Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells

Purpose The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. Method MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. Results The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. Conclusions LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future (AU)

Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells.

PURPOSE: The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. METHODS: MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. RESULTS: The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. CONCLUSIONS: LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future.

Correlation between kidney and peripheral nerve functions in Type 2 diabetes.

BACKGROUND: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes. AIM: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD). DESIGN: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center. METHOD: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study. RESULTS: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2. CONCLUSION: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

Phase transitions in a programmable quantum spin glass simulator.

Understanding magnetic phases in quantum mechanical systems is one of the essential goals in condensed matter physics, and the advent of prototype quantum simulation hardware has provided new tools for experimentally probing such systems. We report on the experimental realization of a quantum simulation of interacting Ising spins on three-dimensional cubic lattices up to dimensions 8 × 8 × 8 on a D-Wave processor (D-Wave Systems, Burnaby, Canada). The ability to control and read out the state of individual spins provides direct access to several order parameters, which we used to determine the lattice's magnetic phases as well as critical disorder and one of its universal exponents. By tuning the degree of disorder and effective transverse magnetic field, we observed phase transitions between a paramagnetic, an antiferromagnetic, and a spin-glass phase.

Real-world use of elbasvir-grazoprevir in patients with chronic hepatitis C: retrospective analyses from the TRIO network.

BACKGROUND: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. AIM: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States. METHODS: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12). RESULTS: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. CONCLUSION: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin.

Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma.

Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized. Patients and methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV. Results: Of the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%. Conclusions: Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world treatment-naïve, genotype 1 hepatitis C infected patients.

BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study.

Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.

Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network.

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.

The value of serial plasma nuclear and mitochondrial DNA levels in acute spontaneous intra-cerebral haemorrhage.

BACKGROUND: Increased plasma nuclear and mitochondrial DNA levels may be connected to disease severity following spontaneous intra-cerebral haemorrhage (ICH). This study tested the hypothesis that plasma nuclear and mitochondrial DNA levels are substantially increased in acute ICH and can predict treatment outcomes. METHODS: Serial plasma nuclear and mitochondrial DNA levels were examined in 60 consecutive patients admitted within 24 h after onset of spontaneous ICH and in 60 volunteer control subjects. Additional samples were obtained on days 4, 7, 10, and 14 after onset of ICH regardless of clinical deterioration. RESULTS: Only plasma nuclear DNA, not plasma mitochondrial DNA, levels in patients with spontaneous ICH significantly correlated with Glasgow Coma Scale (GCS) (r = -0.467, P = 0.001) and ICH volume (r = 0.515, P ≤ 0.001) on presentation. Plasma nuclear DNA levels increased significantly from day 1 to day 7 in patients with poor outcome. Higher plasma nuclear DNA levels (cut-off value >18.7 ng/ml) on presentation were associated with poor outcomes in spontaneous ICH patients. CONCLUSION: Plasma nuclear DNA levels reflect the severity of cerebral damage such that higher levels are associated with poorer outcome. Plasma nuclear DNA level can be considered a neuropathologic marker of acute spontaneous ICH.

Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine-melphalan conditioning for treatment of mature T-cell lymphomas.

Among non-Hodgkin's lymphoma subtypes, T-cell phenotype confers a poor clinical prognosis. For more aggressive histologies, patients frequently present with advanced disease that is inherently chemoresistant. For cutaneous histologies, disease progresses less rapidly, but is debilitating and often incurable in the long term. Here we report the retrospective analysis of data from 27 patients with mature T-cell lymphoma treated with salvage allogeneic haematopoietic cell transplantation at the City of Hope, Duarte, CA, USA, using a reduced-intensity fludarabine/melphalan conditioning regimen between the years 2001 and 2008. Eleven of the twenty-seven patients had cutaneous T-cell lymphoma (CTCL). The majority of patients had advanced disease at the time of transplant (17/27 or 63%). Median follow-up was 36 months. We observed a 2-year OS of 55%, a PFS of 47% and a cumulative incidence of relapse/progression and non-relapse mortality (NRM) of 30 and 22%, respectively. For CTCL, patients had a 2-year PFS of 45% and NRM of 27% compared with patients with other histologies, who had a PFS of 62% and NRM of 19%. Overall, our results suggest that meaningful long-term survival rates and disease control can be achieved with acceptable non-relapse mortality in patients with mature T-cell lymphomas, including CTCL using reduced-intensity conditioning with melphalan and fludarabine.

