A Case of Giant Cutaneous Lopez Type III Meningioma of the Scalp.

Meningiomas are the most common central nervous system (CNS) tumors. Extracranial meningiomas are rare, constituting 2% of all meningiomas. We describe a case of Lopez type III meningioma of the scalp in a 72-year-old gentleman who had a long-standing giant scalp mass and presented with recent mild left-sided limb weakness and numbness. Magnetic resonance imaging (MRI) of the skull demonstrated a right frontoparietal tumor extending through the skull into the scalp. Tumor excision revealed World Health Organization (WHO) grade 1 meningioma. Clinicians should correlate a cutaneous skull mass and new onset of neurological symptoms. Cutaneous meningioma is an important differential diagnosis.

Analysis of the population genetic structure using microsatellite markers in goat populations in Taiwan.

Due to the poor growth rate of the Taiwan black (TB) goat in Taiwan, many exotic breeds were brought into breeding schemes to improve TB goat. However, the excessive cross-breeding of alien species with TB goat has decreased its population numbers, genetic variation and biodiversity. Therefore, TB goat population considered an endemic species in Taiwan that needed to be conservation. The objective of the present study was to analyze the genetic structure and TB goat using genetic markers for genetic improvement and to sustain germplasm conservation and utilization. 15 microsatellite markers, divided into three sets, were used to analyze 690 goats sampled from 10 goat populations. The average number of alleles (Na) and effective alleles (Ne) was 11.87 ± 3.93 and 5.093 ± 1.768, respectively. The average expected heterozygosity (HE) and observed heterozygosity (HO) was 0.780 ± 0.084 and 0.602 ± 0.116, respectively. The average polymorphic information content (PIC) was 0.747 ± 0.103; FIS was 0.058 ± 0.075. All 15 microsatellite markers were highly polymorphic. The genetic distances between individuals were estimated to construct a phylogenetic tree. In present study, the 690 goat samples were divided into 8 clusters. The results indicated that these 15 microsatellite markers successfully clustered goat populations in Taiwan and could assist in the preservation of TB goats.

Impact of Comorbidities on Lung Cancer Screening Evaluation.

OBJECTIVES: We used data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine the impact of self-reported chronic obstructive pulmonary disease, coronary artery disease, stroke, and diabetes mellitus on diagnostic complications in lung cancer screening evaluation. METHODS: In our analysis, we included individuals from the usual care and intervention (annual chest x-ray) of the lung cancer screening trial with equal or greater than 55 years of age with a 20 pack-year smoking history who had undergone an invasive procedure. We performed multivariate logistic regression analysis to estimate the association of comorbidity on procedure complication. Our primary outcome was the incidence of major or moderate complications. RESULTS: Features associated with high-risk complication included older age (OR = 1.03 per year, P = .001), history of coronary artery disease (OR = 1.40, P = .03), history of diabetes mellitus (OR = 0.41, P < .001, current smoking status (OR = 1.46, P ≤ .001), surgical biopsy (OR = 7.39, P < .001), needle biopsy (OR = 1.94, P < .001), and other invasive procedure (OR = 1.58, P < .001). We did not find an associated with complication and history of stroke (OR = 0.84, P = .53) or chronic obstructive pulmonary disease (OR = 1.27, P = .06). CONCLUSION: Patient and procedure-level factors may alter the benefits of lung cancer screening. Data concerning individual risk factors and high-risk complications should therefore be incorporated into diagnostic algorithms to optimize clinical benefit and minimize harm. Further study and validation of the risk factors identified herein are warranted.

Dynamic image clustering from projected coordinates of deep similarity learning.

Commonly used clustering algorithms typically require user parameters such as the number of clusters to be divided. Density-based algorithms do not have such requirements but are not suitable for high dimensional data. Recent studies have merged the cluster assignment task with deep similarity learning. In this paper, we propose a novel framework to perform dynamic image clustering without prior knowledge of the cluster count. A deep learning model first learns data similarity from scratch, followed by the use of a coordinate learning model to project high dimensional data onto a two-dimensional space. A new clustering algorithm, raster clustering, is proposed to evaluate and classify the projected data. This mechanism can be applied in high dimensional data clustering like image data, and it allows the prediction of unseen data in a consistent way without the need for consolidating with training data.

