Intact Recognition Memory and Altered Hippocampal Glucocorticoid Receptor Signaling in Fkbp5-deficient Mice Following Acute Uncontrollable Stress

The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5-knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5-knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5-knockout mice, but the levels of phosphorylated GR were lower in Fkbp5-knockout mice than in wild-type mice. Wild-type and Fkbp5-knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5-knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.

From Bound Cells Comes a Sound Mind: The Role of Neuronal Growth Regulator 1 in Psychiatric Disorders

Cell-to-cell adhesion is important for maintenance of brain structure and function. Abnormal neuronal cell adhesion and loss of its connectivity are considered a main cause of psychiatric disorders such as major depressive disorder (MDD). Various cell adhesion molecules (CAMs) are involved in neuronal cell adhesions and thereby affect brain functions such as learning and memory, cognitive functions, and psychiatric functions. Compared with other CAMs, neuronal growth regulator 1 (Negr1) has a distinct functioning mechanism in terms of its cross-talk with cytokine receptor signaling. Negr1 is a member of the immunoglobulin LON (IgLON) family of proteins and is involved in neuronal outgrowth, dendritic arborization, and synapse formation. In humans, Negr1 is a risk gene for obesity based on a genome-wide association study. More recently, accumulating evidence supports that it also plays a critical role in psychiatric disorders. In this review, we discuss the recent findings on the role of Negr1 in MDD, focusing on its regulatory mechanism. We also provide evidence of putative involvement of Negr1 in other psychiatric disorders based on the novel behavioral phenotypes of Negr1 knockout mice.

Chronic Cerebral Hypoperfusion Induces Alterations of Matrix Metalloproteinase-9 and Angiopoietin-2 Levels in the Rat Hippocampus

Angiogenic factors contribute to cerebral angiogenesis following cerebral hypoperfusion, and understanding these temporal changes is essential to developing effective treatments. The present study examined temporal alterations in angiogenesis-related matrix metalloproteinase-9 (MMP-9) and angiopoietin-2 (ANG-2) expression in the hippocampus following bilateral common carotid artery occlusion (BCCAo). Male Wistar rats (12 weeks of age) were randomly assigned to sham-operated control or experimental groups, and expression levels of MMP-9 and ANG-2 were assessed after BCCAo (1 week, 4 weeks, and 8 weeks), using western blotting. Protein expression increased 1 week after BCCAo and returned to control levels at 4 and 8 weeks. In addition, immunofluorescence staining demonstrated that the MMP-9- and ANG-2-positive signals were primarily observed in the NeuN-positive neurons with very little labeling in non-neuronal cells and no labeling in endothelial cells. In addition, these cellular locations of MMP-9- and ANG-2-positive signals were not altered over time following BCCAo. Other angiogenic factors such as vascular endothelial growth factor and hypoxia-inducible factor did not differ from controls at 1 week; however, expression of both factors increased at 4 and 8 weeks in the BCCAo group compared to the control group. Our findings increase understanding of alterations in angiogenic factors during the progression of cerebral angiogenesis and are relevant to developing effective temporally based therapeutic strategies for chronic cerebral hypoperfusion-associated neurological disorders such as vascular dementia.

An Intraosseous Schwannoma Combined with a Subchondral Fracture of the Femoral Head: a Case Report and Literature Review

Schwannomas are benign nerve sheath tumors that are typically located in soft tissue. Occasionally, schwannomas involve osseous structures. These intraosseous schwannomas are generally benign neoplasms that account for less than 0.2% of primary bone tumors. Schwannomas are very rarely observed in long bones. We present a case of a schwannoma affecting the proximal femur with a coincident subchondral fracture of the femoral head. A 38-year-old-male presented with left hip pain without deteriorating locomotor function. Plain film radiographs displayed a lobulating contoured lesion within the intertrochanteric portion of the femur. The magnetic resonance imaging (MRI) scans showed a tumor occupying the intertrochanteric region. Diffuse bone marrow edema, especially in the subchondral and head portions of the femur that was possibly due to the subchondral insufficiency fracture was also noted. The lesion was surgically excised and bone grafting was performed. Histologically, there was diffuse infiltrative growth of the elongated, wavy, and tapered cells with collagen fibers, which are findings that are characteristic of intraosseous schwannoma. Although very rare, intraosseous schwannoma should be included in the differential diagnosis of radiographically benign-appearing, non-aggressive lesions arising in the femur. The concomitant subchondral fracture of the femoral head confounded the correct diagnosis of intraosseous schwannoma in this case.

