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In recent years, researchers have studied various methods for transferring data in a network-separated environment, and the most representative method is the use of inaudible frequency signals like ultrasonic waves. This method has the advantage of being able to transfer data without other people noticing, but it has the disadvantage that speakers must exist. In a laboratory or company, external speakers may not be attached to each computer. Therefore, this paper presents a new covert channel attack that transfers data using internal speakers on the computer's motherboard. The internal speaker can also produce a sound of the desired frequency, and, therefore, data can be transferred using high frequency sounds. We encode data into Morse code or binary code and transfer it. Then we record it using a smartphone. At this time, the location of the smartphone can be any distance within 1.5 m when the length per bit is longer than 50 ms, such as on the computer body or on the desk. Data are obtained by analyzing the recorded file. Our results show that data is transferred from a network-separated computer using an internal speaker with 20 bits/s in maximum.
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BACKGROUND AND AIMS: We investigated the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genotype and the risk of diabetes mellitus (DM) using a biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) cohort and a longitudinal observational cohort. METHODS: Associations between genotypes and the prevalence of DM were evaluated with stratification according to the histological severity of NAFLD in the Boramae cohort (n = 706). A longitudinal cohort consisting of nondiabetic individuals with ≥2 health checkups was then selected to investigate the risk of incident DM according to the genotype (the GENIE cohort; n = 4998). RESULTS: Among subjects with NAFLD in the Boramae cohort, the G allele was independently associated with a lower prevalence of DM in both NAFL (odds ratio [OR] per 1 allele, 0.66; 95% confidence interval [CI], 0.46-0.97) and nonalcoholic steatohepatitis (OR per 1 allele, 0.59; 95% CI, 0.38-0.92). This result was replicated in the longitudinal GENIE cohort. The G allele was associated with a lower risk of incident DM during the median follow-up of 60 months in subjects with NAFLD (hazard ratio, 0.65; 95% CI, 0.45-0.93). In contrast, G allele carriers without NAFLD showed higher odds for DM in the context of the Boramae cohort (OR, 2.44; 95% CI, 1.00-5.95). CONCLUSIONS: These findings clarify conflicting results regarding the association between the PNPLA3 rs738409 genotype and the risk of DM, demonstrating a clear difference between subjects with and without NAFLD; this difference might be explained by the low metabolic risk in genetic NAFLD.
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Aciltransferases , Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Fosfolipases A2 Independentes de Cálcio , Aciltransferases/genética , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Predisposição Genética para Doença , Genótipo , Humanos , Lipase/genética , Lipase/metabolismo , Fígado/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Fosfolipases A2 Independentes de Cálcio/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD's effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes. METHODS: We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score. FINDINGS: During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01-1.03 for all-cause; 1.07, 1.04-1.10 for CVD; 1.12, 1.09-1.14 for cancer; and 2.63, 2.50-2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10-1.12), CVD- (HR, 95% CI 1.11, 1.09-1.14), cancer- (HR, 95% CI 1.17, 1.15-1.19), and liver disease-related (HR, 95% CI 2.38, 2.29-2.49) mortality. CONCLUSION: Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hepatopatias , Neoplasias , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Causas de Morte , Fígado Gorduroso/diagnóstico , FibroseRESUMO
The highly selective detection of trace gases using transparent sensors at room temperature remains challenging. Herein, transparent nanopatterned chemiresistors composed of aligned 1D Au-SnO2 nanofibers, which can detect toxic NO2 gas at room temperature under visible light illumination is reported. Ten straight Au-SnO2 nanofibers are patterned on a glass substrate with transparent electrodes assisted by direct-write, near-field electrospinning, whose extremely low coverage of sensing materials (≈0.3%) lead to the high transparency (≈93%) of the sensor. The sensor exhibits a highly selective, sensitive, and reproducible response to sub-ppm levels of NO2 , and its detection limit is as low as 6 ppb. The unique room-temperature NO2 sensing under visible light emanates from the localized surface plasmonic resonance effect of Au nanoparticles, thereby enabling the design of new transparent oxide-based gas sensors without external heaters or light sources. The patterning of nanofibers with extremely low coverage provides a general strategy to design diverse compositions of gas sensors, which can facilitate the development of a wide range of new applications in transparent electronics and smart windows wirelessly connected to the Internet of Things.
