The Difference between Serum Vitamin D Level and Depressive Symptoms in Korean Adult Women before and after Menopause: The 5th (2010–2012) Korean National Health and Nutrition Examination Survey

Background@#The relationship between serum vitamin D levels and depressive symptoms has not been consistent in previous studies in Korean women. Menopause is known to be related to depression and vitamin D. @*Methods@#This study included 11,573 women from the 5th Korea National Health and Nutrition Examination Survey. Serum vitamin D levels were divided into four groups according to quartiles, and depressive symptoms were collected into two groups. Multiple logistic regression analysis was conducted in each group of women before and after menopause. @*Results@#Compared with the highest vitamin D group, the lowest vitamin D group did not show significant differences in all females (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.78-1.22). In premenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 0.75; 95% CI, 0.53-1.07), third quartile (OR, 0.70; 95% CI, 0.49-1.00) and fourth quartile (OR, 0.62; 95% CI, 0.43-0.92) respectively, and they were statistically significant (P=0.016). In postmenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 1.06; 95% CI, 0.78-1.44), third quartile (OR, 1.18; 95% CI, 0.87-1.61), and fourth quartile (OR, 1.27; 95% CI, 0.98-1.66) respectively; however, they were not statistically significant (P=0.057). @*Conclusions@#Depression symptoms increased with a decrease in serum vitamin D in premenopausal women, but the opposite trend was observed in postmenopausal women. In future studies, if the relationship between blood vitamin D and depression is studied, the menopausal status of women can be used as an important criterion.

Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

BACKGROUND@#Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males.Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate In vitro. Therefore, there is a need for an alternative source of LCs. @*METHODS@#To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. @*RESULTS@#HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. @*CONCLUSION@#We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

BACKGROUND@#Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males.Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate In vitro. Therefore, there is a need for an alternative source of LCs. @*METHODS@#To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. @*RESULTS@#HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. @*CONCLUSION@#We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

Implant survival and risk factor analysis in regenerated bone: results from a 5-year retrospective study

Purpose@#The aims of this study were to evaluate the 5-year cumulative survival rate (CSR) of implants placed with guided bone regeneration (GBR) compared to implants placed in native bone, and to identify factors contributing to implant failure in regenerated bone. @*Methods@#This retrospective cohort study included 240 patients who had implant placement either with a GBR procedure (regenerated bone group) or with pristine bone (native bone group). Data on demographic features (age, sex, smoking, and medical history), location of the implant, implant-specific features, and grafting procedures and materials were collected.The 5-year CSRs in both groups were estimated using Kaplan-Meier analysis. Risk factors for implant failure were analyzed with a Cox proportional hazards model. @*Results@#In total, 264 implants in the native bone group and 133 implants in the regenerated bone group were analyzed. The 5-year CSRs were 96.4% in the regenerated bone group and 97.5% in the native bone group, which was not a significant difference. The multivariable analysis confirmed that bone status was not an independent risk factor for implant failure. However, smoking significantly increased the failure rate (hazard ratio, 10.7; P=0.002). @*Conclusions@#The 5-year CSR of implants placed in regenerated bone using GBR was comparable to that of implants placed in native bone. Smoking significantly increased the risk of implant failure in both groups.

Implant survival and risk factor analysis in regenerated bone: results from a 5-year retrospective study

Purpose@#The aims of this study were to evaluate the 5-year cumulative survival rate (CSR) of implants placed with guided bone regeneration (GBR) compared to implants placed in native bone, and to identify factors contributing to implant failure in regenerated bone. @*Methods@#This retrospective cohort study included 240 patients who had implant placement either with a GBR procedure (regenerated bone group) or with pristine bone (native bone group). Data on demographic features (age, sex, smoking, and medical history), location of the implant, implant-specific features, and grafting procedures and materials were collected.The 5-year CSRs in both groups were estimated using Kaplan-Meier analysis. Risk factors for implant failure were analyzed with a Cox proportional hazards model. @*Results@#In total, 264 implants in the native bone group and 133 implants in the regenerated bone group were analyzed. The 5-year CSRs were 96.4% in the regenerated bone group and 97.5% in the native bone group, which was not a significant difference. The multivariable analysis confirmed that bone status was not an independent risk factor for implant failure. However, smoking significantly increased the failure rate (hazard ratio, 10.7; P=0.002). @*Conclusions@#The 5-year CSR of implants placed in regenerated bone using GBR was comparable to that of implants placed in native bone. Smoking significantly increased the risk of implant failure in both groups.

