Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (PMP22) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Among them, miR-381 could target 3′ untranslated region (3′UTR) of PMP22 in vitro based on Western botting and quantitative Real Time-PCR (qRT-PCR) results. In vivo efficacy of miR-381 was assessed by administration of LV-miR-381, an miR-381 expressing lentiviral vector, into the sciatic nerve of C22 mice by a single injection at postnatal day 6 (p6). Administration of LV-miR-381 reduced expression level of PMP22 along with elevated level of miR-381 in the sciatic nerve. Rotarod performance analysis revealed that locomotor coordination of LV-miR-381 administered C22 mice was significantly enhanced from 8 weeks post administration. Electrophysiologically, increased motor nerve conduction velocity was observed in treated mice. Histologically, toluidine blue staining and electron microscopy revealed that structural abnormalities of myelination were improved in sciatic nerves of LV-miR-381 treated mice. Therefore, delivery of miR-381 ameliorated the phenotype of peripheral neuropathy in CMT1A mouse model by down-regulating PMP22 expression. These data suggest that miRNA can be used as a potent therapeutic strategy to control diseases with copy number variations such as CMT1A.
Animals ; Demyelinating Diseases ; In Vitro Techniques ; Mice ; MicroRNAs ; Microscopy, Electron ; Myelin Sheath ; Neural Conduction ; Peripheral Nervous System Diseases ; Phenotype ; Sciatic Nerve ; Tolonium Chloride ; Tooth Diseases ; Untranslated Regions

OBJECTIVE: To define optimal method that calculate the safe direction of cervical pedicle screw placement using computed tomography (CT) image based three dimensional (3D) cortical shell model of human cervical spine.METHODS: Cortical shell model of cervical spine from C3 to C6 was made after segmentation of in vivo CT image data of 44 volunteers. Three dimensional Cartesian coordinate of all points constituting surface of whole vertebra, bilateral pedicle and posterior wall were acquired. The ideal trajectory of pedicle screw insertion was defined as viewing direction at which the inner area of pedicle become largest when we see through the biconcave tubular pedicle. The ideal trajectory of 352 pedicles (eight pedicles for each of 44 subjects) were calculated using custom made program and were changed from global coordinate to local coordinate according to the three dimensional position of posterior wall of each vertebral body. The transverse and sagittal angle of trajectory were defined as the angle between ideal trajectory line and perpendicular line of posterior wall in the horizontal and sagittal plane. The averages and standard deviations of all measurements were calculated.RESULTS: The average transverse angles were 50.60º±6.22º at C3, 51.42º ±7.44º at C4, 47.79º ±7.61º at C5, and 41.24º ±7.76º at C6. The transverse angle becomes more steep from C3 to C6. The mean sagittal angles were 9.72º ±6.73º downward at C3, 5.09º±6.39º downward at C4, 0.08º ±6.06º downward at C5, and 1.67º ±6.06º upward at C6. The sagittal angle changes from caudad to cephalad from C3 to C6.CONCLUSION: The absolute values of transverse and sagittal angle in our study were not same but the trend of changes were similar to previous studies. Because we know 3D address of all points constituting cortical shell of cervical vertebrae. we can easily reconstruct 3D model and manage it freely using computer program. More creative measurement of morphological characteristics could be carried out than direct inspection of raw bone. Furthermore this concept of measurement could be used for the computing program of automated robotic screw insertion.
Cervical Vertebrae ; Female ; Humans ; Image Processing, Computer-Assisted ; Methods ; Pedicle Screws ; Spine ; Volunteers

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies

Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters.
Breast Neoplasms ; Cell Death ; Doxorubicin* ; Drug Therapy ; Neoplastic Stem Cells ; NF-E2-Related Factor 2 ; P-Glycoprotein ; Recurrence ; Transcription Factors ; Up-Regulation

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure.
Follow-Up Studies ; Humans ; Hyaluronic Acid* ; Hypersensitivity ; Injections, Subcutaneous ; Male ; Necrosis ; Penis* ; Plastics ; Premature Ejaculation ; Residual Volume ; Transplants

Intracranial atherosclerotic disease (ICAD) causes up to 10% of all ischemic strokes, and the rate of recurrent vascular ischemic events is very high. Important predictors of vulnerability in atherosclerotic plaques include the degree of stenosis and the underlying plaque morphology. Vascular wall MRI can provide information about wall structures and atherosclerotic plaque components. High-resolution (HR)-MRI in ICAD poses a greater challenge in the neurologic fields, because a high in-plane resolution and a high signal-to-noise ratio are required for vessel wall imaging of ICAD. Until now, plaque imaging of ICAD has focused on assessing the presence of a plaque and evaluating the plaque load. Going forward, evaluation of plaque vulnerability through analysis of imaging characteristics will be a critical area of research. This review introduces the acquisition protocol for HR-MRI in ICAD and the current issues associated with imaging.
Atherosclerosis ; Cerebral Arteries ; Constriction, Pathologic ; Magnetic Resonance Imaging* ; Plaque, Atherosclerotic ; Signal-To-Noise Ratio ; Stroke

BACKGROUND/AIMS: Colonoscopic polypectomy should be performed on the five to seven hour of clock (standard position). However, outcomes of polypectomy at non-standard positions have not yet been investigated. This study was to compare the clinical outcomes of colonoscopic polypectomy including procedure time, status of resection margin and complications between standard and non-standard position. METHODS: Patients who underwent screening colonoscopy were prospectively recruited from Oct 2011 to Feb 2012 at Dongguk University Ilsan Hosptial, Goyang, Korea. Standard position was defined as polyps which were located from 5 to 7 hour of clock on colonoscopic view. RESULTS: A total of 168 adenomatous polyps of 114 patients were investigated. Mean size of polyp was 7.1+/-3.2 mm. The most common shape of polyps was sessile in 77 cases (45.8%). Mean overall procedure time per patient was 25.5+/-12.3 min. 130 adenomatous polyps were resected in standard position (77.4%) and 38 polyps were in non-standard position (22.6%). Overall complete resection rate was 63.7% and immediate bleeding rate was 9.8%. There was no significant difference in overall polypectomy time per polyp (2.9+/-1.3 min vs. 3.0+/-1.8 min, P=0.32). Complete resection rates and complication were not statistically different. CONCLUSIONS: There was no difference according to procedure time, status of resection margin and complications between standard position and non-standard position. Colonoscopic polypectomy is thus safe and feasible on any position.
Adenomatous Polyps ; Colonic Polyps ; Colonoscopy ; Hemorrhage ; Humans ; Korea ; Mass Screening ; Polyps ; Prospective Studies

No abstract available.

No abstract available.