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Cultured muscle tissue-based protein products, also known as cultured meat, are produced through in vitro myogenesis involving muscle stem cell culture and differentiation, and mature muscle cell processing for flavor and texture. This review focuses on the in vitro myogenesis for cultured meat production. The muscle stem cell-based in vitro muscle tissue production consists of a sequential process: (1) muscle sampling for stem cell collection, (2) muscle tissue dissociation and muscle stem cell isolation, (3) primary cell culture, (4) upscaled cell culture, (5) muscle differentiation and maturation, and (6) muscle tissue harvest. Although muscle stem cell research is a well-established field, the majority of these steps remain to be underoptimized to enable the in vitro creation of edible muscle-derived meat products. The profound understanding of the process would help not only cultured meat production but also business sectors that have been seeking new biomaterials for the food industry. In this review, we discuss comprehensively and in detail each step of cutting-edge methods for cultured meat production. This would be meaningful for both academia and industry to prepare for the new era of cellular agriculture.
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Carne , Mioblastos , Técnicas de Cultura de Células , Separação Celular , Carne/análise , Músculo EsqueléticoRESUMO
OBJECTIVE: The association between nonfunctioning adrenal incidentalomas (NFAIs) and cardiometabolic diseases remains controversial. This retrospective cohort study investigated whether NFAIs are related with prevalent and incident cardiometabolic diseases. METHODS: This study included 154 patients with biochemically confirmed NFAIs and 1:3 age and sex-matched controls without adrenal incidentalomas (n = 462) among subjects who underwent abdominal computed tomography at a single healthcare center in 2003-2012. Electronic medical records were reviewed for comorbidities at baseline and during a mean follow-up of 7.5 years. The logistic regression analysis for prevalent cardiometabolic diseases and the survival analysis for incident cardiometabolic diseases were performed. RESULTS: The subjects were 55.7±8.8 years of age and predominantly male (73.1%). The NFAI group had a higher body mass index compared to the age and sex-matched control group (25.1±2.8 vs. 24.0±2.8 kg/m2; P<.001). In a cross-sectional design, covariate-adjusted logistic regression showed significantly higher odds ratios (ORs) for diabetes mellitus and hypertension in the NFAI group (adjusted OR [95% confidence interval [CI]], 1.89 [1.17 to 3.06] and 2.26 [1.47 to 3.50], respectively). The NFAI group had a 2-fold higher risk of insulin resistance (adjusted ORs [95% CI], 2.03 [1.06 to 3.90]). Moreover, NFAI subjects with diabetes mellitus had a greater increase in size of adrenal lesions than those without diabetes mellitus (3.4±5.5 vs. 1.4±5.5 mm; P =.048). However, in the survival analysis, the incidence of any cardiometabolic diseases did not differ between the NFAI and control groups. CONCLUSION: NFAIs are related to prevalent diabetes mellitus or hypertension in our cross-sectional study. However, the presence of NFAIs did not affect the development of cardiometabolic diseases. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AI = adrenal incidentaloma; BMI = body mass index; CI = confidence interval; CT = computed tomography; HbA1c = hemoglobin A1c; HOMA-IR = homeostasis model assessment of insulin resistance; HU = Hounsfield units; MACE = mild autonomous cortisol excess; NFAI = nonfunctioning adrenal incidentaloma; OR = odds ratio.
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Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/epidemiologia , Estudos Transversais , Humanos , Hidrocortisona , Estudos Longitudinais , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: Osteoporosis is hard to detect before it manifests symptoms and complications. In this study, we evaluated machine learning models for identifying individuals with abnormal bone mineral density (BMD) through an analysis of spine X-ray features extracted by deep learning to alert high-risk osteoporosis populations. MATERIALS AND METHODS: We retrospectively used data obtained from health check-ups including spine X-ray and dual-energy X-ray absorptiometry (DXA). Consecutively, we selected people with normal and abnormal bone mineral density. From the regions of interest of X-ray images, deep convolutional networks were used to generate image features. We designed prediction models for abnormal BMD using the image features trained by machine learning classification algorithms. The performances of each model were evaluated. RESULTS: From 334 participants, 170 images of abnormal (T scores < - 1.0 standard deviations (SD)) and 164 of normal BMD (T scores > = - 1.0 SD) were used for analysis. We found that a combination of feature extraction by VGGnet and classification by random forest based on the maximum balanced classification rate (BCR) yielded the best performance in terms of the area under the curve (AUC) (0.74), accuracy (0.71), sensitivity (0.81), specificity (0.60), BCR (0.70), and F1-score (0.73). CONCLUSION: In this study, we explored various machine learning algorithms for the prediction of BMD using simple spine X-ray image features extracted by three deep learning algorithms. We identified the combination for the best performance in predicting high-risk populations with abnormal BMD.
