ABSTRACT
The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.
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Purpose@#We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a lowenergy X-ray source. @*Materials and Methods@#Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, singlearm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8–12 weeks after surgery. @*Results@#A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. @*Conclusion@#Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival.Trial Registration: Clinical trial registration No. (NCT03273374).
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Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.
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Background@#Intestinal protozoan infection is one of the main causes of gastrointestinal diseases. Protozoa are usually detected by direct smear microscopy, concentration techniques, or special stains; however, these techniques are labor-intensive and require well-trained technicians. Therefore, molecular techniques involving polymerase chain reaction (PCR) have been developed to satisfy the need for unbiased and rapid analytical methods with high sensitivity and specificity. In this study, the BD MAXTM Enteric Parasite Panel (EPP) (Becton, Dickinson and Company, USA), designed to detect Cryptosporidium parvum and/or hominis, Giardia lamblia, and Entamoeba histolytica, and the AllplexTM Gastrointestinal Parasite Assays (AGPA) (Seegene Inc., Korea), designed to detect Cryptosporidium species, G. lamblia, E. histolytica, Blastocystis hominis, Dientamoeba fragilis, and Cyclospora cayetanensis were compared to determine whether any of these assays could become a useful tool for detecting intestinal protozoan infections in Korea. @*Methods@#We investigated 295 fecal samples using EPP and AGPA. Then we confirmed the positive results with the conventional and nested PCR. Consistent detection by conventional PCR, nested PCR, and one of the multiplex panels was considered “true positive.” @*Results@#Out of 295 samples, 17 were true positives for B. hominis and 2 were true positives for E. histolytica. EPP detected parasites in only two samples owing to its design; however, its true positive detection rate was 100% (2/2). AGPA detected parasites in 24 samples with 79.2% (19/24) true positives. @*Conclusions@#The incidence of protozoan, especially B. hominis, infection may be more prevalent than expected. AGPA could be an effective tool for screening protozoan infections.
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This study aims to improve the organizational system of the Korean Medical Association by comparing its governance to that of the Austrian Medical Chamber. The Austrian Medical Chamber is a legal entity and an interest group, composed of the members of nine provincial Medical Chambers. The composition, authority, and duties of the Austrian Medical Chamber are detailed in the Medical Law, and its publicity as a self-regulatory institution is legally guaranteed, such as health care policy decisions and participation in the justice system. The Austrian Medical Chamber enhances the consistency and connectivity of its work with the provincial Medical Chambers through the obligatory participation of their board members. It allows the provincial Medical Chambers to responsibly perform their duties. The Austrian Medical Chamber and related medical laws can be a role model for the Korean Medical Association to achieve authority as a self-regulatory organization.
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The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.
Subject(s)
Body Weight , Brain , Internal Capsule , Methods , Primates , SkullABSTRACT
PURPOSE: Chronic pancreatitis (CP) is progressive inflammatory disease that leads to irreversible destruction of the pancreatic parenchyma. The main indications for surgical intervention in cases involving CP are intractable pain, suspicion of malignancy, and failure of other methods. However, there is no report related to Frey's procedure in Korea; hence, we aimed to investigate and analyze our institution's experience and determine the benefits of surgical treatment for CP. METHODS: This was a retrospective study of 24 patients with CP who underwent Frey's procedure at Gangnam Severance Yonsei University between January 2007 and December 2017. Preoperative exocrine and endocrine pancreatic function, perioperative finding (blood loss, operation time), postoperative complications were evaluated. Statistical analytics were chi-square test, Fisher exact tests, and Wilcoxon signed-rank test and Mann-Whitney U-test. RESULTS: Surgery was performed due to alcohol-derived CP in 12 of 24 patients (50%) and due to pancreatic stones in 15 of 24 patients (62.5%). Two patients had postoperative complications which were managed conservatively. After surgery, 7 of 24 patients were prescribed with exocrine medication. Comparison of the preoperative and postoperative conditions showed that glycated hemoglobin had no significant differences. After surgery, only 5 patients (21%) complained of intermittent abdominal pain. CONCLUSION: In conclusion, Frey's procedure appears to be a less burdensome surgical procedure. Thus, it could be the first option for management of patients with large pancreatic stone.
