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BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.
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Ejercicio Físico , Accidente Cerebrovascular Isquémico , Neoplasias , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Neoplasias/epidemiología , Neoplasias/complicaciones , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Anciano , Factores de Riesgo , Adulto , Supervivientes de Cáncer/estadística & datos numéricos , República de Corea/epidemiología , Incidencia , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
OBJECTIVE: To examine the associations between the allergic triad (asthma, allergic rhinitis, atopic dermatitis) and risk of dementia. METHODS: Participants comprised 6,785,948 adults aged ≥40 years who participated in a national health examination in 2009 without any history of dementia before baseline. From 2009 to 2017, we prospectively investigated the associations between physician-diagnosed allergic diseases and risk of incident dementia (all-cause, Alzheimer's disease [AD], vascular dementia [VaD]) ascertained using national health insurance claims data. RESULTS: During 8.1 years of follow-up, 260,705 dementia cases (195,739 AD, 32,789 VaD) were identified. Allergic diseases were positively associated with dementia risk. Compared with individuals without allergic diseases, multivariable hazard ratios (HRs) of all-cause dementia were 1.20 (95% confidence interval [CI] 1.19-1.22) in those with asthma, 1.10 (95% CI 1.09-1.12) with allergic rhinitis, 1.16 (95% CI 1.11-1.21) with atopic dermatitis, and 1.13 (95% CI 1.12-1.14) with any of these allergies. Similarly, individuals with any of the allergic triad had a higher risk of AD (HR 1.16, 95% CI 1.14-1.17) and VaD (HR 1.04; 95% CI 1.01-1.06) than those without any allergic disease. As the number of comorbid allergic diseases increased, the risk of dementia increased linearly (Ptrend ≤ 0.002). Compared with individuals without allergies, those with all three allergic diseases had substantially increased risk of all-cause dementia (HR 1.54, 95% CI 1.35-1.75), AD (HR 1.46; 95% CI 1.25-1.70), and VaD (HR 1.99, 95% CI 1.44-2.75). INTERPRETATION: Asthma, allergic rhinitis, and atopic dermatitis were significantly associated with increased risk of all-cause dementia and subtypes, with dose-effect relationships with the severity of allergic diseases. ANN NEUROL 2023;93:384-397.
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Enfermedad de Alzheimer , Asma , Demencia Vascular , Dermatitis Atópica , Rinitis Alérgica , Adulto , Humanos , Enfermedad de Alzheimer/epidemiología , Asma/epidemiología , Rinitis Alérgica/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. METHODS: This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 103/µL) / HDL cholesterol (mmol/L). RESULTS: In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [ß = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07-1.91], and CMB (aOR = 1.51, 95% CI = 1.03-2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P < 0.001), lacunes (P < 0.001), and CMBs (P < 0.001). CONCLUSIONS: High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs.
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Enfermedades de los Pequeños Vasos Cerebrales , Monocitos , Humanos , Masculino , Persona de Mediana Edad , HDL-Colesterol , Estudios Retrospectivos , Estudios Transversales , Imagen por Resonancia Magnética , Inflamación/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/complicacionesRESUMEN
Bone morphogenetic proteins (BMPs) have tremendous therapeutic potential regarding the treatment of bone and musculoskeletal disorders due to their osteo-inductive ability. More than twenty BMPs have been identified in the human body with various functions, such as embryonic development, skeleton genesis, hematopoiesis, and neurogenesis. BMPs can induce the differentiation of MSCs into the osteoblast lineage and promote the proliferation of osteoblasts and chondrocytes. BMP signaling is also involved in tissue remodeling and regeneration processes to maintain homeostasis in adults. In particular, growth factors, such as BMP-2 and BMP-7, have already been approved and are being used as treatments, but it is unclear as to whether they are the most potent BMPs that induce bone formation. According to recent studies, BMP-9 is known to be the most potent inducer of the osteogenic differentiation of mesenchymal stem cells, both in vitro and in vivo. However, its exact role in the skeletal system is still unclear. In addition, research results suggest that the molecular mechanism of BMP-9-mediated bone formation is also different from the previously known BMP family, suggesting that research on signaling pathways related to BMP-9-mediated bone formation is actively being conducted. In this study, we performed a phosphorylation array to investigate the signaling mechanism of BMP-9 compared with BMP-2, another influential bone-forming growth factor, and we compared the downstream signaling system. We present a mechanism for the signal transduction of BMP-9, focusing on the previously known pathway and the p53 factor, which is relatively upregulated compared with BMP-2.
