OBJECTIVE: Spinal instrumentation without fusion often fails due to biological failure of intervertebral joints (spontaneous fusion, degeneration, etc). The purpose of this study is to investigate the influence of fixation rigidity on viability of intervertebral joints. METHODS: Twenty pigs in growing period were subjected to posterior segmental fixation. Twelve were fixed with a rigid fixation system(RF) while eight were fixed with a flexible unconstrained implant(FF). At the time of the surgery, a scoliosis was created to monitor fixation adequacy. The pigs were subjected to periodic radiological examinations and 12pigs (six in RF, six in FF) were euthanized at 12-18months postoperatively for analysis. RESULTS: The initial scoliotic curve was reduced from 31+/-5degrees to 27+/-8degrees in RF group (p=0.37) and from 19+/-4degrees to 17+/-5degrees in FF group (p=0.21). Although severe disc degeneration and spontaneous fusion of facet joints were observed in RF group, disc heights of FF group were well maintained without major signs of degeneration. CONCLUSION: The viability of the intervertebral joints depends on motion spinal fixation. Systems allowing intervertebral micromotion may preserve the viability of intervertebral discs and the facet joint articular cartilages while maintaining a reasonably stable fixation.
Cartilage, Articular ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Joints* ; Scoliosis ; Swine ; Zygapophyseal Joint

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated immunologic responses to external stimuli, which induce various inflammatory mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells, inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a signature event in nasal polyps (NP). These inflammatory mediators are novel potential therapeutic targets for recalcitrant CRS. This article reviews recent publications regarding endotypes and endotype-based therapeutic strategies in CRS and NP.
Asthma ; Cytokines ; Epithelial Cells ; Immunoglobulin E ; Immunoglobulins ; Interleukin-13 ; Interleukin-33 ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Lymphocytes ; Nasal Polyps ; Phenotype ; Precision Medicine* ; Prognosis ; T-Lymphocytes

During experimental Eimeria infections in chickens, facilities are often contaminated by fecal oocysts known to be highly resistant to both chemical and enzymatic treatments. Thus, studies using experimental Eimeria infections have been limited due to the difficulty of complete elimination of residual oocysts from both cages and facilities. To overcome this limitation, simple, inexpensive, and disposable cages were constructed from cardboard boxes and tested during experimental Eimeria maxima infections. The cages were used in animal rooms with only a 1.7% evidence of coccidia contamination between adjacent cages. No significant differences in fecal oocyst output and body weight gain were noted between animals housed in disposable cages and animals housed in wire control cages. This cage design is a useful means for preventing oocyst contamination during experimental conditions, suggesting that this disposable cage design could be used for other avian infectious disease studies.
Animals ; Chickens ; Coccidiosis/transmission/*veterinary ; Disposable Equipment/*utilization ; Eimeria/*isolation & purification ; *Environmental Microbiology

This study was conducted to investigate tiamulin (TML) residues in the edible tissues of orally dosed broiler chickens and to re-establish the withdrawal time (WT). Thirty-six healthy Ross broiler chickens were administered 0.5 (TML-1) and 2.5 kg (TML-2) per ton feed, respectively, of the drug containing TML 78 g/kg for 10 days. Twenty-four tissue samples were collected from 6 chickens in each of the TML-1 and TML-2 groups on 0, 1, 3, and 5 days after drug administration, respectively. The residual concentrations of TML were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation coefficient of the calibration curves was 0.9978 to 0.9998, and the limits of detection and the limits of quantification (LOQ) were in the range of 0.03 to 0.06, and 0.1 to 0.2 µg/kg, respectively. Recoveries ranged between 89.0% to 116.7%, and the coefficients of variation were less than 13.9%. After the drug administration, TML in the TML-1 and TML-2 groups was detected above the LOQ in 1 and 6 samples of liver, respectively, at day 0, and in 1 liver sample from both groups on day one. At 3 days after administration, TML was detected below the LOQ in all samples of TML-1 and TML-2. The calculated WT of TML in both TML-1 and TML-2 using the WT calculation program WT 1.4 was 0 days. In conclusion, the developed analytical method is suitable for detection, and the calculated WT of TML in poultry edible tissues is shorter than the current recommended WT of 7 days for TML in broiler chickens.

OBJECTIVES: This study was conducted to develop a Korean version of the Participatory Action Oriented Training (PAOT) program and training materials for improvement of agricultural working environments. METHODS: The PAOT manual and checklist were developed on the basis of the original English version of the training materials, a questionnaire survey of agricultural health and safety professionals, and a brainstorming conference. Good example pictures were collected through visits to agricultural workers' houses, and an easily understandable picture was drawn by an animation specialist. A PAOT action manual and five types of action checklists were developed for use in different agricultural environments. Each action checklist contained six categories and 38 items of agricultural health and safety principles; the six categories were material storage and handling, work stations and tools, machine safety, physical environment, working schedule and organization, and basic health and safety management. Incorporating these training materials, a one-day Korean PAOT program was developed. RESULTS: Among 307 candidate agricultural workers from four rural Korean villages, 94 workers (59 males, 35 females) participated in a PAOT from July 2007 to Oct 2008. The PAOT program was successful and the mean self-estimated satisfaction score of the participants was greater than 90%. CONCLUSIONS: A Korean PAOT program and training materials were successfully developed and applied to Korean agricultural workers. Although more studies are needed, it is expected that PAOT will greatly contribute to the improvement of agricultural working conditions and health and safety through the use of agricultural workers' self initiatives.
Appointments and Schedules ; Checklist ; Farmers ; Handling (Psychology) ; Humans ; Korea ; Male ; Safety Management ; Specialization ; Surveys and Questionnaires

