Cognitive and behavioral effects of lamotrigine and carbamazepine monotherapy in patients with newly diagnosed or untreated partial epilepsy

AbstractPurposeIn this prospective study, we compared the long-term cognitive and behavioral effects of lamotrigine (LTG) and carbamazepine (CBZ) in patients with newly diagnosed or untreated partial epilepsy.MethodsThis was a multicenter, open-label, randomized study that compared monotherapy with LTG and CBZ in newly diagnosed or untreated patients with partial epilepsy. We employed an 8-week titration period and a 40-week maintenance period. Neuropsychological tests, Symptom Check List-90, and QOLIE-31 were assessed at baseline, 16 weeks, and 48 weeks after drug treatment. A group-by-time interaction was the primary outcome measure and was analyzed by use of the linear mixed model.ResultsA total of 110 patients were eligible and 73 completed the 48-week study (LTG, n=39; CBZ, n=34). Among the cognitive tests, significant group-by-time interaction was identified only in phonemic fluency of Controlled Oral Word Association Task (p=0.0032) and Stroop Color–Word Interference (p=0.0283), with a significant better performance for LTG group. All other neuropsychological tests included did not show significant group-by-time interactions. Among the subscales of Symptom Check List-90, significant group-by-time interactions were identified in Obsessive-Compulsive (p=0.0005), Paranoid Ideation (p=0.0454), Global Severity Index (p=0.0194), and Positive Symptom Total (p=0.0197), with a significant improvement for CBZ group. QOLIE-31 did not show significant group-by-time interactions.ConclusionOur data suggest that epilepsy patients on LTG have better performance on phonemic fluency and the task of Stroop Color–Word Interference than do patients on CBZ, whereas patients on CBZ had more favorable behavioral effects on two subscales and two global scores of Symptom Check List-90 than did patients on LTG

Molecular mechanism underlying the apoptotic modulation by ethanol extract of Pseudolarix kaempferi in mucoepidermoid carcinoma of the salivary glands

Background Pseudolarix kaempferi is a traditional Chinese natural product that possesses the potential cytotoxic effects against cancer. However, the precise molecular mechanism underlying its cytotoxic effects has not yet been completely elucidated. Here, we clarify the mechanism via which the ethanol extract of P. kaempferi (EEPK) leads to cytotoxicity mediated by apoptosis in mucoepidermoid carcinoma (MEC) originating from the salivary glands. Methods We investigated the mechanism underlying the anticancer efficacy of EEPK in human MEC in vitro by assessing mitochondrial dysfunction, mRNA levels, and morphological changes in apoptotic cell nuclei as well as by using a cytotoxicity assay, flow cytometric analysis, and western blotting. Results EEPK inhibited the growth of two human MEC cells and stimulated the induction of caspase-mediated apoptosis that was accompanied by mitochondrial membrane depolarization. Compared with the vehicle control groups, EEPK decreased myeloid cell leukemia-1 (Mcl-1) expression in both cells whereas it significantly decreased B cell lymphoma-2 (Bcl-2) expression in MC3 cells only. The EEPK-induced altered Mcl-1 expression was caused by translational inhibition and proteasomal degradation. Additionally, EEPK significantly increased p-Bcl-2 (Ser70) expression regardless of its total forms by facilitating the activation of the c-Jun N-terminal kinase (JNK) signaling pathway, which exhibited cell context dependency. Nevertheless, JNK activation following EEPK treatment was, at least in part, required for the proapoptotic efficacy of EEPK in both cells. Conclusions This study revealed that EEPK-induced alterations of Mcl-1 inhibition and JNK/Bcl-2 phosphorylation cause apoptosis and provided basic preclinical data for future clinical trials regarding therapy for patients with MEC. Graphic abstrac

Collagen Immobilization on Ultra-thin Nanofiber Membrane to Promote In Vitro Endothelial Monolayer Formation

