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BACKGROUND/OBJECTIVE: Healthy weight maintenance before and during pregnancy has a significant effect on pregnancy outcomes; however, there are no specific guidelines for gestational weight gain in pregnant Korean women. Therefore, we investigated the impact of pre-pregnancy body mass index (BMI) and gestational weight gain on the risk of maternal and infant pregnancy complications in pregnant Korean women. METHODS: Study participants comprised 3454 singleton pregnant women from the Korean Pregnancy Outcome Study who had baseline examination and pregnancy outcome data. Maternal pre-pregnancy BMI and gestational weight gain were categorized according to the Asia-pacific regional guidelines and the Institute of Medicine recommendations, respectively. The primary outcome was any adverse outcomes, defined as the presence of one or more of the following: hypertensive disorders of pregnancy, gestational diabetes mellitus, peripartum depressive symptom, cesarean delivery, delivery complications, preterm birth, small or large weight infant, neonatal intensive care unit admission, or a congenital anomaly. Multiple logistic regression models were applied to examine the independent and combined impact of pre-pregnancy BMI and gestational weight gain on the risk of maternal and infant outcomes. RESULTS: Obesity before pregnancy significantly increased the risk of perinatal adverse outcomes by more than 2.5 times [odds ratio (OR): 2.512, 95% confidence interval (CI): 1.817-3.473]. Compared to that in women with appropriate gestational weight gain, women with excessive weight gain had a 36.4% incremental increase in the risk of any adverse outcomes [OR: 1.364, 95% CI: 1.115-1.670]. Moreover, women who were overweight or obese before pregnancy and had excessive gestational weight gain had a three-fold increase in the risk of adverse outcomes [OR: 3.460, 95% CI: 2.210-5.417]. CONCLUSION: This study highlights the need for appropriate weight recommendations before and during pregnancy to prevent perinatal complications in Korean women of childbearing age.
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Peso Corporal/fisiología , Complicaciones del Embarazo/fisiopatología , Adulto , Índice de Masa Corporal , Femenino , Ganancia de Peso Gestacional/fisiología , Humanos , Oportunidad Relativa , Embarazo , Complicaciones del Embarazo/epidemiología , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricos , República de Corea/epidemiología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Korean Pregnancy Outcome Study (KPOS) was established to investigate the determinants of adverse pregnancy outcomes among Korean women. METHODS: We recruited 4,537 pregnant women between 2013 and 2017 from two tertiary centers located in Seoul, Korea, and a total of 4,195 Korean women met inclusion criteria in the baseline analysis. A range of data on socio-demographics, past medical histories, reproductive information, health-related behaviors, psychological health and clinical information were obtained using interviewer-based questionnaires and clinical assessment at 12, 24, and 36 gestational weeks (GW), delivery and 6-8 weeks postpartum. Blood samplings were performed at 12, 24 and 36 GW, and placental tissues were obtained after delivery. The main outcome of this study was pregnancy-related complications including gestational diabetes mellitus (GDM), gestational hypertension, and screening positive for peripartum depression. Depression was assessed using the Korean version of the Edinburgh Postnatal Depression Scale, and a score of ≥10 indicated a positive screen for depression. RESULTS: Among 4,195 eligible pregnant women with a median age of 33.0 years, 3,565 (85.0%) pregnancy outcomes were available in this study, including 30 miscarriages, 16 stillbirths, and 3,519 deliveries. Mean gestational age was 38.8 GW, and mean birth weight was 3,236 gram. The prevalence of pregnancy complications of GDM, hypertensive disorders, and screening positive of depression during pregnancy and postpartum was 7.0%, 1.4%, 27.8%, and 16.6%, respectively. CONCLUSIONS: We designed KPOS to identify the determinants of pregnancy-related outcomes, and it may provide effective strategies for the prevention of pregnancy complications in Korean pregnant women.