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Densidade Óssea , Aprendizado de Máquina , Osteoporose/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia/métodos , Coluna Vertebral/diagnóstico por imagem , Absorciometria de Fóton/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , República da Coreia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Although Enterococcus faecalis is known as a commensal microorganism in the gastrointestinal tract, it is linked to various foodborne infections. In addition, biofilm formation in E. faecalis is associated with the infections by exacerbating inflammation. Hence, we demonstrated that bacteriocins produced by Pediococcus acidilactici exhibited antibiofilm and anti-inflammatory activities against E. faecalis. Bacteriocins of P. acidilactici K10 and HW01 strains significantly reduced biofilm formation by E. faecalis on surfaces of polystyrene (p < 0.005 and p < 0.01 at 24 h, respectively) and stainless steel (p < 0.005 and p < 0.01 at 72 h, respectively), while both bacteriocins did not effectively reduce the growth of E. faecalis planktonic cells. Moreover, extracellular polymeric substances (EPSs) produced by E. faecalis were substantially decreased in the presence of P. acidilactici bacteriocin (p < 0.005), suggesting that E. faecalis biofilm formation was reduced by decreasing the production of EPSs, but not by killing bacteria. The bacteriocin of P. acidilactici also reduced the adhesion of E. faecalis to human intestinal epithelial cells (p < 0.005). Furthermore, both bacteriocins significantly inhibited E. faecalis-induced interleukin-8 production in human intestinal epithelial cells (p < 0.01 for K10 bacteriocin and p < 0.005 for HW01 bacteriocin). These results suggest that the bacteriocin of P. acidilactici can eradicate E. faecalis biofilms and inhibit the E. faecalis-induced inflammatory response in intestinal epithelial cells.
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Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bacteriocinas/farmacologia , Biofilmes/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Pediococcus acidilactici/química , Aderência Bacteriana , Células CACO-2 , Humanos , Viabilidade Microbiana , Aço InoxidávelRESUMO
BACKGROUND: We aim to provide sagittal and pelvic parameters according to different age groups in an asymptomatic population all over 30 years old and to investigate the possible causes of changes in these parameters. METHODS: Whole-spine, standing lateral radiographs were taken in 128 asymptomatic Korean people over 30 years old. The spinal parameters (the total thoracic kyphosis (TTK), maximal lumbar lordosis (MLL), total lumbar lordosis (TLL), lower lumbar lordosis (LLL), thoracolumbar junctional angle (TLJA), and lumbar inclination (LI)), pelvic parameters (pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT)), and spinal balance parameters (spinal balance, sacropelvic balance, and spinopelvic balance) were measured. The body mass index, body protein mass, waist line, skeletal muscle mass, and body fat mass were also measured for potential causes. RESULTS: TTK and TLJA were significantly increased in the group over 70 years of age compared to the other age groups (p = 0.0002, <0.001). TLL was significantly decreased in the group over 70 years of age (p = 0.002), whereas the PI values were similar to PI even in over 70-year age group. LLL did not differ in the group over 70 years of age (p = 0.29), gradually increasing with an increase in age. SS was significantly decreased and PT was significantly increased in the group over 70 years of age as compared to the other age groups (p = 0.049, 0.049, respectively). PI was similar in all age groups (p = 0.75). Spinal balance was significantly decreased in the group over 70 years of age (p = <0.0001). PT was significantly associated with body protein mass and skeletal muscle mass (p = 0.01, 0.001, respectively). Body protein mass and skeletal muscle mass were significantly lower in the group over 70 years of age (p = 0.02, 0.02) and were possible causes. CONCLUSIONS: Several sagittal and pelvic parameters are different in asymptomatic adults over 70 years of age. Decreased body protein mass and skeletal muscle mass are possible causes of these changes.
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Lordose/epidemiologia , Postura , Coluna Vertebral/diagnóstico por imagem , Adulto , Idoso , Doenças Assintomáticas , Feminino , Humanos , Lordose/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , República da CoreiaRESUMO
BACKGROUND: It is not clear how severe metabolic syndrome (MS) affects the development of coronary atherosclerosis. METHODS: This was an observational, retrospective cohort study with Koreans who received health check-ups voluntarily. A total of 2426 subjects had baseline and follow-up coronary artery calcium score (CACS) data. Among them, 1079 had coronary computed tomography angiography (CCTA) data. We compared baseline CACS and any progression in subjects with and without MS. A more detailed analysis was conducted for coronary artery disease (CAD), which was defined by coronary artery stenosis (≥50 %), multivessel involvement, and coronary plaques in those patients with CCTA data. RESULTS: At baseline, subjects with MS (34.0 %, n = 825) had higher CACS and more significant coronary artery stenosis, multivessel involvement, and atheromatous plaques than those without MS (P < 0.05 for all). In the follow-up (median 1197 days), subjects with MS showed significant increases in CACS and progression of CAD compared with counterparts without MS, in parallel with the numbers of MS components. Finally, MS was a significant predictor for the progression of CACS (hazard ratio 1.32; 95 % confidence interval 1.06-1.64) and progression of coronary artery stenosis and/or development of vulnerable plaque (hazard ratio 1.47, 95 % confidence interval 1.01-2.15) after adjusting for other cardiovascular risk factors. CONCLUSIONS: Subjects with MS showed progression of CAD as assessed by CACS and CCTA over ~3 years. Therefore, more vigilant screening for coronary vascular health is needed among those with MS.
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Cálcio/metabolismo , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Síndrome Metabólica/complicações , Tomografia Computadorizada Multidetectores , Adulto , Idoso , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/efeitos adversos , Placa Aterosclerótica/complicações , Estudos Retrospectivos , Fatores de Risco , Calcificação Vascular/complicaçõesRESUMO
OBJECTIVES: The purpose of this study was to stratify the malignancy risk of US features, with an emphasis on nodule echogenicity. METHODS: A total of 1,058 nodules of 824 consecutive patients (236 malignant and 822 benign) were included in this study. Malignancy risk of each nodule was analyzed according to US features, with an emphasis on nodule echogenecity, and was stratified into 4-tier categories. RESULTS: In multivariate analysis, isoechogenicity, indistinct margin, non-solid internal content, and parallel orientation were predictive of benign nodules (P < 0.002), while hypoechogenicity, marked hypoechogenicity, spiculated/microlobulated margin, solid content, nonparallel orientation (taller than wide), microcalcification, and macrocalcification were predictive of malignancy (P ≤ 0.037). Although the presence of US features associated with malignancy was significantly predictive of malignancy in hypoechoic and markedly hypoechoic nodules (P ≤ 0.004), it was not associated with malignancy in isoechoic or hyperechoic nodules. Thyroid nodules could be stratified into four categories according to the malignancy risk: benign (risk 0%), probably benign (risk ≤ 5%), indeterminate (risk > 5 and < 50%), and suspicion of malignancy (risk > 50%). CONCLUSIONS: The US-based four-tier categorization system will be useful for predicting the risk of malignancy and decisions regarding FNA for thyroid nodules. KEY POINTS: ⢠No US feature was predictive of malignancy in isoechoic nodules. ⢠Isoechoic nodules without calcification can be included in the probably benign category. ⢠We suggest a four-tier categorization stratified primarily by nodule echogenecity. ⢠The four-tier categorization of thyroid nodules will be useful for FNA decisions.
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Calcinose/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha/métodos , Calcinose/diagnóstico por imagem , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia de Intervenção/métodosRESUMO
The present study investigated the bone mineral density (BMD) and the prevalence of osteoporosis in an ossification of the ligamentum flavum (OLF) patient group and a matched control group. We also investigated the correlation of BMD with the number of spine levels exhibiting OLF. From January 1999 to August 2012, 120 patients with spinal OLF underwent dual-energy X-ray absorptiometry at our institute, and 102 of those were included in our study. Control group members were age, sex, and body mass index (BMI) matched to OLF group members on a 1:1 basis. Age, sex, and BMI were similar in the OLF and control groups. BMDs of the OLF and control groups were significantly different in the lumbar spine (mean T-scores: -0.2 ± 1.5 and -0.7 ± 1.5, respectively; p = 0.03). The prevalences of osteopenia and osteoporosis tended to be lower in the OLF group (28.3% and 4.0%, respectively) than those in the control group (31.3% and 9.1%, respectively); however, the differences were not statistically significant (p = 0.41). A significant positive correlation was detected between the lumbar spine BMD and the number of spine levels exhibiting OLF (p = 0.03).