The endothelialization on the poly (epsilon-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (epsilon-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (epsilon-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (epsilon-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (epsilon-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (epsilon-caprolactone) nanofibers and the maintenance of the original structure of poly (epsilon-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (epsilon-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (epsilon-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (epsilon-caprolactone) nanofiber scaffolds.11Ysciescopu

Pancreatic Endocrine Tumors: A Report on a Patient Treated with Sorafenib

A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine tumor and multiple hepatic metastases. Despite optimal treatment with interferon alpha, a somatostatin analog, local therapy with high-intensity focused ultrasound ablation for multiple hepatic metastases, and multiple lines of chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine monotherapy, the tumor progressed. As few chemotherapeutic options were available for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen. Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy. Serial computed tomography scans showed that the primary and metastatic tumors were stable. Thirteen months after beginning targeted therapy, and up to the time of this report, the patient is well without disease progression. We suggest that sorafenib is effective against pancreatic endocrine tumors

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract

Effect of emergency medical service use on time interval from symptom onset to hospital admission for definitive care among patients with intracerebral hemorrhage: a multicenter observational study

Objective This study evaluated whether emergency medical service (EMS) use was associated with early arrival and admission for definitive care among intracerebral hemorrhage (ICH) patients. Methods Patients with ICH were enrolled from 29 hospitals between November 2007 and December 2012, excluding those patients with subarachnoid hemorrhage, traumatic ICH, and missing information. The patients were divided into four groups based on visit type to the definitive hospital emergency department (ED): direct visit by EMS (EMS-direct), direct visit without EMS (non-EMS-direct), transferred from a primary hospital by EMS (EMS-transfer), and transferred from a primary hospital without EMS (non-EMS-transfer). The outcomes were the proportions of participants within early (<1 hr) definitive hospital ED arrival from symptom onset (pS2ED) and those within early (<4 hr) admission from symptom onset (pS2AD). Adjusted odds ratios were calculated to determine the association between EMS use and outcomes with and without inter-hospital transfer. Results A total of 6,564 patients were enrolled. The adjusted odds ratios (95% confidence intervals) for pS2ED were 22.95 (17.73–29.72), 1.11 (0.67–1.84), and 7.95 (6.04–10.46) and those for pS2AD were 5.56 (4.70–6.56), 0.96 (0.71–1.30), and 2.35 (1.94–2.84) for the EMS-direct, EMS-transfer, and non-EMS-direct groups compared with the non-EMS-transfer group, respectively. Through the interaction model, EMS use was significantly associated with early arrival and admission among direct visiting patients but not with transferred patients. Conclusion EMS use was significantly associated with shorter time intervals from symptom onset to arrival and admission at a definitive care hospital. However, the effect disappeared when patients were transferred from a primary hospital

Antitumor effect of TW-37, a BH3 mimetic in human oral cancer

TW-37 is a small molecule B cell lymphoma-2 (Bcl-2) homology 3 mimetic with potential anticancer activities. However, the in vivo anti-cancer effect of TW-37 in human oral cancer has not been properly studied yet. Here, we attempted to confirm antitumor activity of TW37 in human oral cancer. TW-37 significantly inhibited cell proliferation and increased the number of dead cells in MC-3 and HSC-3 human oral cancer cell lines. TW-37 enhanced apoptosis of both cell lines evidenced by annexin V/propidium iodide double staining, sub-G1 population analysis and the detection of cleaved poly (ADP-ribose) polymerase and caspase-3. In addition, TW-37 markedly downregulated the expression of Bcl-2 protein, while not affecting Bcl-xL or myeloid cell leukemia-1. In vivo, TW-37 inhibited tumor growth in a nude mice xenograft model without any significant liver and kidney toxicities. Collectively, these data reveal that TW-37 may be a promising small molecule to inhibit human oral cancer.This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science ICT & Future Planning [2019R1A2C1085896]

Comparison of trauma systems in Asian countries: a cross-sectional study.

OBJECTIVE: This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). METHODS: Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. RESULTS: Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). CONCLUSION: Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies