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This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.
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Antibacterianos , República de Corea , Humanos , Antibacterianos/uso terapéutico , Hospitales , Centros de Atención Terciaria , Pautas de la Práctica en Medicina/estadística & datos numéricos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Masculino , Farmacorresistencia BacterianaRESUMEN
A vertically aligned dichroic dye (VA-Dye) film, whose absorption axis is perpendicular to that of its substrates, was laminated on a display panel in which the absorption axis of the top polarizer was set to 0°. In the vertical viewing angle of the display panel, the absorption axes of the top polarizer and dichroic dye are at right angles to each other, and, so, the light emitted from the display panel can be blocked. In the horizontal viewing angle of the display panel, the absorption axes of the top polarizer and dichroic dye are parallel to each other so that the light emitted from the display panel can be transmitted. Based on these polarization optics, we achieved complete elimination of light emitted in the upward or downward direction of the display panel, while the light emitted to the left and right is transmitted. We also added a designed optical compensation film using a positive biaxial (+B) retarder to the VA-Dye film so that the light emitted in the upward and downward directions of the display panel could be blocked in a wide viewing angle range (not only in the vertical direction, but also in the diagonal direction). The display panel using the VA-Dye film with the +B retarder showed excellent optical performance, such as significantly lower transmittance over a wide viewing angle range in the upward direction and relatively higher transmittance compared to that of a reference panel without the VA-Dye film. In addition, the VA-Dye film can be manufactured with a lower thickness, easier fabrication, and lower cost when compared with other technologies.
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In November 2020, an unusual increase in fungal endophthalmitis cases after cataract surgery was reported to the Korea Disease Control and Prevention Agency, South Korea. We initiated an outbreak investigation to identify the cause. We identified 156 cases nationwide, 62 confirmed and 94 probable. Most case-patients were exposed during surgery to ocular viscoelastic devices (OVDs) from the same manufacturer (company A). We isolated Fusarium spp. from 50 confirmed cases. Molecular identification of 39 fungal isolates from clinical samples and 13 isolates from OVDs confirmed F. oxysporum caused the infections. The risk ratio for fungal endophthalmitis from company A's OVDs was 86.0 (95% CI 27.4-256.9), much higher than risk from other manufacturers' products. We determined this fungal endophthalmitis outbreak was caused by a contaminated lot of OVDs and recommended discontinued use of this product. Early recognition of outbreaks and joint responses from related government agencies can reduce risk for fungal endophthalmitis.
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Extracción de Catarata , Catarata , Endoftalmitis , Infecciones Fúngicas del Ojo , Humanos , Extracción de Catarata/efectos adversos , Endoftalmitis/etiología , Endoftalmitis/microbiología , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/complicaciones , Infecciones Fúngicas del Ojo/microbiología , Brotes de EnfermedadesRESUMEN
BACKGROUND: There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown. OBJECTIVE: To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP). DESIGN: Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen. SETTING: Veterans Health Administration (2011 to 2013). PATIENTS: Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose. MEASUREMENTS: The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months. RESULTS: Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, -15.2% [95% CI, -15.7% to -14.6%] at 3 months and -15.1% [CI, -15.6% to -14.5%] at 12 months) but a slightly larger reduction in mean SBP (-0.8 mm Hg [CI, -1.2 to -0.4 mm Hg] at 3 months and -1.1 mm Hg [CI, -1.6 to -0.6 mm Hg] at 12 months). LIMITATION: Observational data; largely male population. CONCLUSION: Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings. PRIMARY FUNDING SOURCE: National Institute on Aging and Veterans Health Administration.
