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Purpose: Intravenous thrombolysis has emerged as an effective approach to improve the long-term survival and functional status of patients with ischemic stroke. The aim of this study was to assess the impact of a national stroke project on the door-to-needle-time (DNT). Patients and Methods: The patients were divided into pre-construction and construction periods. Construction Measures were performed during the construction period. The DNT and onset-to-needle time (ONT) were compared in two period groups. Results: After participating in the National Stroke Center Project and effective measurements, the thrombolysis treatment metrics were improved significantly. The DNT (IQR) was shortened from 65.0 (54.5,85.0) minutes in the Pre-Construction period to 40.0 (33.0,53.0) minutes in the Construction period (p < 0.001). Similarly, the ONT was reduced from 157.0 (IQR) (115.0,184.0) minutes to 116.0 (87.8,170.0) minutes (p = 0.035). Conclusion: The DNT time and ONT time can be shortened by National Stroke Center Construction projects. More suitable hospitals should be encouraged to participate as the National Stroke Center.

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PURPOSE: This study evaluated the effectiveness of a multiple-intervention program (MIP) on the life satisfaction, social support, and depressive tendencies of older adults. DESIGN: A cross-sectional, pretest-posttest design involving a questionnaire survey was adopted. METHODS: Thirty-seven older adults were recruited from 2 daycare centers for an 8-week MIP comprising 60-min sessions conducted once a week. The questionnaire comprised the Short Portable Mental Status Questionnaire, Geriatric Depression Short Form-15 (GDS-SF15), Life Satisfaction Scale (LSS), and Inventory of Social Support Scale (ISSB). FINDINGS: The participants' average GDS-SF15 score decreased considerably (by 35.3%), their average ISSB score increased from 61.9% to 80.9%, and their average LSS score increased from 48% to 64%. CONCLUSIONS: The outcomes for depressive tendencies, social support, and life satisfaction were measured before and after the intervention, and the participants successfully engaged in the MIP throughout its duration and exhibited improvement. The MIP can serve as a basis for planning group activities for older adults. CLINICAL EVIDENCE: The MIP benefits older adults at daycare centers. Incorporating multiple activities into daily care can help increase the diversity, uniqueness, and innovativeness of a daycare center.

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Healthcare disparities in genomic medicine are well described. Despite some improvements, we continue to see fewer individuals of African American, Asian, and Hispanic ancestry undergo genetic counseling and testing compared to those of European ancestry. It is well established that variant of uncertain significance (VUS) rates are higher among non-European ancestral groups undergoing multi-gene hereditary cancer panel testing. However, pathogenic variant (PV) yields, and genomic data in general, are often reported in aggregate and derived from cohorts largely comprised of individuals of European ancestry. We performed a retrospective review of clinical and ancestral data for individuals undergoing multi-gene hereditary cancer panel testing to determine ancestry-specific PV and VUS rates. An ancestry other than European was reported in 29,042/104,851 (27.7%) of individuals. Compared to Europeans (9.4%), individuals of Middle Eastern ancestry were more likely to test positive for one or more pathogenic variants (12.1%, p = .0025), while African Americans were less likely (7.9%, p < .0001). Asian and Middle Eastern individuals were most likely (34.8% and 33.2%, respectively) to receive a report with an overall classification of VUS, while individuals of Ashkenazi Jewish and European ancestry were least likely (17.1% and 20.4%, respectively). These data suggest that in addition to higher VUS rates, there may be ancestry-specific PV yields. Providing aggregate data derived from cohorts saturated with European individuals does not adequately reflect genetic testing outcomes in minority groups, and interrogation of ancestry-specific data is a step toward a more personalized risk assessment.

