Strumpellin/WASHC5 regulates the structural plasticity of cortical neurons involved in gait coordination.

Strumpellin/Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex subunit 5 (WASHC5) is a core component of the WASH complex, and its mutations confer pathogenicity for hereditary spastic paraplegia (HSP) type SPG8, a rare neurodegenerative gait disorder. WASH complex activates actin-related protein-2/3-mediated actin polymerization and plays a pivotal role in intracellular membrane trafficking in endosomes. In this study, we examined the role of strumpellin in the regulation of structural plasticity of cortical neurons involved in gait coordination. Administration of a lentivirus containing a strumpellin-targeting short hairpin RNA (shRNA) to cortical motor neurons lead to abnormal motor coordination in mice. Strumpellin knockdown using shRNA attenuated dendritic arborization and synapse formation in cultured cortical neurons, and this effect was rescued by wild-type strumpellin expression. Compared with the wild-type, strumpellin mutants N471D or V626F identified in patients with SPG8 exhibited no differences in rescuing the defects. Moreover, the number of F-actin clusters in neuronal dendrites was decreased by strumpellin knockdown and rescued by strumpellin expression. In conclusion, our results indicate that strumpellin regulates the structural plasticity of cortical neurons via actin polymerization.

Effect of pre-operative radiation therapy on surgical outcome in retroperitoneal sarcoma.

Background: A high rate of locoregional recurrence is one of the major difficulties in successful treatment of retroperitoneal sarcoma (RPS). Although pre-operative radiation therapy (RT) is considered a potential way to improve local recurrence, concerns about the associated treatment toxicity and risk of peri-operative complications need to be addressed. Hence, this study investigates the safety of pre-operative RT (preRTx) for RPS. Methods: A cohort of 198 patients with RPS who had undergone both surgery and RT was analyzed for peri-operative complications. They were divided into three groups according to the RT scheme: (1) preRTx group, (2) post-operative RT without tissue expander, and (3) post-operative RT with tissue expander. Results: The preRTx was overall well tolerated and did not affect the R2 resection rate, operative time, and severe post-operative complications. However, the preRTx group was associated with higher incidence of post-operative transfusion and admission to intensive care unit (p = 0.013 and p = 0.036, respectively), where preRTx was an independent risk factor only for the post-operative transfusion (p = 0.009) in multivariate analysis. The median radiation dose was the highest in preRTx group, although no significant difference was demonstrated in overall survival and local recurrence rate. Conclusion: This study suggests that the preRTx does not add significant post-operative morbidity to the patients with RPS. In addition, radiation dose elevation is achievable with the pre-operative RT. However, a meticulous intra-operative bleeding control is recommended in those patients, and further high-quality trials are warranted to evaluate the long-term oncological outcomes.

Effects of External Employment Opportunities, Nursing Professionalism, and Nursing Work Environments on Korean Hospital Nurses' Intent to Stay or Leave.

This study aims to explore Korean Hospital nurses' intent to stay or leave their working environment, and to identify the difference between the intent to stay and the intent to leave by identifying the relationship between external employment opportunities, professionalism, and work environment. Data were collected via an online survey and analyzed using stepwise multiple regression analysis. As a result of the analysis, the intent to stay among Korean hospital nurses was influenced by the work environment, external employment opportunities, education level, and marital status, whereas the intent to leave was influenced by the nursing work environment, marital status, and total clinical experience. As a result, the reflected variables differed. Thus, it can be concluded that hospital nurses' intent to either stay or leave are not concepts that simply contradict each other in the same context but are, in fact, influenced differently by various factors. Nevertheless, it can also be concluded that nursing managers should make efforts to improve the nursing work environment to lower nurses' intent to leave and increase their intent to stay by improving only the nursing work environment.

Size-Dependent Effects of Polystyrene Nanoparticles (PS-NPs) on Behaviors and Endogenous Neurochemicals in Zebrafish Larvae.