OBJECTIVE: Pedicle screw is gaining popularity in pediatric deformities. However, biological response of actively growing spine to rigid pedicle screw fixation remains unclear. The objective of this study is to determine the biological response of growing spine to rigid segmental fixation. METHODS: Twelve mini pigs in actively growing period were subjected to posterior segmental screw -rod instrumentation spanning nine levels and creation of experimental scoliosis. There was no attempt of posterior arthrodesis. The pigs were subjected to periodic radiological examinations and were euthanized at 18 months for analysis. RESULTS: There was no significant fixation failure despite conspicuous growth of the animals. Initial scoliosis of 31+/-5degrees was reduced to 27+/-8degrees at 18 months, but there was no statistical significance (p=0.37). Though there was no change in length of the implant construct, the vertebrae within the instrumented section showed mean longitudinal growth of 6+/-3 mm (p=0.000). The growth occurred at expense of the disc spaces that progressively narrowed with time. On necropsy, the instrumented region was completely fused posteriorly with crossing of the osseous traberculae across the former facet joints. Intervertebral discs were severely atrophic in all the discs with occasional spontaneous fusion. CONCLUSION: Even in the actively growing spine, the force of growth does not overcome the fixation offered by segmental pedicle screws. Longitudinal growth occurs at the expense of the joint spaces and leads to spontaneous intervertebral fusion. Our results may explain the favorable outcomes in pedicle fixations in pediatric population, showing little implant failure or nonunion.
Animals ; Arthrodesis ; Congenital Abnormalities ; Intervertebral Disc ; Joints ; Scoliosis ; Spine* ; Swine ; Zygapophyseal Joint

BACKGROUND: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. METHODS: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years. RESULTS: We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION: This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.
Biomarkers ; DNA Methylation ; DNA ; Epigenomics ; Humans ; Lung Neoplasms ; Lung ; Methods ; Methylation ; Prognosis

BACKGROUND: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. METHODS: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years. RESULTS: We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

BACKGROUND: G93A or A4V mutations in the human Cu/Zn- superoxide dismutase gene (hSOD1) cause familial amyotrophic lateral sclerosis (fALS). However, it has not yet clearly understood how these bring about fALS. We investigated the effects of the G93A or A4V mutations in hSOD1 on the phosphatydilinositol-3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway, and effects of GSK-3 inhibitor on the G93A- or A4V-mutant cells. METHODS: To evaluate those effects, VSC4.1 motoneuron cells were transfected with G93A- or A4V-mutant types of hSOD1 (G93A and A4V cells, respectively) with/without GSK-3 inhibitor were compared with them transfected with wild type (wild cells) in cell viability and intracellular signals, including PI3K/Akt, GSK-3, and caspase-3, 24 hours after neuronal differentiation. RESULTS: Compared with wild cells, MTT assay revealed a greatly reduced viability in G93A and A4V cells without GSK-3 inhibitor. However, treatment with GSK-3 inhibitor increased the viability of G93A and A4V cells. Western blotting showed that PI3K and pAkt were decreased, and GSK-3 and caspase-3 were increased in G93A and A4V cells, and that GSK-3 inhibitor treatment reduced caspase-3 but did not affected PI3K, Akt and GSK-3. CONCLUSIONS: These results suggest that the G93A or A4V mutations induce inhibition of PI3K/Akt and activation of GSK-3 and caspase-3 resulting the vulnerability to oxidative stress, and that GSK-3 mediated cell death mechanism is important in G93A and A4V cell death.
Amyotrophic Lateral Sclerosis ; Blotting, Western ; Caspase 3 ; Cell Death* ; Cell Survival ; Glycogen Synthase Kinase 3 ; Glycogen Synthase* ; Glycogen* ; Humans ; Motor Neurons* ; Neurons ; Oxidative Stress ; Superoxide Dismutase

OBJECTIVE: To investigate the effect of Comprehensive Hand Repetitive Intensive Strength Training (CHRIST) on upper limb function in children with cerebral palsy using motion analysis. METHOD: The subjects in this study included 19 children (10 males, 9 females, mean age=8.8 years) with cerebral palsy. The experimental group (n=10) received CHRIST and general rehabilitation therapy. The control group (n=9) received a home program as well as general rehabilitation therapy. Both groups received 30 sessions of CHRIST or home program training for 60 minutes per session 3 times a week during the 10-week period. The reaching movements were captured by a motion analysis system. Kinematic variables including movement time (MT), mean velocity (MV), normalized jerk score (NJS), mean angular velocity (MAV) and normalized jerk score of the shoulder, elbow and wrist joint with comfortable and fast speed were analyzed between groups and the pre-post training group. RESULTS: After pre- and post-training experimental group, MT, MV, NJS, MAV of shoulder, elbow, wrist and NJS of elbow and wrist improved significantlyin reaching movement of both comfortable and fast speed (p<0.05). However, After pre- and post-training control group, MV improved significantlyin reaching movement of only comfortable speed (p<0.05). Between two groups, MT and MAV of the elbow at comfortable speed and NJS of the elbow at fast speed were statisticallysignificant (p<0.05). CONCLUSION: CHRIST proved to be an effective intervention for improving upper limb extremity function of reaching movement in children with cerebral palsy.
Cerebral Palsy ; Child ; Elbow ; Extremities ; Female ; Hand ; Humans ; Male ; Muscle Strength ; Resistance Training ; Shoulder ; Upper Extremity ; Wrist ; Wrist Joint