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The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in vivo evidence that regional identity in the embryonic cochlea acts as a framework upon which tonotopy-specific properties essential for frequency selectivity in the mature cochlea develop. We found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. In a fate-mapping analysis, we found that FST promotes expansion of apical cochlear cells, contributing to the formation of the apical cochlear domain. SHH, in contrast, is required both for the induction and maintenance of apical identity. In the absence of FST or SHH, mice produce a short cochlea lacking its apical domain. This results in the loss of apex-specific anatomical and molecular properties and low-frequency-specific hearing loss.
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Folistatina , Proteínas Hedgehog , Animais , Camundongos , Folistatina/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Cóclea/fisiologia , Audição/fisiologia , Mamíferos/metabolismoRESUMO
The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.
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Células-Tronco Pluripotentes Induzidas , Placenta , Feminino , Gravidez , Humanos , Placenta/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator de Crescimento Placentário/metabolismo , Trofoblastos/metabolismo , Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/metabolismo , Diferenciação CelularRESUMO
Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.
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Códon sem Sentido , Conexinas/metabolismo , Genes Dominantes , Perda Auditiva Central/genética , Proteínas de Membrana/genética , Animais , Implante Coclear , Feminino , Perda Auditiva Central/metabolismo , Perda Auditiva Central/fisiopatologia , Perda Auditiva Central/cirurgia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linhagem , Percepção da FalaRESUMO
The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.
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The reconfigurable intelligent surface (RIS) and rate-splitting multiple access (RSMA) are considered as promising technologies for the beyond Fifth-Generation (B5G) and Sixth-Generation (6G) wireless systems by controlling the propagation environment, which attenuates the transmitted signal, and by managing the interference by splitting the user message into common and private messages. Because conventional RIS elements have each impedance connected to the ground, the sum-rate performance improvement of the RIS is limited. Therefore, the new RISs, which have impedance elements connected to each other, have been proposed recently. To be more adaptive to each channel, the optimization of the grouping of the RIS elements is required. Furthermore, since the solution of the optimal rate-splitting (RS) power-splitting ratio is complex, the value should be simply optimized to be more practical in the wireless system. In this paper, the grouping scheme of the RIS elements according to the user scheduling and the solution of the RS power-splitting ratio based on fractional programming (FP) are proposed. The simulation results showed that the proposed RIS-assisted RSMA system achieved a high sum-rate performance compared to the conventional RIS-assisted spatial-division multiple access (SDMA) system. Therefore, the proposed scheme can perform adaptively for the channel and has a flexible interference management. Furthermore, it can be a more suitable technique for B5G and 6G.
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Reconfigurable intelligent surface (RIS) has emerged as a promising technology to enhance the spectral efficiency of wireless communication systems. However, if there are many obstacles between the RIS and users, a single RIS may not provide sufficient performance. For this reason, a double RIS-aided communication system is proposed in this paper. However, this system also has a problem: the signal is attenuated three times due to the three channels created by the double RIS. To overcome these attenuations, an active RIS is proposed in this paper. An active RIS is almost the same as a conventional RIS, except for the included amplifier. Comprehensively, the proposed system overcomes various obstacles and attenuations. In this paper, an active RIS is applied to the second RIS. To reduce the power consumption of active elements, a partially active RIS is applied. To optimize the RIS elements, the sum of the covariance matrix is found by using channels related to each RIS, and the right singular vector is exploited using singular value decomposition for the sum of the covariance matrix. Then, the singular value of the sum of the covariance value is checked to determine which element is the active element. Simulation results show that the proposed system has better sum rate performance compared to a single RIS system. Although it has a lower sum rate performance compared to a double RIS with fully active elements, the proposed system will be more attractive in the future because it has much better energy efficiency.