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Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , República de Corea/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
STATEMENT OF PROBLEM: A high metal-ceramic bond strength is important for successful dental restorations. However, studies on the evaluation of the bond strength of porous metal-ceramic restorations compared with conventional ones are scarce. PURPOSE: The purpose of this in vitro study was to compare the bond strength of a porous metal-ceramic structure with conventional metal-ceramic restorations. MATERIAL AND METHODS: Ten porous specimens were fabricated by selective laser sintering (SLS) according to the International Organization for Standardization 9693-1:2012, 10 specimens without porosity by SLS, and 10 cobalt-chromium (Co-Cr) cast specimens without porosity. The ceramic was applied with the pressing method. A 3-point bend test was performed with a universal testing machine, and the data were statistically analyzed by using 1-way analysis of variance (α=.05). RESULTS: The mean ±standard deviation bond strength of the porous group fabricated by SLS was the lowest (35.6 ±9.1 MPa), that of the group without porosity in the casting method was 43.5 ±7.8 MPa, and that of the group without porosity fabricated by SLS was the highest (47.7 ±4.5 MPa); these were statistically similar (P=.058). CONCLUSIONS: Although the porous structure reported the lowest bond strength among the 3 sets of test specimens, its bond strength was higher than the International Standards Organization standard of 25 MPa.
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Recubrimiento Dental Adhesivo , Porcelana Dental , Cerámica , Cromo , Aleaciones de Cromo , Cobalto , Ensayo de Materiales , Aleaciones de Cerámica y Metal , Porosidad , Propiedades de SuperficieRESUMEN
The all-on-4 concept, which is used to rehabilitate edentulous patients, can present with mechanical complications such as screw loosening and fracture. The purpose of this study was to evaluate the stress patterns induced in the prosthetic screws by the different prosthetic screw and abutment designs in the all-on-4 concept using finite element analysis. Von Mises stress values on 6 groups of each screw type, including short and narrow screw, short abutment; short and wide screw, short abutment; long and wide screw, short abutment; short and narrow screw, long abutment; short and wide screw, long abutment; and long and wide screw, long abutment, were compared under a cantilever loading of 200 N that was applied on the farther posterior to the position of the connection between the distal implant and the metal framework. Posterior prosthetic screws showed higher stress values than anterior prosthetic screws. The stress values in posterior prosthetic screws decreased as the length and diameter increased. In conclusion, the long and wide screw design offers advantages in stress distribution when compared with the short and narrow design.
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Pilares Dentales , Implantes Dentales , Tornillos Óseos , Prótesis Dental de Soporte Implantado , Análisis del Estrés Dental , Análisis de Elementos Finitos , Humanos , Estrés MecánicoRESUMEN
BACKGROUND: Middle-aged women experience various menopausal symptoms during the menopause. These symptoms can affect their quality of life and health. Several epidemiological studies reported that obesity associates with menopausal symptoms. The aim of this cross-sectional study was to examine the associations between obesity and multiple menopausal symptoms at different stages of menopause in middle-aged Korean women. METHODS: The study population included women aged 44-56 years who visited a tertiary referral hospital for medical check-ups between November 2012 and March 2013 and were free from serious illness, could comprehend a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Overweight and obesity were defined as body mass index (BMI) of 23-24.9 and ≥25 kg/m2, respectively. RESULTS: Of the 2204 middle-aged women, 929 met the eligibility criteria. Of these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause, respectively. In perimenopause, obese women were significantly more likely to have moderate/severe physical symptoms (MENQOL domain score ≥ 5) than normal or overweight women. In postmenopause, obese women were significantly more likely to have moderate/severe vasomotor symptoms. Multiple linear regression with adjustment for confounders showed that relative to normal weight, obesity in perimenopause and postmenopause associated independently with physical symptoms (beta coefficient = 0.35; P = 0.023) and vasomotor symptoms (beta coefficient = 0.68; P = 0.003), respectively. Overweight did not associate with menopausal symptoms. BMI did not associate significantly with psychosocial or sexual symptoms at either stage of menopause. CONCLUSIONS: Obese women had more frequent menopausal symptoms than normal or overweight women but the associated menopausal symptom differed depending on the menopausal stage. Further studies are required to confirm this result and identify the underlying mechanisms.