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Factor 2 de Diferenciación de Crecimiento , Osteogénesis , Humanos , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular , Factor 2 de Diferenciación de Crecimiento/metabolismo , Osteoblastos/metabolismo , Periostio/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
In rodents, eating at atypical circadian times, such as during the biological rest phase when feeding is normally minimal, reduces fertility. Prior findings suggest this fertility impairment is due, at least in part, to reduced mating success. However, the physiological and behavioral mechanisms underlying this reproductive suppression are not known. In the present study, we tested the hypothesis that mistimed feeding-induced infertility is due to a disruption in the normal circadian timing of mating behavior and/or the generation of pre-ovulatory luteinizing hormone (LH) surges (estrogen positive feedback). In the first experiment, male+female mouse pairs, acclimated to be food restricted to either the light (mistimed feeding) or dark (control feeding) phase, were scored for mounting frequency and ejaculations over 96 h. Male mounting behavior and ejaculations were distributed much more widely across the day in light-fed mice than in dark-fed controls and fewer light-fed males ejaculated. In the second experiment, the timing of the LH surge, a well characterized circadian event driven by estradiol (E2) and the SCN, was analyzed from serial blood samples taken from ovariectomized and E2-primed female mice that were light-, dark-, or ad-lib-fed. LH concentrations peaked 2 h after lights-off in both dark-fed and ad-lib control females, as expected, but not in light-fed females. Instead, the normally clustered LH surges were distributed widely with high inter-mouse variability in the light-fed group. These data indicate that mistimed feeding disrupts the temporal control of the neural processes underlying both ovulation and mating behavior, contributing to infertility.
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Ritmo Circadiano , Ingestión de Alimentos , Infertilidad , Animales , Estradiol/farmacología , Estrógenos , Femenino , Hormona Luteinizante , Masculino , RatonesRESUMEN
AIMS: This study aimed to investigate the molecular characterization and antimicrobial susceptibility of Corynebacterium pseudotuberculosis from skin abscesses of Korean native black goats (KNBG, Capra hircus coreanae) in South Korea. METHODS AND RESULTS: A total of 83 isolates were recovered from skin abscesses of KNBG. Of these isolates, 74 isolates were identified as C. pseudotuberculosis by phospholipase D (PLD) gene-based PCR assay. Each of the isolates possessed all 18 virulence genes (FagA, FagB, FagC, FagD, SigE, SpaC, SodC, PknG, NanH, OppA, OppB, OppC, OppD, OppF, CopC, NrdH and CpaE). The genetic diversity of C. pseudotuberculosis isolates was assessed by the phylogenetic analysis using the concatenated sequences (3073 bp) of five housekeeping genes (fusA, dnaK, infB, groeL1 and leuA) for investigating their genetic diversity. In the results, the isolates belonged to three groups: group 1 (67 isolates), group 2 (one isolate) and group 3 (six isolates) within biovar ovis. However, the groups exhibited low genetic diversity (0.20%-0.41%). In the antimicrobial susceptibility test, most isolates were susceptible to tetracycline, vancomycin, chloramphenicol, ciprofloxacin, erythromycin, enrofloxacin, cefoxitin, ampicillin, gentamycin, cephalothin and doxycycline, whereas they were not susceptible to cefotaxime, trimethoprim and streptomycin. CONCLUSION: This results suggest the involvement of relatively few clones of C. pseudotuberculosis in Korea. Further, present isolates can threaten public health due to potentially virulent strains with all 18 virulence genes and non-susceptible strains to clinically important antibiotics (CIA) and highly important antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the genetic diversity and potential pathogenicity of C. pseudotuberculosis biovar ovis isolates from skin abscesses of KBNG in South Korea, and could provide useful information in controlling its infections.