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The study aims to determine the effect of virtual simulation practice in nursing students using the Virtual Patient Learning System Evaluation (VPLSE) tool. The study uses descriptive research, centering on correlation and regression analysis. 295 nursing students in Grades 3 and 4 who have experienced virtual simulation practice within the past year were included. The main variables of VPLSE comprise four sub-domains: nursing knowledge improvement, clinical competency development, confidence in nursing performance, and nursing care plan application. In addition to the VPLSE, two other tools, measuring virtual presence and self-efficacy, were utilized. The VPLSE was significantly positively correlated with virtual presence and self-efficacy, respectively. The VPLSE subdomain of "clinical competency development" had a strong positive correlation with virtual presence. To increase the effect of virtual simulation education, it is necessary to maintain the advantages of virtual simulation practice, such as freedom from space and time, repeated learning, psychological stability and application of nursing plans.
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Bacharelado em Enfermagem , Treinamento por Simulação , Estudantes de Enfermagem , Humanos , Autoeficácia , Estudantes de Enfermagem/psicologia , Aprendizagem , Competência ClínicaRESUMO
Background: Extracorporeal membrane oxygenation (ECMO) is an accommodation of the cardiopulmonary bypass technique that can support gas exchange and hemodynamic stability. It is used as a salvage maneuver in patients with life-threatening respiratory or cardiac failure that does not respond to conventional treatment. There are few case reports of successful perioperative use of ECMO, especially preoperatively, in liver transplantation (LT). Here, we report an experience of successful anesthetic management in deceased donor liver transplantation (DDLT) by applying perioperative veno-venous (VV) ECMO support in the setting of acute respiratory distress syndrome (ARDS) aggravated by hepatopulmonary syndrome (HPS). Case: A 25-year-old female (156.0 cm, 65.0 kg), without any underlying disease, was referred to our emergency department for decreased mentality. Based on imaging and laboratory tests, she was diagnosed with acute liver failure of unknown cause combined with severe ARDS aggravated by HPS. Since the patient faced life-threatening hypoxemia with a failure of conventional ventilation maneuvers, preoperative VV ECMO was initiated and maintained during the operation. The patient remained hemodynamically stable throughout DDLT, and ARDS showed gradual improvement after the administration of VV ECMO. As ARDS improved, the patient's condition alleviated, and VV ECMO was weaned on postoperative day 6. Conclusions: This case demonstrates that VV ECMO may be a useful therapeutic option not only during the intraoperative and postoperative periods but also in the preoperative period for patients with liver failure combined with reversible respiratory failure.
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Oxigenação por Membrana Extracorpórea , Síndrome Hepatopulmonar , Transplante de Fígado , Síndrome do Desconforto Respiratório , Feminino , Humanos , Adulto , Síndrome Hepatopulmonar/complicações , Síndrome Hepatopulmonar/cirurgia , Doadores Vivos , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/terapiaRESUMO
The Diels-Alder (DA) reaction, a classic cycloaddition reaction involving a diene and a dienophile to form a cyclohexene, is among the most versatile organic reactions. Theories have predicted thermodynamically unfavorable DA reactions on pristine graphene owing to its low chemical reactivity. We hypothesized that metals like Ni could enhance the reactivity of graphene towards DA reactions through charge transfer. The results indeed showed that metal substrates enhanced the reactivity of graphene in the DA reactions with a diene, 2,3-dimethoxy butadiene (DMBD), and a dienophile, maleic anhydride (MAH), with the activity enhancement in the order of Ni > Cu, and both are more reactive than graphene supported on silicon wafer. The rate constants were estimated to be two times higher for graphene supported on Ni than on silicon wafer. The computational results support the experimentally obtained rate trend of Ni > Cu, both predicted to be greater than unsupported graphene, which is explained by the enhanced graphene-substrate interaction reflected in charge transfer effects with the strongly interacting Ni. This study opens up a new avenue for enhancing the chemical reactivity of pristine graphene through substrate selection.