Subject(s)
Humans , Abdominal Pain , Glycated Hemoglobin , Korea , Pain, Intractable , Pancreaticojejunostomy , Pancreatitis, Chronic , Postoperative Complications , Retrospective StudiesABSTRACT
Clostridium difficile is a significant nosocomial and community-acquired pathogen, and is the leading cause of antibiotic-induced diarrhea associated with high morbidity and mortality. Given that the treatment outcome depends on the severity of C. difficile infection (CDI), we aimed to establish an efficient method of assessing severity, and focused on the stool biomarker fecal calprotectin (FC). FC directly reflects the intestinal inflammation status of a patient, and can aid in interpreting the current guidelines, which requires the integration of indirect laboratory parameters. The distinction of 80 patients with CDI versus 71 healthy controls and 30 severe infection cases versus 50 mild cases was possible using FC as a marker. The area under the receiver operating characteristic curves were 0.821 and 0.746 with a sensitivity of 75% and 70% and specificity of 79% and 80%, for severe versus mild cases, respectively. We suggest FC as a predictive marker for assessing CDI severity, which is expected to improve the clinical management of CDI.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Area Under Curve , Biomarkers/analysis , Clostridioides difficile/isolation & purification , Enterocolitis, Pseudomembranous/diagnosis , Enzyme-Linked Immunosorbent Assay , Feces/chemistry , Leukocyte L1 Antigen Complex/analysis , ROC Curve , Severity of Illness IndexABSTRACT
BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
Subject(s)
Astrocytes , Axons , Coloring Agents , Extremities , Glial Fibrillary Acidic Protein , Gliosis , Gray Matter , Internal Capsule , Ischemia , Microscopy , Models, Animal , Models, Theoretical , Myelin Sheath , Necrosis , Neurons , Oligodendroglia , Organelles , Pathology , Plastics , Prevalence , Recovery of Function , Rupture , Stroke , White MatterABSTRACT
BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB) are the leading causes of nosocomial infections. A rapid and sensitive test to detect CRPA and CRAB is required for appropriate antibiotic treatment. We optimized a loop-mediated isothermal amplification (LAMP) assay to detect the presence of bla(VIM-2), bla(IMP-1), and bla OXA-23, which are critical components for carbapenem resistance. METHODS: Two sets of primers, inner and outer primers, were manually designed as previously described. The LAMP buffer was optimized (at 2mM MgSO4) by testing different concentrations of MgSO4. The optimal reaction temperature and incubation time were determined by using a gradient thermocycler. Then, the optimized bla(VIM-2), bla(IMP-1), and bla(OXA-23) LAMP reactions were evaluated by using 120 P. aeruginosa and 99 A. baumannii clinical isolates. RESULTS: Only one strain of the 100 CRPA isolates harbored bla(IMP-1), whereas none of them harbored bla(VIM-2). These results indicate that the acquisition of bla(VIM-2) or bla(IMP-1) may not play a major role in carbapenem resistance in Korea. Fifty two strains of the 75 CRAB isolates contained bla(OXA-23), but none contained bla(VIM-2) and bla(IMP-1) alleles. CONCLUSIONS: Our results demonstrate the usefulness of LAMP for the diagnosis of CRPA and CRAB.
Subject(s)
Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Drug Resistance, Bacterial/genetics , Genes, Bacterial , Nucleic Acid Amplification Techniques , Pseudomonas aeruginosa/genetics , Sensitivity and SpecificityABSTRACT
OBJECTIVE: The purpose of this study is to find the optimal stiffness and volume of bone cement and their biomechanical effects on the adjacent vertebrae to determine a better strategy for conducting vertebroplasty. METHODS: A three-dimensional finite-element model of a functional spinal unit was developed using computed tomography scans of a normal motion segment, comprising the T11, T12 and L1 vertebrae. Volumes of bone cement, with appropriate mechanical properties, were inserted into the trabecular core of the T12 vertebra. Parametric studies were done by varying the volume and stiffness of the bone cement. RESULTS: When the bone cement filling volume reached 30% of the volume of a vertebral body, the level of stiffness was restored to that of normal bone, and when higher bone cement exceeded 30% of the volume, the result was stiffness in excess of that of normal bone. When the bone cement volume was varied, local stress in the bony structures (cortical shell, trabecular bone and endplate) of each vertebra monotonically increased. Low-modulus bone cement has the effect of reducing strain in the augmented body, but only in cases of relatively high volumes of bone cement (>50%). Furthermore, varying the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies. CONCLUSION: The volume of cement was considered to be the most important determinant in endplate fracture. Changing the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies.