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Corynebacterium pseudotuberculosis , Absceso/veterinaria , Animales , Antibacterianos/farmacología , Corynebacterium pseudotuberculosis/genética , Cabras/microbiología , Filogenia , OvinosRESUMEN
Tiron is a potent antioxidant that counters the pathological effects of reactive oxygen species (ROS) production due to oxidative stress in various cell types. We examined the effects of tiron on mitochondrial function and osteoblastic differentiation in human periosteum-derived cells (hPDCs). Tiron increased mitochondrial activity and decreased senescence-associated ß-galactosidase activity in hPDCs; however, it had a detrimental effect on osteoblastic differentiation by reducing alkaline phosphatase (ALP) activity and alizarin red-positive mineralization, regardless of H2O2 treatment. Osteoblast-differentiating hPDCs displayed increased ROS production compared with non-differentiating hPDCs, and treatment with tiron reduced ROS production in the differentiating cells. Antioxidants decreased the rates of oxygen consumption and ATP production, which are increased in hPDCs during osteoblastic differentiation. In addition, treatment with tiron reduced the levels of most mitochondrial proteins, which are increased in hPDCs during culture in osteogenic induction medium. These results suggest that tiron exerts negative effects on the osteoblastic differentiation of hPDCs by causing mitochondrial dysfunction.
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Osteogénesis , Periostio , Humanos , Sal Disódica del Ácido 1,2-Dihidroxibenceno-3,5-Disulfónico , Especies Reactivas de Oxígeno , Peróxido de Hidrógeno/farmacología , Mitocondrias , AntioxidantesRESUMEN
BACKGROUND: Although previous reports have found that obesity intensifies the negative impact of long-term air pollution exposure on the low-density lipoprotein-cholesterol (LDL-C) level, few studies have examined whether the type of abdominal adiposity, such as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and the visceral-to-subcutaneous fat ratio (VSR) affects this relationship. We investigated the association between ambient air pollution and LDL-C in Korean adults and identified whether this association is different by the type of abdominal adiposity. METHODS: A total of 2737 adults were included. Abdominal fat areas were quantified by computed tomography, and the annual average concentration of air pollutants was included in this analysis. RESULTS: In the total sample, none of the air pollutants was associated with LDL-C level in either the crude or adjusted model (all p > 0.05). The association was not significant even in subgroups stratified according to the obesity status defined by body mass index, and no interaction on the LDL-C level was also found (all pint > 0.05). In the subgroup analysis stratified according to adiposity level, particulate matter with an aerodynamic diameter of ≤10 µm (PM10) [ß (SE) = 3.58 (1.59); p = 0.0245] and sulfur dioxide (SO2) exposures [ß (SE) = 2.71 (1.27); p = 0.0330] in the high-VAT group were associated with the increased LDL-C level. Interactions on LDL-C level were also found between VAT level and ambient air pollutants such as PM10 and SO2 (both pint < 0.05). In the analysis of the VSR, PM10 exposure showed a significant interaction on LDL level (pint = 0.0032). However, the strength of these associations was not significant across all SAT subgroup (all pint > 0.05). CONCLUSIONS: In conclusion, we found that association between air pollution exposure and LDL-C level is different by abdominal fat distribution.
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Contaminación del Aire/análisis , LDL-Colesterol/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Obesidad Abdominal/epidemiología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de CoreaRESUMEN
Coxsackievirus and adenovirus receptor (CAR) is present in epithelial and vascular endothelial cell junctions. We have previously shown a hemorrhagic phenotype in germ-line CAR knock-out mouse embryos; we have also found that CAR interacts with ZO-1 and ß-catenin. However, the role of CAR in vascular endothelial junction permeability has not been proven. To understand the roles of CAR in the vascular endothelial junctions, we generated endothelium-specific CAR knockout (CAR-eKO) mice. In the absence of CAR, the endothelial cell layer showed an increase in transmembrane electrical resistance (TER, Ω) and coxsackievirus permeability. Evans blue dye and 70 kDa dextran-FITC were delivered by tail vein injection. We observed increased vascular permeability in the hearts of adult CAR-eKO mice compare with wild-type (WT) mice. There was a marked increase in monocyte and macrophage penetration into the peritoneal cavity caused by thioglycolate-induced peritonitis. We found that CAR ablation in endothelial cells was not significantly increased coxsackievirus B3 (CVB3) induced myocarditis in murine model. However, tissue virus titers were significantly higher in CAR-eKO mice compared with WT. Moreover, CVB3 was detected in the brain of CAR-eKO mice. Endothelial CAR deletion affects the expression of major endothelial junction proteins, such as cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1) in the cultured endothelial cells as well as liver vessel. We suggest that CAR expression is required for normal vascular permeability and endothelial tight junction homeostasis. Furthermore, CVB3 organ penetration and myocarditis severities were dependent on the endothelial CAR level.