Microplastics, small pieces of plastic derived from polystyrene, have recently become an ecological hazard due to their toxicity and widespread occurrence in aquatic ecosystems. In this study, we exposed zebrafish larvae to two types of fluorescent polystyrene nanoparticles (PS-NPs) to identify their size-dependent effects. PS-NPs of 50 nm, unlike 100 nm PS-NPs, were found to circulate in the blood vessels and accumulate in the brains of zebrafish larvae. Behavioral and electroencephalogram (EEG) analysis showed that 50 nm PS-NPs induce abnormal behavioral patterns and changes in EEG power spectral densities in zebrafish larvae. In addition, the quantification of endogenous neurochemicals in zebrafish larvae showed that 50 nm PS-NPs disturb dopaminergic metabolites, whereas 100 nm PS-NPs do not. Finally, we assessed the effect of PS-NPs on the permeability of the blood-brain barrier (BBB) using a microfluidic system. The results revealed that 50 nm PS-NPs have high BBB penetration compared with 100 nm PS-NPs. Taken together, we concluded that small nanoparticles disturb the nervous system, especially dopaminergic metabolites.

Phosphoproteome profiling of hippocampal synaptic plasticity.

The balance between the actions of protein kinases and phosphatases is crucial for neuronal functions, including synaptic plasticity. Although the phosphorylation and dephosphorylation of neuronal proteins are regulated by synaptic plasticity, no systematic analyses of this have yet been conducted. We performed a phosphoproteomic analysis of hippocampal synaptic plasticity using a nano-Acquity/Synapt LC-MS/MS system. Neuronal proteins were extracted from hippocampal tissues and cultured neurons exposed to long-term potentiation (LTP) or long-term depression (LTD). Filter-aided sample preparation (FASP) was performed to remove residual anionic detergents for complete tryptic digestion. Phosphopeptides were then enriched using TiO2 chromatography, followed by immunoaffinity chromatography with an anti-phosphotyrosine antibody. Among the 1500 phosphopeptides identified by LC-MS/MS, 374 phosphopeptides were detected simultaneously in both hippocampal tissues and cultured neurons. Semi-quantification counting the number of spectra of each phosphopeptide showed that 42 of 374 phosphopeptides changed significantly depending on synaptic plasticity. In conclusion, a new proteomic method using sequential enrichment of phosphopeptides and semi-quantification enabled the phosphoproteomic analysis of hippocampal synaptic plasticity.

Analysis of the Effect of Tumor-Grade Change on the Prognosis of Retroperitoneal Sarcoma.

In retroperitoneal sarcoma (RPS), the change in the tumor grade from the primary tumor to the first local recurrence, and the effect of this change on prognosis, are unknown. The aim of this study is to analyze whether these changes affect the prognosis of RPS. Patients who underwent surgery for a first locally recurrent RPS at Samsung Medical Center from January 2001 to February 2020 were included. The pathologic features of primary and recurrent tumors were compared, and the outcomes were measured. A total of 49 patients were investigated. There were 25 patients with different grades of primary and recurrent tumors. The improving, stable, and worsening groups contained 16 (32.7%), 24 (49%), and 9 (18.3%) patients, respectively. There was no significant difference in the prognosis between the three groups. In the analyses of the factors that affect the OS, a high grade of the primary tumor (p = 0.023) and the size of the recurrent tumor (p = 0.032) were statistically significant in both univariate and multivariate analyses. In a factor analysis of the second LR, a high-grade recurrent tumor (p = 0.032) was the only significant factor. There were tumor-grade changes between the primary tumor and recurrent tumor in RPS. However, the most important factor in prognosis is a high grade of the primary tumor.