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OBJECTIVES: Although diffusion tensor imaging (DTI) is widely studied to assess the motor outcome after ischaemic stroke, there is paucity of data regarding outcomes of intracerebral haemorrhage (ICH). The aim of this study was to determine the DTI data from different locations along the corticospinal tract (CST) and association to motor outcome. METHODS: We prospectively recruited patients with deep ICH admitted to our hospital from November 2010 to July 2012.Diffusion tensor imaging was performed within 14  days after the onset of ICH. Fractional anisotropy (FA) was measured along the CST at corona radiata, perihaematomal oedema, cerebral peduncle and pons. Corticospinal tract integrity was classified into three types by diffusion tensor tractography (DTT): type A with preserved CST, type B with partially interrupted CST and type C with completely interrupted CST. Motor outcome was assessed by Motricity index (MI) at admission, after 1 and 3  months. RESULTS: Forty-eight patients were enrolled with a mean age of 62  years. The median time interval from onset of ICH to DTI study was 7  days. The patients in type C had significantly worse MI at admission (P < 0.001), after 1  month (P < 0.001) and after 3  months (P < 0.001) as compared to those with type A and type B. Lower rFA at the corona radiata was significantly correlated with poorer motor outcome at admission, after 1  month and after 3  months. DISCUSSION: Clinical motor outcome of ICH within 2  weeks can be identified with a statistically significant decrease in rFA at the corona radiata.

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Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis.

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BACKGROUND/PURPOSE: In patients with traumatic brain injury, the degree of brain midline shift is related to prognosis. In this study, we evaluated the impact of the presence of a preoperative brain midline shift on the Glasgow Coma Scale (GCS) scores and muscle power (MP) improvement after cranioplasty. METHODS: In this 6-year retrospective cohort study, we compared cranioplasty patients from Taiwan with and without a preoperative brain midline shift. We assigned the patients to the following two groups: the midline shift group and the nonmidline shift group. The GCS score and MP contralateral to the lesion site were recorded and analyzed both prior to and 1 year after the operation. RESULTS: We enrolled 56 cranioplasty patients (35 patients with a midline shift and 21 without a midline shift) and analyzed their complete clinical characteristics. There were significant improvements in the GCS (p = 0.0078), arm MP (p = 0.0056), and leg MP (p = 0.0006) scores after cranioplasty. There was also a significant improvement in the GCS score in the brain midline shift group (0.4 ± 0.149 in the brain midline shift group vs. 0.05 ± 0.48 in the nonmidline shift group, p = 0.03). CONCLUSION: For patients who underwent craniectomy, an improvement in neurological function 1 year after cranioplasty was observed. The patients with brain midline shift showed more improvement in consciousness after cranioplasty than those without a brain midline shift. The presence of a preoperative brain midline shift may be an isolated determinant for the prediction of the outcome after cranioplasty.

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A 23-year-old male presented with a parasellar lesion which was suspected as disseminated intracranial germ cell tumour. The diagnosis of germinoma was made using immunohistochemistry from percutaneous trans-foramen ovale biopsy. This report describes the role of neuronavigation-guided biopsy through the foramen ovale for lesions in the parasellar region.

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BACKGROUND: Symptomatic thoracic compression fracture is one of the most common causes of back pain in elderly. Although vertebroplasty is widely utilized in patients when conservative treatment fails, we introduced an alternative percutaneous technique for the treatment of thoracic compression pain. METHODS: This in a retrospective study. The analysis was performed on 28 consecutive patients who underwent undergoing percutaneous dorsal root ganglion lysis with phenol for the treatment of pain associated with thoracic compression fracture. An acceptable treatment outcome was operationally defined as a pain intensity numerical rating scale (NRS) score of 3 or lower or EQ-5D index of 0.672 or higher. The primary outcome was pain relief and acceptable treatment outcome at 1 day, 1 week, 1 month, and 1 year. RESULTS: Of the 28 cases treated with our procedures, the change in mean NRS score between baseline and one day was -2.5 (95 % CI -1.6 ~ -3.4, p < 0.001), between baseline and one week was -4.7 (-4.1 to -5.3, p < 0.001), between baseline and one month was -5.8 (-5.2 to -6.5, p < 0.001), and between baseline and one year was -6.3 (-5.6 to -7.1, p < 0.001). An acceptable treatment outcome was 14 % one day after the procedure, 46 % at one week, 72 % at one month, and 84 % at one year. Complication rate was 3.6 %. CONCLUSIONS: For thoracic compression fracture patients, percutaneous dorsal root ganglion lysis with phenol is an effective, and safe alternative treatment method worth considering. Pain relief is fast and persists for one year.