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Cardiomiopatías/patología , Cardiomiopatías/virología , Endotelio Vascular/patología , Endotelio Vascular/virología , Enterovirus/fisiología , Índice de Severidad de la Enfermedad , Animales , Antígenos CD/metabolismo , Cadherinas/metabolismo , Permeabilidad Capilar , Células Cultivadas , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Endoteliales/virología , Enterovirus Humano B , Eliminación de Gen , Inflamación/patología , Hígado/metabolismo , Ratones Noqueados , Miocarditis/complicaciones , Miocarditis/virología , Cavidad Peritoneal/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Estabilidad Proteica , Replicación ViralRESUMEN
OBJECTIVES: This study aimed to evaluate the associations between ambient air pollutants, obesity, and kidney function. SUBJECTS/METHODS: We enrolled 3345 people who had undergone health checkups at Seoul National University Hospital. We recorded the annual average concentrations of ambient air pollutants, including particulate matter with an aerodynamic diameter of ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), in each subject's residential area. Various obesity traits, such as body mass index, waist circumference, and visceral and subcutaneous adipose tissue areas, were measured by quantified computerized tomography (CT), and kidney function was assessed in relation to estimated glomerular filtration rate as an indicator of kidney function. RESULTS: High PM10, NO2, SO2, and CO concentrations were significantly associated with decreased kidney function (ß = -2.39 and standard error = 0.32, -1.00 and 0.31, -1.23 and 0.28, and -1.32 and 0.29, respectively), and with the prevalence of chronic kidney disease (CKD). The association between air pollutant concentrations and decreased kidney function, including CKD, was stronger among those with high abdominal adiposity, as defined by CT measurement. For example, the association between increased concentrations of air pollutants and the prevalence of CKD was stronger in the group with greater visceral adiposity than in the group with less visceral adiposity (aORs = 1.29 vs 1.16 for PM10, 1.42 vs 1.21 for SO2, and 1.27 vs 1.11 for CO). CONCLUSIONS: Long-term exposure to higher concentrations of air pollutants was unfavorably associated with kidney function and CKD prevalence, especially in people with abdominal obesity. This may indicate a high susceptibility to air pollutants in obese people.
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Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Riñón/fisiopatología , Obesidad Abdominal/epidemiología , Insuficiencia Renal Crónica/epidemiología , Anciano , Monóxido de Carbono , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Dióxido de Nitrógeno , Material Particulado , República de Corea , Dióxido de AzufreRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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OBJECTIVE: Obesity without metabolic disorder [Ob(+)MD(-)] is a unique subcategory of obesity where individuals are protected from the obesity-related complications. Although conflicting clinical outcomes have been reported, there has been no study of the effects of Ob(+)MD(-) on cerebrovascular disease. In this study, we evaluated the association between the Ob(+)MD(-) phenotype and silent brain infarcts (SBI) in a neurologically healthy population. SUBJECTS/METHODS: We evaluated a consecutive series of healthy volunteers recruited between January 2006 and December 2013. MD(-) status was assessed using five clinical markers: blood pressure, triglycerides, high-density lipoprotein, fasting plasma glucose, and waist circumference. Obesity was defined when body mass index ≥ 25 kg/m2. SBI was defined as asymptomatic, well-defined lesions with a diameter ≥ 3 mm with the same signal characteristics as the cerebrospinal fluid on T1- or T2-weighted images. RESULTS: A total of 3165 subjects were assessed, and 262 (8%) SBI cases were identified. In multivariate analyses, non-obesity with metabolic disorder [Ob(-)MD(+)] (adjusted odds ratio [aOR] = 1.65, 95% confidence interval [CI] = 1.07-2.56, P = 0.025) and obesity with metabolic disorder [Ob(+)MD(+)] (aOR = 1.75, 95% CI = 1.12-2.75, P = 0.014) were closely associated with SBI after adjustment for confounders. Meanwhile, Ob(+)MD(-) did not show any significant association with SBI (aOR = 0.85, 95% CI = 0.20-3.72, P = 0.832). These findings may indicate that metabolic abnormality, irrespective of obesity status, is a main risk factor of SBI. When we compared SBI burdens between the four metabolic phenotypes, the Ob(+)MD(+) and Ob(-)MD(+) groups had higher rates of multiple lesions than the Ob(+)MD(-) and non-obesity without metabolic disorder groups. CONCLUSIONS: The presence of metabolic abnormality, and not obesity per se, is independently associated with the prevalence of SBI in a healthy population.