An Adapted Hybrid Model for Hands-On Practice on Disaster and Military Medicine Education in Undergraduate Medical Students During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial impacts on all aspects of medical education. Modern health systems must prepare for a wide variety of catastrophic scenarios, including emerging infectious disease outbreaks and human and natural disasters. During the COVID-19 pandemic, while the use of traditional teaching methods has decreased, the use of online-based teaching methods has increased. COVID-19 itself and the accompanying infection control measures have restricted full-scale practice. Therefore, we developed an adapted hybrid model that retained adequate hands-on practice and educational equality, and we applied it with a group of undergraduate medical students participating in a mandatory disaster education course in a military medical school. Methods: The course covered the acquisition of skills used in emergency and trauma scenarios through designated interdisciplinary modules on disaster responses. Several asynchronous and synchronous online webinars were used in this one-credit mandatory disaster and military medicine education course. To allow opportunities for hands-on practice and ensure education equality, the students were divided into 15 groups, with 12 students in each group. The hands-on practice exercises were also recorded and disseminated to the students in the designated area for online learning. Results: A total of 164 3rd-year medical students participated in this mandatory disaster and military medicine course during the COVID-19 pandemic. The satisfaction survey response rate was 96.5%. The students were satisfied with the whole curriculum (3.8/5). Most of the free-text comments regarding the course represented a high level of appreciation. The students felt more confident in the knowledge and skills they gained in hands-on exercises than they did in the knowledge and skills they gained in online exercises. The students showed significant improvements in knowledge after the course. Conclusions: We demonstrated that this adapted hybrid arrangement provided an enhanced learning experience, but we also found that medical students were more confident in their knowledge and skills when they had real hands-on practice.

No difference in long-term functional outcomes or survivorship after total knee arthroplasty with or without computer navigation: a 17-year survivorship analysis.

BACKGROUND: The literature comparing the long-term outcomes and survivorship of computer navigation-assisted and conventional total knee replacement (TKR) is sparse. Moreover, of the available comparative studies with follow-up duration of more than 10 years, the results seem to be conflicting. The purpose of this long-term study was to compare the clinical and radiological outcomes, and implant survivorship, of TKR performed with and without computer navigation. METHODS: We retrospectively compared the results of 49 computer-navigated TKRs and 139 conventional TKRs. The mean age of the patients was 67.9 (range 52-81) years for the navigation group and 67.1 (range 50-80) years for the conventional TKR group. The mean duration of follow-up for the conventional and navigation TKR groups was 12.9 and 13.2 years, respectively. Clinical and radiographic follow-up examinations of the patients were performed at 2 weeks, 1 month, 3 months and 6 months post-operatively, and at 1-year intervals thereafter. RESULTS: There were no significant differences in the post-operative Knee Society knee and function score between the two groups. The mean overall deviation from neutral alignment and the radiological outliers were significantly higher in the conventional TKR group. The overall survival rates at 17 years were 92.9% for the navigation group and 95.6% for the conventional TKR group (p = 0.62). CONCLUSIONS: Navigated TKR resulted in fewer radiological outliers; however, this did not translate to better long-term functional outcomes or implant survival.

Radiotherapy-induced glioblastoma: distinct differences in overall survival, tumor location, pMGMT methylation and primary tumor epidemiology in Hong Kong chinese patients.

INTRODUCTION: Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. METHODS: This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy. Survival analysis was performed by Cox proportional hazards regression. RESULTS: A total of 590 adult patients were diagnosed with glioblastoma. 19 patients (3%) had RIGB. The mean age of patients upon diagnosis was 48 years ± 15. The mean latency duration from radiotherapy to RIGB was 14 years ± 8. The mean total dose was 58Gy ± 10. One-third of patients (37%, 7/19) had nasopharyngeal cancer and a fifth (21%, 4/19) had primary intracranial germinoma. Compared to a cohort of 146 de novo glioblastoma patients, RIGB patients had a shorter median OS of 4.8 months versus 19.2 months (p-value: <.001). Over a third of RIGBs involved the cerebellum (37%, 7/19) and was higher than the control group (4%, 6/146; p-value: <.001). A fifth of RIGBs (21%, 3/19) were pMGMT methylated which was significantly fewer than the control group (49%, 71/146; p-value: .01). For RIGB patients (32%, 6/19) treated with re-irradiation, the one-year survival rate was 67% and only 8% for those without such treatment (p-value: .007). CONCLUSION: The propensity for RIGBs to develop in the cerebellum and to be pMGMT unmethylated may contribute to their poorer prognosis. When possible re-irradiation may offer a survival benefit. Nasopharyngeal cancer and germinomas accounted for the majority of original malignancies reflecting their prevalence among Southern Chinese.

