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The objective of our study was to develop a genetically encoded biosensor for quantification of Nedd8, a post-translational modifier that regulates cellular signals through conjugation to other proteins. Perturbations in the balance of free (i.e., unconjugated) and conjugated Nedd8 caused by defects in Nedd8 enzymes or cellular stress are implicated in various diseases. Despite the biological and biomedical importance of Nedd8 dynamics, no method exists for direct quantification of free Nedd8, hindering the study of Nedd8 and activities of its associated enzymes. Genetically encoded biosensors are established as tools to study other dynamic systems, but limitations of current biosensor design methods make them poorly suited for free Nedd8 quantification. We have developed a modular method to design genetically encoded biosensors that employs a target binding domain and two reporter domains positioned on opposite sides of the target binding site. Target quantification is based on competition between target binding and the interaction of the reporter domains. We applied our design strategy to free Nedd8 quantification by developing a selective binder for free Nedd8 and combining it with fluorescent or split nanoluciferase reporters. Our sensors produced quantifiable and specific signals for free Nedd8 and enabled real-time monitoring of deneddylation by DEN1 with a physiological substrate. Our sensor design will be useful for high-throughput screening for deneddylation inhibitors, which have potential in treatment of cancers such as acute lymphoblastic leukemia. The modular design strategy can be extended to develop genetically encoded quantitative biosensors for other proteins of interest.
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Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.
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The internal mammary artery perforator (IMAP) flap has been widely used for chest wall and neck reconstruction. The color of its skin paddle closely resembles that of facial skin, making it attractive for facial reconstruction. However, there has been insufficient investigations reporting the use of free IMAP flap. Furthermore, even in such studies, somewhat invasive procedures, including rib cartilage resection, were employed to ensure sufficient pedicle length, potentially increasing donor morbidity. Our report presents two cases of successful facial defect reconstruction using a free IMAP flap harvested with minimal donor site damage, showing its feasibility. In the first case, a 48-year-old male underwent wide excision for a malignant melanoma on his right cheek, resulting in a 4 × 4.5 cm full-thickness defect. A free IMAP flap with a 2.5 cm pedicle, was harvested without rib cartilage resection, preserving IMA main trunk, and transferred with anastomosed to the angular vessels within the defect. The second patient presented with a 4.5 × 3.5 cm basal cell carcinoma on the left cheek, necessitating wide excision and leaving a 6 × 5 cm defect. A free IMAP flap was harvested with the same approach and successfully reconstructed the defect with connected to the superficial temporal vessels using vascular bridge. Both patients were discharged complication-free, with no recurrence during 24 and 15 months of follow-up, respectively. They were highly satisfied with the final skin color and texture outcomes. Harvesting a free IMAP flap while minimizing donor morbidity may offer an attractive option for facial reconstruction.
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Colgajo Perforante , Procedimientos de Cirugía Plástica , Neoplasias Cutáneas , Humanos , Masculino , Persona de Mediana Edad , Colgajo Perforante/irrigación sanguínea , Procedimientos de Cirugía Plástica/métodos , Neoplasias Cutáneas/cirugía , Arterias Mamarias/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Carcinoma Basocelular/cirugía , Neoplasias Faciales/cirugía , Melanoma/cirugía , Colgajos Tisulares Libres/trasplante , Recolección de Tejidos y Órganos/métodos , Mejilla/cirugíaRESUMEN
BACKGROUND: Glycemic control is crucial in peritoneal dialysis (PD) patients with diabetes. Although fasting blood glucose (FBG) is the most commonly used index to measure blood glucose levels, there is currently no evidence supporting the association between FBG level and mortality risk in PD patients. METHODS: A total of 3548 diabetic PD patients between 2002 and 2018 were enrolled from the National Health Insurance Service database of Korea. We investigated the association between FBG levels and the risk of all-cause and cause-specific mortality. RESULTS: Patients with FBG levels 80-99 mg/dL exhibited the highest survival rates, whereas those with FBG levels ≥180 mg/dL had the lowest survival rates. Compared with FBG levels 80-99 mg/dL, the adjusted hazard ratios and 95% confidence interval for all-cause mortality significantly increased as follows: 1.02 (0.87-1.21), 1.41 (1.17-1.70), 1.44 (1.18-2.75), and 2.05 (1.73-2.42) for patients with FBG 100-124 mg/dL, FBG 125-149 mg/dL, FBG 150-179 mg/dL, and FBG ≥180 mg/dL, respectively. The risk for all-cause mortality also showed an increasing pattern in patients with FBG levels <80 mg/L. The risk of cardiovascular death significantly increased as FBG levels exceeded 125 mg/dL. However, the risk of infection-related and malignancy-related deaths did not show a significant increase with increasing FBG levels. CONCLUSION: There was an increase in the risk of all-cause mortality as FBG levels exceeded 125 mg/dL in PD patients with diabetes, and the risk of cardiovascular death showed a strong correlation with FBG levels compared with other causes of death.