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STUDY DESIGN:: A retrospective analysis of feasibility of intraoperative computed tomography (iCT) navigation for pedicle screw insertion of the thoraco-lumbar spine OBJECTIVES:: This study assessed the feasibility of an iCT navigation system by evaluating the screw insertion time, screw revision time, and learning curve of the iCT surgical team in patients who underwent thoraco-lumbar pedicle screw surgery using this navigation system. SUMMARY OF BACKGROUND DATA:: The iCT navigation system has been reported to improve the accuracy and safety of pedicle screw insertion. However, the assessment of the feasibility of spinal instrumentation guided by iCT navigation system is limited. METHODS:: From the time iCT navigation system was set-up to a period covering 16 months, consecutive patients who underwent thoracic or lumbar spinal pedicle screw surgery were enrolled. The screw insertion and screw revision times were estimated using the system's automatic time recording between the intra-operative CT scans. The insertion time per screw of the first 50 patients not requiring screw revision was also analyzed to evaluate the learning curve of the iCT surgical team. RESULTS:: There were 178 patients with a total of 932 pedicle screws. The cortical breach rate was 3.2% and the screw revision rate was 1.4%. The insertion time per screw was 10.2±6.3▒min and the screw revision time was 13.8±9.9▒min. The learning curve of the iCT surgical team for pedicle screw insertion guided by this navigation system was not steep and experience from less than 10 patients was adequate to provide familiarity with this system. CONCLUSION:: The iCT navigation system is clinically feasible for thoraco-lumbar pedicle screw surgery. It provides high-level safety and accuracy, as well as ease of screw revision when required.

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Ellipticine and its analogues were reported as topoisomerase II inhibitors and promising antitumor agents. In this work, we showed that the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G(1) phase cells after ellipticine treatment appeared at the expense of those that accumulated first at S- and G(2)/M phases during the early stage of treatment. We showed that the progression leading to cell death was impaired by wortmannin, which reverted apoptosis by retaining cells at S- and G(2)/M transition states. The characteristic apoptosis marker p53 activation after treatment appeared first followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared upon co-treatment with wortmannin and the apoptotic phenotype reversed. Furthermore, ellipticine regulated endogenous survival signaling by up-regulating phosphorylated Akt that returned to its basal level later. Furthermore, ellipticine induced nucleus translocalization of p53 and Akt and recruitment of autophagosomes. The autophagic-related cell death was interfered by wortmannin and the suppressed growth reverted. The Akt-related cell death also occurred in p53-deficient cells with stable expression of exogenous p53. The work showed that ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy and apoptotic death as a result of Akt-modulation. Being a topoisomerase II inhibitor, ellipticine proved a regulator in autophagy-related cell death through corporation of p53 and Akt.

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A naturally occurring beta-hairpin peptide (PDB ID 1UAO) was used as a model to study the backbone oxidation of a protein with ab initio calculation at the B3LYB/6-31G(d) without any constraints. The (alpha)C--H bond dissociation energy of three different glycyl radicals located at different sites on the beta-hairpin peptide was calculated to evaluate the site specificity of backbone oxidation. The molecular and electronic structures of these glycyl radicals were analyzed to rationalize this site specificity. The overall molecular structure of the alpha-H abstracted beta-hairpin peptide remained almost unchanged with the exception of the local conformation of the attacked residue. However, the (alpha)C--H bond strength varied dramatically among these different sites.

