Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type.

Importance: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. Objective: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. Design, Setting, and Participants: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Exposures: Bypass surgery and conservative management. Main Outcomes and Measures: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. Results: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). Conclusions and Relevance: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

South Korean Nurse Residency Program for New Graduates: A Posttest Study.

BACKGROUND: Turnover rates among newly graduated nurses are high, increasing the workload for other nurses and hampering organizational productivity. This study investigates the effects of a nurse residency program (NRP), examining clinical competence, job satisfaction, organizational socialization, turnover intention, and turnover rates. METHOD: This study was conducted among newly employed graduate nurses in South Korea. Participants (N = 167) included nurses with less than 6 months of experience (NRP group, n = 52; control group, n = 115). The current results were measured 1 year after initiation of the NRP. RESULTS: The NRP group showed significantly lower turnover intention and turnover rates and substantially better clinical competence, job satisfaction, and organizational socialization. CONCLUSION: Even when applied in the unique South Korean cultural and medical context, the NRP improved job performance and satisfaction as well as organizational socialization and reduced turnover rates and turnover intention among new nurses. Therefore, a systematized NRP should be actively used when new nurses are onboarded. [J Contin Educ Nurs. 202x;5x(x):xx-xx.].

Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Skin-whitening effects of Spergularia marina by suppressing MITF translocation.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.

Treatment outcome comparison of Invisalign vs fixed appliance treatment in first premolar extraction patients.

INTRODUCTION: In this study, we compared the dentitional changes after Invisalign and conventional orthodontic treatment with 4 first premolar extractions. METHODS: This retrospective study included 57 patients whose orthodontic treatment involved the extraction of 4 first premolars because of bialveolar protrusion. A total of 27 patients were treated with Invisalign (mean age, 25.5 ± 5.2 years) and 30 patients with the fixed appliance (mean age, 24.4 ± 5.8 years). The angular and linear changes of the maxillary and mandibular central incisors, second premolars, first molars, and second molars were measured from the recordings on the basis of the lateral cephalograms taken before and after treatment. The angular changes of the canines and second premolars were measured using panoramic radiographs. RESULTS: The overbite and interincisal angle increased significantly in the Invisalign group compared with in the conventional fixed appliance group (P <0.05). The maxillary central incisors showed increased lingual tipping in the Invisalign group (P <0.05), whereas there was no statistically significant difference in the angular change of the mandibular incisors between groups (P >0.05). The maxillary first and second molars showed mesial tipping in the Invisalign group (P <0.05). The maxillary second premolars, first and second molars, and the mandibular second molars showed mesial movement in the Invisalign group (P <0.05). CONCLUSIONS: The Invisalign group showed more statistically significant lingual tipping of the maxillary central incisors, distal tipping of the maxillary canines, and mesial tipping of the maxillary first and second molars after maximum retraction of the anterior teeth compared with the fixed appliance group.

Regulation of Dihydropyrimidinase-like 3 Gene Expression by MicroRNAs in PC12 Cells with Induced Ischaemia and Hypothermia.

Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 ℃ for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.

Prevalence of aortic aneurysms and dissections in patients with systemic vessel aneurysms and dissections; matched case-control study using a national sample cohort.