The Effects of Pilates Mat Exercise on Trunk Muscle Thickness and Balance

PURPOSE: The aim of this study was to identify the effects of Pilates mat exercise may improve trunk muscle thickness and balance in healthy adults. METHODS: Eighteen healthy adults participated in this study. They were randomly assigned to one of two groups: Pilates mat exercise group (n=9) and the control group (n=9). Subjects in Pilates mat exercise group performed the exercises three days per week for 6 weeks, which consisted of warm up, main workout, and cool down. Trunk muscle thickness of the rectus abdominis (RA), internal oblique (IO), external oblique (EO), transverse abdominis (TrA), multifidus (MF), and erector spine (ES) were measured using an ultrasonography. Balance ability was evaluated using Romberg test and limits of stability (LOS). Measurements were performed before training, 3 weeks after training, and 6 weeks after training. RESULTS: There was a significant difference of RA, EO, IO, MF, and ES according to the main effect of time (p<0.05). There was a significant difference of EO, MF, ES, Romberg, and LOS according to interaction effect between the time and group (p<0.05). There was a significant difference only for LOS according to the main effect of the group (p<0.05). CONCLUSION: Pilates mat exercise did increase trunk muscle thickness and balance. However, the effect with respect to trunk thickness was limited. Pilates mat exercise appears to be more effective in improving muscles related to trunk extension and balance.

Factors Associated with Disclosure of Sexual Abuse of Children and Adolescent Victims

OBJECTIVES: The purpose of this study was to analyze the factors related to the disclosure patterns of sexual abuse in children and adolescent victims. METHODS: A sample of 153 children and adolescents who visited the Sunflower children's Center (Incheon) between January 1, 2011 and December 31, 2012 were analyzed. The medical records of the victims were reviewed retrospectively. RESULTS: Ninety (58.8%) subjects made a disclosure of sexual abuse voluntarily. The revelation was most commonly made to a parent. The severity and duration of sexual abuse were related to the disclosure patterns. In addition, the group that displayed below average intelligence, particularly subjects in the group with borderline intellectual functioning, tended to disclose their history of abuse less voluntarily than the subjects with normal intelligence. CONCLUSION: The current study provides insight into the factors that affect disclosure patterns in children and adolescent sexual abuse victims. To prevent sexual abuse, we suggest that special legal assistance and social concern be required for children and adolescents with borderline intellectual functioning.

Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer's disease

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Abeta) but not with the extracellular APP/Abeta. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.

Mapping the dementia research area at the micro-level using co-terms analysis and positioning for traditional herbal medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To identify the position of traditional herbal medicine in dementia research field using mapping technology.</p><p><b>METHODS</b>Keywords for dementia and traditional herbal medicine for treating dementia were used to extract scientific articles from the Web of Science database from January 2000 to July 2010. A co-occurrence matrix was created based on the concurrent set of author's keywords occurring in each scientific article, and technology network maps were created from similarity index matrices.</p><p><b>RESULTS</b>Twenty specialized research areas were identified in the dementia field, and the relationship strength was 0.2-0.6. Many research fields were associated with diagnosis and risk factors for dementia. Additionally, the mechanism or cause of dementia is an actively studied field. Traditional herbal medicine for treating dementia was located on a map near the cortical dementia diagnosis and therapy, and frontotemporal dementia research field with a relationship strength of 0.53 and 0.31-0.33 respectively, which demonstrates that traditional herbal medicine for dementia occupies an independent research area with a relationship to existing scientific research fields.</p><p><b>CONCLUSION</b>Traditional herbal medicine can provide an alternative and complementary approach for treating dementia as evidenced by a scientific mapping analysis.</p>