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Densidade Óssea , Ligamento Amarelo , Ossificação Heterotópica/complicações , Osteoporose/epidemiologia , Absorciometria de Fóton , Idoso , Estudos de Casos e Controles , Feminino , Fêmur , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/patologia , Osteoporose/diagnósticoRESUMO
BACKGROUND: Primary aldosteronism (PA) is associated with increased metabolic risks. However, controversy exists as to which subtype of PA has a higher metabolic risk between bilateral and lateralized PA. This study aimed to assess the body composition of 2 PA subtypes, bilateral PA and lateralized PA, according to sex and autonomous cortisol secretion (ACS) and their contribution to comorbidities. DESIGN AND METHODS: A total of 400 patients with PA (females, n = 210) and 1:10 age- and sex-matched healthy controls (n = 4000) were enrolled. The skeletal muscle area (SMA), subcutaneous fat area, and visceral fat area (VFA) at the third lumbar spine were calculated using abdominal computed tomography-based body composition analysis. RESULTS: Patients with bilateral PA had higher body mass index (BMI) in both sexes (all P < .05). Hemoglobin A1c level and the prevalence of diabetes were higher in female patients with bilateral PA than in those with lateralized PA (all P < .05). The VFA/BMI ratio was significantly higher in bilateral PA patients than in lateralized PA patients (5.77 ± 2.69 vs 4.56 ± 2.35 in men; 4.03 ± 2.58 vs 2.53 ± 2.05 in women, all P < .001). PA patients with ACS showed decreased SMA compared to those without ACS. Compared with healthy controls, all patients with bilateral PA and female patients with lateralized PA showed significantly higher VFA and VFA/BMI. CONCLUSIONS: Patients with bilateral PA were more obese and had higher VFA levels than those with lateralized PA. Despite a milder form of PA, this metabolically unfavorable visceral fat distribution may lead to a higher metabolic risk in patients with bilateral PA.
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Diabetes Mellitus , Hiperaldosteronismo , Masculino , Humanos , Feminino , Composição Corporal , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Diabetes Mellitus/epidemiologia , Índice de Massa Corporal , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/metabolismoRESUMO
BACKGROUND: Heart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. OBJECTIVE: We aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (<50% reduction), sustainer (reference group), and increaser groups. RESULTS: During a median follow-up of 5.1 (IQR 4.0-6.1) years, there were 13,879 HF cases (7.8 per 1000 person-years). Compared to sustainers, smoking cessation was associated with lower risks of HF (adjusted hazard ratio [aHR] 0.90, 95% CI0.86-0.95), whereas increasers showed higher risks of HF than sustainers; heavy smokers who increased their level of smoking had a higher risk of HF (aHR 1.13, 95% CI 1.04-1.24). In the case of reducers, the risk of HF was not reduced but rather increased slightly (reducer I: aHR 1.14, 95% CI 1.08-1.21; reducer II: aHR 1.03, 95% CI 0.98-1.09). Consistent results were noted for subgroup analyses including type 2 diabetes severity, age, and sex. CONCLUSIONS: Smoking cessation was associated with a lower risk of HF among patients with type 2 diabetes, while increasing smoking amount was associated with a higher risk for HF than in those sustaining their smoking amount. There was no benefit from reduction in smoking amount.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , FumantesRESUMO
AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. METHODS AND RESULTS: Among 4300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2, and ASXL1, in order. During the follow-up (median 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (P < 0.001), indicating an elevated risk of ASCVD associated with CHIP [adjusted hazard ratio (HR) 2.49; 95% confidence interval (CI) 1.45-4.29; P < 0.001]. Notably, with high levels of LDL cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20; 95% CI 3.14-12.23; P < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index 4.94; 95% CI 1.08-22.53; P = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had a significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. CONCLUSION: The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.
In this cohort study of 4300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of LDL cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of 'early' stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.
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Biomarcadores , LDL-Colesterol , Hematopoiese Clonal , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , República da Coreia/epidemiologia , LDL-Colesterol/sangue , Medição de Risco , Biomarcadores/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/sangue , Fatores de Risco , Angiografia por Tomografia Computadorizada , Prevalência , Angiografia Coronária , Mutação , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/genéticaRESUMO
Age-related body composition changes such as sarcopenia and obesity affect functional decline in the elderly. We investigated the relationship between body composition parameters and functional limitation in older Korean adults. We enrolled 242 men and 231 women aged ≥ 65 yr from the Korean elderly cohort. We used appendicular skeletal muscle mass (ASM) divided by height(2) (ASM/Ht(2)) and ASM divided by weight (ASM/Wt). The isokinetic strength of knee extensor muscles were measured using an isokinetic device. Functional limitations were assessed using the Short Physical Performance Battery (SPPB) score less than nine. Men within the bottom tertile of ASM/Ht(2) confer an increased risk for functional limitation compared with those within the top tertile (OR, 6.24; 95% CI, 1.78-22.0). However, in women, subjects within the lowest ASM/Wt tertile had a higher risk compared with those within the highest tertile instead of ASM/Ht(2) (OR, 7.60; 95% CI, 2.25-25.7). Leg muscle strength remained the strong measure even after controlling for muscle mass only in women. Only large waist circumference was positively associated with functional limitation only in women. We might consider a different muscle index to assess functional limitation according to the gender.