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Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Antihipertensivos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Estudios Retrospectivos , Estados Unidos , VeteranosRESUMEN
We propose a method, called bi-point input, for convolutional neural networks (CNNs) that handle variable-length input features (e.g., speech utterances). Feeding input features into a CNN in a mini-batch unit requires that all features in each mini-batch have the same shape. A set of variable-length features cannot be directly fed into a CNN because they commonly have different lengths. Feature segmentation is a dominant method for CNNs to handle variable-length features, where each feature is decomposed into fixed-length segments. A CNN receives one segment as an input at one time. However, a CNN can consider only the information of one segment at one time, not the entire feature. This drawback limits the amount of information available at one time and consequently results in suboptimal solutions. Our proposed method alleviates this problem by increasing the amount of information available at one time. With the proposed method, a CNN receives a pair of two segments obtained from a feature as an input at one time. Each of the two segments generally covers different time ranges and therefore has different information. We also propose various combination methods and provide a rough guidance to set a proper segment length without evaluation. We evaluate the proposed method on the spoofing detection tasks using the ASVspoof 2019 database under various conditions. The experimental results reveal that the proposed method reduces the relative equal error rate (EER) by approximately 17.2% and 43.8% on average for the logical access (LA) and physical access (PA) tasks, respectively.
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Redes Neurales de la Computación , Bases de Datos FactualesRESUMEN
Background: Current guidelines for the therapeutic monitoring of vancomycin recommend dosing based on the area under the concentration-time curve (AUC) to achieve clinical efficacy while reducing nephrotoxicity. Although a wide range of nephrotoxicity thresholds have been reported, few studies have documented clinical outcomes based on AUC-guided vancomycin dosing in Korea. Objective: The aim of the study was to evaluate whether a relationship exists between AUC and treatment outcomes in vancomycin treated patients in methicillin-resistant Staphylococcus aureus bacteremia. Furthermore, this study tries to estimate AUC threshold for treatment failure and nephrotoxicity. Methods: The records of adult patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin for ≥72 hours without dialysis between April 2013 and April 2021, were reviewed retrospectively. Treatment success was defined as defervescence and blood culture sterilization by day 7. Nephrotoxicity was defined as an increase in serum creatinine levels ≥0.3 mg/dL or a 50% increase from baseline on 2 consecutive days. Bayesian estimation was used to predict individual vancomycin AUC. Both classification and regression tree and receiver operating characteristic curve analyses were performed to estimate the optimal AUC thresholds for vancomycin efficacy and nephrotoxicity. Results: Of 118 patients, 61 (51.7%) experienced treatment failure and 42 (35.6%) developed acute kidney injury. The vancomycin AUC threshold for predicting acute kidney injury was 615.0 mg· hr/L. In the multivariate analysis, AUC ≥615.0 mg· hr/L was a significant risk factor for nephrotoxicity (adjusted odds ratio [aOR]â¯=â¯5.24; 95% CI, 1.8-14.65). The lower threshold for treatment failure was not defined because it was not statistically significant. Risk factors for treatment failure included low body mass index (aORâ¯=â¯0.82; 95% CI, 0.70-0.96), severity of acute illness represented by complicated infection (aORâ¯=â¯77.56; 95% CI, 16.7-359.4) and comorbidities, such as solid organ tumors (aORâ¯=â¯6.61; 95% CI, 1.19-36.81) and cerebrovascular disease (aORâ¯=â¯6.05; 95% CI, 1.17-31.23). Conclusions: Although AUC-guided vancomycin dosing was associated with a reduced risk of acute kidney injury, its ability to predict clinical outcomes was modest. Further studies are needed to define the AUC therapeutic range to maximize efficacy and minimize nephrotoxicity. (Curr Ther Res Clin Exp. 2023; 83:XXX-XXX).
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Background and Objectives: Transient receptor potential melastatin 7 (TRPM7) is a unique channel protein, and functionally responsible for transportation of calcium and magnesium. Physiologically, the TRPM7 channel is involved in homeostasis of calcium and magnesium, and cell survival. TRPM7 expression is up-regulated in many cancers as malignant behaviors of cancer cells, and its deficiency suppresses their growth. Materials and Methods: In this study, we aimed to analyze clinical and prognostic characteristics of TRPM7 expression in colorectal cancers (CRC) using The Cancer Genome Atlas. Results: High expression of TRPM7 was observed in younger patients with rectal cancer (p = 0.0002). By quantitative correlation analysis, TRPM7 was negatively correlated with age (R = −0.239, p = 0.003) and p53 (R = −0.240, p = 0.002). Furthermore, it was positively correlated with APC expression (R = 0.534, p < 0.001) and KRAS expression (R = 0.319, p < 0.001). In colon cancer, there were no variables that showed a significant correlation with TRPM7. Survival analysis found that TRPM7 expression did not have any prognostic value in colon and rectal cancers. Conclusions: Our study highlights that TRPM7 expression in CRC, particularly in rectal cancer, may be a potential marker. Future studies are needed to provide deeper insights into the role of TRPM7 in rectal cancer.
