CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway

Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-beta-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-alpha IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.

Immunogenicity and Safety of Trivalent Inactivated Influenza Vaccine: A Randomized, Double-Blind, Multi-Center, Phase 3 Clinical Trial in a Vaccine-Limited Country

Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic

Synthesis and Solubility Study of the Polyamides Containing 4,4'-(9- fluorenylidene)dianiline in the Backbone as an Antireflecting Spin-on Hardmask Materials

Due to the continuous demand for smaller microelectronic devices, there exists a need to reduce the size of structural shapes in microelectronics and other related industries. Toward this end, effective lithographic techniques are essential to achieve a reduction in the size of microelectronic structures. Typical lithographic processes involve etch resistant photoresist underlying materials having antireflecting properties at a certain wavelength exposure. In this work, such materials were synthesized by the step-polymerization of diamines 2,2'-bis(3-amino- 4-hydroxyphenyl)hexafluoropropane (6FP) and 4,4'-(9-fluorenylidene)dianiline (BAFL) with a variety of diacid chlorides [terepthaloyl, isophthaloyl, glutaryl, and succinyl chlorides] and characterized by 1H NMR in tetrahydrofuran (THF-d8), and gel permeation chromatography (GPC) using polystyrene standards. The effect of the structure of the components on the copolymer solubility in mixture of propylene glycol monoethylether acetate (PGMEA) and cyclohexanone used in microelectronics processing was studied by UV-visible spectroscopy. The solubility of the copolymers was found to be in trade-off relationship with BAFL content needed for its antireflective properties and high plasma etch resistance. The polymers that were prepared by using the equimolar mixture of isophthaloyl dichloride and glutaryl dichloride equimolar mixture showed the best solubility, processability and functionality and are applicable as spin-on antireflecting hardmask materials for deep ultra violet (DUV) litfhography technology. They showed good coatability, chemical resistance, plasma etch resistance, and plasma etch selectivity

Feasibility Study of Free-Hand Technique for Pedicle Screw Insertion at C7 without Fluoroscopy-Guidance

Study DesignRetrospective interventional study.PurposeTo introduce a free-hand pedicle screw (PS) insertion technique without fluoroscopic guidance in the C7 vertebra and evaluate the procedure's feasibility and radiologic outcomes.Overview of LiteratureAlthough PS insertion at C7 has been recognized as a critical procedure in posterior cervical fusion surgery, conventional techniques for C7 PS have several limitations.MethodsThirty two patients (64 screws) who underwent PS insertion in C7 with the novel technique were included in this study. Postoperative clinical and radiological outcomes were evaluated. Special attention was paid to the presence of any problems in the screw position including cortical breaches of the PS and encroachment of the PS into the spinal canal or the vertebral foramen. This novel technique for PS insertion in C7 without fluoroscopy guidance had three key elements. First, the ideal PS entry point was chosen near the C6–7 facet joint using preoperative images. Second, the convergent angle distance was measured at axial computed tomography (CT) imaging, which defined the distance between the tip of C7 spinous process and the extended line passing through the pedicle axis from the ideal entry point. Third, the cranial-caudal angle distance was measured in sagittal CT images, which defined the distance between the tip of the C7 spinous process and the extended line passing through the pedicle axis.ResultsCortical breach on postoperative CT images was observed in three screws. All violated only the lateral wall of the affected pedicle. The breached screws occurred in the initial five cases. Postoperative neurologic deterioration was not observed in any patient, regardless of cortical breaching.ConclusionsThe novel technique successfully allows for C7 PS to be placed and is associated with a low rate of cortical breach

A Nationwide Survey of Lymphangioleiomyomatosis in Korea: Recent Increase in Newly Diagnosed Patients

In 2007, the Korean Interstitial Lung Disease Society had collected clinical data of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990 through nationwide survey, which showed that LAM patients had increased sharply after 2004. The present study was performed to show the clinical features of Korean patients with LAM, and to establish the reason for the recent increase in the diagnosis. All 63 patients were women and the mean age at diagnosis was 36 yr. The most common presenting symptom was dyspnea and 8 patients had tuberous sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared with patients diagnosed after 2004 (n=34), the patients diagnosed before 2004 (n=29) complained with dyspnea more (P=0.016) and had lower FEV1% predicted (P=0.003), and DLco% predicted (P=0.042). The higher proportion of patients diagnosed after 2004 showed the normal chest radiography, and they were detected by routine chest CT screening (P=0.016). This study showed that clinical features of Korean patients with LAM were not different from those reported elsewhere. It is concluded that the reason for the increase of newly diagnosed patients is the result of increase in detection of the early stage LAM by the widespread use of chest CT screening

Prognostic Factors for Postsurgical Recovery of Deltoid Palsy due to Cervical Disc Herniations