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Non-orthogonal multiple access (NOMA) has great potential to implement the fifth-generation (5G) requirements of wireless communication. For a NOMA traditional detection method, successive interference cancellation (SIC) plays a vital role at the receiver side for both uplink and downlink transmission. Due to the complex multipath channel environment and prorogation of error problems, the traditional SIC method has a limited performance. To overcome the limitation of traditional detection methods, the deep-learning method has an advantage for the highly efficient tool. In this paper, a deep neural network which has bi-directional long short-term memory (Bi-LSTM) for multiuser uplink channel estimation (CE) and signal detection of the originally transmitted signal is proposed. Unlike the traditional CE schemes, the proposed Bi-LSTM model can directly recover multiuser transmission signals suffering from channel distortion. In the offline training stage, the Bi-LTSM model is trained using simulation data based on channel statistics. Then, the trained model is used to recover the transmitted symbols in the online deployment stage. In the simulation results, the performance of the proposed model is compared with the convolutional neural network model and traditional CE schemes such as MMSE and LS. It is shown that the proposed method provides feasible improvements in performance in terms of symbol-error rate and signal-to-noise ratio, making it suitable for 5G wireless communication and beyond.
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Redes de Comunicação de Computadores , Noma , Algoritmos , Humanos , Redes Neurais de Computação , Razão Sinal-RuídoRESUMO
A cell-free massive multiple input multiple output (MIMO) system is an attractive network model that is in the spotlight in 5G and future communication systems. Despite numerous advantages, the cell-free massive MIMO system has a problem in that it is difficult to operate in reality due to its vast amount of calculation. The user-centric cell-free massive MIMO model has a more feasible and scalable benefit than the cell-free massive MIMO model. However, this model has the disadvantage that as the number of users in the area increases, there are users who do not receive the service. In this paper, the proposed scheme creates connections for unserved users under a user-centric scheme without additional access point (AP) installation and disconnection for existing users. A downlink user-centric cell-free massive MIMO system model in which the APs are connected to the central processing unit (CPU) and the APs and users are geographically distributed is considered. First, the downlink spectral efficiency formula is derived and applied to the user-centric cell-free massive MIMO system. Then, the proposed scheme and power control algorithm are applied to the derived formula. The simulation results show that the unserved users within the area disappear by using the proposed scheme, while the bit error rate (BER) performance and sum rate improve compared to the existing scheme. In addition, it is shown that the proposed scheme works well even with a very large number of users in the area, and a significant service performance improvement for the worst 10% of users and the overall improvement of per-user throughput for the bottom 70% of users are ensured.
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Algoritmos , Simulação por ComputadorRESUMO
Background and Objectives: It is crucial to prevent osteoporosis in patients receiving long-term glucocorticoid (GC) treatment. This study aimed to investigate the frequency and associated factors of preventive care for glucocorticoid-induced osteoporosis (GIOP) in Korea. Materials and Methods: Using the Korean National Health Insurance Service database, we identified 37,133 individuals aged ≥ 20 years who commenced long-term (≥90 days) oral GC between 2011 and 2012. High-quality GIOP preventive care was defined as either a bone mineral density (BMD) test, calcium and/or vitamin D supplementation, or prescription osteoporosis medications within 6 months of GC initiation. Multivariable logistic regression models were used to calculate odds ratios (ORs) for associated factors for high-quality GIOP preventive care. Results: The mean age was 49.8 years, and 18,476 (49.8%) patients were female. The frequency of high-quality GIOP preventive care was only 3.68% (BMD test, 1.46%; osteoporosis medications, 1.65%; calcium/vitamin D, 1.63%). Increasing age (OR = 2.53, p < 0.001; 40-49 years, OR = 3.99, p < 0.001; 50-59 years, OR = 5.17, p < 0.001; 60-69 years, OR = 8.07, p < 0.001; ≥70 years, respectively), systemic autoimmune disease (OR = 3.08, p < 0.001), rural residence (OR = 1.19, p = 0.046), concomitant hyperthyroidism (OR = 1.58, p = 0.007), and malignancy (OR = 1.59, p < 0.001) were significantly associated with a higher likelihood of receiving high-quality GIOP preventive care. Male sex (OR = 0.26, p < 0.001) and GC prescription in primary care clinics and nursing hospitals (OR = 0.66, p < 0.001) were associated with a lower rate of high-quality GIOP preventive care. Conclusions: Most Korean patients treated with GC did not receive appropriate preventive care for GIOP in real-world practice. More efforts are needed by clinicians to prevent, screen, and treat GIOP.
