Reliability-based design optimization for a vertical-type breakwater with multiple limit-state equations under Korean marine environments varying from sea to sea.

In this study, as part of basic research aimed at enhancing the accuracy of load and resistance coefficients to ensure their suitability for practical design and promoting the application of underutilized reliability-based design in Korea, the author conducts optimal design based on the reliability analysis of a vertical-type breakwater in the seas off of Haeundae, Yeosu, Mokpo, Gunsan, and Incheon-representative ports in Korea. In doing so, the author utilized the double-loop approach, which simultaneously addresses a reliability problem nested within an optimization process, employing the Polak-He optimization algorithm. To mitigate the substantial numerical effort required by the double-loop approach based on the Polak-He optimization algorithm, which necessitates the gradients of both cost and constraint functions, the subset simulation method was employed. In this process, the author deliberately refrained from using design waves of a specific return period and linear probabilistic models such as the Gaussian distribution, especially concerning wave and lift forces, often viewed as barriers to the widespread application of reliability-based design in Korea. Instead, the author focused on characterizing the uncertainties associated with the wave force, lift force, and overturning moment-variables that significantly impact the integrity of vertical-type breakwaters-by developing probabilistic models for these random variables directly from long-term in situ wave data. These models capture the varied characteristics of the Korean marine environment from sea to sea. In this way, the need for additional assumptions concerning the interrelationship between significant wave and maximum wave heights, along with the wave period, can be eliminated. Following Occam's razor principle, which suggests that explanations constructed with the smallest possible set of assumptions are superior, the reliability-based design optimization of a vertical-type breakwater presented in this study demonstrates promise in terms of simplicity and practicality. The limit state of the vertical-type breakwater was defined to encompass sliding, overturning, and collapse failures, and the strong interrelations between the wave force, lift force, and overturning moment were described using the Nataf joint distribution. As anticipated, simulation results show that solely considering sliding failure, as in the current reliability-based design platform in Korea, leads to an underestimated failure probability. Furthermore, ensuring a consistent failure probability for vertical-type breakwaters using design waves with a specific return period, as in past studies, is not feasible. In contrast, this study demonstrated that breakwaters optimally designed to meet the reliability index requirement of ß = 3.5-4 consistently maintain a target failure probability in all sea areas.

Pulsed Radiofrequency Neuromodulation for Post-Stroke Shoulder Pain in Patients with Hemorrhagic Stroke.

Objective: Post-stroke shoulder pain (PSSP) is a common complication that limits the range of motion (ROM) of the shoulder, the patient's rehabilitation and in turn, affects the patients' quality of life (QOL). Several treatment modalities such as sling, positioning, strapping, functional electrical stimulation (FES), and nerve block have been suggested in literatures, however none of the treatments had long-term effects for PSSP. In this study, the authors evaluated clinical efficacy of pulsed radiofrequency (PRF) neuromodulation on the suprascapular nerve for PSSP, and suggested it as a potential treatment with long-term effect. Methods: This retrospective case series was conducted at a single center, a private practice institution. From 2013 to 2021, 13 patients with PSSP underwent PRF neuromodulation of the suprascapular nerve. The primary outcome measure was the visual analog scale (VAS) score. The secondary outcome measurements included the shoulder ROM, disability assessment scale (DAS), modified Ashworth scale (mAS), modified Rankin scale (mRS), and EuroQol-5 dimension-3L questionnaire (EQ-5D-3L) scores. These parameters were evaluated before PRF modulation, immediately after PRF modulation, and every three months until the final follow-up visit. Results: Six men and seven women were enrolled, and all patients were followed-up for a minimum of 12 months. The mean VAS score was 7.07 points before PRF neuromodulation and 2.38 points immediately post-procedure. Shoulder ROM for abduction and flexion, DAS for pain, mRS, and EQ-5D-3L demonstrated marked improvement. No complications were reported. Conclusion: PRF neuromodulation of the suprascapular nerve is an effective modality in patients with PSSP, and has long-term effect of pain relief, improvement of QOL.

Tat-RAN attenuates brain ischemic injury in hippocampal HT-22 cells and ischemia animal model.