Alternations of Septal-hippocampal System in the Adult Wistar Rat with Spatial Memory Impairments Induced by Chronic Cerebral Hypoperfusion

In the current investigation, the status of the septo-hippocampal cholinergic pathway and hippocampal mitogen-activated protein kinase (MAPK) signaling was examined in male Wistar rats with chronic cerebral hypoperfusion, which showed cognitive deficits based on assessment on a version of the Morris water maze. Chronic cerebral hypoperfusion was induced by bilateral common artery occlusion and maintained for 12 weeks until behavioral testing. Chronic cerebral hypoperfusion was shown to induce memory impairments and microglial activation in regions of white matter, including the fimbria of hippocampus. Choline acetyltransferase expression of the basal forebrain and expression of hippocampal MAPKs was decreased in rats with BCCAo compared to control rats. The results of this study suggest that cognitive decline induced by chronic cerebral hypoperfusion could be related to dysfunction of the basal forebrain cholinergic system and reduction of hippocampal MAPK activities.

Finite Element Analysis of Reconstruction of Mandibular Symphysis Defects Using Reconstruction Plates

Striatal CREB Phosphorylation Following Cued/Response Learning in the Water Maze Differ in Two Inbred Strains of Mice

Much evidence shows that the hippocampus and striatum play roles as important neural substrates for spatial/place and cued/response learning, respectively. This experiment was conducted to investigate the engagement of the striatum in cued/response learning. The engagement of the striatum was assessed after either place or cue training by determining levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) in these two mouse strains. Results revealed that striatal CREB levels in both strains of mice were not significantly increased after cued/response learning comparing to place training mediated by the hippocampus. However, striatal pCREB of DBA/2 mice was significantly higher after cued/response training in comparison to place learning, while striatal pCREB levels on C57BL/6 mice did not differ in cued learning versus place learning. These findings indicate that striatal pCREB, specifically associated with cued/response learning, is closely tied to differences in cued/responses strategy preference between C57BL/6 and DBA/2 mice.

The Suppressive Effect of Rifampicin in Animal Model of Hemophilic Synovitis / 대한류마티스학회지

OBJECTIVE: Hemophilic arthropathy, which results from recurrent intra-articular bleeding, is a proliferative synovitis, but the sequence of pathogenic events in hemophilic synovitis (HS) is not known in detail. To investigate the pathogenic mechanism of HS and to evaluate the suppressive effect of rifampicin for HS, we designed this study. METHODS: Twenty normal male New Zealand white rabbits weighing approximately 2,000 gm were used for this study. We injected 1 mL of autologous whole blood of the rabbits into the right knee joint and normal saline into the left knee joint (control) thrice a week for 10 weeks and sacrificed 10 of them. We injected 10 mg of rifampicin into the right knee joint of HS, which is 5 rabbits of remained 10, once a week from 11th week until 15th week. At 11th week and 20th week, the rabbits were sacrificed and both knee joints of each rabbit were opened, synovial membrane specimens were collected and examined pathologically and biologically such as mRNA of IL-1, TNF-alpha, MMP-1 and MMP-3 in hemophilic synovium using by real-time quantitative PCR method (comparative Ct method). RESULTS: At 20th week, in rifampicin treated group showed decreased proliferative, and infiltrated mononuclear cells compared with control group. And mRNA of TNF-alpha, IL-1 and MMP-3 levels were decreased also. CONCLUSION: In animal model of HS, histological changes showed the same as human hemophilic synovitis. And this study suggested that rifampicin has a controlling effect on the inflammatory process of HS by suppression of inflammatory cytokine production in the experimental hemophilic synovitis model.

Prediction of Force on the Spine Using Three-Dimensional Mathematical Model / 대한척추외과학회지

Mechanical factors in the human body are considered to play a dominant role in low back pain problems. Various spinal structures, including muscles, act in unison to resist the external load. An estimation of the muscle forces in this structure requires a knowledge of the orientation, location and area of cross-section of the muscles to complete the formulation of a truly threedimensional mathematical model of the spine. The geometric parameters which are calculated were the line of action, the centroid and physiologic area of cross-section of each muscle as a function of the spinal level. This geometric data were obtained from CT scans of 11 subjects participating in this study.