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Conservadores da Densidade Óssea , Osteoporose , Adulto , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Pristine graphene is fairly inert chemically, and as such, most application-driven studies use graphene oxide, or reduced graphene oxide. Using substrates to modulate the reactivity of graphene represents a unique strategy in the covalent functionalization of this otherwise fairly inert material. It was found that the reactivity of pristine graphene towards perfluorophenyl azide (PFPA) can be enhanced by a metal substrate on which graphene is supported. Results on the extent of functionalization, defect density, and reaction kinetics all show that graphene supported on Ni (G/Ni) has the highest reactivity toward PFPA, followed by G/Cu and then G/silicon wafer. DFT calculations suggest that the metal substrate stabilizes the physisorbed nitrene through enhanced electron transfer to the singlet nitrene from the graphene surface assisted by the electron rich metal substrate. The G/Ni substantially stabilizes the singlet nitrene relative to G/Cu and the free-standing graphene. The product structure is also predicted to be substrate dependent. These findings open up opportunities to enhance the reactivity of pristine graphene simply through the selection of the substrate. This also represents a new and powerful approach to increasing the reactivity of singlet nitrenes through direct electronic communication with graphene.
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This paper reports the fabrication and mechanical properties of macroscale graphene fibers (diameters of 10 to 100 µm with lengths upwards of 2 cm) prepared from a single sheet of single-layer graphene grown via chemical vapor deposition (CVD). The breaking strength of these graphene fibers increased with consecutive tensile test measurements on a single fiber, where fiber fragments produced from a prior test exhibited larger breaking strengths. Additionally, we observed an overall reduction of surface folds and wrinkles, and an increase in their alignment parallel to the tensile direction. We propose that a foundation of this property is the plastic deformations within the fiber that accumulate through sequential tensile testing. Through this cyclic method, our best fiber produced a strength of 2.67 GPa with a 1 mm gauge length.
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The Korean Society of Maternal Fetal Medicine proposed the first Korean guideline on prenatal aneuploidy screening and diagnostic testing, in April 2019. The clinical practice guideline (CPG) was developed for Korean women using an adaptation process based on good-quality practice guidelines, previously developed in other countries, on prenatal screening and invasive diagnostic testing for fetal chromosome abnormalities. We reviewed current guidelines and developed a Korean CPG on invasive diagnostic testing for fetal chromosome abnormalities according to the adaptation process. Recommendations for selected 11 key questions are: 1) Considering the increased risk of fetal loss in invasive prenatal diagnostic testing for fetal genetic disorders, it is not recommended for all pregnant women aged over 35 years. 2) Because early amniocentesis performed before 14 weeks of pregnancy increases the risk of fetal loss and malformation, chorionic villus sampling (CVS) is recommended for pregnant women who will undergo invasive prenatal diagnostic testing for fetal genetic disorders in the first trimester of pregnancy. However, CVS before 9 weeks of pregnancy also increases the risk of fetal loss and deformity. Thus, CVS is recommended after 9 weeks of pregnancy. 3) Amniocentesis is recommended to distinguish true fetal mosaicism from confined placental mosaicism. 4) Anti-immunoglobulin should be administered within 72 hours after the invasive diagnostic testing. 5) Since there is a high risk of vertical transmission, an invasive prenatal diagnostic testing is recommended according to the clinician's discretion with consideration of the condition of the pregnant woman. 6) The use of antibiotics is not recommended before or after an invasive diagnostic testing. 7) The chromosomal microarray test as an alternative to the conventional cytogenetic test is not recommended for all pregnant women who will undergo an invasive diagnostic testing. 8) Amniocentesis before 14 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 9) CVS before 9 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 10) Although the risk of fetal loss associated with invasive prenatal diagnostic testing (amniocentesis and CVS) may vary based on the proficiency of the operator, the risk of fetal loss due to invasive prenatal diagnostic testing is higher in twin pregnancies than in singleton pregnancies. 11) When a monochorionic twin is identified in early pregnancy and the growth and structure of both fetuses are consistent, an invasive prenatal diagnostic testing can be performed on one fetus alone. However, an invasive prenatal diagnostic testing is recommended for each fetus in cases of pregnancy conceived via in vitro fertilization, or in cases in which the growth of both fetuses differs, or in those in which at least one fetus has a structural abnormality. The guidelines were established and approved by the Korean Academy of Medical Sciences. This guideline is revised and presented every 5 years.