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Neoplasias del Recto , Canales Catiónicos TRPM , Humanos , Canales Catiónicos TRPM/genética , Pronóstico , Magnesio , Calcio , Proteínas Serina-Treonina Quinasas , ColonRESUMEN
Iron oxyhydroxide (FeOOH) nanostructures of different shapes were successfully synthesized on flexible textile cloth of polyester using a novel and simple technique based on hydrolysis method. The technique used herein is newly designed specifically to improve the efficiency in terms of energy, simplicity and cost involved in large scale synthesis of nanostructured thin films. Additionally, the morphology of nano-sized iron oxyhydroxide could be tuned into different shapes through variation in the type of precursors used for synthesis. The uniformity and adhesion of the depositions were also found to be excellent as examined by qualitative techniques. The as-deposited samples exhibited monoclinic and orthorhombic structures of FeOOH. A significant variation in the shape of as-deposited FeOOH nanostructures with change in precursor was observed through morphological studies, which displayed lance-shaped, rounded clusters and rod-like growth features in different cases. The nanocrystalline FeOOH can be directly applied to attract and trap phosphate from water reservoirs, thus contributing to environmental solutions. The proposed technique can also be utilized to deposit larger areas, which could be suitable for practical applications.
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The abilities of the new Vitek 2 AST-YS08 (YS08) and Sensititre YeastOne (SYO) systems to detect the resistances of Candida isolates to azoles and echinocandins were evaluated. In total, 292 isolates, including 28 Candida albicans (6 Erg11 and 2 Fks mutants), 57 Candida parapsilosis (26 Erg11 mutants), 24 Candida tropicalis (10 Erg11 and 1 Fks mutants), and 183 Candida glabrata (39 Pdr1 and 13 Fks mutants) isolates, were tested. The categorical agreements (CAs) between the Clinical and Laboratory Standards Institute (CLSI) method and YS08 fluconazole MICs obtained using clinical breakpoints were 92.4% (C. albicans), 96.5% (C. parapsilosis), and 87.0% (C. tropicalis), and the CAs between the CLSI and SYO MICs were 92.3% (C. albicans), 77.2% (C. parapsilosis), 100% (C. tropicalis), and 98.9% (C. glabrata). For C. glabrata, the CAs with the CLSI micafungin MICs were 92.4% and 55.5% for the YS08 micafungin and caspofungin MICs, respectively; they were 100%, 95.6%, and 98.9% for the SYO micafungin, caspofungin, and anidulafungin MICs, respectively. YS08 does not provide fluconazole data for C. glabrata; the CA with the CLSI fluconazole MIC was 97.8% for the YS08 voriconazole MIC, using an epidemiological cutoff value (ECV) of 0.5 µg/ml. Increased CAs with the CLSI MIC were observed for the YS08 MIC using CLSI ECVs (for fluconazole and C. tropicalis, 100%; for micafungin and C. glabrata, 98.9%) and for the SYO MIC using method-specific ECVs (for fluconazole and C. parapsilosis, 91.2%; for caspofungin and C. glabrata, 98.9%). Therefore, the YS08 and SYO systems may have different abilities to detect mechanisms of azole and echinocandin resistance in four Candida species; the use of method-specific ECVs may improve the performance of both systems.