Rubinstein-Taybi syndrome in diverse populations.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations.

Pilot study of a longitudinal integrated disaster and military medicine education program for undergraduate medical students.

Disaster medicine education in medical curricula is scarce and frequently nonexistent. It is reasonable to initiate educational approaches for physicians in this field at the medical school level. An understanding of disaster medicine and the health care system during massive casualty incidents has been recommended as an integral part of the medical curriculum in the United States and Germany.The goal of the reformed curriculum was to develop a longitudinal integrated disaster and military medicine education program extending from the first year to the sixth year based on previously separated clinical and military medicine topics. Emergency medicine physicians, military emergency medical technicians, and Tactical Combat Casualty Care instructors formed an interprofessional faculty group and designed a learning curriculum.A total of 230 medical students participated in the revised disaster preparedness curriculum. Satisfaction survey response rates were high (201/230, 87.4%). Most of the free-text comments on the program were highly appreciative. The students considered the number of teaching hours for the whole program to be adequate. The students showed significant improvements in knowledge and judgment regarding disaster medicine after the program.We found that medical students were highly interested, were appreciative of, and actively participated in this longitudinal integrated disaster and military medicine education program, but gaps existed between the students' scores and the educators' expectations. The educators believed that the students needed more disaster preparedness knowledge and skills.

Hypoalbuminemia and obesity class II are reliable predictors of peri-prosthetic joint infection in patient undergoing elective total knee arthroplasty

Background@#Malnutrition is a common and modifiable risk factor for postoperative complications and adverse outcomes in orthopedics. The purpose of this study was to identify biomarkers of malnutrition in patients undergoing elective total knee arthroplasty (TKA) that are predictive of adverse in-hospital postoperative complications, to facilitate the identification of at-risk patients for nutritional optimization before surgery. @*Methods@#A total of 624 patients who underwent elective TKA between 2013 and 2017 were evaluated; potential biomarkers of preoperative malnutrition, including hypoalbuminemia (serum albumin < 3.5 g/dL), total lymphocyte count (TLC < 1500 cells/mm3), and body mass index (BMI), were assessed for any association with in-hospital postoperative complications. @*Results@#The prevalence of hypoalbuminemia, low TLC, overweight, obesity class I, and obesity class II were, respectively 2.72%, 33.4%, 14.8%, 44.5%, and 26.9%. There was a significant association between hypoalbuminemia and obesity class II (BMI ≥ 30.0 kg/m2) with rates of peri-prosthetic joint infection, and no significant association between such complications and low TLC, overweight, or obesity class I. Logistic regression analysis showed that patients with hypoalbuminemia or being in obesity class II with gouty arthritis were more likely to suffer from peri-prosthetic joint infection. @*Conclusions@#Hypoalbuminemia and obesity class II together is a reliable biomarker of preoperative malnutrition for predicting peri-prosthetic joint infection after elective TKA, whereas low TLC, overweight, and obesity class I were not significantly associated with an increased risk of such complications.

Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty

Background@#Total knee arthroplasty (TKA) is associated with significant perioperative blood loss and postoperative allogenic blood transfusion. Tranexamic acid (TXA) reversibly blocks lysine binding sites on plasminogen molecules and inhibits plasmin formation. Comparisons of the efficacy and safety of intra-articular and intravenous TXA in primary TKA have not previously been reported. @*Methods@#A prospective randomized trial was conducted in 150 patients who underwent TKA, and these patients were randomized into three groups. Patients in Group A were injected by intra-articular TXA according to body weight (20 mg/kg). Patients in Group B received a standard dose of intra-articular TXA (2000 mg), and those in Group C were infused with TXA according to body weight (20 mg/kg) before tourniquet deflation and again 3 h later. Baseline characteristics and data collected at blood transfusion were compared. Differences among four time points (baseline, day 0, day 2, and day 5) were carried out using ANOVA. @*Results@#The hemoglobin levels at postoperative day 5 were 10.6 g/dL for Group A, 10.6 g/dL for Group B, and 10.7 g/dL for Group C. The drain output was 399 ml for Group A, 314 ml for Group B, and 305 ml for Group C (p = 0.03). Group C had significantly less drain output than Group A after post hoc comparisons (p = 0.05), whereas no significant difference was observed between Group A and B (p = 0.09) or between Group B and C. @*Conclusion@#The weight-adjusted dose of TXA administered intravenously significantly reduced the drain output but not the total blood loss when compared with the weight-adjusted dose of TXA administered intra-articularly. No significant difference was observed in the other parameters among the three groups.Trial registrationThe Joint CUHK-NTEC CREC, CRE-2013.644-T. Registered 1 March 2014.

Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty

Background@#Total knee arthroplasty (TKA) is associated with significant perioperative blood loss and postoperative allogenic blood transfusion. Tranexamic acid (TXA) reversibly blocks lysine binding sites on plasminogen molecules and inhibits plasmin formation. Comparisons of the efficacy and safety of intra-articular and intravenous TXA in primary TKA have not previously been reported. @*Methods@#A prospective randomized trial was conducted in 150 patients who underwent TKA, and these patients were randomized into three groups. Patients in Group A were injected by intra-articular TXA according to body weight (20 mg/kg). Patients in Group B received a standard dose of intra-articular TXA (2000 mg), and those in Group C were infused with TXA according to body weight (20 mg/kg) before tourniquet deflation and again 3 h later. Baseline characteristics and data collected at blood transfusion were compared. Differences among four time points (baseline, day 0, day 2, and day 5) were carried out using ANOVA. @*Results@#The hemoglobin levels at postoperative day 5 were 10.6 g/dL for Group A, 10.6 g/dL for Group B, and 10.7 g/dL for Group C. The drain output was 399 ml for Group A, 314 ml for Group B, and 305 ml for Group C (p = 0.03). Group C had significantly less drain output than Group A after post hoc comparisons (p = 0.05), whereas no significant difference was observed between Group A and B (p = 0.09) or between Group B and C. @*Conclusion@#The weight-adjusted dose of TXA administered intravenously significantly reduced the drain output but not the total blood loss when compared with the weight-adjusted dose of TXA administered intra-articularly. No significant difference was observed in the other parameters among the three groups.Trial registrationThe Joint CUHK-NTEC CREC, CRE-2013.644-T. Registered 1 March 2014.

Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma.

BACKGROUND: Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC. METHODS: We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes. RESULTS: Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P < .001). Early AFP responders, compared with early AFP nonresponders, exhibited significantly longer overall survival (OS) (median, 28.0 vs 11.2 months, P = .048) and progression-free survival (PFS) (median, 15.2 vs 2.7 months, P = .002). After adjusting for other clinicopathological variables and treatments, early AFP response remained an independent predictor for longer OS (hazard ratio [HR] = 0.089, 95% confidence interval [CI] = 0.018-0.441; P = .003) and PFS (HR = 0.128, 95% CI = 0.041-0.399; P < .001). CONCLUSION: Early AFP response was associated with higher treatment efficacy of ICIs for advanced HCC. Additional validation studies are nonetheless warranted.

The importance of aspirin, catheterization accuracy, and catheter design in external ventricular drainage-related hemorrhage: a multicenter study of 1002 procedures.