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Glucemia , Causas de Muerte , Ayuno , Diálisis Peritoneal , Humanos , Masculino , Femenino , Diálisis Peritoneal/mortalidad , Persona de Mediana Edad , Glucemia/análisis , Ayuno/sangre , República de Corea/epidemiología , Anciano , Factores de Riesgo , Adulto , Tasa de Supervivencia , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Diabetes Mellitus/mortalidad , Diabetes Mellitus/sangreRESUMEN
The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.
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Adipogénesis , Metabolismo Energético , Fucosa , Alimentos Funcionales , Obesidad , Polisacáridos , Algas Marinas , Pez Cebra , Animales , Metabolismo Energético/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Algas Marinas/química , Fucosa/metabolismo , Adipogénesis/efectos de los fármacos , Ratones , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Humanos , Sulfatos/química , Sulfatos/metabolismo , PPAR gamma/metabolismo , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/química , Fármacos Antiobesidad/uso terapéutico , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/metabolismoRESUMEN
Trivariate joint modeling for longitudinal count data, recurrent events, and a terminal event for family data has increased interest in medical studies. For example, families with Lynch syndrome (LS) are at high risk of developing colorectal cancer (CRC), where the number of polyps and the frequency of colonoscopy screening visits are highly associated with the risk of CRC among individuals and families. To assess how screening visits influence polyp detection, which in turn influences time to CRC, we propose a clustered trivariate joint model. The proposed model facilitates longitudinal count data that are zero-inflated and over-dispersed and invokes individual-specific and family-specific random effects to account for dependence among individuals and families. We formulate our proposed model as a latent Gaussian model to use the Bayesian estimation approach with the integrated nested Laplace approximation algorithm and evaluate its performance using simulation studies. Our trivariate joint model is applied to a series of 18 families from Newfoundland, with the occurrence of CRC taken as the terminal event, the colonoscopy screening visits as recurrent events, and the number of polyps detected at each visit as zero-inflated count data with overdispersion. We showed that our trivariate model fits better than alternative bivariate models and that the cluster effects should not be ignored when analyzing family data. Finally, the proposed model enables us to quantify heterogeneity across families and individuals in polyp detection and CRC risk, thus helping to identify individuals and families who would benefit from more intensive screening visits.
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The October 29, 2022, Seoul Halloween Crowd Crush (SHCC) caused the loss of 159 lives, making it the deadliest global mass-gathering disaster between 2018 and 2022. Despite the fact that years have passed since the incident, there remains a significant gap in research addressing the mental health of citizens to evaluate their recovery progress. Therefore, in this study, a survey was conducted to assess citizens' anxiety, depression, post-traumatic stress disorder (PTSD), and well-being after the SHCC. The data were analyzed using t-tests, analysis of variance (ANOVA), correlations, a Kruskal-Wallis test, and post hoc tests. The citizens' well-being differed significantly by victimization status, with direct victims showing languishing well-being (p = .036). PTSD severity level was higher in victims and direct witnesses (p < .001). Victims and direct witnesses exhibited worse outcomes in subjective, social, and psychological well-being as well as in PTSD (p < .001). Well-being exhibited a significant negative correlation with PTSD (r = - .247, p < .001). The results of the analysis suggest the SHCC's psychological impact has endured not only for victims and direct witnesses but also for media-exposed citizens. Offering continuous psychological support and fostering positive self-perceptions and social interactions are crucial for their recovery and well-being enhancement.
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Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/epidemiología , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , República de Corea/epidemiología , Salud Mental , Depresión/epidemiología , Depresión/psicología , Encuestas y Cuestionarios , Adulto Joven , Ansiedad/epidemiología , Ansiedad/psicología , Anciano , Seúl/epidemiologíaRESUMEN
Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.