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Infarto Encefálico , Síndrome Metabólico , Obesidad , Infarto Encefálico/complicaciones , Infarto Encefálico/epidemiología , Estudios Transversales , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Análisis Multivariante , Obesidad/complicaciones , Obesidad/epidemiología , República de Corea , Factores de RiesgoRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH). METHODS: We assessed health check-up participants aged 40-79 years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique. RESULTS: A total of 2615 participants were evaluated (median age: 56 years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06-1.81). Further quantitative analyses showed a positive dose-response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (ß = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR. CONCLUSIONS: A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD.
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Glucemia/análisis , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Trastornos del Metabolismo de la Glucosa/sangre , Resistencia a la Insulina , Triglicéridos/sangre , Adulto , Anciano , Enfermedades Asintomáticas , Biomarcadores/sangre , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Estudios Transversales , Ayuno/sangre , Femenino , Trastornos del Metabolismo de la Glucosa/diagnóstico , Trastornos del Metabolismo de la Glucosa/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Seúl/epidemiologíaRESUMEN
BACKGROUND: Robotic rehabilitation of stroke survivors with upper extremity dysfunction may yield different outcomes depending on the robot type. Considering that excessive dependence on assistive force by robotic actuators may interfere with the patient's active learning and participation, we hypothesised that the use of an active-assistive robot with robotic actuators does not lead to a more meaningful difference with respect to upper extremity rehabilitation than the use of a passive robot without robotic actuators. Accordingly, we aimed to evaluate the differences in the clinical and kinematic outcomes between active-assistive and passive robotic rehabilitation among stroke survivors. METHODS: In this single-blinded randomised controlled pilot trial, we assigned 20 stroke survivors with upper extremity dysfunction (Medical Research Council scale score, 3 or 4) to the active-assistive robotic intervention (ACT) and passive robotic intervention (PSV) groups in a 1:1 ratio and administered 20 sessions of 30-min robotic intervention (5 days/week, 4 weeks). The primary (Wolf Motor Function Test [WMFT]-score and -time: measures activity), and secondary (Fugl-Meyer Assessment [FMA] and Stroke Impact Scale [SIS] scores: measure impairment and participation, respectively; kinematic outcomes) outcome measures were determined at baseline, after 2 and 4 weeks of the intervention, and 4 weeks after the end of the intervention. Furthermore, we evaluated the usability of the robots through interviews with patients, therapists, and physiatrists. RESULTS: In both the groups, the WMFT-score and -time improved over the course of the intervention. Time had a significant effect on the WMFT-score and -time, FMA-UE, FMA-prox, and SIS-strength; group × time interaction had a significant effect on SIS-function and SIS-social participation (all, p < 0.05). The PSV group showed better improvement in participation and smoothness than the ACT group. In contrast, the ACT group exhibited better improvement in mean speed. CONCLUSIONS: There were no differences between the two groups regarding the impairment and activity domains. However, the PSV robots were more beneficial than ACT robots regarding participation and smoothness. Considering the high cost and complexity of ACT robots, PSV robots might be more suitable for rehabilitation in stroke survivors capable of voluntary movement. Trial registration The trial was registered retrospectively on 14 March 2018 at ClinicalTrials.gov (NCT03465267).