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Composição Corporal , Joelho/fisiologia , Força Muscular/fisiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Idoso , Envelhecimento , Índice de Massa Corporal , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Obesidade/metabolismo , República da Coreia/epidemiologia , Sarcopenia/metabolismo , Fatores Sexuais , Circunferência da CinturaRESUMO
BACKGROUND: Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time. METHODS: We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project. RESULTS: A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic ß-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level. CONCLUSION: We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.
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Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Humanos , Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Jejum , Estudos Prospectivos , República da Coreia/epidemiologiaRESUMO
Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes. Methods: This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated. Results: Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02-1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09-2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40-3.00, p < 0.001). Conclusion: The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/epidemiologia , LDL-Colesterol , Hematopoiese Clonal , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de RiscoRESUMO
The seriousness of the diseases caused by aging have recently gained attention. Alzheimer's disease (AD), a chronic neurodegenerative disease, accounts for 60-80% of senile dementia cases. Continuous research is being conducted on the cause of Alzheimer's disease, and it is believed to include complex factors, such as genetic factors, the accumulation of amyloid beta plaques, a tangle of tau protein, oxidative stress, cholinergic dysfunction, neuroinflammation, and cell death. Sinapic acid is a hydroxycinnamic acid found in plant families, such as oranges, grapefruit, cranberry, mustard seeds, and rapeseeds. It exhibits various biological activities, including anti-inflammatory, anti-oxidant, anti-cancer, and anti-depressant effects. Sinapic acid is an acetylcholine esterase inhibitor that can be applied to the treatment of dementia caused by Alzheimer's disease and Parkinson's disease. However, electrophysiological studies on the effects of sinapic acid on memory and learning must still be conducted. Therefore, it was confirmed that sinapic acid was effective in long-term potentiation (LTP) using organotypic hippocampal segment tissue. In addition, the effect on scopolamine-induced learning and memory impairment was measured by oral administration of sinapic acid 10 mg/kg/day for 14 days, and behavioral experiments related to short-term and long-term spatial memory and avoidance memory were conducted. Sinapic acid increased the activity of the field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after TBS, and restored fEPSP activity in the CA1 region suppressed by scopolamine. The scopolamine-induced learning and memory impairment group showed lower results than the control group in the Y-maze, Passive avoidance (PA), and Morris water maze (MWM) experiments. Sinapic acid improved avoidance memory, short and long-term spatial recognition learning, and memory. In addition, sinapic acid weakened the inhibition of the brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and the activation of prostaglandin-endoperoxide synthase 2 (COX-2) and interleukin 1 beta (IL-1ß) induced by scopolamine in the hippocampus. These results show that sinapic acid is effective in restoring LTP and cognitive impairment induced by the cholinergic receptor blockade. Moreover, it showed the effect of alleviating the reduction in scopolamine-induced BDNF and TrkB, and alleviated neuroinflammatory effects by inhibiting the increase in COX-2 and IL-1ß. Therefore, we showed that sinapic acid has potential as a treatment for neurodegenerative cognitive impairment.
RESUMO
Cellular agriculture is an emerging research field of agribiotechnology that aims to produce agricultural products using stem cells, without sacrificing animals or cultivating crops. Cultivated meat, as a representative cellular product of cellular agriculture, is being actively researched due to global food insecurity, environmental, and ethical concerns. This review focuses on the application of stem cells, which are the seeds of cellular agriculture, for the production of cultivated meat, with emphasis on deriving and culturing muscle and adipose stem cells for imitating fresh meat. Establishing standards and safety regulations for culturing stem cells is crucial for the market entry of cultured muscle tissue-based biomaterials. Understanding stem cells is a prerequisite for creating reliable cultivated meat and other cellular agricultural biomaterials. The techniques and regulations from the cultivated meat industry could pave the way for new cellular agriculture industries in the future.