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Doenças Genéticas Inatas/diagnóstico , Diagnóstico Pré-Natal/métodos , Síndrome da Imunodeficiência Adquirida/diagnóstico , Amniocentese , Aneuploidia , Amostra da Vilosidade Coriônica , Aberrações Cromossômicas , Doenças Genéticas Inatas/prevenção & controle , Idade Gestacional , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Cuidado Pré-Natal , República da CoreiaRESUMO
In 2019, the Korean Society of Maternal-Fetal Medicine developed the first Korean clinical practice guidelines for prenatal aneuploidy screening and diagnostic testing. These guidelines were developed by adapting established clinical practice guidelines in other countries that were searched systematically, and the guidelines aim to assist in decision making of healthcare providers providing prenatal care and to be used as a source for education and communication with pregnant women in Korea. This article delineates clinical practice guidelines specifically for maternal serum screening for fetal aneuploidy and cell-free DNA (cfDNA) screening. A total of 19 key questions (12 for maternal serum and 7 for cfDNA screening) were defined. The main recommendations are: 1) Pregnant women should be informed of common fetal aneuploidy that can be detected, risks for chromosomal abnormality according to the maternal age, detection rate and false positive rate for common fetal aneuploidy with each screening test, limitations, as well as the benefits and risks of invasive diagnostic testing, 2) It is ideal to give counseling about prenatal aneuploidy screening and diagnostic testing at the first prenatal visit, and counseling is recommended to be given early in pregnancy, 3) All pregnant women should be informed about maternal serum screening regardless of their age, 4) cfDNA screening can be used for the screening of trisomy 21, 18, 13 and sex-chromosome aneuploidy. It is not recommended for the screening of microdeletion, 5) The optimal timing of cfDNA screening is 10 weeks of gestation and beyond, and 6) cfDNA screening is not recommended for women with multiple gestations. The guideline was reviewed and approved by the Korean Academy of Medical Sciences.
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Ácidos Nucleicos Livres/sangue , Transtornos Cromossômicos/diagnóstico , Diagnóstico Pré-Natal/métodos , Adulto , Aneuploidia , Transtornos Cromossômicos/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Cariotipagem , Idade Materna , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/genética , Gravidez , Primeiro Trimestre da Gravidez , República da CoreiaRESUMO
Hepatic fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), primarily collagen, within the liver. Because reactive oxygen species (ROS) has been implicated in its pathogenesis, the use of antioxidants as a potential treatment has been broadly explored. Here, we investigated the hepatoprotective properties of ramalin (RM), a compound extracted from the Antarctic lichen Ramalina terebrata, against hepatic fibrosis in vitro and in vivo. RM suppressed hepatic stellate cell (HSC) activation in vitro without any significant signs of adverse effects on the cells tested, and the accumulation of ECM was dramatically reduced in the liver tissue. Oral administration of RM in rats noticeably improved the gross appearance of the liver with increased body and liver weight relative to the DMN injected rats, and all of the serum biochemical markers returned to the normal range. RM treatment have ameliorated hepatic fibrosis in rats induced by DMN by repressing α-smooth muscle actin (α-SMA) and upregulating heme oxygenase-1 (HO-1). In addition, RM significantly reduced collagen accumulation, and levels of malondialdehyde (MDA) and hydroxyproline (HP) in the liver tissue of DMN injected rats. The efficacy exerted by RM was through erythroid 2-related factor 2 (Nrf2) mediated antioxidant response proteins such as HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO-1). Our results show the beneficial effect of RM against the progression of hepatic fibrosis.