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Most trigeminal neuralgia is attributable to vascular compression of the root entry zone of the trigeminal nerve at the pons. Only about 5-10% of trigeminal neuralgia cases are caused by direct compression by ipsilateral cerebellopontine angle tumors. Trigeminal neuralgia caused by contralateral posterior fossa tumors are extremely rare. Cases in which neuralgia is caused by a contralateral supratentorial tumor have been seldom reported. This report describes a case of large meningioma in the left occipital region. The patient's right facial pain subsided gradually after tumor excision. This neuralgia is likely due to a displaced adjacent vessel that developed following brainstem distortion by the tumor.

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Stroke is a common cause of death and severe disability among adults in developed countries. Cigarette smoking adversely affects human health in many ways and is considered to be a risk factor for a stroke. However, the mechanism that determines the relative importance of neurotrophins in this process remains unclear. To study the effect of chronic cigarette smoking on ischemic stroke, in situ hybridization and immunohistochemistry were employed to detect the mRNA and protein expression of neurotrophin-3 (NT-3), respectively, which is thought to play a critical role in protection against neuronal death in brain ischemia. Rats, with or without chronic cigarette smoking, were subjected to 20 min of transient forebrain ischemia. Distribution and quantification of mRNA and protein of NT-3 in the whole hippocampus and the cell death in the hippocampal CA1-CA3 regions were determined in these rats. Experimental results show that chronic cigarette smoking produces a significantly delay and persistent down-regulation of ischemia-induced NT-3 mRNA and protein changes at 6-24h post-ischemia, and seemingly increases neuron death 7 days after reperfusion. These experimental results indicate that by influencing NT-3 expression, directly or indirectly, chronic cigarette smoking has a potentially harmful effect when acute brain ischemia attacks.

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Nerve growth factor (NGF) is well-established as a trophic factor that plays a crucial role in neuroregeneration and plasticity after brain insults. Dexamethasone (DEX), a powerful glucocorticoid steroid, has long been used in the clinical management of neurological disorders. We examined the relationship between NGF and DEX after an ischemic insult to the brain. In situ hybridization was used to measure NGF mRNA expression in the rat hippocampus after 20 min of transient forebrain ischemia. Immunostaining for NGF protein was performed using the avidin-biotin peroxidase method. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was also used to study the astrocyte reaction in the hippocampal CA1 area. Ischemic brain from rats not treated with DEX had a 2 and 3 fold increase in NGF mRNA compared to sham-operated rats at 4 and 6 h after ischemia, respectively. The NGF mRNA expression returned to basal levels 12 h to 7 days post-ischemia. Treatment with DEX potentiated the ischemia-induced increase of NGF mRNA to 4 times that of sham-operated rats at 6 h following reperfusion and NGF protein expression was similarly elevated. Additionally, the number of GFAP positive astrocytes in the CA1 region in the ischemic rats was markedly increased. These data suggest that DEX may play a role in modulating NGF mRNA expression in the hippocampal neuronal response to brain ischemia.

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The cellular events in traumatic brain injury (TBI) are complicated, and the factors mediating neurotrophins to protect and repair the injured brain cells are only beginning to be identified. This study examined the effect of dexamethasone (DEX) on neurotrophin-3 (NT-3) expression following TBI. Levels of NT-3 mRNA and protein in rat hippocampus were measured using in situ hybridization and immunohistochemistry, respectively. After TBI, the NT-3 mRNA expression was down-regulated during the first 24 h. DEX reversed the post-traumatic reduction of NT-3 mRNA expression at 2, 4, 6, and 12 h in the hippocampus, and also decreased the cell death in hippocampal hilum and supraventricular cerebral cortex after 7 days. The NT-3 protein levels generally corresponded to the mRNA levels in the hippocampal region. DEX enhanced the NT-3 expression after TBI, indicating that post-traumatic neuroprotection in the hippocampus is at least partially mediated by NT-3 and thus can be modulated by DEX treatment.

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