Subject(s)
Bone Cements , Finite Element Analysis , Spine , Sprains and Strains , VertebroplastyABSTRACT
OBJECTIVE: To compare the pregnancy outcomes of in vitro fertilization (IVF) twins with those of spontaneous twins based on their chorionicities. METHODS: We performed a retrospective analysis of 598 twin pregnancies beyond 24 weeks of gestation delivered from October 1994 to December 2003. Subjects were grouped into the spontaneous group (n=392) and the IVF group (n=206) and then subgrouped into dichorionic (n=193, spontaneous vs. n=156, IVF) and monochorionic (n=154, spontaneous vs. n=34, IVF) subgroups. First, the obstetric and perinatal outcomes were compared between the spontaneous group and the IVF group regardless of their chorionicity. Second, the same outcome variables were compared between the spontaneous and the IVF group with same chorionicity. RESULTS: There was a significant increase in the incidence of preterm deliveries before 37 weeks of gestation in IVF twins (74.5% spontaneous vs. 82.5% IVF, p=0.031). However, the gestational age at delivery was not significantly different (34.5+/-2.86 weeks vs. 34.2+/-0.28 weeks). Antepartum admission was also significantly increased in IVF group (4.6% vs. 9.2%, p<0.001). We were unable to observe any significant difference in perinatal outcomes between the two groups other than increased in utero fetal demise in utero in the IVF group (0.3% vs. 1.5%, p<0.05). When we reanalyzed pregnancy outcomes based on chorionicity, there were more frequent admission to neonatal intensive care unit (42.7% vs. 52.6%, p<0.05) and necrotizing enterocolitis (0.5% vs. 3.5%, p<0.05) in dichorionic twins of the IVF group. In monochorionic twins, the incidence of placenta previa was increased in the IVF twin group (0% vs. 11.8%, p<0.001). CONCLUSION: In the IVF twins, the incidence of placenta previa was increased in monochrionic twins and the incidence of neonatal intensive care unit admission and necrotizing enterocolitis were also increased in dichorionic twins.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Pregnancy , Chorion , Enterocolitis, Necrotizing , Fertilization in Vitro , Gestational Age , Incidence , Intensive Care, Neonatal , Placenta Previa , Pregnancy Outcome , Pregnancy, Twin , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the subcellular localization of nuclear factor kappa B (NF-kappa B) in term human fetal membranes and myometrium during labor. METHODS: Fetal membranes and myometrial tissue were collected from term pregnant women undergoing cesarean delivery after labor (n=4) and before labor (n=4). An immunostaining was done with NF-kappa B p65 antibody. The intensity and distribution of nuclear immunostaining of NF-kappa B p65 subunit were evaluated visually using a semiquantitative analysis. RESULTS: NF-kappa B p65 was present in all tissues studied, and it was localized principally in the cytoplasm of cells of amnion and chorion. But, NF-kappa B p65 was localized more abundant in the nucleus than in the cytoplasm in myometrial cells. In amnion, chorion and myometrium, the staining scores of nuclear NF-kappa B did not show any difference between the after-labor group and before-labor group. CONCLUSION: In human term gestational tissues, subcellular localization of NF-kappa B showed cytoplasmic predominance in amnion and chorion, and nuclear predominance in myometrium. But these subcellular localizations did not change during labor.
Subject(s)
Animals , Female , Humans , Mice , Amnion , Chorion , Cytoplasm , Extraembryonic Membranes , Myometrium , NF-kappa B , Pregnant Women , Transcription Factor RelAABSTRACT
The surface characteristics of titanium have been shown to have an important role in contact ossseointegration around the implant. Anodizing at high voltage produces microporous structure and increases thickness of surface titanium dioxide layer. The aim of present study was to analyse the response of rat calvarial osteoblast cell to commercially pure titanium and Ti-6Al-4V anodized in 0.06 mol/l beta-glycerophosphate and 0.03 mol/l sodium acetate. In this study, rat calvarial osteoblasts were used to assay for cell viability and cell proliferation on the implant surface at 1, 2, 4, 7 days. 1. Surface roughness was 1.256micrometer at 200V, and 1.745micrometer at 300V. 2. The thickness of titanium oxide layer was increased 1micrometer with the increase of 50V. 3. The proliferation rate of osteoblastic cells was increased with the increase of the surface roughness and the thickness of titanium oxide layer. 4. There was no difference in cell viability and cell proliferation between commercially pure titanium and Ti- 6Al-4V anodized at the same condition. In conclusion, the titanium surface modified by anodizing was biocompatible, produced enhanced osteoblastic response. The reasons of enhanced osteoblast response might be due to reduced metal ion release by thickened and stabilized titanium dioxide layer and microporous rough structures.