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Antioxidantes/uso terapêutico , Glutamatos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Animais , Antioxidantes/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Dimetilnitrosamina , Progressão da Doença , Glutamatos/química , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Ratos , Elementos de Resposta , Transdução de Sinais/efeitos dos fármacosRESUMO
The-state-of-art CRISPR/Cas9 is one of the most powerful among the approaches being developed to rescue fundamental causes of gene-based inheritable diseases. Several strategies for delivering such genome editing materials have been developed, but the safety, efficacy over time, cost of production, and gene size limitations are still under debate and must be addressed to further improve applications. In this study, we evaluated branched forms of the polyethylenimine (PEI) - branched PEI 25 kDa (BPEI-25K) - and found that it could efficiently deliver CRISPR/Cas9 plasmids. Plasmid DNA expressing both guide RNA and Cas9 to target the Slc26a4 locus was successfully delivered into Neuro2a cells and meditated genome editing within the targeted locus. Our results demonstrated that BPEI-25K is a promising non-viral vector to deliver the CRISPR/Cas9 system in vitro to mediate targeted gene therapy, and these findings contribute to an understanding of CRISPR/Cas9 delivery that may enable development of successful in vivo techniques.
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Sistemas CRISPR-Cas , Sistemas de Liberação de Medicamentos , Terapia Genética , Neuroblastoma/terapia , Plasmídeos , Polietilenoimina/química , Transportadores de Sulfato/antagonistas & inibidores , Animais , Proliferação de Células , Camundongos , Neuroblastoma/genética , Transportadores de Sulfato/genética , Células Tumorais CultivadasRESUMO
Human Papillomavirus (HPV) infection is the most common sexually transmitted infection and is associated with the development of cervical cancer. The purpose of this report is to provide the literature evidences on selecting the HPV vaccine for national immunization program (NIP) in Korea. To complete these tasks, we reviewed domestic and foreign literature on the current status of HPV infection, efficacy and effectiveness of HPV vaccine, safety of vaccine and cost effectiveness analysis of vaccination business. Given that the median age of first sexual intercourse is continuing to fall, this may have serious implications for HPV infection and cervical cancer incidence at the age of 20s. The World Health Organization recommends that the HPV vaccination should be included in the NIP being implemented in each country. Both the bivalent and quadrivalent vaccines have a 90% or greater preventive efficacy on cervical intraepithelial lesion 2-3 and cervical cancer by the HPV 16 or HPV 18. In the future, if HPV vaccination rate as part of NIP increases, it is expected that the incidence of HPV infection, genital warts, and cervical precancerous lesions will be decreased in the vaccination age group. Therefore, in order to increase the HPV vaccination rate at this point in Korea, social consensus and efforts such as the introduction and promotion of HPV vaccine to the NIP according to appropriate cost-effectiveness analysis are required.
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Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Programas de Imunização , Infecções por Papillomavirus/economia , Infecções por Papillomavirus/epidemiologia , República da Coreia/epidemiologia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: The purpose of this study was to examine post-traumatic stress, depression, anxiety, and complicated grief in Korean high school students who experienced a peer suicide. METHODS: A total of 956 students were included in the statistical analysis. One week after a peer suicide, a school-based crisis intervention program was conducted. The cohort was followed-up at one week and five months after a peer suicide. The program consists of screening tests, educational sessions, and further interview with psychiatric specialists for the selected group. Screening tests were conducted for all students to measure the Child Report of Post-traumatic Symptoms (CROPS), the post-traumatic stress symptoms (The University of California at Los Angeles post-traumatic stress disorder [PTSD] reaction index; UCLA-PTSD-RI), the anxiety symptoms (The Korean-Beck Anxiety Inventory; K-BAI), the depressive symptoms (The Korean-Beck Depression Inventory-II; K-BDI-II), and the complicated grief reaction (The Inventory of Complicated Grief; ICG). For statistical analysis, the SPSS Statistics 21.0 program was used. RESULTS: At baseline and five months follow-ups, 8.6% and 2.9% of the students showed post-traumatic stress symptoms. At five months follow-up, there was a statistically significant decline in the post-traumatic stress symptoms, anxiety, depression, and complicated grief among the 'trauma group.' A higher proportion of the female students showed post-traumatic stress symptoms after the incident of peer suicide than the male students. CONCLUSION: School-based crisis intervention helps improvement of trauma-related symptoms. It might be an effective way to prevent suicide spreading among students by alleviating trauma-related symptoms.