Search

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59–0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI. [ABSTRACT FROM AUTHOR]

Landslides that occur near residential regions are most commonly a result of shallow slope failure, which takes place as a consequence of heavy rainfall during the monsoon season, causing loss to human life and property. In this study, the characteristics of the volumetric water content (VWC) gradient were analyzed to predict shallow slope failure which was reproduced based on flume experiments performed at various slope conditions. The VWC gradient values were calculated for each measurement position and slope depth. Moreover, the VWC gradient characteristics during the occurrence and nonoccurrence of shallow slope failures were compared to those of an actual site that did not undergo slope failure. Our results show that the probability of failure increases with an increase in the VWC gradient value. Additionally, early warning criteria are proposed by dividing the range of the VWC gradient value into four stages in which the failure rate rapidly increased. Full-scale flume experiments were performed to simulate an actual site in terms of its scale, and the appropriate sensor installation positions were proposed to effectively predict the probability of failure. [ABSTRACT FROM AUTHOR]

Background: Midface concavity is a relatively common facial feature in East Asian populations. Paranasal augmentation is becoming an increasingly popular procedure for patients with mild concavity and normal occlusion. In this study, we evaluate clinical outcomes following a series of paranasal augmentation., Methods: A retrospective review was performed for patients with Class I occlusion who had undergone bilateral paranasal augmentation using custom-made silicone implants, between October 2005 and September 2013. Patient charts were reviewed for demographic information, concomitant operations, and postoperative complications. Preoperative and postoperative (1-month) photographs were used to evaluate operative outcome., Results: The review identified a total of 93 patients meeting study criteria. Overall, aesthetic outcomes were satisfactory. Five-millimeter thick silicone implant was used in 81 cases, and the mean augmentation was 4.26 mm for this thickness. Among the 93 patients, 2 patients required immediate implant removal due to discomfort. An additional 3 patients experienced implant migration without any extrusion. Nine patients complained of transient paresthesia, which had resolved by 2 weeks. There were no cases of hematoma or infection. All patients reported improvement in their lateral profile and were pleased at follow-up. Complications that arose postoperatively included 9 cases of numbness in the upper lip and 3 cases of implant migration. All cases yielded satisfactory results without persisting complications. Sensations were fully restored postoperatively after 1 to 2 weeks., Conclusion: Paranasal augmentation with custom-made silicone implants is a simple, safe, and inexpensive method that can readily improve the lateral profile of a patient with normal occlusion. When combined with other aesthetic procedures, paranasal augmentation can synergistically improve outcome and lead to greater patient satisfaction., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Although botulinum toxin type A has been shown to inhibit the formation of hypertrophic scars, little is known about the underlying mechanisms of action. Studies have reported that botulinum toxin type A is able to inhibit fibroblast proliferation and transforming growth factor (TGF)-β1 expression; therefore, in this study, the authors evaluated its effect on the differentiation of fibroblasts derived from normal and hypertrophic scar tissue., Methods: Under local anesthesia, tissue specimens from 10 scars (five normal mature scars and five hypertrophic scars) were obtained from nine patients who visited the authors' department for scar revision. Fibroblasts isolated from the tissue specimens were cultured until confluent and pretreated with TGF-β1 to induce differentiation before treatment with botulinum toxin type A. Expression of the myofibroblast marker α-smooth muscle actin in cell cultures was evaluated by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. Fibroblast-to-myofibroblast differentiation was further evaluated by immunocytochemistry and confocal microscopy., Results: The authors' results showed that α-smooth muscle actin mRNA and protein levels were significantly lower in the botulinum toxin type A-treated group than in the control group (treated with TGF-β1 only) of fibroblasts derived from hypertrophic scars, but not fibroblasts derived from normal scars. Immunocytochemistry results also showed that fibroblast-to-myofibroblast differentiation was significantly decreased after botulinum toxin type A treatment in fibroblasts derived from hypertrophic scars., Conclusion: The authors' results show that botulinum toxin type A directly inhibits fibroblast-to-myofibroblast differentiation in vitro, and indicate its potential for use in treating wounds expected to develop into hypertrophic scars after trauma, burn, or surgery., Clinical Question/level of Evidence: Therapeutic, V.