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Contaminantes Atmosféricos , Síndromes de Ojo Seco , Humanos , Estudios Retrospectivos , Masculino , Femenino , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/epidemiología , Persona de Mediana Edad , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Anciano , Material Particulado/efectos adversos , Material Particulado/análisis , Adulto , Lágrimas/metabolismo , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Humedad/efectos adversos , Conceptos Meteorológicos , Ozono/efectos adversos , Ozono/análisis , TemperaturaRESUMEN
Biocides are present in personal care (including preservatives or antibacterials), pest control, and disinfectant products (including non-agricultural insecticides, fungicides, and disinfectants), and their long-term exposure may induce adverse health effects in humans. Therefore, in this study, we assessed the exposure levels and major exposure predictors of biocides among nationally representative Korean adults. The target group included adults (≥19 years) participating in the Korean National Environmental Health Survey (KoNEHS) 2015-2020. We employed survey-weighted multiple regression analysis and conditional inference trees analysis to assess the associations between demographic characteristics, behavioral sources (including personal care product use, pesticide use, and dietary patterns), and urinary levels of phenol (triclosan [TCS]), parabens (methyl paraben [MP], ethyl paraben [EP], propyl paraben [PP], and butyl paraben [BP]), and the pyrethroid insecticide metabolite (3-phenoxybenzoic acid [3-PBA]). Urinary EP, BP, and 3-PBA levels were higher in South Korean adults compared with those in Western countries. Major exposure predictors for MP, EP, and PP included the use of personal care products such as sunscreen, makeup, and hair care products in KoNEHS 2018-2020. Major exposure predictors for TCS and BP were vegetable consumption, and those for 3-PBA were mosquitocide use during summer in KoNEHS 2018-2020. However, these predictors were not observed in KoNEHS 2015-2017. Collectively, our findings suggest that biocide exposure predictors vary according to changes in product use and diet habits of individuals. Therefore, developing strategies to mitigate biocide exposure based on the demographic and behavioral characteristics of the general population is imperative.
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BACKGROUND: With the growing popularity of the use of free flaps, surgeons may frequently encounter situations necessitating the performance of multiple free flap surgeries in a single day. Given its prolonged duration and technical complexity, concerns remain regarding their safety. This study investigated whether a single surgeon conducting multiple free flap surgeries in a day heightens the risk of complications. METHODS: Patients who underwent free flap-based reconstruction from March 2002 to May 2023 were reviewed and categorized into 3 groups: one flap per day (Group 1), multiple flaps per day on the same patient (Group 2), and multiple flaps per day on different patients (Group 3). Outcomes, particularly perfusion-related complications (PRCs), were compared. RESULTS: In total, 1910 cases were analyzed: 1570 in Group 1, 126 in Group 2, and 214 in Group 3. Over time, the proportion of cases in Group 3 increased. Group 3 had fewer breast reconstruction cases but more lower extremity reconstructions, with a higher prevalence of chronic wounds. Although the rates of PRCs varied among groups, multivariable analysis exhibited no association of performing multiple flaps in a day with their occurrence, regardless of breast or nonbreast reconstruction. The rate of arterial insufficiency was significantly higher in group 3 compared with group 1 after adjusting for other variables. CONCLUSIONS: Performing multiple free flaps in a single day may not significantly increase the risks of overall PRCs. However, there appears to be a higher incidence of arterial insufficiency, emphasizing the need for careful planning and precise execution of procedures.
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Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Humanos , Colgajos Tisulares Libres/irrigación sanguínea , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversos , Estudios Retrospectivos , Adulto , Anciano , Cirujanos/estadística & datos numéricosRESUMEN
Salted and fermented seafood (jeotgal) is known for its long shelf life and unique flavor. Despite the existence of various types of salted seafood, the factors influencing this quality have yet to be identified. These factors are essential for improving the quality of salted seafood, optimizing the fermentation process, and advancing the industrialization of fermented foods. Therefore, in this study, we explored microbial dynamics and changes in quality characteristics in three salted seafood items - salted anchovies (MJ), salted cutlass offal (GJ), and salted croakers (HJ), over a 24-month fermentation period. Distinct microbial community profiles, dominated by Tetragenococcus halophilus, Halanaerobium fermentans, and Chromohalobacter canadensis in MJ, GJ, and HJ, respectively, affect the metabolic pathways and the corresponding flavor profiles. The pH of all samples ranged from 5.7-6.0. The titratable acidity was highest in MJ at 1.4% and lowest in HJ at approximately 0.7%. Salinity was below 25% in all samples but slightly lower in MJ. Significant differences were observed in the amino acid, nucleotide, and overall metabolite profiles. MJ exhibited the highest amino acid and nitrogen-related factor levels, such as glutamic acid and hypoxanthine, enhancing flavor complexity. Correlation analysis revealed significant associations among the types, metabolites, and microbial communities. Microbial survival mechanisms in high-salt environments result in the production of unique metabolites, including umami and aroma components as well as precursors of biogenic amines, which can affect the overall quality of the final product. These differences were primarily influenced by the fish type rather than the fermentation time. Our findings provide foundational insights for enhancing fermentation strategies, improving product consistency, and advancing the industrial application of microbial management in seafood fermentation. This study not only fills a significant gap in the current understanding of fermented seafood but also outlines practical approaches for industry applications for the optimization of product quality.