Oxidative stress plays a key role in the pathogenesis of neuronal injury, including ischemia. Ras-related nuclear protein (RAN), a member of the Ras superfamily, involves in a variety of biological roles, such as cell division, proliferation, and signal transduction. Although RAN reveals antioxidant effect, its precise neuroprotective mechanisms are still unclear. Therefore, we investigated the effects of RAN on HT-22 cell which were exposed to H2O2-induced oxidative stress and ischemia animal model by using the cell permeable Tat-RAN fusion protein. We showed that Tat-RAN transduced into HT-22 cells, and markedly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation under oxidative stress. This fusion protein also controlled cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis (Caspase-3, p53, Bax and Bcl-2). In the cerebral forebrain ischemia animal model, Tat-RAN significantly inhibited both neuronal cell death, and astrocyte and microglia activation. These results indicate that RAN significantly protects against hippocampal neuronal cell death, suggesting Tat-RAN will help to develop the therapies for neuronal brain diseases including ischemic injury.

Protective Effects of PEP-1-GSTA2 Protein in Hippocampal Neuronal Cell Damage Induced by Oxidative Stress.

Glutathione S-transferase alpha 2 (GSTA2), a member of the glutathione S-transferase family, plays the role of cellular detoxification against oxidative stress. Although oxidative stress is related to ischemic injury, the role of GSTA2 against ischemia has not been elucidated. Thus, we studied whether GSTA2 prevents ischemic injury by using the PEP-1-GSTA2 protein which has a cell-permeable protein transduction domain. We revealed that cell-permeable PEP-1-GSTA2 transduced into HT-22 cells and markedly protected cell death via the inhibition of reactive oxygen species (ROS) production and DNA damage induced by oxidative stress. Additionally, transduced PEP-1-GSTA2 promoted mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB) activation. Furthermore, PEP-1-GSTA2 regulated Bcl-2, Bax, cleaved Caspase-3 and -9 expression protein levels. An in vivo ischemic animal model, PEP-1-GSTA2, markedly prevented the loss of hippocampal neurons and reduced the activation of microglia and astrocytes. These findings indicate that PEP-1-GSTA2 suppresses hippocampal cell death by regulating the MAPK and apoptotic signaling pathways. Therefore, we suggest that PEP-1-GSTA2 will help to develop the therapies for oxidative-stress-induced ischemic injury.

Tat-Thioredoxin-like protein 1 attenuates ischemic brain injury by regulation of MAPKs and apoptosis signaling.

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H2O2-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury. [BMB Reports 2023; 56(4): 234-239].

Updated Genome-Wide Association Study of Intracranial Aneurysms by Genotype Correction and Imputation in Koreans.

OBJECTIVE: Compared to European, Japanese, and Chinese populations, genetic studies on intracranial aneurysms (IAs) in Koreans are lacking. We conducted an updated genome-wide association study (GWAS) to more accurately identify candidate variations predicting IA by genotype correction and imputation than in the first Korean GWAS. METHODS: We performed a high-throughput imputation of single-nucleotide polymorphisms (SNPs) and genotype missing values for 250 IA and 296 controls. Out of a total of 7,333,746 sites with an imputation R2 score of ≥0.5, 6,105,212 SNPs were analyzed. A high-throughput GWAS was performed after adjusting for clinical variables and 4 principal component analysis values. RESULTS: A total of 39 SNPs reached a significant genome-wide threshold (P < 5 × 10-8). After pruning by pairwise linkage disequilibrium (r2 < 0.8), 11 SNPs were consistently associated with IA. Six tagging SNPs, including rs3120004, rs1851347, rs1522095, rs7779989, rs12935558, rs3826442, and rs2440154, showed strong linkage disequilibrium tower tagging haplotype structures. Among them, rs3120004 tagged a large and strong haplotype structure between LOC440704 and RGS18 genes in 1q31.2 (odds ratio, 2.34; 95% confidence interval, 1.74-3.14; P = 1.4 × 10-8). The rs2440154 (SLC47A1, 17p11.2) SNP increased the risk of IA most significantly (odds ratio, 2.90; 95% confidence interval, 2.07-4.08; P = 8.2 × 10-10). The region encompassing rs3826442 (MYH13, 17p13.1) showed a high recombination rate of approximately 70 cM/Mbp. CONCLUSIONS: Our updated GWAS using high-throughput imputation approaches can be an informative milestone in understanding IA formation via susceptibility loci in this stage before large-scale genome-wide association meta-analysis.

Association of Haptoglobin Phenotype With Neurological and Cognitive Outcomes in Patients With Subarachnoid Hemorrhage.