Mucin hypersecretion and overproduction are frequent manifestations of respiratory disease. Determining the physiological function of airway mucin is presently considered more important than identifying the relevant signaling pathways. The lack of a full-length human mucin 8 (MUC8) cDNA sequence has hindered the generation of a Muc8 knockout mouse line. Thus, the precise physiological functions of MUC8 are unclear. Herein, we investigated the function of MUC8 using a small-interfering RNA (siRNA)-mediated genetic silencing approach in human airway epithelial cells. Herein, intracellular IL-1α production was stimulated by an ATP/P2Y2 complex. While ATP/P2Y₂ increased IL-1α secretion in a time-dependent manner, treatment with P2Y₂-specific siRNA significantly decreased IL-1α secretion. Moreover, ATP increased P2Y₂-mediated upregulation of MUC8 expression; however, IL-1α significantly decreased the extent to which ATP/P2Y₂ upregulated MUC8 expression. Interestingly, treatment with MUC8-specific siRNA decreased the production of anti-inflammatory cytokines (TGF-β and IL-1 receptor antagonist) and increased the production of inflammatory cytokines (IL-1α and IL-6) in our system. In addition, siRNA-mediated knockdown of MUC8 expression dramatically increased the secretion of inflammatory chemokines and resulted in an approximately threefold decrease in cell chemotaxis. We propose that MUC8 may function as an anti-inflammatory mucin that participates in inflammatory response by attracting immune cells/cytokines to the site of inflammation. Our results provide new insight into the physiological function of MUC8 and enhance our understanding of mucin overproduction during airway inflammation., (Copyright © 2015 the American Physiological Society.)

Glycogen synthase kinase 3β (GSK3β) participates in many cellular processes, and its dysregulation has been implicated in a wide range of diseases such as obesity, type 2 diabetes, cancer, and Alzheimer disease. Inactivation of GSK3β by phosphorylation at specific residues is a primary mechanism by which this constitutively active kinase is controlled. However, the regulatory mechanism of GSK3β is not fully understood. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) has multiple biological functions that occur as the result of phosphorylation of diverse proteins that are involved in metabolism, synaptic function, and neurodegeneration. Here we show that GSK3β directly interacts with and is phosphorylated by Dyrk1A. Dyrk1A-mediated phosphorylation at the Thr(356) residue inhibits GSK3β activity. Dyrk1A transgenic (TG) mice are lean and resistant to diet-induced obesity because of reduced fat mass, which shows an inverse correlation with the effect of GSK3β on obesity. This result suggests a potential in vivo association between GSK3β and Dyrk1A regarding the mechanism underlying obesity. The level of Thr(P)(356)-GSK3β was higher in the white adipose tissue of Dyrk1A TG mice compared with control mice. GSK3β activity was differentially regulated by phosphorylation at different sites in adipose tissue depending on the type of diet the mice were fed. Furthermore, overexpression of Dyrk1A suppressed the expression of adipogenic proteins, including peroxisome proliferator-activated receptor γ, in 3T3-L1 cells and in young Dyrk1A TG mice fed a chow diet. Taken together, these results reveal a novel regulatory mechanism for GSK3β activity and indicate that overexpression of Dyrk1A may contribute to the obesity-resistant phenotype through phosphorylation and inactivation of GSK3β., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Cephalometric analysis is essential for planning treatment in maxillofacial and aesthetic facial surgery. Although photometric analysis of the Korean nose has been attempted in the past, anthropometry of the deeper nasal structures in the same population based on computerized tomography (CT) has not been published. We therefore measured three anthropometric parameters of the nose on CT scans in our clinical series of patients., Methods: We conducted the current retrospective study of a total of 100 patients (n=100) who underwent a CT-guided radiological measurement at our institution during a period ranging from January of 2008 to August of 2010. In these patients, we took three anthropometric measurements: the nasofrontal angle, the pyramidal angle, and the linear distance between the nasion and the tip of the nasal bone., Results: The mean nasofrontal angle was 131.14° in the male patients and 140.70° in the female patients. The mean linear distance between the nasion and the tip of the nasal bone was 21.28 mm and 18.02 mm, respectively. The mean nasal pyramidal angle was 112.89° and 103.25° at the level of the nasal root, 117.49° and 115.60° at the middle level of the nasal bone, and 127.99° and 125.04° at the level of the tip of the nasal bone, respectively., Conclusions: In conclusion, our data will be helpful in the preparation of silicone implants for augmentation and/or corrective rhinoplasty in ethnic Korean people.