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Background: Phosphatidylinositol 3-kinase (PI3K) regulates cellular development and energy homeostasis. However, the roles of its subunits in organ development remain largely unknown. Methods: We explored the roles of PI3K catalytic subunits in steroidogenic factor 1 (SF1)-expressing cells through knockout (KO) of the p110α and p110ß subunits. Results: We examined mice with a double KO of p110α and p110ß in SF1-expressing cells (p110αß KOSF1). Although these animals exhibited no significant changes in the development of the ventromedial hypothalamus, we noted pronounced hypotrophy in the adrenal cortex, testis, and ovary. Additionally, corticosterone and aldosterone levels were significantly reduced. The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110αß KOSF1 mice. Conclusion: The data demonstrate the specific roles of PI3K catalytic subunits in the development and function of SF1-expressing organs.
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OBJECTIVES: This study investigated caregivers' job image, abilities, and educational needs, which are rapidly increasing owing to an aging society. DESIGN: A self-administered written survey was conducted at 12 general hospitals in Korea from February 1, 2022 to March 15, 2023. SAMPLE: A total of 451 caregivers participated in the survey as subjects of analysis, and 560 nurses participated as external observers. MEASUREMENTS: The caregivers' self-assessment results regarding job performance, educational needs, and retraining needs were compared with those of external observers. RESULTS: Caregivers evaluated themselves significantly higher in all areas of job performance compared to the evaluations of external observers. In particular, the caregivers' self-evaluation of their abilities in "Recording and Reporting," "Basic Resuscitation," "Safety and Infection Control," and "Understanding Major Illnesses" was different from the evaluation of nurses. Both the caregivers and external observers agreed on the need for caregiver retraining, with 1-2 hours of supplementary training every 12 months being the most preferred amount of retraining. CONCLUSIONS: There was a significant difference between caregivers' self-evaluations of their capabilities and the external observers' evaluations. Therefore, systematic professional caregiver retraining is necessary.
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The ubiquitous use of mosquito repellents in homes across Asia, Africa, and South America is related with human exposure to indoor volatile organic compounds (VOCs). There are three primary types of mosquito repellents: those in the form of coils, mats, and liquids. The repellent mechanisms of these products are distinct, resulting in the generation of varying types of VOCs during the repellent process. In this study, the emission characteristics of commercial coil-, mat-, and liquid-type mosquito repellents were observed in a laboratory chamber using real-time measurement. A previously developed personal passive sampler, ePTFE PS, was used to quantify personal exposure to indoor VOCs while 86 volunteers habitually used those three representative types for 3 h in their residence. Notable increase of indoor benzene was observed for coil- and mat-type mosquito repellents, while α-pinene concentration increased significantly following the use of liquid-type mosquito repellent. The average incremental cancer risks for benzene were 10-6 to 10-4 for adults following the use of coil- and mat-type mosquito repellents. The average non-cancer risks for all chemicals were <1 after the use of three types of mosquito repellents. Considering the potential human health risks associated with byproducts (e.g., particulate matter or carbon monoxide from incomplete combustion) emitted after mosquito coil use, further research on this topic is warranted.
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Contaminación del Aire Interior , Repelentes de Insectos , Compuestos Orgánicos Volátiles , Repelentes de Insectos/análisis , Compuestos Orgánicos Volátiles/análisis , Humanos , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Vivienda , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Medición de Riesgo , Adulto , Benceno/análisis , Culicidae/efectos de los fármacosRESUMEN
Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 µg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 µg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.
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Monitoreo Biológico , Plomo , Humanos , Plomo/sangre , Plomo/toxicidad , Plomo/farmacocinética , República de Corea , Adulto , Masculino , Monitoreo Biológico/métodos , Medición de Riesgo/métodos , Toxicocinética , Femenino , Persona de Mediana Edad , Modelos Biológicos , Exposición a Riesgos Ambientales , Adulto Joven , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/sangre , Contaminantes Ambientales/farmacocinéticaRESUMEN
A nonparametric method proposed by DeLong et al in 1988 for comparing areas under correlated receiver operating characteristic curves is used widely in practice. However, the DeLong method as implemented in popular software quietly deletes individuals with any missing values, yielding potentially invalid and/or inefficient results. We simplify the DeLong algorithm using ranks and extend it to accommodate missing data by using a mixed model approach for multivariate data. Simulation results demonstrate the validity and efficiency of our procedure for data missing at random. We illustrate our proposed procedure in SAS, Stata, and R using the original DeLong data.