Background: To assess the association of haptoglobin (Hp) phenotype with neurological and cognitive outcomes in a large cohort of patients with subarachnoid hemorrhage (SAH). Methods: This prospective multicenter study enrolled patients with aneurysmal SAH between May 2015 and September 2020. The Hp phenotype was confirmed via Western blots. The relative intensities of α1 in individuals carrying Hp2-1 were compared with those of albumin. Multivariable logistic and Cox proportional-hazard regression analyses were used to identify the risk factors for 6-month and long-term outcomes, respectively. Results: A total of 336 patients including the phenotypes Hp1-1 (n = 31, 9.2%), Hp2-1 (n = 126, 37.5%), and Hp2-2 (n = 179, 53.3%) were analyzed. The Hp phenotype was closely associated with 6-month outcome (p = 0.001) and cognitive function (p = 0.013), and long-term outcome (p = 0.002) and cognitive function (p < 0.001). Compared with Hp1-1 as the reference value, Hp2-2 significantly increased the risk of 6-month poor outcome (OR: 7.868, 95% CI: 1.764-35.093) and cognitive impairment (OR: 8.056, 95% CI: 1.020-63.616), and long-term poor outcome (HR: 5.802, 95% CI: 1.795-18.754) and cognitive impairment (HR: 7.434, 95% CI: 2.264-24.409). Long-term cognitive impairment based on the Hp phenotype was significantly higher in patients under 65 years of age (p < 0.001) and female gender (p < 0.001). A lower relative α1/albumin intensity (OR: 0.010, 95% CI: 0.000-0.522) was associated with poor outcome at 6 months but not cognitive impairment in patients with SAH expressing Hp2-1. Conclusion: Hp2-2 increased the risk of poor neurological outcomes and cognitive impairment compared with Hp1-1. For Hp2-1, higher relative α1 intensities were related to 6-month favorable outcomes.

Impact of renal impairment on short-term outcomes following endovascular thrombectomy for acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: The impact of renal impairment on the outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. AIMS: We registered a protocol in September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. Renal impairment was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at three months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage. SUMMARY OF REVIEW: Eleven studies involving 3453 patients were included. For the unadjusted outcomes, renal impairment was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39-0.62) and higher mortality (OR, 2.55; 95% CI, 2.03-3.21). Renal impairment was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63-1.00) and symptomatic intracerebral hemorrhage (OR, 1.41; 95% CI, 0.95-2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45-0.77), mortality (OR, 2.23, 95% CI, 1.45-3.43), and symptomatic intracerebral hemorrhage (OR, 1.34; 95% CI, 0.85-2.10). CONCLUSIONS: We presented the first systematic review to demonstrate that renal impairment is associated with fewer functional independence and higher mortality. Future endovascular thrombectomy studies should publish complete renal estimated glomerular filtration rate data to facilitate prognostic studies and permit estimated glomerular filtration rate to be analyzed in a continuous variable.Systematic Review Registration: PROSPERO CRD42020191309.

Multiple Impact Damage in GLARE Laminates: Experiments and Simulations.

Experiments and finite element simulations for multiple impact were performed on GLARE 5-2/1 and aluminum 2024-T3. Experiments were conducted on aluminum 2024-T3 and GLARE 5-2/1 at diverse impact energies to produce BVID (barely visible impact damage) and CVID (clearly visible impact damage). The finite element model was developed for multiple impact analysis using ABAQUS software and was confirmed by comparing the finite element analysis outcomes with experimental results. The two- and three-dimensional failure criteria model was applied to predict multiple impact behavior such as load-time history, maximum deflection-impact energy history, and damage progression. In addition, a user subroutine VUMAT was created to represent a three-dimensional progressive failure and was linked with ABAQUS. FEM results showed good agreement with experimental data.

Transduced Tat-PRAS40 prevents dopaminergic neuronal cell death through ROS inhibition and interaction with 14-3-3σ protein.

Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. However, the roles of PRAS40 in dopaminergic neuronal cell death have not yet been examined. Here, we examined the roles of Tat-PRAS40 in MPP+- and MPTP-induced dopaminergic neuronal cell death. Our results showed that Tat-PRAS40 effectively transduced into SH-SY5Y cells and inhibited DNA damage, ROS generation, and apoptotic signaling in MPP+-induced SH-SY5Y cells. Further, these protective mechanisms of Tat-PRAS40 protein display through phosphorylation of Tat-PRAS40, Akt and direct interaction with 14-3-3σ protein, but not via the mTOR-dependent signaling pathway. In a Parkinson's disease animal model, Tat-PRAS40 transduced into dopaminergic neurons in mouse brain and significantly protected against dopaminergic cell death by phosphorylation of Tat-PRAS40, Akt and interaction with 14-3-3σ protein. In this study, we demonstrated for the first time that Tat-PRAS40 directly protects against dopaminergic neuronal cell death. These results indicate that Tat-PRAS40 may provide a useful therapeutic agent against oxidative stress-induced dopaminergic neuronal cell death, which causes diseases such as PD.