BACKGROUND: External ventricular drainage (EVD) is the commonest neurosurgical procedure performed in daily neurosurgical practice, but relatively few studies have investigated the incidence and risk factors of its related hemorrhagic complications. METHODS: This was a multicenter retrospective review of consecutive EVD procedures. Patients 18 years or older who underwent EVD and had a routine postoperative computed tomography (CT) scan performed within 24 hours were included. EVD-related hemorrhage was defined as new intracranial hemorrhage immediately adjacent or within the ventricular catheter trajectory. The volume of hemorrhage and the position of the catheter tip were assessed. A review of patient-, disease-, and surgery-related factors including the ventricular catheter design utilized was conducted. The Bonferroni correction was applied to the alpha level of significance (0.05) for multivariable analysis. RESULTS: Nine hundred sixty-two patients underwent 1002 EVD performed by neurosurgeons in the operating theater. Sixteen percent (154) of patients were on aspirin before the procedure. Thirty-four percent (333) of patients had intracerebral hemorrhage, 25% (251) had aneurysmal subarachnoid hemorrhage and 16% (158) had traumatic brain injury. The mean duration from EVD to the first postoperative CT scan was 20 ± 4 h. EVD-related hematomas were detected after 81 procedures with a per-catheter risk of 8.1%. Mean hematoma volume was 1.2 ± 3.3 ml. Most were less than 1 ml (grade I, 79%, 64), 1 to 15 ml (grade II) in 20% (16) and a single clot larger than 15 ml (grade III, 1%) were detected. Clinically significant hemorrhage that resulted in catheter occlusion occurred in 1.7% (17) of procedures. Most catheters (62%, 625) were optimally placed, i.e., its tip being within the ipsilateral frontal horn or third ventricle. Three non-antibiotic-impregnated ventricular catheter designs were used with 55% (550) being the 2.2-mm Integra™ catheter, 14% (137) being the 2.8-mm Medtronic™ catheter, and 31% (315) being the 3.1-mm Codman™ catheter. Independent significant predictors for EVD-related hemorrhage were the preoperative prescription of aspirin (adjusted OR 1.94; 95% CI 1.10-3.44), catheter malposition (aOR 1.99; 95% CI 1.22-3.23), and use of the 2.8-mm Medtronic™ catheter (aOR 4.22; 95% CI 2.39-7.41). CONCLUSIONS: The per-catheter risk of hemorrhage was 8.1%, but the incidence of symptomatic hemorrhage was low. The only patient risk factor was aspirin intake. This is the first study to evaluate and establish an association between catheter malposition and catheter design with EVD-related hemorrhage.

Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay.

BACKGROUND: We report here clinical, cytogenetic and molecular data for a pair of monochorionic diamniotic twins with paternal isodisomy for chromosome 19. Both twins presented with dysmorphic features and global developmental delay. This represents, to our knowledge, the first individual human case of paternal uniparental disomy for chromosome 19 (UPD19). METHODS: Whole-exome sequencing, together with conventional karyotype and SNP array analysis were performed along with genome-wide DNA methylation array for delineation of the underlying molecular defects. RESULTS: Conventional karyotyping on amniocytes and lymphocytes showed normal karyotypes for both twins. Whole-exome sequencing did not identify any pathogenic sequence variants but >5000 homozygous exonic variants on chromosome 19, suggestive of UPD19. SNP arrays on blood and buccal DNA both showed paternal isodisomy for chromosome 19. Losses of imprinting for known imprinted genes on chromosome 19 were identified, including ZNF331, PEG3, ZIM2 and MIMT1. In addition, imprinting defects were also identified in genes located on other chromosomes, including GPR1-AS, JAKMP1 and NHP2L1. CONCLUSION: Imprinting defects are the most likely cause for the dysmorphism and developmental delay in this first report of monozygotic twins with UPD19. However, epigenotype-phenotype correlation will require identification of additional individuals with UPD19 and further molecular analysis.

Fibrillization of ß-Amyloid Peptides via Chemically Modulated Pathway.

The aggregation of ß-amyloid peptides is closely associated with Alzheimer's disease. We have used liposomes to modulate the early aggregation events of 40-residue ß-amyloid peptides. The spatial confinement provided by liposomes leads to the formation of nonfibrillar aggregates of ß-amyloid peptides. These on-pathway ß-sheet intermediates were used to seed the fibrillization of the monomer peptides. Solid-state NMR spectroscopy revealed that the resultant fibrils have a more uniform structure than those formed in liposome-free solution.

Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong.

AIM: The aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients. PATIENTS AND METHODS: A multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed. RESULTS: A total of 198 patients, with a mean age of 55 years (range: 18-88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8 months, and 11 months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8 months postoperatively (range: 1 day-75 months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21-4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49-6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32-8.40). CONCLUSIONS: Antiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy are at risk. We suggest, contrary to present practice, that primary seizure prophylaxis be given only during the perioperative period and resumed when they occur. We also recommend avoidance of aromatic AED due to their association with idiosyncratic adverse effects.