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Ejercicio Físico/fisiología , Menopausia/fisiología , Obesidad/complicaciones , Sobrepeso/complicaciones , Perimenopausia/fisiología , Posmenopausia/fisiología , Sistema Vasomotor/fisiología , Adulto , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Calidad de Vida/psicología , República de Corea/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Measures to address gender-specific health issues are essential due to fundamental, biological differences between the sexes. Studies have increasingly stressed the importance of customizing approaches directed at women's health issues according to stages in the female life cycle. In Korea, however, gender-specific studies on issues affecting Korean women in relation to stages in their life cycle are lacking. Accordingly, the Korean Study of Women's Health-Related Issues (K-Stori) was designed to investigate life cycle-specific health issues among women, covering health status, awareness, and risk perceptions. METHODS: K-Stori was conducted as a nationwide cross-sectional survey targeting Korean women aged 14-79 years. Per each stage in the female life cycle (adolescence, childbearing age, pregnancy & postpartum, menopause, and older adult stage), 3000 women (total 15,000) were recruited by stratified multistage random sampling for geographic area based on the 2010 Resident Registration Population in Korea. Specialized questionnaires per each stage (total of five) were developed in consultation with multidisciplinary experts and by reflecting upon current interests into health among the general population of women in Korea. This survey was conducted from April 1 to June 31, 2016, at which time investigators from a professional research agency went door-to-door to recruit residents and conducted in-person interviews. DISCUSSION: The study's findings may help with elucidating health issues and unmet needs specific to each stage in the life cycle of Korean women that have yet to be identified in present surveys.
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Estado de Salud , Fenómenos Fisiológicos Reproductivos , Salud de la Mujer , Adolescente , Adulto , Anciano , Concienciación , Estudios Transversales , Femenino , Humanos , Menopausia/fisiología , Persona de Mediana Edad , Mujeres Embarazadas , República de Corea/epidemiología , Proyectos de Investigación , Conducta Sexual , Adulto JovenRESUMEN
BACKGROUND: Although the prevalence of hypertension is higher in postmenopausal women than in premenopausal women, little is known about changes in blood pressure (BP) during the menopausal transition. We evaluated BP according to the menopausal transition and associated factors in healthy Korean women. METHODS: This cross-sectional study involved 2037 women aged 44 to 56 years who presented at a health-screening center in Seoul, Korea, from November 2012 to March 2013. The association between BP and menopausal transition and the risk factors related to elevated BP were determined using multiple linear regression analyses. Menopausal status was divided by four groups as premenopause, early menopausal transition, late menopausal transition and postmenopause. RESULTS: Both systolic and diastolic blood pressure (SBP and DBP) differed significantly according to the menopausal status. BP showed the greatest difference between early and late menopausal transition. After adjusting for variables related to hypertension, SBP (ß = 2.753, p < 0.01) and DBP (ß = 1.746, p = 0.02) were significantly higher in late than early menopausal transition. The prevalence of hypertension was significantly different between early and late menopausal transition (1.4 vs. 6.1 %). Waist circumference, glucose, and triglycerides were positively and significantly associated with SBP and DBP during menopause. CONCLUSIONS: BP and the prevalence of hypertension were significantly associated with period between early and late menopausal transition, suggesting that changes in BP during the menopausal transition are significant. Therefore, frequent monitoring will be needed for early detection of hypertension during the menopausal transition.
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Presión Sanguínea , Estado de Salud , Menopausia/fisiología , Adulto , Determinación de la Presión Sanguínea/métodos , Femenino , Humanos , Hipertensión/diagnóstico , Modelos Lineales , Tamizaje Masivo/métodos , República de CoreaRESUMEN
BACKGROUND & AIMS: The circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality. METHODS: This prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005-2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity. RESULTS: The median (interquartile range) of 25(OH)D level was 55.8 (40.8-71.8) nmol/L. During a median follow-up of 14.3 years, 2250 deaths were recorded. Compared with participants with a 25(OH)D level <30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥75 nmol/L) were associated with a lower risk of all-cause mortality: HR (95% CI) of 0.82 (0.69-0.98), 0.74 (0.62-0.88), and 0.69 (0.57-0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI: 0.39-0.77) for a 25(OH)D level ≥75 nmol/L compared with <30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men. CONCLUSIONS: Vitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50-60 nmol/L may contribute to longevity and warrants further investigation.