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Dispositivo Exoesqueleto , Robótica/instrumentación , Rehabilitación de Accidente Cerebrovascular/instrumentación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Robótica/métodos , Accidente Cerebrovascular/fisiopatología , Rehabilitación de Accidente Cerebrovascular/métodos , Extremidad Superior/fisiopatologíaRESUMEN
Nuclear factor kappa B (NF-κB) regulates inflammatory gene expression and represents a likely target for novel disease treatment approaches, including skeletal disorders. Several plant-derived sesquiterpene lactones can inhibit the activation of NF-κB. Parthenolide (PTL) is an abundant sesquiterpene lactone, found in Mexican Indian Asteraceae family plants, with reported anti-inflammatory activity, through the inhibition of a common step in the NF-κB activation pathway. This study examined the effects of PTL on the enhanced, in vitro, osteogenic phenotypes of human periosteum-derived cells (hPDCs), mediated by the inflammatory cytokine tumor necrosis factor (TNF)-α. PTL had no significant effects on hPDC viability or osteoblastic activities, whereas TNF-α had positive effects on the in vitro osteoblastic differentiation of hPDCs. c-Jun N-terminal kinase (JNK) signaling played an important role in the enhanced osteoblastic differentiation of TNF-α-treated hPDCs. Treatment with 1 µM PTL did not affect TNF-α-treated hPDCs; however, 5 and 10 µM PTL treatment decreased the histochemical detection and activity of alkaline phosphatase (ALP), alizarin red-positive mineralization, and the expression of ALP and osteocalcin mRNA. JNK phosphorylation decreased significantly in TNF-α-treated hPDCs pretreated with PTL. These results suggested that PTL exerts negative effects on the increased osteoblastic differentiation of TNF-α-treated hPDCs by inhibiting JNK signaling.
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Asteraceae/química , Inflamación/tratamiento farmacológico , Osteogénesis/efectos de los fármacos , Sesquiterpenos/farmacología , Diferenciación Celular/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Hidrolasas/genética , Inflamación/genética , Inflamación/patología , Proteínas Quinasas JNK Activadas por Mitógenos , Lactonas/química , Lactonas/farmacología , Sistema de Señalización de MAP Quinasas , FN-kappa B , Osteoblastos/efectos de los fármacos , Osteogénesis/genética , Periostio/efectos de los fármacos , Periostio/crecimiento & desarrollo , Fenotipo , Fosforilación/efectos de los fármacos , Fosforilación/genética , Sesquiterpenos/química , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.
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Eosinofilia/etiología , Toxocariasis/complicaciones , Toxocariasis/epidemiología , Alcoholismo , Animales , Anticuerpos Antihelmínticos/sangre , Biomarcadores/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/epidemiología , Conducta Alimentaria , Femenino , Humanos , Masculino , Carne/efectos adversos , Prevalencia , Estudios Prospectivos , República de Corea/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios , Toxocara canis/inmunología , Toxocariasis/diagnóstico , Toxocariasis/parasitologíaRESUMEN
INTRODUCTION: The registration of cone-beam computed tomography (CBCT) images and digital dental models is required for the design and manufacturing of dental devices such as implant guides and surgical wafers. This study aims to register intraoral scan (IS) models and cast scan (CS) models onto CBCT images using 3-dimensional (3D) planning software and evaluate the registration accuracy according to scanning methods and 3D planning software. METHODS: The CBCT image of an artificial skull model with reference markers was taken. The CS model and the IS model were obtained from the same skull model, registered onto the CBCT image using 3D planning software packages providing manual registration (MR) function and point-based registration (PR) functions, and set as the experimental groups. After registration, shell to shell deviations and positional differences between the reference model and the experimental models were evaluated. RESULTS: The shell to shell deviations ranged from 0.03 to 0.18 mm. Deviations in both the maxilla and mandible were significantly different according to scanning methods and software packages. In the anteroposterior direction, the IS-MR and CS-MR groups showed significantly different positions. In the superoinferior direction, the MR and PR groups showed significantly different positions. CONCLUSIONS: The registration using the PR function of the 3D planning software packages was significantly more accurate than the registration using the MR function. There was no significant difference between the registrations using the IS model and the CS model when using the PR functions.
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Imagenología Tridimensional , Modelos Dentales , Tomografía Computarizada de Haz Cónico , Maxilar , Programas InformáticosRESUMEN
Periodontitis is a progressive inflammatory disease that affects roughly half of American adults. Colonization of the oral cavity by the Gram-negative bacterial pathogen Porphyromonas gingivalis is a key event in the initiation and development of periodontal disease. Adhesive surface structures termed fimbriae (pili) mediate interactions of P. gingivalis with other bacteria and with host cells throughout the course of disease. The P. gingivalis fimbriae are assembled via a novel mechanism that involves proteolytic processing of lipidated precursor subunits and their subsequent polymerization on the bacterial surface. Given their extracellular assembly mechanism and central roles in pathogenesis, the P. gingivalis fimbriae are attractive targets for anti-infective therapeutics to prevent or treat periodontal disease. Here we confirm that conserved sequences in the N and C termini of the Mfa1 fimbrial subunit protein perform critical roles in subunit polymerization. We show that treatment of P. gingivalis with peptides corresponding to the conserved C-terminal region inhibits the extracellular assembly of Mfa fimbriae on the bacterial surface. We also show that peptide treatment interferes with the function of Mfa fimbriae by reducing P. gingivalis adhesion to Streptococcus gordonii in a dual-species biofilm model. Finally, we show that treatment of bacteria with similar peptides inhibits extracellular polymerization of the Fim fimbriae, which are also expressed by P. gingivalis These results support a donor strand-based assembly mechanism for the P. gingivalis fimbriae and demonstrate the feasibility of using extracellular peptides to disrupt the biogenesis and function of these critical periodontal disease virulence factors.