Hospital Arrival Rate within Golden Time and Factors Influencing Prehospital Delays among Patients with Acute Myocardial Infarction

PURPOSE: This research was done to identify the hospital arrival rate and factors related to prehospital delay in arriving at an emergency medical center within the golden time after symptom onset in patients with acute myocardial infarction (AMI). METHODS: Data used in the research was from the National Emergency Department Information System of the National Emergency Medical Center which reported that in 2014, 9,611 patients went to emergency medical centers for acute myocardial infarction. Prehospital time is the time from onset to arrival at an emergency medical center and is analyzed by subdividing arrival and delay based on golden time of 2 hour. RESULTS: After onset of acute myocardial infarction, arrival rate to emergency medical centers within the golden time was 44.0%(4,233), and factors related to prehospital delay were gender, age, region of residence, symptoms, path to hospital visit, and method of transportation. CONCLUSION: Results of this study show that in 2014 more than half of AMI patients arrive at emergency medical centers after the golden time for proper treatment of AMI. In order to reduce prehospital delay, new policy that reflects factors influencing prehospital delay should be developed. Especially, public campaigns and education to provide information on AMI initial symptoms and to enhance utilizing EMS to get to the emergency medical center driectly should be implemented for patients and/or caregivers.

Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.

Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.

The Effect of Sexual Abuse on Posttraumatic Psychiatric Symptoms in Children and Adolescents with Sexual Abuse

OBJECTIVES: The purpose of this study is to examine the effects of the characteristics of victim and sexual abuse on posttraumatic psychiatric symptoms in children and adolescents with a history of sexual abuse. METHODS: A total of 137 children and adolescents were recruited from the Seoul Sunflower Children Center, a nation-funded sexual violence victim protection center, from January 2009 to December 2013. We collected the demographic data of the victims and the Trauma Symptom Checklist for Children (TSCC) from victims. We hypothesized victims' age, sex, and intelligence quotient, and the characteristics of sexual abuse as the affecting factors of posttraumatic psychiatric symptoms. Descriptive analysis and hierarchical regression analysis were performed for analysis of demographic data, TSCC scores, and psychiatric symptoms. RESULTS: The victims' age and the characteristics of sexual abuse were significantly related to the traumatic distress of sexual abuse. R-square was 23% for anxiety, 39% for depression, 21% for posttraumatic stress, and 37% for dissociation on TSCC. CONCLUSION: This study suggests that victims' age, type, frequency and duration of exposure, and disclosure of sexual abuse are significant affecting factors on posttraumatic psychiatric symptoms in children and adolescents. Exploration of psychiatric symptoms other than posttraumatic symptoms, and relations between pretraumatic and posttraumatic psychiatric symptoms is needed through collection of larger samples.

Activation of small Rho GTPases by blebbistatin in PC12 cells / 동물의과학연구지

Neuronal differentiation is a complex biological process accompanying cytoskeletal reorganization, including neurite outgrowth and growth cone formation. Therefore, neuronal differentiation is critically regulated by actin-related signaling proteins, such as small Rho GTPases, guanine nucleotide exchange factors (GEFs), and myosins. This study will demonstrate the change in activity of three small Rho GTPases, Rac, Cdc42, and Rho A, by treatment with blebbistatin (BBS), a specific inhibitor for myosin, during bFGF-induced neurite outgrowth in PC12 cells. Treatment with BBS induced morphological changes in growth cones and neurites during differentiation. A marked increase in protrusion and filopodia structures in growth cones, the shaft of neuritis, and cell membranes was observed in the cells treated with BBS. Activity of Rho GTPases showed the alterations in response to BBS. Activities of both Rac and Rho A were inhibited by BBS in a time-dependent manner. By contrast, Cdc42 activity was not changed by BBS. These results suggest that inactivation of myosin II by BBS induced morphological changes in neurites and growth cones and distinct regulation of three Rho GTPases during differentiation of PC12 cells.