Experimental Study for Defining Range of Motion Required for Daily Activities in Wrist Joint / 대한정형외과학회잡지

PURPOSE: The knowledge of characteristics of wrist joint motion is essential to develop the artificial joint because injury of wrist joint is common onset in industrialized world. MATERIALS AND METHODS: Total of 25 different daily activities were tested on 15 subjects who did not show any abnormality of their joint functions. RESULTS: For left (right) wrist joint, least functional range of motion were 36.7. +/- 16.5. (S.D) (47.4. +/- 15.6.) and 40.7. +/- 15.3. (S.D) (33.5. +/- 9.7.) for joint flexion and extension, and 26.3. +/- 11.3. (S.D) (30.5. +/- 7.5.) and 22.9. +/- 9.2. (S.D) (23.0. +/- 10.5.) for joint radial and ulnar deviation, respectively. CONCLUSION: Least range of motion obtained in this study can be used as a basic data to design artificial joint and set a goal for surgeon to achieve appropriate treatment from patients because results revealed that any significant differences were not found in least functional range of motion between left and right wrist joint to perform activity daily living (ADL) .

Meaurement of the Muscle Fatigue Patterns using Electromyography Technique / 대한정형외과학회잡지

Injuries and pains of musculoskeletal joint in human body is common onset in industrialized world. However, muscle fatigue plays a very significant role in contributing causes of many pains associated with musculoskeletal joints. Based on this hypothesis, degree of muscle fatigue was investigated using electromyography measurement technique during isometric and concentric/eccentric muscle contractions. Different response of the muscle fatigue between two different muscle contractions (isometric and concentric/eccentric contractions) was examined by comparison of parameters which were median frequency, median power and RMS value. Healthy 16 young persons without previous musculoskeletal diesease history were tested with Noraxon Myosystem 2000 EMG measurement system. In this study, two different exercises were performed. First exercise was concentric/eccentric exercise. Second exercise was isometric muscle contraction. In the case of the isometric exercise, median frequency was decreased, but median power and RMS were increased. However, during the concentric/eccentric exercse, median frequency was increased, but median power and RMS were decreased. Both of those revealed that the pattern of the median frequency was W type, but median power and RMS were M type as time passed. In this study, the patterns of the muscle fatigue during concentric/eccentric exercise as well as isometric exercise were identified. It will be helpful to prevent musculoskeletal injury from over-working andexercising.

Clinical Application of Instep Flap / 대한정형외과학회잡지

Soft-tissue defects over the plantar forefoot, plantar heel, Achilles tendon and distal parts of lower leg are often troublesome to cover with a simple graft or local flap due to limited mobility of surrounding skin and poor circulation in these area. Soft-tissue reconstruction in these regions should provide tissue components similar to the original lost tissue, supply durability and minimal protective pressure sensation and result in a donor site that is well tolerated. We analysed 14 cases that were treated with the instep flap due to soft-tissue defects over these regions from JuL 1990 to Oct. 1995. All flaps were viable and successful at follow-up. 1. The age ranged from 5 years to 70 years, and 13 cases were male and 1 case was female. 2. The sites of soft-tissue loss were the plantar forefoot (l case), plantar heel (9 cases), Achilles tendon (3 cases), and distal part of lower leg (1 case). 3. The causes of soft-tissue loss were simple soft-tissue injury (l case), crushing injury of the 1st toe (1 case), post-traumatic infection and necrosis (11 cases) and traction sore (1 case). 4. The associated injury were open distal tibio-fibular fractures (2 cases), medial malleolar fracture of the ankle (1 case), Achilles tendon ruptures (4 cases) and 1st metatarsophalangeal disarticulation (1 case), open calcaneus fracture (1 case) and femur shaft fracture (1 case). 5. The size of flap was from 3 1 cm to 5 10 cm (average 4 5 cm). 6. We could not find post-operative necrosis and infection, non-viability and gait disturbance caused by the instep flap surgery except limitation of the ankle joint in 1 case. In conclusion, this study demonstrates that the instep flap should be considered as another valuable technique in the reconstruction of these regions.