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Algoritmos , Área Bajo la Curva , Simulación por Computador , Curva ROC , Humanos , Modelos Estadísticos , Estadísticas no Paramétricas , Interpretación Estadística de Datos , Análisis MultivarianteRESUMEN
AIMS: Cardiovascular health is acknowledged as a crucial concern among cancer survivors. Socioeconomic status (SES) is an essential but often neglected risk factor for cardiovascular disease (CVD). We conducted this study to identify the relationship between SES and CVD mortality in cancer survivors. METHODS AND RESULTS: Using the National Health Insurance Service-National Health Examinee database, we identified cancer survivors diagnosed and surviving beyond 5 years post-diagnosis. SES was assessed based on insurance premiums and classified into 5 groups. The primary outcome was overall CVD mortality. This study analyzed 170 555 individuals (mean age 60.7 ± 11.9 years, 57.8% female). A gradual increase in risk was observed across SES groups: adjusted hazard ratios (95% confidence intervals) for overall CVD mortality were 1.15 (1.04-1.26), 1.28 (1.15-1.44), 1.31 (1.18-1.46), and 2.13 (1.30-3.49) for the second, third, and fourth quartile, and medical aid group (the lowest SES group) compared to the highest SES group, respectively (p for trend < 0.001). The lowest SES group with hypertension exhibited a 3.4-fold higher risk of CVD mortality compared to the highest SES group without hypertension. Interaction analyses revealed that low SES synergistically interacts with hypertension, heightening the risk of CVD mortality (synergy index 1.62). CONCLUSION: This study demonstrates a significant correlation between low SES and increased CVD mortality among cancer survivors. Particularly, the lowest SES group, when combined with hypertension, significantly escalates CVD mortality. Our findings underscore the critical importance of recognizing SES as a significant risk factor for CVD mortality in this population of cancer survivors.
Our population-based cohort study, involving over 170 000 cancer survivors, demonstrates a significant association between socioeconomic status (SES) and cardiovascular disease (CVD) mortality.
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PURPOSE: Comminuted coronal shear fractures of the distal humerus represent rare injuries and are difficult to treat, especially comminuted capitellum and trochlear fractures (Dubberley Type III). The on-table reconstruction technique of comminuted articular fractures may be an option, although it has not been reported in the coronal shear fracture of the distal humerus. The aim of the present case series is to determine the functional and radiological outcomes of on-table reconstructed Dubberley III fractures. METHODS: A retrospective review was conducted of 10 patients with Dubberley type III fractures in coronal shear fractures of the capitellum and trochlea who underwent an 'on-table' reconstruction technique between January 2009 and October 2019. All patients were evaluated using the disabilities of the arm, shoulder, and hand (DASH) score, American Shoulder and Elbow Surgeons(ASES) score, Mayo Elbow Score Performance Index (MEPI) score and at least 4 years later. RESULTS: All cases achieved union. At the final follow-up, the mean range of elbow motion was 11.5°of flexion contracture and 131.9° of further flexion. The mean DASH score was 21.2 (5.7) points (range 13.3-32.5). The mean ASES score was 88.6 ± 7.4 (range, 77 to 100). The mean MEPI score was 87 (10) points (range 70-100). In complication, partial osteonecrosis of capitellum is developed in one patient. One patient had heterotopic ossification without functional impairment. CONCLUSION: The on-table reconstruction technique can be a reliable option in the surgical treatment of complex distal humerus fractures. This technique allows anatomical reduction of comminuted capitellum and trochlea, with a low risk of avascular necrosis over 4 years of follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.
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Articulación del Codo , Fracturas Conminutas , Fracturas del Húmero , Rango del Movimiento Articular , Humanos , Masculino , Estudios Retrospectivos , Femenino , Fracturas del Húmero/cirugía , Fracturas del Húmero/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Fracturas Conminutas/cirugía , Fracturas Conminutas/diagnóstico por imagen , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Fijación Interna de Fracturas/métodos , Anciano , Estudios de Seguimiento , Procedimientos de Cirugía Plástica/métodos , Adulto JovenRESUMEN
BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.