Relationship between White Matter Changes and Cognitive Dysfunction in the Elderly with Subjective Memory Complaint

OBJECTIVES: The purpose of this study is to evaluate the relationship between the severity of white matter changes (WMC), risk factors and cognitive domains, including executive function profiles. METHOD: Forty nine subjects over 55 years with subjective memory complaints were assessed with MRI and neuropsychological tests. The WMC were assessed by MRI T2-FLAIR images and divided into 3 groups of mild vs. moderate vs. severe and 2 groups of mild-moderate vs. severe by using Mantyla's criteria and Fazeka's criteria. The risk factors were examined in hypertension, heart disease history and chemistry Lab. Medical conditions which affect to cognitive dysfunction and definite dementia were also excluded. RESULTS: Comparing 3 groups, hypertension was identified as a risk factor of the WMC. Comparing 2 groups, total cholesterol and LDL were identified for as the risk factor of WMC. The severity of WMC was significantly associated with cognitive disturbances and their main effect on cognition was working memory and inhibition. CONCLUSION: The risk factors of the WMC in the elderly were hypertension, hyperlipidemia. The severity of WMC appears to be associated with executive dysfunction in the elderly.

Comparison of Processed Nerve Allograft and Laminin Derived Peptide Incorporated Nerve Conduit for Peripheral Nerve Regeneration / 대한정형외과학회잡지

PURPOSE: To compare a processed nerve allograft, laminin derived peptide incorporated nerve conduit, and autograft in terms of electrodiagnostic testing and nerve histomorphometry for peripheral nerve regeneration in a rabbit sciatic nerve defect model. MATERIALS AND METHODS: Thirty New Zealand white rabbits were divided into three groups, and a unilateral 15 mm sciatic nerve defect was made. Group I, II and III was repaired with a reversed autograft, a processed acellular nerve allograft, and a laminin derived peptide incorporated nerve conduit, respectively. At twelve weeks, the animals were evaluated with the compound muscle action potential, wet muscle weight, and nerve histomorphometric parameters such as nerve area, number of axons, and myelin thickness. RESULTS: At twelve weeks, the compound muscle action potential for group I, II and III was 54.1%, 38.2% and 26.4%, respectively. Significant differences were found between the three groups (p<0.001, group I vs II; p<0.001, group I vs III; p<0.001, group II vs III). The wet muscle weight for group I, II and III was 57.8%, 54.4% and 43.9%, respectively. Group I had significantly more muscle weight than group III (p<0.001), but the difference was not significant with group II (p=0.256). Group II and III showed a significant difference (p=0.002). The number of axons in group III decreased and the shape of the axon was irregular, even though the nerve area and myelin thickness were similar in the three groups. CONCLUSION: An autograft remains the gold standard to repair a segmental nerve defect. Processed allograft demonstrated superior nerve recovery compared to the laminin derived peptide incorporated nerve conduit.