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The Korea Nurses' Health Study (KNHS) is an ongoing, large-scale, prospective cohort study of women nurses, focusing on the effects of occupational, environmental, and lifestyle factors on the health of women. The first KNHS survey was performed in 2013-2014 (n=20,613). As of December 2023, 11 follow-up surveys have been conducted. Participants who were pregnant were asked to participate in the early pregnancy survey (n=2,179) and postpartum survey after giving birth (n=2,790). The main variables included socio-demographic, work-related, lifestyle, physical, mental, and women's health factors. Blood, urine, and toenail samples were collected from a participant subgroup of the first survey (n=1,983). The subgroups of the second survey completed a food frequency questionnaire in 2019 (n=300) and 2021 (n=871). In 2020, a subgroup of the first survey answered a coronavirus disease 2019-related survey (n=975). To examine various health-related factors in young adults, new participants were added to the KNHS cohort in the 11th (n=1,000) and 12th (n=1,002) surveys. The KNHS cohort will help identify health and illness determinants in Korean women. Data can be accessed at https://coda.nih.go.kr/frt/index.do.
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Enfermeras y Enfermeros , Salud de la Mujer , Humanos , Femenino , República de Corea/epidemiología , Adulto , Estudios Prospectivos , Enfermeras y Enfermeros/estadística & datos numéricos , Enfermeras y Enfermeros/psicología , COVID-19/epidemiología , Embarazo , Estudios de Cohortes , Encuestas Epidemiológicas , Estado de Salud , Adulto Joven , Persona de Mediana EdadRESUMEN
Several composite materials are being investigated as reinforcement fillers for surgery simulations. This study presents an artificial composite material with properties similar to those of the human bone, which may be used in surgery simulations. Moreover, considering the potential toxicity of debris generated during sawing, a safe epoxy-based composite material was synthesized using cellulose nanocrystals (CNCs) and bioceramics (i.e., hydroxyapatite, Yttria stabilized zirconia oxide, Zirconia oxide), which were used to mimic the stiffness of human bone. To examine the change in mechanical properties according to the composition, 1, 3, and 5 wt% of CNCs were mixed with 5 wt% of the bioceramics. When CNCs were added at 1 wt%, there was a confirmed change in the non-linear stiffness and ductility. The CNC-added specimen fractured when forming a nano-network around the local CNCs during curing. In contrast, the specimen without CNCs was more densely structured, and combined to form a network of all specimens such that a plastic region could exist. Thus, this study successfully manufactured a material that could mimic longitudinal and transverse characteristics similar to those of real human bone, as well as exhibit mechanical properties such as strength and stiffness. Bioceramics are harmless to the human body, and can be used by controlling the added quantity of CNCs. We expect that this material will be suitable for use in surgery simulations.
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Liver fibrosis is a common consequence of various chronic liver injuries, including virus infection and ethanol. Activated hepatic stellate cells (HSCs) contribute to liver fibrosis through the accumulation of extracellular matrix proteins, including type I alpha collagen (COL1A). The activation of adenosine monophosphate-activated protein kinase (AMPK) modulates HSCs activation, but its underlying mechanism remains unclear. Here, we report that AMPK inhibits transforming growth factor (TGF)-ß-induced fibrogenic property of HSCs by regulating transcriptional coactivator p300. We treated human (LX-2) and rat (CFSC-2G) HSC lines with TGF-ß to induce fibrogenic activation of HSCs. Pharmacological activation of AMPK by treatment with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), metformin, or adiponectin lowered TGF-ß-induced expression of COL1A and myofibroblast marker alpha-smooth muscle actin (α-SMA). Transient transduction of constitutively active AMPKα (caAMPKα) was sufficient to attenuate COL1A and α-SMA expression, whereas an AMPK inhibitor considerably abrogated the inhibitory effect of AICAR on fibrogenic gene expression. Although AMPK significantly suppressed Smad-dependent transcription, it did not affect TGF-ß-stimulated phosphorylation, nuclear localization, or DNA-binding activity of Smad2/3. AICAR rather attenuated TGF-ß-induced Smad3 interaction with transcriptional coactivator p300 accompanying with reduction of Smad3 acetylation. Moreover, AICAR induced not only physical interaction between AMPK and p300 but also proteasomal degradation of p300 protein. Our data provide substantial evidence that AMPK could be a novel therapeutic target for treatment of liver fibrosis, by demonstrating the underlying mechanism of AMPK-induced antifibrotic function in HSCs.