Removal of malformation in cerebral proliferative angiopathy: illustrative case.

BACKGROUND: Cerebral proliferative angiopathy (CPA) is a rare vascular disorder distinct from arteriovenous malformation. Because of the disorder's rarity, there is still a controversy on the most promising treatment method for CPA. However, several meta-analysis articles suggest indirect vascularization such as encephalo-duro-arterio-synangiosis as an effective way of treating symptoms that are medically uncontrolled. OBSERVATIONS: The authors describe a case of an 11-year-old boy with this disease, who had epilepsy that was intractable despite conservative management. The patient recovered from his symptoms after the vascular malformation was surgically removed. This is the first reported case of surgical removal in CPA. LESSONS: Although further investigation on the best treatment for CPA is needed, the authors believe surgical intervention may also be an effective treatment modality when a patient presents with persisting symptoms.

Clinical Efficacy of Pulsed Radiofrequency Treatment Targeting the Mid-cervical Medial Branches for Intractable Cervicogenic Headache.

OBJECTIVE: Cervicogenic headache has been known to originate from the convergence of the upper 3 cervical and trigeminal afferents. The administration of conservative treatments, interventional procedures, and more recently, pulsed radiofrequency, has been used to relieve cervicogenic headache. In this study, the authors evaluated the clinical efficacy and safety of pulsed radiofrequency targeting the mid-cervical medial branches. MATERIALS AND METHODS: From September 2012 until December 2017, 395 patients were diagnosed with cervicogenic headache based on the third edition of the International Classification of Headache Disorders. The authors treated them conservatively at first, and those patients with nonresolution of pain were treated with mid-cervical medial branches block applied from C3 to C5 twice. Subsequently, if any patient continued to experience persistent pain, the authors classified them as having intractable cervicogenic headache and performed pulsed radiofrequency treatment targeting the mid-cervical medial branches from C3 to C5 bilaterally. The authors analyzed their demographics and used a Visual Analogue Scale to assess their pain for 12 months. RESULTS: Fifty-seven patients were enrolled in this study. The mean age was 49.8 years, and the mean duration of symptoms was 47.7 months. The mean Visual Analogue Scale score was 6.21 before pulsed radiofrequency treatment, and it improved to 1.54 immediately after the procedure without the symptoms recurring for a minimum of 12 months. There were no severe complications, such as vascular or nerve injuries. CONCLUSIONS: In patients with intractable cervicogenic headache, pulsed radiofrequency treatment targeting the mid-cervical medial branches resulted in a satisfactory, long-lasting outcome without serious complications.

A Prospective Observational Study of Return to Work after Single Level Lumbar Discectomy.

OBJECTIVE: Lumbar disc herniation (LDH) is a common disease, and lumbar discectomy (LD) is a common neurosurgical procedure. However, there is little previous data on return to work (RTW) after LD. This study investigated the period until the RTW after LD prospectively. Clinically, the pain state at the time of RTW also checked. RTW failure rate 6 months after surgery also investigated. METHODS: Patients with daily/regular jobs undergoing LD between September 2014 and December 2018 were enrolled. Pain was assessed by the Oswestri Disability Index (ODI) and the Numeric Rate Scale (NRS). Employment type was divided into self-employed, regular and contracted. Monthly telephone interviews were conducted to check RTW status and self-estimated work capability after surgery. RESULTS: Sixty-seven patients enrolled in this study. Three patients failed to RTW, and three others resigned within 6 months after surgery. The preoperative NRS and ODI were 7.2±1.2 and 22.1±7.9, respectively. The average time to RTW was 5.1±6.0 weeks. At RTW, NRS was 1.5±1.8 and ODI was 6.3±3.9. Amongst patients that successfully returned to work were 16 self-employed workers, 42 regular employees, and three contracted workers. The time to RTW of self-employed, regular, and contracted workers were 5.9±8.8, 4.2±4.3 and 13.3±2.3 weeks, respectively (p=0.011). Thirty-six of the patients that returned to work self-reported a 22.8±15.6% reduction in work capability at 6 months. CONCLUSION: RTW may vary depending on the employment status. In this study, we found that while employment type may affect the length to RTW, most patients were able to RTW and >40% of patients reported no loss of work capabilities 6 months postoperatively, hopefully alleviating some patient hesitation towards LD.

Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury.

It is well known that oxidative stress participates in neuronal cell death caused production of reactive oxygen species (ROS). The increased ROS is a major contributor to the development of ischemic injury. Indoleamine 2,3-dioxygenase 1 (IDO-1) is involved in the kynurenine pathway in tryptophan metabolism and plays a role as an anti-oxidant. However, whether IDO-1 would inhibit hippocampal cell death is poorly known. Therefore, we explored the effects of cell permeable Tat-IDO-1 protein against oxidative stress-induced HT-22 cells and in a cerebral ischemia/reperfusion injury model. Transduced Tat-IDO-1 reduced cell death, ROS production, and DNA fragmentation and inhibited mitogen-activated protein kinases (MAPKs) activation in H2O2 exposed HT-22 cells. In the cerebral ischemia/ reperfusion injury model, Tat-IDO-1 transduced into the brain and passing by means of the blood-brain barrier (BBB) significantly prevented hippocampal neuronal cell death. These results suggest that Tat-IDO-1 may present an alternative strategy to improve from the ischemic injury. [BMB Reports 2020; 53(11): 582-587].

Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling.

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H2O2-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.

Seizure incidence of angiogram-negative subarachnoid hemorrhage: An updated meta-analysis.

BACKGROUND: To provide updated information on seizure events and patterns in patients with angiogram-negative subarachnoid hemorrhage based on the initial hemorrhage patterns: perimesencephalic subarachnoid hemorrhage (PMH) vs non-PMH. METHODS: A review of online database literature from January 1990 to November 2017 was systematically performed. In case of heterogeneity <50%, a fixed effect model was used. Publication bias was determined using Begg funnel plot and the trim-and-fill method. RESULTS: A total of 9 studies with 645 patients were included for final analysis after excluding one study without any seizure within either cohort. PMH patients had lower seizure rates (odds ratio, 0.393; 95% CI, 0.158-0.978) compared with non-PMH patients. The funnel plot showed a relatively asymmetric pattern, suggesting possible publication bias. After correction of the forest plot, the adjusted odds ratio was 0.362 (95% CI, 0.148-0.886), indicating significant relationships between PMH and lower incidence of seizure. CONCLUSION: PMH is associated with lower seizure risk than non-PMH. However, possible publication bias could be a concern to the interpretation. Additional meta-analyses based on individual patient data from prospective large-scale studies are necessary.

Association of Endothelin Receptor Type A with Intracranial Aneurysm in 20,609 East Asians: An Updated Meta-Analysis.

INTRODUCTION: Genome-wide association studies have reported an association between the EDNRA gene and intracranial aneurysm (IA) in European and Japanese populations; however, there is no study on this polymorphism in other Asian populations. Therefore, we performed an extensive large-scale meta-analysis for association of the rs6841581 variant of EDNRA with IA susceptibility in East Asian population. METHODS: We conducted a systemic review via electronic search for papers published between January 2002 and February 2019. We used fixed and random effect models and applied the inverse variance method. The statistical power of the result was estimated in the genome-wide significant threshold under an additive inheritance model. RESULTS: Our meta-analysis included 5873 patients with IA and 14,736 non-IA controls from 6 independent populations: 4 Japanese, 1 Chinese, and 1 Korean. The risk (major) G allele of rs6841581 showed the highest significant association with the increased risk of IA under the fixed effect model in the East-Asian population (odds ratio = 1.244, 95% confidence interval: 1.174-1.318, P = 1.36E-13). The rs6841581 variant showed sufficient statistical power (80.3%) in this meta-analysis under the additive model. In subsequent analysis, the frequencies of the risk G allele showed similar pattern in all of the Japanese, Chinese, and Korean populations (69%, 80%, and 78%, respectively). In the in silico functional analysis, none of the functional variants was correlated with rs6841581. CONCLUSIONS: The genetic variant of EDNRA, rs6841581, was significantly associated with increased risk of IA. Our findings indicate that it could be used as an IA-predicting variant in East Asian populations.

Retrospective Chronologic Computed Tomography Analysis of Bone Flap Fusion and Resorption After Craniotomy and Autologous Cryopreserved Cranioplasty.