Eight Years of Follow-Up Study with Regard to Defense Mechanisms in Medical Students / 신경정신의학

OBJECTIVES: The purpose of this study was to evaluate the changes in defense mechanisms in medical students as they progress towards becoming a doctor. METHODS: Ninety premedical students were enrolled from Soonchunhyang University. All subjects were evaluated at baseline, during their 6th year of medical school, during their 4th year as a practicing doctor by the Ewha defense Mechanisms Test which contained 20 defense mechanisms and 4 factors (unstable, narcissistic, self-negative, and avoidant). In the end, 60 subjects were included in the analysis. RESULTS: During the period from premedical student to medical doctor, the use of passive-aggressive, acting-out, displacement, somatization, dissociation, projection, denial, regression, and distortion decreased significantly. Also, there was a significant difference in the use of defense mechanisms from the time as a premedical student to a medical student. However, there was no significant difference in the period from medical student to medical doctor. CONCLUSION: We concluded that the use of unstable and avoidant defense scales decreased in the course of becoming a doctor from a premedical student, compared to mature or stable defense scales.

Implant failure associated with oral bisphosphonate-related osteonecrosis of the jaw

PURPOSE: The aim of this study is to report a case of oral bisphosphonate-related osteonecrosis of the jaw (BRONJ) resulting in implant failure. METHODS: A patient suspected of having BRONJ was referred to the Department of Periodontology, Kyung Hee University School of Dentistry for the evaluation and treatment of exposed bone around implants. RESULTS: The patient, who had been taking oral bisphosphonates (BPs) for about a year, was successfully treated with systemic antibiotics, chlorhexidine mouth rinse, explantation, and surgical debridement of necrotic bone. CONCLUSIONS: The results of this case suggest that a patient taking BPs orally should be treated cautiously. Appropriate management including cessation of BPs and respective dental treatment may reduce the development of BRONJ.

Treatment of Compensatory Hyperhidrosis with Botulinum Toxin A: A case report

Conventional thoracoscopic sympathectomy is an effective method in treating palmar-axillary hyperhidrosis. However, this may result in a postoperatively compensatory hyperhidrosis. Conservative treatments of compensatory hyperhidrosis consist of aluminum chloride, anticholinergics, iontrophoresis, and botulinum toxin A injections. Surgical treatments in compensatory hyperhidrosis include excision of axillary tissue, liposuction, and thoracoscopic sympathectomy. Intradermal injection of botulinum toxin A has used to treat focal axillary or palmar hyperhidrosis. Botulinum toxin A bestows significant benefits with few side-effects and is well-tolerated, with beneficial results lasting from 4-16 months. We report a case illustrating the beneficial use of botulinum toxin A in a 25-year-old healthy male patient with compensatory sweating of the flank after thoracoscopic sympathectomy. Modified Minor's starch iodine test was used to allow accurate assess the impact of hyperhidrosis on the patient. In conclusion, Botulinum toxin type A is a valuable therapy for compensatory sweating after endoscopic thoracic sympathectomy.

Involvement of betaPIX in angiotensin II-induced migration of vascular smooth muscle cells

Angiotensin II (Ang II) stimulates migration of vascular smooth muscle cell (VSMC) in addition to its contribution to contraction and hypertrophy. It is well established that Rho GTPases regulate cellular contractility and migration by reorganizing the actin cytoskeleton. Ang II activates Rac1 GTPase, but its upstream guanine nucleotide exchange factor (GEF) remains elusive. Here, we show that Ang II-induced VSMC migration occurs in a betaPIX GEF-dependent manner. betaPIX-specific siRNA treatment significantly inhibited Ang II-induced VSMC migration. Ang II activated the catalytic activity of betaPIX towards Rac1 in dose- and time-dependent manners. Activity reached a peak at 10 min and declined close to a basal level by 30 min following stimulation. Pharmacological inhibition with specific kinase inhibitors revealed the participation of protein kinase C, Src family kinase, and phosphatidylinositol 3-kinase (PI3-K) upstream of betaPIX. Both p21-activated kinase and reactive oxygen species played key roles in cytoskeletal reorganization downstream of betaPIX-Rac1. Taken together, our results suggest that betaPIX is involved in Ang II-induced VSMC migration.