The Role of Preoperative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Retroperitoneal Sarcoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used to predict pathologic grades based on the maximum standardized uptake value (SUVmax) in soft tissue sarcoma and bone sarcoma. In retroperitoneal sarcoma (RPS), the effectiveness of PET was not well known. This study was designed to investigate the association of SUVmax with histopathologic grade and evaluate the usefulness of 18F-FDG PET/CT before operation. Patients at Samsung Medical Center undergoing primary surgery for retroperitoneal sarcoma with preoperative 18F-FDG PET/CT imaging between January 2001 and February 2020 were investigated. The relationship between SUVmax and histologic features was assessed. The association of SUVmax with overall survival (OS), local recurrence (LR), and distant metastasis (DM) were studied. Of the total 129 patients, the most common histologic subtypes were liposarcoma (LPS; 68.2%) and leiomyosarcoma (LMS; 15.5%). The median SUVmax was 4.5 (range, 1- 29). Moreover, SUVmax was correlated with tumor grade (p < 0.001, Spearman coefficient; 0.627) and mitosis (p < 0.001, Spearman coefficient; 0.564) and showed a higher value in LMS (12.04 ± 6.73) than in dedifferentiated liposarcoma (DDLPS; 6.32 ± 4.97, p = 0.0054). SUVmax was correlated with pathologic parameters (tumor grade and mitosis) in RPS and was higher in the LMS group than the DDLPS group. The optimal SUVmax threshold to distinguish high tumor grade was 4.8. Those with a SUVmax greater than the threshold showed poor prognosis regarding OS, LR, and DM (p < 0.001).

Nanoplasmonic immunosensor for the detection of SCG2, a candidate serum biomarker for the early diagnosis of neurodevelopmental disorder.

The neural circuits of the infant brain are rapidly established near 6 months of age, but neurodevelopmental disorders can be diagnosed only at the age of 2-3 years using existing diagnostic methods. Early diagnosis is very important to alleviate life-long disability in patients through appropriate early intervention, and it is imperative to develop new diagnostic methods for early detection of neurodevelopmental disorders. We examined the serum level of secretogranin II (SCG2) in pediatric patients to evaluate its potential role as a biomarker for neurodevelopmental disorders. A plasmonic immunosensor performing an enzyme-linked immunosorbent assay (ELISA) on a gold nanodot array was developed to detect SCG2 in small volumes of serum. This nanoplasmonic immunosensor combined with tyramide signal amplification was highly sensitive to detect SCG2 in only 5 µL serum samples. The analysis using the nanoplasmonic immunosensor revealed higher serum SCG2 levels in pediatric patients with developmental delay than in the control group. Overexpression or knockdown of SCG2 in hippocampal neurons significantly attenuated dendritic arborization and synaptic formation. These results suggest that dysregulated SCG2 expression impairs neural development. In conclusion, we developed a highly sensitive nanoplasmonic immunosensor to detect serum SCG2, a candidate biomarker for the early diagnosis of neurodevelopmental disorders.

Postoperative Outcomes of Distal Pancreatectomy for Retroperitoneal Sarcoma Abutting the Pancreas in the Left Upper Quadrant.

BACKGROUND: En bloc resection of the tumor with adjacent organs is recommended for localized retroperitoneal sarcoma (RPS). However, resection of the pancreas is controversial because it may cause serious complications, such as pancreatic fistula or bleeding. Thus, we evaluated the outcomes of distal pancreatectomy (DP) in pancreas-abutting RPS of the left upper quadrant (LUQ). METHODS: We retrospectively reviewed all consecutive patients who underwent surgery for RPS between September 2001 and April 2020. We selected 150 patients with all or part of their tumor located in the LUQ on preoperative computed tomography. Eighty-six patients who had tumors abutting the pancreas were finally enrolled in our study. RESULTS: Fifty-three patients (53/86; 61.6%) were included in the non-DP group, and 33 patients (33/86; 38.4%) were included in the DP group. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the non-DP group and DP group (p = 0.290 and p = 0.550). In the DP group, grade B pancreatic fistulae occurred in 18.2% (6/33) of patients, but grade C pancreatic fistulae were absent, and microscopic pancreatic invasion was noted in 42.4% (14/33) of patients. During multivariate analysis, microscopic pancreatic invasion was deemed a risk factor for local recurrence (p = 0.029). However, there were no significant differences on preoperative computed tomography findings between the pancreatic invasion and non-invasion groups. CONCLUSION: DP is a reasonable procedure for pancreas-abutting RPS located at the LUQ when both complications and complete resection are considered.

Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis.

PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT-/- null and PTPRT-D401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant-dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder.

A study on the intent to leave and stay among hospital nurses in Korea: A cross-sectional survey.

AIMS: To investigate the intent to leave or stay among Korean hospital nurses, and to identify what factors influence their intent to leave or stay. BACKGROUND: Previous studies have simply measured nurses' intent to leave or stay; however, this study examines the associations of intent to leave and intent to stay with influential factors among Korean hospital nurses. METHODS: A cross-sectional study was conducted with 267 nurses working at four general hospitals in South Korea. RESULT: The influencing factors on intent to leave were organisational commitment, practice environment and burnout, while intent to stay was influenced by organisational commitment. CONCLUSION: The study demonstrates that, for Korean hospital nurses, intent to leave and intent to stay are not simply contrary concepts, but are different concepts influenced by varying factors. IMPLICATIONS FOR NURSING MANAGEMENT: This study clarifies the difference between the concepts of intent to stay and intent to leave, and demonstrates that the variables affecting Korean nurses' intent to stay and intent to leave differ from each other. Therefore, focusing on improving nurses' intent to either leave or stay would be effective when developing personnel management policies for nurses, thereby contributing to enhancing nursing practice.

Unveiling the pathway to Z-DNA in the protein-induced B-Z transition.

Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B-Z transition in those sequences. Due to the high junction energy, an intermediate B* state has to accumulate prior to the B-Z transition. Our study showing the stable B* state supports the active picture for the protein-induced B-Z transition that occurs under a physiological setting.

Effects of nurses' emotional intelligence on their organizational citizenship behavior, with mediating effects of leader trust and value congruence.

AIM: To investigate the causal relationship between nurses' emotional intelligence and their organizational citizenship behavior and the possible mediating effects of leader trust and value congruence. METHODS: The participants were 348 nurses who were working in a general hospital in a metropolitan area. The data were collected from December 16, 2012 to February 20, 2013. The hypothetical model of emotional intelligence, organizational citizenship behavior, leader trust, and value congruence was fitted to the actual data via structural equation modeling. RESULT: The leaders' emotional intelligence had a direct positive effect on leader trust and value congruence; however, the nurses' own emotional intelligence had a negative effect on these two variables. Furthermore, leader trust had a direct positive effect on organizational citizenship behavior; value congruence had no such relationship. The nurses' emotional intelligence had a partial, indirect effect on organizational citizenship behavior via leader trust. CONCLUSION: In a nursing organization, it is necessary to build a system, such as mentoring, to be able to exchange emotions actively among the members in order to enhance emotional intelligence and have the same values between leaders and members throughout open communication. Therefore, nurse managers can contribute greatly to the enhancement of organizational performance by promoting members' organizational citizenship behavior through improving their relationships with them and gaining their trust, while concurrently making efforts to further develop their emotional intelligence.

A Preliminary Study on the Effectiveness of the Peer Relationship Enhancement Program in Adolescents at Risk for Internet and Smartphone Addiction.

OBJECTIVES: The purpose of this study is to evaluate the preliminary effects of the Peer Relationship Enhancement Program in adolescents deemed to be in an at-risk group for Internet and smartphone addiction. METHODS: The study group consisted of 33 adolescent participants (24 boys and 9 girls) at risk of Internet and smartphone addiction in small and medium-sized cities. The subjects participated in 8 consecutive sessions of the Peer Relationship Enhancement Program. The Korean Internet Addiction Proneness Scale, the Korean Smartphone Addiction Proneness Scale, the Real-Ideal Self Discrepancy Scale, the UCLA Loneliness Scale, the Peer Intimacy Scale, and the Escaping from the Self Scale were evaluated before the initial and after the final session. A paired t-test was performed to statistically analyze the data. RESULTS: The Peer Relationship Enhancement Program led to a significant decrease (p<0.05) in self-reported measures of The Korean Internet Addiction Proneness Scale, the Korean Smartphone Addiction Proneness Scale, and the Real-Ideal Self Discrepancy Scale. CONCLUSION: The Peer Relationship Enhancement Program reduces the risk of Internet and smartphone addiction and effectively prevents the associated problems.

Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.

KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.

A Predictive Model on North Korean Refugees' Adaptation to South Korean Society: Resilience in Response to Psychological Trauma.

PURPOSE: This study investigated prediction of North Korean refugees' adaptation to the South Korean society and verified the goodness of fit between a hypothetical model and actual data in order to suggest the best model. METHODS: This survey was conducted with 445 North Korean refugees living in a metropolitan area. Data were collected from September 1st to November 20th, 2012, and analyzed using SPSS Windows 18.0 and AMOS 17.0. RESULTS: Traumatic experiences of North Korean refugees increased self-efficacy and psychological trauma. Acculturation stress decreased self-efficacy and increased passive coping. Self-efficacy affected active and passive coping, decreased psychological trauma, and increased resilience. Resilience is successful adaptation and refers to North Korean refugees' abilities to adapt effectively to stress. In particular, self-efficacy as the main parameter affecting resilience was confirmed. CONCLUSIONS: The results suggest that resilience can be improved through self-efficacy. It was the most significant factor decreasing psychological trauma and increasing resilience. Therefore, we need to develop programs for self-efficacy. The results also provide basic data for policy making for North Korean refugees.

Patterns and Factors associated with Complementary and Alternative Medicine Use among Korean Postpartum Women.

PURPOSE: This study was conducted to identify the pattern and factors associated with women's use of complementary and alternative medicine (CAM) during postpartum in Korea. METHODS: With a descriptive survey design, data of 423 postpartum women were collected via online and offline surveys. RESULTS: A total of 251 women (59.3%) reported CAM use during postpartum. Eating animal-based foods (65.3%), plant-based health foods (52.2%), and using oriental medicine (31.8%) were commonly used in postpartum women. The reason for using CAM were physical recovery (39.1%), breastfeeding (29.7%), weight loss (24.8%), prevention of postpartum complications (5.1%), and others (1.3%). People who recommended CAM use was mainly family (41.3%), and expense of using CAM was 751,188 Korea won. Most women discussed CAM use with doctor (44.9%), and 29.3% of women didn't even consult CAM use with health care providers. Most of (72.3%) women were satisfied with CAM use. Higher level of education and monthly income, being employed, primipara, normal range of gestational weight gain, no abortion experience, and no maternal complication were significantly associated with CAM use in postpartum women. CONCLUSION: Results of this study were somewhat different from those of western research. Findings offer baseline data of CAM use in postpartum women, and health care providers need to understand it when they care for them.

Effects of role stress on nurses' turnover intentions: The mediating effects of organizational commitment and burnout.

AIM: This paper was designed to extend the extant research regarding factors related to nurses' turnover intentions. METHODS: This survey-based study was based on a path analysis designed to verify a hypothesized causal model involving nurses' role stress, organizational commitment, turnover intentions, and burnout. This study distributed 500 questionnaires to nurses in general hospitals with more than 500 beds located in Seoul, Korea, during 16-30 April 2012. RESULTS: Role conflict, an underlying factor in role stress, had no significant effect on role stress, but the results showed that role ambiguity reduced organizational commitment. On the other hand, role conflict and role ambiguity increased the level of burnout. Organizational commitment reduced turnover intentions, and burnout increased turnover intentions. Role conflict and role ambiguity had no direct effect on turnover intentions, but they had indirect effects on organizational commitment and burnout. CONCLUSION: To reduce nurses' turnover rate, this study recommends developing plans to improve their organizational commitment because it mediates role stress and turnover intention.