Objective: Aneurysms in systemic arteries are rare, and little is known about their relationship with aortic aneurysms. In this study, we aimed to evaluate the prevalence of aortic aneurysms and dissections (AAD) in patients with other systemic vessel aneurysms and dissections (OVAD) and identify their potential risk factors. Methods: This cross-sectional study used a nationwide representative cohort sample from the Korea National Health Insurance Service-National Sample Cohort database. We defined OVAD as systemic vessel aneurysms and dissections excluding intracranial and aortic dissections and aneurysms. With a total of 690 OVAD patients and 2,760 non-OVAD matched controls, we investigated the prevalence of AAD in patients with OVAD and potential risk factors for their concurrence using the χ2 test and logistic regression. Results: The prevalence of AAD in patients with OVAD was 10.6% (73/690) and 0.3% (9/2,760) in patients with non-OVAD. The adjusted odds ratio (OR) for having concurrent AAD with OVAD was 37.56 (95% CI: 18.29-77.12, p < 0.001) after stratification by sex, age, income, region of residence and after adjustment for hypertension, diabetes mellitus, dyslipidemia, and extent of disability. The adjusted ORs of AAD were significantly higher in females [adjusted OR = 47.63 (95% CI: 10.72-211.55)], and individuals aged ≥60 years [adjusted OR = 28.18 (95% CI: 13.42-59.17)], as well as those without hypertension [adjusted OR = 95.44 (95% CI: 18.21-500.23)], diabetes mellitus [adjusted OR = 46.39 (95% CI: 18.85-114.17)], without dyslipidemia [adjusted OR = 60.99 (95% CI: 20.83-178.56), p < 0.001 for all]. The prevalence of AAD significantly differed by according to specific sites of OVAD in carotid artery, upper extremity artery, iliac artery, lower extremity artery, and splanchnic artery (p < 0.001 for all). Conclusions: The prevalence of AAD in patients with OVAD was 37.56 times higher than that in the matched population. We may approach aneurysms as systemic diseases and further investigations of pathophysiology would help to clarify the relationships between AAD and OVAD.

Patulin alleviates hepatic lipid accumulation by regulating lipogenesis and mitochondrial respiration.

AIMS: The aim of this study is to evaluate the effects of patulin on hepatic lipid metabolism and mitochondrial oxidative function and elucidate the underlying molecular mechanisms. MAIN METHODS: The effects of patulin on hepatic lipid accumulation were evaluated in free fatty acid-treated AML12 or HepG2 cells through oil red O staining, triglyceride assay, real-time polymerase chain reaction, and western blotting. Alteration of mitochondrial oxidative capacity by patulin treatment was determined using Seahorse analysis to measure the oxygen consumption rate. KEY FINDINGS: The increased amounts of lipid droplets induced by free fatty acids were significantly reduced by patulin treatment. Patulin markedly activated the CaMKII/AMP-activated protein kinase (AMPK)/proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathway in hepatocytes, reduced the expression of sterol regulatory element binding protein 1c (SREBP-1c) and lipogenic genes, and increased the expression of genes related to mitochondrial fatty acid oxidation. In addition, patulin treatment enhanced the mitochondrial consumption rate and increased the expression of mitochondrial oxidative phosphorylation proteins in HepG2 hepatocytes. The effects of patulin on anti-lipid accumulation; SREBP-1c, PGC-1α, and carnitine palmitoyltransferase 1 expression; and mitochondrial oxidative capacity were significantly prevented by compound C, an AMPK inhibitor. SIGNIFICANCE: Patulin is a potent inducer of the AMPK pathway, and AMPK-mediated mitochondrial activation is required for the efficacy of patulin to inhibit hepatic lipid accumulation. This study is the first to report that patulin is a promising bioactive compound that prevents the development and worsening of fatty liver diseases, including non-alcoholic fatty liver disease, by improving mitochondrial quality and lipid metabolism.

Long-Term Outcomes of Ruptured Blood Blister-Like Aneurysms with Multiple (≥2) Overlapping Stents and Coiling: A Single-Center Experience.