Feeding behavior is one of the most essential activities in animals, which is tightly regulated by neuroendocrine factors. Drosophila melanogaster short neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY) regulate food intake. Understanding the molecular mechanism of sNPF and NPY signaling is critical to elucidate feeding regulation. Here, we found that minibrain (mnb) and the mammalian ortholog Dyrk1a, target genes of sNPF and NPY signaling, [corrected] regulate food intake in Drosophila melanogaster and mice. In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway. Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake. Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a transgenic mice exhibited decreased FOXO acetylation and increased NPY expression in the hypothalamus, and [corrected] increased food intake. Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals., Competing Interests: The authors have declared that no competing interests exist.

With the gradual increase of cases using fillers, cases of patients treated by non-medical professionals or inexperienced physicians resulting in complications are also increasing. We herein report 2 patients who experienced acute complications after receiving filler injections and were successfully treated with adipose-derived stem cell (ADSCs) therapy. Case 1 was a 23-year-old female patient who received a filler (Restylane) injection in her forehead, glabella, and nose by a non-medical professional. The day after her injection, inflammation was observed with a 3×3 cm skin necrosis. Case 2 was a 30-year-old woman who received a filler injection of hyaluronic acid gel (Juvederm) on her nasal dorsum and tip at a private clinic. She developed erythema and swelling in the filler-injected area A solution containing ADSCs harvested from each patient's abdominal subcutaneous tissue was injected into the lesion at the subcutaneous and dermis levels. The wounds healed without additional treatment. With continuous follow-up, both patients experienced only fine linear scars 6 months postoperatively. By using adipose-derived stem cells, we successfully treated the acute complications of skin necrosis after the filler injection, resulting in much less scarring, and more satisfactory results were achieved not only in wound healing, but also in esthetics.

Two genes on chromosome 21, namely dual specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) and regulator of calcineurin 1 (RCAN1), have been implicated in some of the phenotypic characteristics of Down syndrome, including the early onset of Alzheimer disease. Although a link between Dyrk1A and RCAN1 and the nuclear factor of activated T cells (NFAT) pathway has been reported, it remains unclear whether Dyrk1A directly interacts with RCAN1. In the present study, Dyrk1A is shown to directly interact with and phosphorylate RCAN1 at Ser(112) and Thr(192) residues. Dyrk1A-mediated phosphorylation of RCAN1 at Ser(112) primes the protein for the GSK3β-mediated phosphorylation of Ser(108). Phosphorylation of RCAN1 at Thr(192) by Dyrk1A enhances the ability of RCAN1 to inhibit the phosphatase activity of calcineurin (Caln), leading to reduced NFAT transcriptional activity and enhanced Tau phosphorylation. These effects are mediated by the enhanced binding of RCAN1 to Caln and its extended half-life caused by Dyrk1A-mediated phosphorylation. Furthermore, an increased expression of phospho-Thr(192)-RCAN1 was observed in the brains of transgenic mice overexpressing the Dyrk1A protein. These results suggest a direct link between Dyrk1A and RCAN1 in the Caln-NFAT signaling and Tau hyperphosphorylation pathways, supporting the notion that the synergistic interaction between the chromosome 21 genes RCAN1 and Dyrk1A is associated with a variety of pathological features associated with DS.

Down syndrome (DS) is associated with many neural defects, including reduced brain size and impaired neuronal proliferation, highly contributing to the mental retardation. Those typical characteristics of DS are closely associated with a specific gene group "Down syndrome critical region" (DSCR) on human chromosome 21. Here we investigated the molecular mechanisms underlying impaired neuronal proliferation in DS and, more specifically, a regulatory role for dual-specificity tyrosine-(Y) phosphorylation-regulated kinase 1A (Dyrk1A), a DSCR gene product, in embryonic neuronal cell proliferation. We found that Dyrk1A phosphorylates p53 at Ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor H19-7 cells. In addition, Dyrk1A-induced p53 phosphorylation at Ser-15 led to a robust induction of p53 target genes (e.g. p21(CIP1)) and impaired G(1)/G(0)-S phase transition, resulting in attenuated proliferation of H19-7 cells and human embryonic stem cell-derived neural precursor cells. Moreover, the point mutation of p53-Ser-15 to alanine rescued the inhibitory effect of Dyrk1A on neuronal proliferation. Accordingly, brains from embryonic DYRK1A transgenic mice exhibited elevated levels of Dyrk1A, Ser-15 (mouse Ser-18)-phosphorylated p53, and p21(CIP1) as well as impaired neuronal proliferation. These findings suggest that up-regulation of Dyrk1A contributes to altered neuronal proliferation in DS through specific phosphorylation of p53 at Ser-15 and subsequent p21(CIP1) induction.