Fracture - Dislocation of the Body of the hamate / 대한정형외과학회잡지

Fracture-Dislocation of the the body of the hamate is rare in carpal bone fractures. Recently, we experienced two patients with coronal fracture of the dorsal aspect of the hamate with dorsal subluxation of metacarpal bases of the ring and little fingers. The mechanism of injury was by indirect blow with c1enched fist in two patients. Two patients were treated with closed reduction and plaster immobilization for 6 weeks and physical theraphy. At 13 and 14 weeks follow-up respectively, two patients had no funtional limitation, no complaints referable to hand, and nearly solid union on radiographs. We report two cases of fracture of the the body of the hamate bone, associated with dorsal subluxation of hamatometacarpal joint treated by conservative methods and review of literatures.

Tuberculous Osteomyelitis on the Proximal Humerus after BCG vaccination: a case report / 대한정형외과학회잡지

Tuberculosis of the bone and joints is either one of the generalized manifestation or solitary localized lesion. The involvement of bone after Bacille Calmette Guerin (BCG) vaccination is very rare. We experienced a case of which developed tuberculous osteomyelitis after BCG vaccination. The case is a 14-month-old male. The patient had the history of BCG vaccination 1 year ago. The presenting symptoms were swelling, redness and discharge of the left shoulder. The lesion in the left proximal humerus was mainly erosive lesion with minimal periosteal reaction. We are going to report a case of 14-month-old child with tuberculous osteomyelitis after BCG vac-cination with brief review of literature.

The Results of Open Release in Carpal Tunnel Syndrome / 대한정형외과학회잡지

Forry-two symptomatic hands of 29 patients with carpal tunnel syndrome operated during the period from Marth 1986 to December 1993 were analized in clinical aspect. Among 29 patients, 3(10.3%) were male and 26(89.7%)were female. The syndrome occured on the right side in 10(34.5%) patients, on the left in 6(20.7%) patients, and on both in 13(44.8%) patients. The causes of the syndrome were idiopathic(90.5%), trauma(7.1%), mass(2.4%). Paresthesia(57.1%) was the most common chief complanit, followed by numbness(35.7%), pain(21.4%), weakness(9.5%). Thenar muscie atrophy occured in 84.8%, positive Tinel sign in 83.3% and positive Phalen sign in 90.0%. Delay of motor conduction velocity of median nerve was noted in all cases and delay of sensory nerve conduction velocity in all cases. Denervation finding such as fibrillation or sharp waves were seen in all cases. The carpal tunnel release was performed in all cases, and 31 cases were treated by carpal tunnel tunnel release with internal neurolysis. 35 cases(83.3%) were excellent or good results. The cases were long duration were poorer results. No significant difference was found between the results in cases treated by carpal tunnel release alone and those in cases treated by carpal tunnel release with internal neurolysis of median nerve.

Finger Lengthening by Callotasis / 대한정형외과학회잡지

Indications for bone lengthening in the hand are less common than for the lower extremity. From 1991 to 1993 authors had performed nine hand bone lengthenings in the eight patients, based on callotasis and chondrodiastasis, Average age at the time of surgery was 18 years old(from 4 to 31 years old). Diagnoses included traumatic amputations in 7 cases and congenital syndactyly of both hand with hypoplastic digits in 2 cases. Sites of lengthening were metacarpal bone in 7 cases, phalangeal bone in 2 cases. Eight of 9 lengthening procedures resulted in complete consolidation of the bone gap after the single stage procedure. In one case secondary bone graft was required for the bone defect. Average consolidation period was 16 weeks(from 10 weeks to 22 weeks). Average gained length was 14.6mm (from 6 to 30mm) and average percent of gained digital bone length was 48%. There were minimal complications including marginal necrosis of skin, numbness and bone tip exposure and were responsed to conservative manage, but stump revision for bone tip exposure was performed in one case. In all cases followed to completion and for 1 to 3 years postoperatively, there was improvement of function with key pinch. The callotasis lengthening is one of the useful method of short hand bone lengthening to improve function of hand and cosmetic demand.