OBJECTIVE: To evaluate the long-term feasibility of multiple overlapping stents (≥2) with or without coiling for treating blood blister-like aneurysms (BBAs). METHODS: BBAs treated with stent-assisted coiling or stent-only therapy wasincluded. BBAs with atypical anatomical locations, other endovascular or surgical techniques performed, and delayed treatment (>48 hours) were excluded. Medical records of patients and procedures were retrospectively reviewed. RESULTS: Seventeen patients with BBAs were identified, and 15 were treated with stent-assisted coiling and 2 with stent-only therapy. Triple overlapping stents were performed in seven patients, double stents in nine, and a single stent with coiling in 1. One patient experienced in-stent fibrin formation and received intra-arterial tirofiban. Complementary treatment was required in four patients. Three patients were initially treated with double (3/9) and 1 with triple stents (1/7). Three recurred in the acute period (≤6 weeks) and 1 recurred 14 months after treatment. Three of 17 patients with Hunt Hess grade 5 died early. Thirteen patients were available for long-term angiographic follow-up (13.8 ± 8.9 months). Final angiography showed complete aneurysm occlusion in all patients without in-stent stenosis or perforating vessel occlusion. Clinical follow-up data were available for all 14 surviving patients (66.8 ± 40.9 months). Eight patients had favorable outcomes, five had unfavorable outcomes, and 1 died of a subarachnoid hemorrhage-unrelated cause. Delayed infarct or hemorrhage was not documented. CONCLUSIONS: Even in the era of flow diverter stents, the use of multiple overlapping stents with or without coiling can be a feasible alternative for treating ruptured BBAs.

Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis.

Dynamic alteration of DNA methylation leads to various human diseases, including nonalcoholic fatty liver disease (NAFLD). Although C-Maf-inducing protein (Cmip) has been reported to be associated with NAFLD, its exact underlying mechanism remains unclear. Here, we aimed to elucidate this mechanism in NAFLD in vitro and in vivo. We first identified alterations in the methylation status of the Cmip intron 1 region in mouse liver tissues with high-fat high-sucrose diet-induced NAFLD. Knockdown of DNA methyltransferase (Dnmt) 1 significantly increased Cmip expression. Chromatin immunoprecipitation assays of AML12 cells treated with oleic and palmitic acid (OPA) revealed that Dnmt1 was dissociated and that methylation of H3K27me3 was significantly decreased in the Cmip intron 1 region. Conversely, the knockdown of Tet methylcytosine dioxygenase 2 (Tet2) decreased Cmip expression. Following OPA treatment, the CCCTC-binding factor (Ctcf) was recruited, and H3K4me3 was significantly hypermethylated. Intravenous Cmip siRNA injection ameliorated NAFLD pathogenic features in ob/ob mice. Additionally, Pparγ and Cd36 expression levels were dramatically decreased in the livers of ob/ob mice administered siCmip, and RNA sequencing revealed that Gbp2 was involved. Gbp2 knockdown also induced a decrease in Pparγ and Cd36 expression, resulting in the abrogation of fatty acid uptake into cells. Our data demonstrate that Cmip and Gbp2 expression levels are enhanced in human liver tissues bearing NAFLD features. We also show that Dnmt1-Trt2/Ctcf-mediated reversible modulation of Cmip methylation regulates the Gbp2-Pparγ-Cd36 signaling pathway, indicating the potential of Cmip as a novel therapeutic target for NAFLD.

ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5.

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.

Depression or Anxiety According to Management Modalities in Patients With Unruptured Intracranial Aneurysms.

BACKGROUND: In the treatment of unruptured intracranial aneurysms, the risk was usually estimated by objective neurological sequelae. However, their effects on depression and anxiety are rare and remain controversial. We aimed to evaluate the risk of depression and anxiety in patients with unruptured intracranial aneurysm stratified by management strategies in a population-based, longitudinal cohort study. METHODS: Using the Korean National Health Insurance Research Database, 71 750 patients with unruptured intracranial aneurysms between 2008 and 2011 were identified and followed up until the end of 2020. The risk of depression and anxiety was compared among management strategies with respect to age, sex, and medical comorbidities. RESULTS: The Kaplan-Meier survival curves indicated that the treatment (clipping and endovascular treatment) group developed depression more frequently than the observation group (P<0.001). The adjusted hazard ratio was 1.11 (95% CI, 1.07-1.15) in the treatment group. According to the management modality, the Kaplan-Meier survival curves indicated that clipping and endovascular treatment groups developed depression more frequently than the observation group (P<0.0001). The adjusted hazard ratio was 1.15 (95% CI, 1.10-1.21) for clipping and 1.07 (95% CI, 1.02-1.12) for endovascular treatment. The depression risk was higher with advanced age (hazard ratio for 45-64 years, 1.37 [95% CI, 1.29-1.45] and hazard ratio for ≥65 years, 2.04 [95% CI, 1.92-2.17]). The risk for anxiety did not differ among the management modalities. CONCLUSIONS: In this study, the risk of depression was slightly greater after clipping surgery than endovascular treatment. Data on treatment-related, long-term psychological outcomes, such as depression, may aid decision-making for preventive treatment of asymptomatic unruptured intracranial aneurysm patients.