Study DesignRetrospective multicenter study.PurposeWe aimed to investigate prognostic factors affecting postsurgical recovery of deltoid palsy due to cervical disc herniation (CDH).Overview of LiteratureLittle information is available about prognostic factors affecting postsurgical recovery of deltoid palsy due to CDH.MethodsSixty-one patients with CDH causing deltoid palsy (less than grade 3) were included in this study: 35 soft discs and 26 hard discs. Average duration of preoperative deltoid palsy was 11.9 weeks. Thirty-two patients underwent single-level surgery, 22 two-level, four three-level, and three four-level. Patients with accompanying myelopathy, shoulder diseases, or peripheral neuropathy were excluded from the study.ResultsDeltoid palsy (2.4 grades vs. 4.5 grades, p<0.001) and radiculopathy (6.4 points vs. 2.1 points, p<0.001) significantly improved after surgery. Thirty-six of 61 patients (59%) achieved full recovery (grade 5) of deltoid palsy, with an average time of 8.4 weeks. Longer duration of preoperative deltoid palsy and more severe radiculopathy negatively affected the degree of improvement in deltoid palsy. Age, gender, number of surgery level, and disc type did not affect the degree of improvement of deltoid palsy. Contrary to our expectations, severity of preoperative deltoid palsy did not affect the degree of improvement. Due to the shorter duration of preoperative deltoid palsy, in the context of rapid referral, early surgical decompression resulted in significant recovery of more severe grades (grade 0 or 1) of deltoid palsy compared to grade 2 or 3 deltoid palsy.ConclusionsEarly surgical decompression significantly improved deltoid palsy caused by CDH, irrespective of age, gender, number of surgery level, and disc type. However, longer duration of deltoid palsy and more severe intensity of preoperative radiating pain were associated with less improvement of deltoid palsy postoperatively

The Effect of Passive Smoking on Asthma Symptoms, Atopy, and Airway Hyperresponsiveness in Schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey

The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics

Smoking is associated with poor symptom control and impaired therapeutic responses in asthma. A total of 843 patients with asthma were recruited. The patients received treatment for 1 yr according to the severity of their asthma. We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution computed tomography (HRCT), the number of near-fatal asthma attacks, and physiological fixed airway obstruction between the smoking and nonsmoking groups. The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex-smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not different between the smoking and nonsmoking groups, the total IgE was higher among the smokers than the nonsmokers. Compared with the nonsmoking group, the smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and 75% of FVC. A greater prevalence of emphysema and a significantly higher number of asthmatic patients with fixed airway obstruction were detected in the smoking versus nonsmoking group. The 37.5% of asthmatic patients who were former or current smokers showed decreased pulmonary function and increased IgE, emphysema on HRCT, and fixed airway obstruction, indicating that smoking can modulate the clinical and therapeutic responses in asthma

A Sternum-Disk Distance Method to Identify the Skin Level for Approaching a Surgical Segment without Fluoroscopy Guidance during Anterior Cervical Discectomy And Fusion

Study DesignA retrospective review of prospectively collected data.PurposeTo introduce the sternum-disk distance (SDD) method for approaching the exact surgical level without C-arm guidance during anterior cervical discectomy and fusion (ACDF) surgery and to evaluate its accuracy and reliability.Overview of LiteratureAlthough spine surgeons have tried to optimize methods for identifying the skin level for accessing the operative disk level without C-arm guidance during ACDF, success has rarely been reported.MethodsIn total, 103 patients who underwent single-level ACDF surgery with the SDD method were enrolled. The primary outcome measure was the accuracy of the SDD method. The secondary outcome measures were the mean SDD value at each cervical level from the cranial margin of the sternum in the neutral and extension positions of the cervical spine and the inter- and intra-observer reliability of the SDD outcome determined using repeated measurements by three orthopedic spine surgeons.ResultsThe SDD accuracy (primary outcome measure) was indicated in 99% of the patients (102/103). The mean SDD values in the neutral-position magnetic resonance imaging (MRI) were 108.8 mm at C3–C4, 85.3 mm at C4–C5, 64.4 mm at C5–C6, 44.3 mm at C6–C7, and 24.1 mm at C7–T1; and those in the extension-position MRI were 112.9 mm at C3–C4, 88.7 mm at C4–C5, 67.3 mm at C5–C6, 46.5 mm at C6–C7, and 24.3 mm at C7–T1. The Cohen kappa coefficient value for intra-observer reliability was 0.88 (excellent reliability), and the Fleiss kappa coefficient value for inter-observer reliability as reported by three surgeons was 0.89 (excellent reliability).ConclusionsBased on the results of the present study, we recommend performing ACDF surgery using the SDD method to determine the skin level for approaching the surgical cervical segment without fluoroscopic guidance

Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study

<p>Abstract</p> <p>Background</p> <p>Aspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. <it>FSIP1</it>, also known as <it>HDS10</it>, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by α disintegrin and metalloproteinase 33 (<it>ADAM33</it>), which is an asthma susceptibility gene. It has also been known that the <it>FSIP1 </it>gene is expressed in airway epithelium.</p> <p>Objectives</p> <p>Aim of this study is to find out whether <it>FSIP1 </it>polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes.</p> <p>Methods</p> <p>We conducted association study between 66 single nucleotide polymorphisms (SNPs) of the <it>FSIP1 </it>gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of <it>FSIP1 </it>and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates.</p> <p>Results</p> <p>Initially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected <it>P</it>-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that <it>FSIP1 </it>gene might be a susceptibility gene for aspirin intolerance in asthmatics.</p> <p>Conclusion</p> <p>Although our findings did not suggest that SNPs of <it>FSIP1 </it>had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in <it>FSIP1 </it>and AIA occurrence among asthmatics in a Korean population.</p