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Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/fisiología , Regulación Bacteriana de la Expresión Génica/fisiología , Porphyromonas gingivalis/fisiología , Biopelículas , Escherichia coli/metabolismo , Proteínas Fimbrias/genética , Porphyromonas gingivalis/citología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Gonadal steroids play an integral role in male sexual behavior, and in most rodent models, this relationship is tightly coupled. However, many other species, including humans, continue to demonstrate male sex behavior in the absence of gonadal steroids, and the mechanisms that regulate steroid-independent male sex behavior are not well understood. Approximately 30% of castrated male B6D2F1 hybrid mice display male sex behavior many months after castration, allowing for the investigation of individual variation in steroidal regulation of male sex behavior. During both the perinatal and peripubertal periods of development, the organizational effects of gonadal steroids on sexual differentiation of the neural circuits controlling male sex behavior are well-documented. Several factors can alter the normal range of gonadal steroids or their receptors which may lead to the disruption of the normal processes of masculinization and defeminization. It is unknown whether the organizational effects of gonadal hormones during puberty are necessary for steroid-independent male sex behavior. However, gonadal steroids during puberty were not necessary for either testosterone or estradiol to activate male sex behavior in adulthood. Furthermore, activation of male sex behavior was initiated sooner in hybrid male mice castrated prior to puberty that were administered estradiol in adulthood compared to those that were provided testosterone. The underlying mechanisms by which gonadal hormones, during both the perinatal and peripubertal developmental periods of sexual differentiation, organize the normal maturation of neural circuitry that regulates steroid-independent male sex behavior in adult castrated B6D2F1 male mice warrants further investigation.
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Hormonas Esteroides Gonadales/fisiología , Conducta Sexual Animal , Maduración Sexual/fisiología , Animales , Estradiol/farmacología , Femenino , Hormonas Esteroides Gonadales/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Orquiectomía , Diferenciación Sexual/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Esteroides/farmacología , Esteroides/fisiología , Testosterona/farmacología , Testosterona/fisiologíaRESUMEN
BACKGROUND: Triglycerides (TG)/high-density lipoprotein (HDL) cholesterol ratio is a marker of small/dense low-density lipoprotein particles, which are closely associated with various metabolic and vascular diseases. However, the role of TG/HDL cholesterol ratio in cerebrovascular diseases has not been well studied. In this study, we evaluated the relationship between TG/HDL cholesterol ratio and the presence of silent brain infarct (SBI) in a neurologically healthy population. METHODS: We retrospectively evaluated consecutive participants in health check-ups between January 2006 and December 2013. SBI was defined as an asymptomatic, well-defined lesion with a diameter of ≥3 mm on T1- or T2-weighted images. TG/HDL cholesterol ratio was calculated after dividing absolute TG levels by absolute HDL cholesterol levels. RESULTS: Of 3172 healthy participants, 263 (8.3%) had SBI lesions. In multivariate analysis, TG/HDL cholesterol ratio was independently associated with SBI (adjusted odds ratio [aOR] = 1.16, 95% confidence interval [CI] = 1.00 to 1.34, P = 0.047). This association was prominent in males (aOR = 1.23, 95% CI = 1.03 to 1.48, P = 0.021), but not in females. In the analyses of the relationships between lipid parameters and SBI lesion burden, TG/HDL cholesterol ratio was positively correlated, and total cholesterol/TG ratio was negatively correlated with SBI lesion burden, in dose-response manners (P for trend = 0.015 and 0.002, respectively). CONCLUSIONS: The TG/HDL cholesterol ratio was positively associated with the prevalence of SBI in a neurologically healthy population.