Therapeutic hypothermia in patients with poor-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Therapeutic hypothermia improves the prognosis of patients with poor-grade subarachnoid hemorrhage (SAH). We investigated the clinical and radiological effects of therapeutic hypothermia in patients with poor-grade SAH. METHODS: Clinical and radiological data were compared between patients who underwent mild hypothermic treatment and those who underwent treatment without hypothermia. RESULTS: Among 670 patients with SAH, 72 had poor-grade SAH. After early clipping or coiling of the aneurysm, 25 patients underwent mild hypothermia and the remaining 47 patients underwent no hypothermia. The medical complication occurrence rates were similar between the hypothermia treatment and control groups. Significantly, cerebral edema was reduced in patients in the hypothermia group (44 %) compared with those in the no-hypothermia group (9 %) (p = 0.025). The poor clinical outcome rate (modified Rankin scale score > 4) assessed at discharge (p = 1.000) and 3 months after admission (p = 0.688) was similar between the two groups. However, 1 month after admission, the mortality rate of the hypothermia group (20.0 %) was remarkably lower than that of the control group (46.8 %) (p = 0.025). Multivariate logistic regression showed the therapeutic hypothermia was the most effective treatment for decreasing the mortality (OR = 4.86, P = 0.023). CONCLUSION: Mild hypothermia treatment appears to be feasible and safe for patients with poor-grade SAH. The study supports mild hypothermia treatment and its neuroprotective effects in patients with poor-grade SAH.

Basic Fibroblast Growth Factor Induces Cholinergic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are considered a potential tool for regenerating damaged tissues due to their great multipotency into various cell types. Here, we attempted to find the appropriate conditions for neuronal differentiation of tonsil-derived MSCs (TMSCs) and expand the potential application of TMSCs for treating neurological diseases. METHODS: The TMSCs were differentiated in DMEM/F-12 (Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12) supplemented with various neurotrophic factors for 7-28 days to determine the optimal neuronal differentiation condition for the TMSCs. The morphologies as well as the levels of the neural markers and neurotransmitters were assessed to determine neuronal differentiation potentials and the neuronal lineages of the differentiated TMSCs. RESULTS: Our initial study demonstrated that DMEM/F12 supplemented with 50 ng/mL basic fibroblast growth factor with 10 µM forskolin was the optimal condition for neuronal differentiation for the TMSCs. TMSCs had higher protein expression of neuronal markers, including neuron-specific enolase (NSE), GAP43, postsynaptic density protein 95 (PSD95), and synaptosomal-associated protein of 25 kDa (SNAP25) compared to the undifferentiated TMSCs. Immunofluorescence staining also validated the increased mature neuron markers, NeuN and synaptophysin, in the differentiated TMSCs. The expression of glial fibrillar acidic protein and ionized calcium-binding adaptor molecule 1 the markers of astrocytes and microglia, were also slightly increased. Additionally, the differentiated TMSCs released a significantly higher level of acetylcholine, the cholinergic neurotransmitter, as analyzed by the liquid chromatography-tandem mass spectrometry and showed an enhanced choline acetyltransferase immunoreactivity compared to the undifferentiated cells. CONCLUSION: Our study suggests that the optimized condition favors the TMSCs to differentiate into cholinergic neuron-like phenotype, which could be used as a possible therapeutic tool in treating certain neurological disorders such as Alzheimer's disease.

