP and other BPs in multivariable regression analysis was significantly associated with increasing BP. The prevalence of white-coat hypertension and masked hypertension in 107 individuals not taking antihypertensive medication was 25.4-26.8% and 30.6-33.3% based on ausAOBP, daytime ABP, and average HBP, respectively. The prevalence of white-coat uncontrolled hypertension and masked uncontrolled hypertension in 76 of those taking antihypertensive medication was 31.7-34.1% and 17.1-37.1%, respectively. CONCLUSION: This study showed a large disparity between office BP and out-of-office BP which became more pronounced when office BP by auscultation increased, suggesting that various BP measurement methods should be used to more accurately assess BP status.
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Monitoreo Ambulatorio de la Presión Arterial , Hipertensión , Masculino , Humanos , Femenino , Presión Sanguínea/fisiología , Antihipertensivos/uso terapéutico , Estudios Prospectivos , Hipertensión/epidemiologíaRESUMEN
This study presents an efficient super-resolution (SR) method for targets observed by satellite synthetic aperture radar (SAR). First, a small target image is extracted from a large-scale SAR image and undergoes proper preprocessing. The preprocessing step is adaptively designed depending on the types of movements of targets. Next, the principal scattering centers of targets are extracted using the compressive sensing technique. Subsequently, an impulse response function (IRF) of the satellite SAR system (IRF-S) is generated using a SAR image of a corner reflector located at the calibration site. Then, the spatial resolution of the IRF-S is improved by the spectral estimation technique. Finally, according to the SAR signal model, the super-resolved IRF-S is combined with the extracted scattering centers to generate a super-resolved target image. In our experiments, the SR capabilities for various targets were investigated using quantitative and qualitative analysis. Compared with conventional SAR SR methods, the proposed scheme exhibits greater robustness towards improvement of the spatial resolution of the target image when the degrees of SR are high. Additionally, the proposed scheme has faster computation time (CT) than other SR algorithms, irrespective of the degree of SR. The novelties of this study can be summarized as follows: (1) the practical design of an efficient SAR SR scheme that has robustness at a high SR degree; (2) the application of proper preprocessing considering the types of movements of targets (i.e., stationary, moderate motion, and complex motion) in SAR SR processing; (3) the effective evaluation of SAR SR capability using various metrics such as peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), focus quality parameters, and CT, as well as qualitative analysis.
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Compresión de Datos , Radar , Algoritmos , Relación Señal-RuidoRESUMEN
Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.
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Envejecimiento/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Ácidos Grasos/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Factores de Transcripción/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/enzimología , Proteínas de Caenorhabditis elegans/genética , Dieta , Sacarosa en la Dieta/farmacología , Inducción Enzimática/efectos de los fármacos , Ácido Graso Desaturasas/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Estudio de Asociación del Genoma Completo , Glucosa/metabolismo , Glucosa/farmacología , Glucosa/toxicidad , Interferencia de ARN , Proteínas de Unión a los Elementos Reguladores de Esteroles/genética , Factores de Transcripción/genéticaRESUMEN
Ligand of Numb-protein X 2 (LNX2) is an E3 ubiquitin ligase that is known to regulate Notch signaling by participating in NUMB protein degradation. Notch signaling is important for differentiation and proliferation in mammals, and plays a significant role in blastocyst formation during early embryonic development. In this study, we investigated Lnx2 in mouse preimplantation embryos. Expression analysis showed that Lnx2 is expressed in oocytes and preimplantation embryos. Lnx2-knockdown embryos normally progress to the morula stage, but the majority of them do not develop into normal blastocysts. Transcript analysis revealed that the expression levels of genes critical for cell lineage specification, including octamer-binding transcription factor 4 (Oct4), are increased in Lnx2 knockdown embryos. Furthermore, the expression levels of Notch and Hippo signaling-related genes are also increased by Lnx2 knockdown. Collectively, our results show that Lnx2 is important for blastocyst formation in mice, suggest that this may act via lineage specification of inner cell mass, and further show that Lnx2 may be involved in transcriptionally regulating various genes implicated in early embryonic development.