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Proteínas Quinasas Activadas por AMP/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Células Estrelladas Hepáticas/enzimología , Cirrosis Hepática/metabolismo , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Animales , Línea Celular Transformada , Marcación de Gen , Células Estrelladas Hepáticas/citología , Humanos , Cirrosis Hepática/enzimología , Cirrosis Hepática/patología , Ratas , Factor de Crecimiento Transformador beta1/fisiologíaRESUMEN
In an attempt to improve properties of polycaprolcatone-starch blend, this study uses zein as coupling agent in preparing the blend through a single-step process. Zein, which has affinity to both polar and non-polar groups, is expected to improve miscibility between the blends' constituents and its overall biocompatibility. Mechanical properties of the blend were tested and further characterizations (Fourier transform infrared spectroscopy, thermal properties) were performed to analyze the effect of zein as an addition to the blend's physical properties. The blend's biocompatibility was examined by indirect methods (contact angle and weight gain after immersion in simulated body fluid) and in vitro analysis. No significant effect on the blend's strength and stiffness was caused by adding zein. Hydrophilicity and cell affinity were improved when zein was added. Zein did not perform as a coupling agent that improved miscibility between polycaprolactone and starch, but its addition improved the blend's biocompatibility.
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Materiales Biocompatibles/química , Proteínas de Plantas/química , Poliésteres/química , Almidón/química , Módulo de Elasticidad , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Resistencia a la TracciónRESUMEN
Background: The purpose of this in vitro study is to fabricate a novel metal-ceramic prosthesis with a porous structure, to compensate for the disadvantages associated with the design of existing prostheses, and to measure the internal fit of this prosthesis. Materials and Methods: In this in vitro study, the mandibular first molar was scanned from the dental computer-aided-design to design a 3 mm porous structure frame. The frame was produced using the lamination method and fired in a pressed ceramic. For comparison, pore-free specimens were fabricated by selective laser sintering (SLS) as described above, and porous specimens were fabricated by casting (total n = 30). The internal fit was then measured using a digital microscope (at 100× magnification), and the data were analyzed using one-way ANOVA (α = 0.05). Results: The total mean internal discrepancies for each group were 42.32 ± 22.50 µm for the porous structure SLS group (PS-group), 107.54 ± 38.75 µm for no-porous casting group (group), and 121.36 ± 50.19 µm for the no-porous SLS group (group), with significant differences (P < 0.05) among all groups. Conclusion: The internal discrepancies of porous structure crown fabricated by SLS were smaller than that of no-porous crown fabricated by casting and SLS. Based on these laboratory findings, further studies should be conducted to evaluate the feasibility of the newly designed porous structure and press ceramic prosthesis to determine whether they can be applied in clinical practice.
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Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (-503/-498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression.
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Regulación Neoplásica de la Expresión Génica , Neoplasias/metabolismo , Receptores Virales/biosíntesis , Elementos de Respuesta , Factor de Transcripción Sp1/metabolismo , Proteínas Supresoras de Tumor/biosíntesis , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , Células Hep G2 , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Neoplasias/patologíaRESUMEN
OBJECTIVE: The study aimed to evaluate the degree of menopausal hormonal therapy (MHT) use and the related trends, as well as the characteristics of Korean women who used MHT by type of hormone therapy. METHODS: Women aged ≥40 years were selected using data from the Korea National Insurance Service-National Sample Cohort 2002-2013 database. MHT entailed either estrogen therapy or estrogen plus progestogen therapy, as categorized by the Anatomical Therapeutic Chemical system. The prevalence of MHT use was calculated as the number of women with prescriptions annually and the level of hormone consumption was calculated using the defined daily dose (DDD). RESULTS: The proportion of MHT users among women aged ≥40 years was 7.8 % in 2002, which decreased to 6.3 % in 2013. The overall MHT consumption level in 2002 was 27.5 DDDs/1000 inhabitants/day. There was a sharp decline in the first few years after 2002 and this value decreased to 12.5 DID in 2013; however, the decrease had lessened from 2006 to 2013 and differed by HT type, administration route, age, and income level. During the 11-year follow-up, over 70 % of women were prescribed MHT for less than 1 year, while only 11.8 % had a prescription for 3 years or more, and women who started treatment at age 45-59 years showed longer treatment duration. CONCLUSIONS: Since 2002, MHT use among Korean women, especially overall MHT consumption, has declined remarkably. Regarding the pattern of use among women who took hormone preparations during 2002-2013, MHT was used around menopause, over the short term only, and at low dose.