EveryBOTy Counts: Examining Human-Machine Teams in Open Source Software Development.

In this study, we explore the future of work by examining differences in productivity when teams are composed of only humans or both humans and machine agents. Our objective was to characterize the similarities and differences between human and human-machine teams as they work to coordinate across their specialized roles. This form of research is increasingly important given that machine agents are becoming commonplace in sociotechnical systems and playing a more active role in collaborative work. One particular class of machine agents, bots, is being introduced to these systems to facilitate both taskwork and teamwork. We investigated the association between bots and productivity outcomes in open source software development through an analysis of hundreds of project teams. The presence of bots in teams was associated with higher levels of productivity and higher work centralization in addition to greater amounts of observed communication. The adoption of bots in software teams may have tradeoffs, in that doing so may increase productivity, but could also increase workload. We discuss the theoretical and practical implications of these findings for advancing human-machine teaming research.

miR-3189-targeted GLUT3 repression by HDAC2 knockdown inhibits glioblastoma tumorigenesis through regulating glucose metabolism and proliferation.

BACKGROUND: Epigenetic regulations frequently appear in Glioblastoma (GBM) and are highly associated with metabolic alterations. Especially, Histone deacetylases (HDACs) correlates with the regulation of tumorigenesis and cell metabolism in GBM progression, and HDAC inhibitors report to have therapeutic efficacy in GBM and other neurological diseases; however, GBM prevention and therapy by HDAC inhibition lacks a mechanism in the focus of metabolic reprogramming. METHODS: HDAC2 highly express in GBM and is analyzed in TCGA/GEPIA databases. Therefore, HDAC2 knockdown affects GBM cell death. Analysis of RNA sequencing and qRT-PCR reveals that miR-3189 increases and GLUT3 decreases by HDAC2 knockdown. GBM tumorigenesis also examines by using in vivo orthotopic xenograft tumor models. The metabolism change in HDAC2 knockdown GBM cells measures by glucose uptake, lactate production, and OCR/ECAR analysis, indicating that HDAC2 knockdown induces GBM cell death by inhibiting GLUT3. RESULTS: Notably, GLUT3 was suppressed by increasing miR-3189, demonstrating that miR-3189-mediated GLUT3 inhibition shows an anti-tumorigenic effect and cell death by regulating glucose metabolism in HDAC2 knockdown GBM. CONCLUSIONS: Our findings will demonstrate the central role of HDAC2 in GBM tumorigenesis through the reprogramming of glucose metabolism by controlling miR-3189-inhibited GLUT3 expression, providing a potential new therapeutic strategy for GBM treatment.

Recent Trends in Prostate Biopsy Complication Rates and the Role of Aztreonam in Periprocedural Antimicrobial Prophylaxis-A Nationwide Population-Based Study from Korea.

An increase in the rate of complications after prostate biopsy (PB) due to increased antibiotic-resistant bacteria is a global issue. We report the safety of aztreonam as a prophylactic antibiotic in patients undergoing PB. We investigated the complication rates according to several antibiotic regimens, including aztreonam. We hypothesized that PB complications increased following a rise in antibiotic-resistant bacteria. We examined the annual rates of complications among patients in our hospital (clinical cohort) and the Korea Health Insurance Review and Assessment Service (HIRA) cohort. Data regarding complications, hospitalization, emergency room (ER) visits, and febrile urinary tract infections occurring within 2 weeks after PB were recorded. The rate of complications was significantly lower in patients who received oral quinolone and intravenous aztreonam than in those who received oral quinolone. The complication rates did not increase throughout the study period. Additionally, 1754 patients from the HIRA cohort were included. The rates of complications, hospitalizations, and ER visits did not increase among these patients. Oral quinolone combined with intravenous aztreonam reduced the rate of febrile complications compared to quinolone alone and was safe to use after PB. Therefore, we recommend intravenous aztreonam with oral quinolone as a prophylactic antibiotic regimen before PB.