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Candida , Equinocandinas , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Azoles/farmacología , Candida/genética , Farmacorresistencia Fúngica/genética , Equinocandinas/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Neurotoxic effects of phthalate during pregnancy on immature brain of the offspring or mature brains of the mothers remain unclear. We examined the effect of dibutyl phthalate (DBP) exposure during gestation and lactation on the maternal behavior of mother mice and neurodevelopment in pups. METHODS: Pregnant mice were treated orally with DBP (0, 50 and 100 mg/kg/day, N = 20 per group) from gestational day 13 to postnatal day (PND) 15. Maternal behavior was measured using pup retrieval and nest shape test at postpartum day 4. For the pups, the neurodevelopment was measured using negative geotaxis, cliff avoidance at PND 7, swimming test and olfactory orientation at PND 14. RNA and protein expressions in the brain cortex of 50 mg/kg/day and control group (0 mg/kg/day) were analyzed using microarray and Western blot analysis. Nissl-stained sections at the coronal level of interaural 2.56 mm, bregma -1,23 mm, were used for counting of dark cortical neurons in mother and pup mice. RESULTS: DBP treated mother mice (50 and 100 mg/kg/day) showed poor maternal behavior, poor nesting and retrieval behavior compared to the control group (0 mg/kg/day). In brain cortex, DBP-treated mothers showed decrease in protein expression of Nr4a3, Egr1, Arc, BDNF and phosphorylation of AKT and CREB, were also decreased in cortex of DBP-treated mothers. Pups exposed to DBP showed significantly decreased scores in negative geotaxis at PND 7 and swimming scores and olfactory orientation tests at PND 14. The cortex of the DBP exposed pups showed increase in expression of dopamine receptor D2 gene. Nissl staining showed that the dark neurons were increased in cortex of DBP treated mothers and DBP exposed pups. Suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain. CONCLUSION: DBP exposure during gestation and lactation cause impairment in maternal behaviors and downregulation of neuronal plasticity and survival signals. Pups of mothers with exposed to DBP, showed delayed neurodevelopment and dark neurons increase in brain cortex, suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain.
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Dibutil Ftalato , Conducta Materna , Sistema Nervioso , Efectos Tardíos de la Exposición Prenatal , Animales , Dibutil Ftalato/toxicidad , Femenino , Humanos , Lactancia , Conducta Materna/efectos de los fármacos , Exposición Materna , Ratones , Ratones Endogámicos C57BL , Madres , Sistema Nervioso/crecimiento & desarrollo , Plasticidad Neuronal , EmbarazoRESUMEN
Sutaehwan (STH) has been used in Korean medicine for the treatment of abortus habitualis such as fetal restlessness in the uterus. Previously, we reported that a modified formulation of STH, Sutaehwan-Gami, has phytoestrogen-like properties in an ovariectomized menopausal rat model. However, the therapeutic effects of STH and the precise mechanisms by which STH affects various menopausal symptoms remain poorly understood. The current study was designed to explore the effects of a modified form of STH on menopausal anxiety, depression and heart hypertrophy and its mechanisms in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal mouse models. VCD-induced menopausal model mice were fed a modified form of STH, which contained water extract of 3 herbs (called STH_KP17001) at a dose of 100 or 300 mg/kg/d or as a positive control, estradiol at a dose of 0.2 mg/kg/d with standard mouse pellets for 13 weeks. The results show that STH_KP17001 significantly restored the VCD-induced weight reduction of uterine and ovary through the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in the uterus and ovary. Moreover, STH_KP17001 showed slight proliferative effects and estrogen receptor α phosphorylation in MCF-7 cells. Treatment with STH_KP17001 reversed VCD-induced anxiety and depression through AMP-activated protein kinase (AMPK) activation and brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex, while improving heart hypertrophy through inactivation of inhibitor of kappaB α (IκBα) in the heart. The results indicate that STH_KP17001 improves menopause-induced anxiety, depression and heart hypertrophy, implying its protective role for the management of menopausal symptoms.
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Ansiedad/prevención & control , Cardiomegalia/prevención & control , Depresión/prevención & control , Menopausia/psicología , Extractos Vegetales/farmacología , Animales , Ciclohexenos , Modelos Animales de Enfermedad , Femenino , Humanos , Células MCF-7 , Medicina Tradicional Coreana , Ratones Endogámicos C57BL , Extractos Vegetales/aislamiento & purificación , Compuestos de ViniloRESUMEN
Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.