Correlation of Plasma Homocysteien and Folate Levels with White Matter Changes in Alzheimer's Disease Patients

OBJECTIVES: To explore the relationship of white matter changes (WMC) on magnetic resornance imaging (MRI) with plasma homocysteine and folate levels in Alzheimer's disease (AD) patients. METHODS: Forty-one patients with probable AD were evaluated on WMC on brain MRI, plasma homocysteine and folate levels, and cerebrovascular risk factors. Subjects were divided into two groups according to WMC scores (lower group with or = 5). WMC were assessed by a scale of the European Task Force on Age-Related WMC. RESULTS: Plasma homocysteine levels were correlated with right frontal WMC and have a tendency of correlation with left frontal WMC. When subjects were divided into two groups: higher plasma homocysteine group (> or = 14 micronmol/L) and lower plasma homocysteine group (< 14 micronmol/L), the former was significantly higher than the latter in both frontal WMC. In a logistic regression analysis, higher plasma homocysteine were not a significant risk factor for higher WMC. Increasing age was a only significant risk factor for higher WMC and correlated with both frontal WMC. There was no relationship folate with any WMC. CONCLUSION: It is possible that plasma homocysteine levels have a region-specific correlation with frontal WMC in AD. However, it is important that effect of age on the relationship should be considered.

Lidocaine attenuates the expression of ERK1/2 and CREB in a neuropathic pain model of rats / 대한마취과학회지

BACKGROUND: In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2, p38 MAPK, and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. The current study was designed to determine if lidocaine had an effect on the development of neuropathic pain in response to SCI. METHODS: Male Sprague Dawley rats were anesthetized and then received a L5-L6 spinal nerve ligation (neuropathic rats). The levels of intracellular cell-signaling protein, ERK 1/2 and CREB were then assessed by western blot analysis of samples collected from a sham operated (control) group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and 5% lidocaine (NP + Lido) group. RESULTS: The increased levels of ERK 1/2 and CREB protein that were observed in the neuropathic pain model were reduced by continuous infusion of 5% lidocaine. CONCLUSIONS: The current results suggest that lidocaine therapy may be an effective method of preventing and treating central neuropathic pain following SCI, and that these effects may occur via the reduced expression of ERK 1/2 and CREB in the intracellular cell-signaling pathway.

Cement leakage into subcutaneous tissue after kyphoplasty: A case report

We describe a case of cement leakage from the pedicle of vertebrae to the subcutaneous tissue after kyphoplasty.We attempted to remove all cement leakage, but residual cement remained in the paraspinal tissue without any neurological complications.This case illustrates the importance of the right timing of cement injection and when to detach the bone-filler device from the cement.

Low dose ketamine reduces the induction of ERK1/2 and CREB signaling protein in a neuropathic pain model of rats / 대한마취과학회지

BACKGROUND: In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2 MAPK and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. This study was conducted to determine if low dose ketamine had an effect on the activation of ERK 1/2 and CREB in the development of neuropathic pain. METHODS: This study was conducted to evaluate ERK 1/2 and CREB protein in a sham operated (control) group, neuropathic pain and normal saline (NP + NS) group and neuropathic pain and ketamine (NP + Keta) group. To accomplish this, male Sprague-Dawley rats were anesthetized and then subjected to L5-L6 spinal nerve ligation (SNL, neuropathic rats). The total amounts of ERK 1/2 and CREB protein were then assessed by western blot analysis. In addition, changes in the amounts of ERK 1/2 and CREB mRNA were evaluated by RT-PCR. RESULTS: There was a significant increase in the amount of ERK 1/2 and CREB in the NP + NS group when compared with the sham group. However, the amount of ERK 1/2 and CREB protein induced due to SNL were significantly reduced by continuous infusion with ketamine in the NP + Keta group. CONCLUSIONS: The results of this study revealed a positive linkage between NMDA receptors and the ERK-CREB signaling pathway. Therefore, NMDA receptors could be the target of future therapeutic approaches. Additionally, the results of the present study provide additional evidence that low dose ketamine effectively prevents and treats central neuropathic pain following SNL.