BACKGROUND: In open brain surgery, fixation of the bone flap is the final procedure. The bone flaps then fuse naturally. The objective of this study was to investigate the chronological process of bone fusion after craniotomy and autologous cranioplasty. METHODS: Retrospective data were collected from patients who underwent craniotomy or cranioplasty after August 2004 and had at least 1 computed tomography (CT) scan at 3 months postsurgery. The patients were divided into a craniotomy group and a cranioplasty group. Head CT scans were analyzed to evaluate bone fusion and resorption. RESULTS: Records from 978 patients who underwent craniotomy or cranioplasty between September 2004 and November 2015 were reviewed; 369 patients were eligible for the final analysis (craniotomy, n = 276; cranioplasty, n = 93). The mean cryopreservation period for the bone flap in the cranioplasty group was 49.3 days. The mean patient age was 51.4 ± 18.1 years in the craniotomy group and 51.6 ± 17.1 years in the cranioplasty group. Head CT scans showed bone fusion rates of 76.6% in the craniotomy group and 53.3% in the cranioplasty group at 6 months postsurgery (P = 0.015) and 78.6% and 78.1%, respectively, at 1 year postsurgery (P = 0.951). There was also a significant difference in the bone flap resorption rate between the 2 groups. CONCLUSIONS: Bone flap fusion rates after craniotomy and cranioplasty were significantly different before 12 months, but not significantly different thereafter. Bone resorption occurred more frequently in the cranioplasty group over time.

Correlation Between Altered DNA Methylation of Intergenic Regions of ITPR3 and Development of Delayed Cerebral Ischemia in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is related to the major causes of morbidity and mortality in patients following subarachnoid hemorrhage (SAH); however, little is known about the role of epigenetics in the pathogenesis of DCI. We investigated the specific DNA methylation profile that may affect the expression of inositol 1-,4-,5-trisphosphate receptor (ITPR3) responsible for cerebral vasospasm following SAH. METHODS: We prospectively studied patients with SAH between March 2015 and October 2018. The degree of methylation in the distal intergenic region (IGR) located on ITPR3 and gene expression were measured using methylation-specific polymerase chain reaction (MSP) and quantitative real-time polymerase chain reaction (qPCR). To investigate the regulatory mechanims of DNA hypermethylation, we further analyzed the mRNA expression of DNA methyltransferase (DNMT1) and ten-eleven translocation enzymes (TET1, TET2, and TET3). RESULTS: A total of 42 patients were included in our analysis. Patients with SAH and DCI had significantly higher levels of methylation intensity of distal IGR upstream of ITPR3 than those without DCI (median, 0.941 [interquartile range (IQR), 0.857-0.984] versus (0.670 [IQR, 0.543-0.761]; P < 0.001). In addition, patients with DCI showed decreased mRNA expression of ITPR3 compared with patients without DCI (median, 0.039 [IQR, 0.030-0.045] vs. 0.047 [IQR, 0.038-0.064]; P = 0.0328). Patients with DCI had higher DNMT1 expression (P < 0.001) and lower TET1 expression (P = 0.040) than those without DCI; however, differences in TET2 and TET3 levels between the 2 groups were not statistically significant. CONCLUSIONS: Hypermethylation of the distal IGR located upstream of ITPR3 is related to greater DCI development in patients with SAH. Further studies of the precise mechanisms of methylation degree and DCI development using in vitro and in vivo models are needed.

Rapid Healing and Remodeling Process of Pediatric Seat-Belt Fracture without Surgical Treatment.

Pediatric seat-belt fracture is a rare condition, and its management has not been well defined. The authors report a case of pediatric Chance fracture that was managed conservatively and that demonstrated rapid bone healing. A 7-year-old boy presented with back pain after a motor vehicle accident. Plain lumbar spine radiography, three-dimensional computed tomography (CT), and magnetic resonance imaging revealed a seat-belt fracture type C (classified by Rumball and Jarvis), and the patient's condition was managed conservatively. The patient started to ambulate with a brace 2 weeks after the injury. Spine CT performed 100 days after the injury revealed a remodeled fracture, and dynamic radiography did not show any evidence of instability or kyphotic deformity. We suggest that if there are no neurological deficits or severe deformities, then a pediatric seat-belt fracture should be managed conservatively, because the bone healing process is far more rapid in children than it is in adults and because of possible growth problems after surgery.