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Estrógenos/uso terapéutico , Terapia de Reemplazo de Hormonas , Progestinas/uso terapéutico , Adulto , Anciano , Estudios de Cohortes , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Menopausia , Persona de Mediana Edad , República de Corea/epidemiologíaRESUMEN
The mechanics of damage and fracture process in unidirectional carbon fiber reinforced polymer (CFRP) composites subjected to shear loading (Mode II) were examined using the experimental method of the three-point end-notch flexure (3ENF) test. The CFRP composite consists of [0o]16 with an insert film in the middle plane for a starter defect. A 3ENF test sample with a span of 50 mm and interface delamination crack length of 12.5 mm was tested to yield the load vs. deformation response. A sudden load drop observed at maximum force value indicates the onset of delamination crack propagation. The results are used to extract the energy release rate, GIIC, of the laminates with an insert film starter defect. The effect of the starter defect on the magnitude of GIIC was examined using the CFRP composite sample with a Mode II delamination pre-crack. The higher magnitude of GIIC for the sample with insert film starter defect was attributed to the initial straight geometry of the notch/interface crack and the toughness of the resin at the notch front of the fabricated film insert. The fractured sample was examined using a micro-computerized tomography scanner to establish the shape of the internal delamination crack front. Results revealed that the interface delamination propagated in a non-uniform manner, leaving a curved-shaped crack profile.
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Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure. Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a major ethanol oxidation enzyme, by 4-methylpyrazole (4-MP) has therapeutic effects. We found that ethanol consumption (5%) 2 weeks before pregnancy resulted in a decrease in the number of viable fetuses and abnormal fetal development, and these effects were accompanied by impaired maternal glucose homeostasis and hepatic steatosis during pregnancy. Neonates of ethanol-fed mice had postnatal macrosomia and significantly decreased growth rates during the lactation period. However, treatment with 4-MP, a CYP2E1 inhibitor, markedly ameliorated the reduction in insulin action and glucose disposal responsiveness in the livers of ethanol-fed mice. Blockage of CYP2E1 significantly reduced the alteration in hepatic lipid deposition, fatty acid oxidation, mitochondrial energy status, and macrophage infiltration observed in ethanol-fed mice. Finally, there was a positive correlation between postnatal macrosomia or growth retardation and increased inflammatory responses. Collectively, our study suggests that even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders.
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Consumo de Bebidas Alcohólicas/efectos adversos , Inhibidores del Citocromo P-450 CYP2E1/administración & dosificación , Macrosomía Fetal/tratamiento farmacológico , Glucosa/metabolismo , Complicaciones del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Animales , Animales Recién Nacidos , Inhibidores del Citocromo P-450 CYP2E1/farmacología , Modelos Animales de Enfermedad , Hígado Graso/inducido químicamente , Femenino , Desarrollo Fetal/efectos de los fármacos , Macrosomía Fetal/inducido químicamente , Homeostasis/efectos de los fármacos , Ratones , EmbarazoRESUMEN
Taxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervical cancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervical cancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73beta small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)-overexpressed cells, paclitaxel enhanced apoptosis through increased alpha and beta isoform expression of TAp73; however, these events were attenuated in cells containing inactive COOH-terminal-deleted ATF3 [ATF3(DeltaC)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73beta-overexpressed or TAp73beta siRNA-cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73beta is expressed, but not in ATF3(DeltaC) or TAp73beta siRNA-transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p21 or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73beta by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73beta, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73beta and ATF3 are recruited directly to the p21 and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73beta's stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73beta, suggesting a functional link between ATF3 and TAp73beta.