Bioconcentration, metabolism and neurotoxicity of the organophorous flame retardant 1,3-dichloro 2-propyl phosphate (TDCPP) to zebrafish.

Organophosphate flame retardants are ubiquitous environmental contaminants; however, knowledge is limited regarding their environmental health risks and toxicity. Here, we investigated the effects of acute and long-term exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) to the nervous system of zebrafish. Zebrafish embryos (2 h post-fertilization) were exposed to TDCPP (0-100 µg/L) for 6 months up until sexual maturation. Concentrations of TDCPP and its metabolic product (bis(1,3-dichloro-2-propyl) phosphate, BDCPP) were measured in the tissues of 5 day post-fertilization (dpf) larvae. There was no effect on locomotion, acetylcholinesterase activity, levels of the neurotransmitters dopamine and serotonin, and expression of mRNAs and proteins related to central nervous system development (e.g., myelin basic protein, α1-tubulin) in any exposure group. However, in adult fish, reductions of dopamine and serotonin levels were detected in the brains of females but not males. Downregulation of nervous system development genes was observed in both the male and female brain tissues. TDCPP concentrations were measured in adult fish tissues including the brain, and greater levels were detected in females. Our results showed that females are more sensitive to TDCPP stress than males in terms of TDCPP-induced neurotoxicity. We demonstrate that long-term exposure to lower concentrations of TDCPP in fish can lead to neurotoxicity.

High-dose simvastatin for aneurysmal subarachnoid hemorrhage: a multicenter, randomized, controlled, double-blind clinical trial protocol.

BACKGROUND: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage. However, no clinical data are available to answer whether a high-dose regimen is more effective than a normal-dose regimen, even though the biochemical actions and related neuroprotective mechanisms are thought to be dose related. OBJECTIVE: To determine whether 80 mg simvastatin daily (high dose) over 3 weeks initiated within 96 hours of the ictus will reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with 40 mg simvastatin daily (normal dose), leading to improvements in clinical outcomes and thus cost-effectiveness. METHODS: The study design is a randomized, controlled, double-blind clinical trial (www.ClinicalTrials.gov; identifier: NCT01077206). Two hundred forty patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers are being recruited over 3 years. The primary outcome measure is the presence of delayed ischemic deficits. Secondary outcome measures include modified Rankin Disability Score at 3 months and cost-effectiveness analysis. EXPECTED OUTCOMES: This will be the first study to clarify whether high-dose simvastatin is better than normal-dose simvastatin for patients with acute aneurysmal subarachnoid hemorrhage in terms of neurological outcomes and cost-effectiveness. DISCUSSION: In the present trial, we compare high-dose and normal-dose simvastatin; we know that another ongoing phase III multicenter trial (Simvastatin in Aneurysmal Subarachnoid Haemorrhage; http://www.stashtrial.com/home.html) is comparing normal-dose and no simvastatin. When the results are interpreted together, the research question of a possible beneficial effect of high-dose simvastatin in acute aneurysmal subarachnoid hemorrhage could be answered.

A harpin-induced ethylene-responsive factor regulates plant growth and responses to biotic and abiotic stresses.

Harpin protein induces disease resistance in diverse plant species. Transcriptome study of tomato (Solanum lycopersicum) genome indicated that harpin activated cellular events of transcription regulation, signaling transduction, stress response, membrane transporting, photosynthesis and cell wall biosynthesis. Among the harpin-induced genes, the expression of tomato ethylene-response factor 5 (designated as SlERF5) was induced to the highest level. The amino acid sequence of SlERF5 was closely related to that of CaEREBP-C4, NtERF4 and NsERF4. Overexpression of SlERF5 in Arabidopsis thaliana activated a large number of genes involved in signaling pathways of disease resistance, redox system, abiotic response and protein phosphorylation. Seedlings of transgenic plants exhibited hypersensitive response to exogenous ABA and increased tolerance to salt stress. In summary, the results of this study suggest that SlERF5 is a transcription activator for genes involved in the responses to ABA, biotic and abiotic stress. Thus, harpin may exert its effect on plant growth and defense response through activation of SlERF5 transcription factors.