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Diferenciación Celular/efectos de los fármacos , Interleucina-6/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteocitos/metabolismo , Ligando RANK/metabolismo , Ácido Zoledrónico/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Biomarcadores , Comunicación Celular , Línea Celular , Expresión Génica , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Janus Quinasa 2/metabolismo , Ratones , Modelos Biológicos , Osteogénesis/efectos de los fármacos , Ligando RANK/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin. Although melatonin treatment did not affect the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), it markedly inhibited the activation of NF-κB and subsequent induction of nuclear factor of activated T cell cytoplasmic 1(NFATc1). Thus, our results suggest that melatonin could suppress osteoclast differentiation through downregulation of NF-κB pathway with concomitant decrease in the NFATc1 transcription factor induction. Furthermore, melatonin seems to have an anti-osteoclastogenic effect independent of plasma membrane melatonin receptors. In addition to previously reported properties of melatonin, our study proposes another aspect of melatonin and bone homeostasis.
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Resorción Ósea/metabolismo , Melatonina/metabolismo , Osteoclastos/metabolismo , Animales , Resorción Ósea/genética , Diferenciación Celular/efectos de los fármacos , Expresión Génica , Silenciador del Gen , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Ligando RANK/metabolismo , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , Transducción de Señal/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Células Madre/metabolismoRESUMEN
Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the α-synuclein (α-syn) gene. Mutant α-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T α-synuclein (α-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were reduced in the α-syn Tg but not WT mice by sub-toxic MPTP injection. In the adhesive removal test, time to remove paper was significantly increased only in the homo α-syn Tg mice. In the challenging beam test, the hemi and homo α-syn Tg mice spent significantly longer time to traverse as compared to that of WT group. In order to find out responsible proteins related with vulnerability of mutant α-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were significantly decreased in the α-syn Tg mice. Moreover, A53T α-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T α-syn mice can be explained by downregulation of DJ-1.
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The suppressor of cytokine signaling 2 (SOCS2) has been reported to be involved in astroglial reactions and adult neurogenesis in the ischemic hippocampus. To elucidate whether SOCS2 is implicated in the pathophysiology of stroke, we investigate spatiotemporal regulation and identification of cell phenotypes expressing SOCS2 after transient focal cerebral ischemia. Weak hybridization signals for SOCS2 mRNA were constitutively observed in striatal neurons and upregulation of SOCS2 mRNA was induced in association with nestin-positive cells in stroke-lesioned rats. Analysis of the characteristics and phenotypes of SOCS2/nestin double-labeled cells revealed spatial differences between infarct and peri-infarct areas. SOCS2/nestin double-labeled cells in the infarct area were associated with the vasculature and were highly proliferative. In contrast, the double-labeled cells in the peri-infarct area were indeed glial fibrillary acidic protein (GFAP)-positive reactive astrocytes forming the glial scar, although nestin-negative reactive astrocytes also exhibited weak SOCS2 expression. In addition, induction of SOCS2 expression was observed in Iba1-positive cells showing a macrophage-like phenotype with amoeboid morphology; these cells were predominantly localized in the infarct area. In the peri-infarct area, only a small proportion of Iba1-positive cells with the morphology of brain macrophages expressed SOCS2 and most activated stellate microglial cells with thick and short processes exhibited weak or negligible SOCS2 expression. Thus, our results revealed the phenotypic and functional heterogeneity of SOCS2-expressing cells within infarct and peri-infarct areas, suggesting the involvement of SOCS2 in astroglial reactions and activation/recruitment of brain macrophages and its potential role in perivascular progenitors/stem cells after ischemic stroke.
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BACKGROUND: The best therapeutic option for diabetic end-stage renal disease (DMESRD) has not been established among living donor kidney transplantation (LDKT), deceased donor kidney transplantation (DDKT), simultaneous pancreas and kidney transplantation (SPK), and dialysis. METHODS: We retrospectively analyzed the outcomes of DMESRD patients at two Korean centers from February 2000 to December 2011. RESULTS: Among 674 patients, 295 underwent kidney transplantation (LDKT, 175; DDKT, 72; and SPK, 48), while 379 were still on dialysis. The dialysis group had a higher mortality rate than the transplantation group. From the time after dialysis initiation, LDKT group had a better patient survival rate than DDKT registration group and SPK registration group. From the time after transplantation, LDKT had a better patient survival rate than DDKT; however, there was no significant difference between LDKT and SPK. In SPK, patient survival and kidney or pancreas graft survival rates were not different between types 1 and 2 DMESRD. CONCLUSION: LDKT is better than waiting for SPK/DDKT in DMESRD patients, if a living donor is available, and this conclusion may be unique to Korea where waiting time for SPK is long. SPK can be used in non-obese Asians with type 2 as well as type 1 DMESRD.