Asunto(s)
Factor de Transcripción Activador 3/metabolismo , Apoptosis/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Paclitaxel/farmacología , Proteínas Supresoras de Tumor/metabolismo , Neoplasias del Cuello Uterino/patología , Sitios de Unión , Línea Celular Tumoral , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Femenino , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Nucleares/química , Proteínas Nucleares/genética , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Estructura Terciaria de Proteína , Transporte de Proteínas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Termodinámica , Activación Transcripcional/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/química , Proteínas Supresoras de Tumor/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
Nitration products (nitroalkenes) of linoleic acid (LNO(2)) and oleic acid (OA-NO(2)) can act as endogenous PPARgamma ligands with electrophilic properties to exert anti-inflammatory effects on atherosclerotic plaques in the vasculature. Here, we show that OA-NO(2) and LNO(2) prevent tumor necrosis factor alpha (TNFalpha)-stimulated inflammatory and atherogenic responses in human umbilical vein endothelial cells (HUVECs). Both OA-NO(2) and LNO(2) prevented TNFalpha-stimulated release of the cytokines, IL-6, IL-8, IL-12/p40, IFNgamma, MCP-1, and IP-10, and inhibited NF-kappaB activation. OA-NO(2) and LNO(2) also blocked TNFalpha-induced expression of the adhesion molecules, ICAM-1, VCAM-1, and E-selectin, and suppressed monocyte adhesion to HUVECs. In each case, OA-NO(2) was more potent and efficacious than was LNO(2), possibly due to increased stability in aqueous media. Collectively, these results substantiate a new functional role for nitrated fatty acids, demonstrating that OA-NO(2) and LNO(2) exert an anti-inflammatory function against the inflammatory cascade initiated by the representative pro-inflammatory cytokine, TNFalpha.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aterosclerosis/inmunología , Citocinas/antagonistas & inhibidores , Ácidos Linoleicos/farmacología , Nitratos/farmacología , Nitrocompuestos/farmacología , Ácido Oléico/farmacología , Células Cultivadas , Citocinas/inmunología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Humanos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Selective laser sintering (SLS) is a new type of additive material manufacturing technology. The development of precise 3D metal printing technology has enabled the printing of complicated metal structures, particularly in the medical field. Finding a way to integrate new technologies with Co-Cr alloys for the precision manufacturing of dental restoration materials and a way to improve the metal-ceramic bonding strength of the materials have become a key focus of dental restoration clinical trials. The purpose of this study is to evaluate bonding strength and ceramic adhesion between metal and ceramics using Co-Cr specimens with different porous structures manufactured using SLS technology. According to the international standard ISO9693:1999, we printed three sets of 10 rectangular Co-Cr alloy test specimens of the same size (25â¯×â¯3â¯×â¯0.5â¯mm) using an SLS-3D metal printer and fused a ceramic layer (8 x 3â¯×â¯1.1â¯mm) to the center of the Co-Cy alloy test specimen. Before testing, we conducted stress and fracture simulation analysis on three specimen types (no holes, circular-shaped holes, and rhombic-shaped holes), using ABAQUS results to predict the results of three-point bending tests. These simulation results were then compared with the experimental data. We used three-point bending tests to assess the bonding strength of the fabricated metal-ceramic bonding surface. We also used a digital microscope (100× and 200×) to observe the surface conditions of the samples. Finally, we analyzed the results using one-way analysis of variance. The ABAQUS bending simulations indicated that the bending energy decreased sequentially for the hole-free, circular-hole and rhombic-hole specimens. Similarly, when the three types of test specimen were manufactured using SLS, significant differences in bending energy were observed between the rhombic-hole specimens and both the hole-free (Pâ¯<â¯0.05) and circular-hole specimens (Pâ¯<â¯0.05). In addition, the bond strength for all groups was higher than the international minimum standard of 25â¯MPa (33.36⯱â¯3.17â¯MPa). In this research, the bond strength of all three metal-ceramic test specimens was higher than the international minimum standard of 25â¯MPa set by ISO1999/9693. However, the circular porous design did not show previous diversity with other porous shape design. In addition, due to limitations in the accuracy of 3D printing using SLS, the structural advantages our proposed specimen design are difficult to verify. Therefore, we plan to develop new structural designs to improve the bonding strength of metal-ceramic structures in future work.