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Diabetes Mellitus Tipo 1/mortalidad , Diabetes Mellitus Tipo 2/mortalidad , Rechazo de Injerto/mortalidad , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Trasplante de Páncreas/mortalidad , Diálisis Renal/mortalidad , Cadáver , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Donadores Vivos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Bioactivity-guided isolation of a methanolic extract of Euphorbia fischeriana led to the isolation of four new abietane-type diterpenoids, fischeriolides A-D (1-4), together with 11 known diterpenoids. Their structures were elucidated based on the interpretation of 1D and 2D NMR spectroscopic and HRESIMS data. The absolute configuration of compound 3 was determined by single-crystal X-ray diffraction analysis and electronic circular dichroism methods. Compounds 5-9 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values in the range 4.9-12.6 µM.
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Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Euphorbia/química , Óxido Nítrico/biosíntesis , Animales , Antineoplásicos Fitogénicos/química , Cristalografía por Rayos X , Diterpenos/química , Medicamentos Herbarios Chinos/química , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Conformación Molecular , Estructura Molecular , Raíces de Plantas/química , República de CoreaRESUMEN
MicroRNAs (miRNAs) are critical in the maintenance, differentiation, and lineage commitment of stem cells. Stem cells have the unique property to differentiate into tissue-specific cell types (lineage commitment) during cell division (self-renewal). In this study, we investigated whether miR-34a, a cell cycle-regulating microRNA, could control the stem cell properties of adipose tissue-derived stem cells (ADSCs). First, we found that the expression level of miR-34a was increased as the cell passage number was increased. This finding, however, was inversely correlated with our finding that the overexpression of miR-34a induced the decrease of cell proliferation. In addition, miR-34a overexpression decreased the expression of various cell cycle regulators such as CDKs (-2, -4, -6) and cyclins (-E, -D), but not p21 and p53. The cell cycle analysis showed accumulation of dividing cells at S phase by miR-34a, which was reversible by co-treatment with anti-miR-34a. The potential of adipogenesis and osteogenesis of ADSCs was also decreased by miR-34a overexpression, which was recovered by co-treatment with anti-miR-34a. The surface expression of stem cell markers including CD44 was also down-regulated by miR-34a overexpression as similar to that elicited by cell cycle inhibitors. miR-34a also caused a significant decrease in mRNA expression of stem cell transcription factors as well as STAT-3 expression and phosphorylation. Cytokine profiling revealed that miR-34a significantly modulated IL-6 and -8 production, which was strongly related to cellular senescence. These data suggest the importance of miR-34a for the fate of ADSCs toward senescence rather than differentiation.
Asunto(s)
Adipogénesis/genética , Ciclo Celular/genética , Senescencia Celular/genética , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo , Células Madre/citología , Tejido Adiposo/citología , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/genética , Humanos , Receptores de Hialuranos/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , MicroARNs/antagonistas & inhibidores , Oligorribonucleótidos Antisentido/farmacología , Osteogénesis/genética , Células Madre/fisiologíaRESUMEN
This study evaluated antismoking advertisements in South Korean television by drawing upon a Health Communication article by Cohen, Shumate, and Gold (2007) and on Gold, Cohen, and Shumate's (2008) typology. This study examined the theories and messages in South Korean antismoking advertisements. First, South Korean antismoking advertisements primarily targeted adults. In addition, the advertisements for adults normally used statistical evidence, whereas those for adolescents often used testimonial evidence. In terms of the type of performance, narration was often used in advertisements for both adults and adolescents. Second, the most prevalent persuasive health message used social norms, whereas the most prevalent affective appeal used fear appeals. Third, antismoking advertisements in South Korea mentioned more benefits of not smoking than barriers to not smoking. This study also identified the message difference in the U.S. and South Korean antismoking advertisements.