Assessing the chronic neuropsychologic sequelae of human immunodeficiency virus-negative cryptococcal meningitis by using diffusion tensor imaging.

BACKGROUND AND PURPOSE: The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms. MATERIALS AND METHODS: Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed. RESULTS: Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up. CONCLUSIONS: The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.

The experiences of non-operative treatment in patients with bacterial brain abscess.

Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.

The value of serial plasma nuclear and mitochondrial DNA levels in adult community-acquired bacterial meningitis.

BACKGROUND: Increased levels of plasma nuclear and mitochondrial DNA have been reported in critically ill patients. We tested the hypothesis that plasma nuclear and mitochondrial DNA are substantially increased in acute bacterial meningitis and decrease after antimicrobial therapy, and that plasma nuclear and mitochondrial DNA levels can predict treatment outcomes. METHODS: We examined serial plasma nuclear and mitochondrial DNA levels in 22 adult community-acquired bacterial meningitis (ACABM) patients. The plasma nuclear and mitochondrial DNA levels were also evaluated in 11 aseptic meningitis patients and 22 volunteer subjects during the study period. RESULTS: All of the both bacterial and aseptic meningitis groups had a higher plasma DNA levels on admission as compared with those of volunteer groups. Levels of plasma nuclear and mitochondrial DNA in ACABM cases were significantly increased initially and substantially decreased thereafter. Both plasma nuclear DNA and plasma mitochondrial DNA levels at presentation are significantly negative correlate with modified Barthel Index (average) (r = -0.639, P = 0.004 and r = -0.551, P = 0.018) at 3 months after discharge (average), respectively, in this study. Both higher plasma nuclear (cutoff value of >169 ng/ml) and mitochondrial DNA levels (cutoff value of >58.9 ng/ml) at presentation were associated with poor outcome in ACABM patients. CONCLUSION: Based on our results, the higher plasma DNA levels were associated with a poorer outcome. Therefore, we look forward to more prospective multicenter investigations specifically to confirm the predictive value of plasma DNA levels in outcome prediction.

Dynein motor contributes to stress granule dynamics in primary neurons.

Mobilization and translation of mRNAs, two important events believed to involve stress granules (SGs), in neurons are important for their survival and activities. However, the formation and disassembly of SGs in neurons remains unclear. By using an arsenite-induced neuronal stress model of rat primary spinal cord neuron cultures, we demonstrate the formation of SGs that contain common SG components and RNAs in both stressed neuronal cell bodies and their neurites. By employing small interfering RNA (siRNA) knockdown, we discovered that dynein motor subunit localizes in SG, and is important for SG assembly in neurons. Under stress, dynein motor subunit also facilitates translational repression and enhances the formation and integrity of SG in neurons. By blocking the energy source of dynein motor, both the formation and disassembly of SG are attenuated. These findings demonstrate, for the first time, that dynein motor complex plays a critical role in the dynamics of neuronal SGs, as well as translation of certain mRNAs.

Factors predictive of outcome in patients with de novo status epilepticus.

BACKGROUND: About 50% of status epilepticus (SE) patients have no previous history of epilepsy, but often have worse outcome. The aim of this study was to evaluate potential risk factors that are predictive of poor outcome in non-selected de novo status epilepticus patients. METHODS: Eighty-three adult status epilepticus patients without a pre-existing history of epilepsy that were admitted to hospital for treatment were enrolled in this 11-year retrospective study. The baseline prognostic variables were analyzed based on stepwise logistic regression analysis after a minimum of one-and-half years of follow-up. RESULTS: The overall fatality rate was 55.4% (46/83) during the study period. Poor outcome was associated with older age, presence of refractory status epilepticus, potential fatal etiologies, lower GCS score at presentation and level of consciousness on admission. The results of stepwise logistic regression demonstrated that age on presentation and potential fatal etiologies were independently associated with presence of poor outcome, and any increase in age by 1 year increases poor outcome by 7.5%. CONCLUSION: The outcome for those with de novo status epilepticus is poor and this poor outcome may be attributed to the older age at onset and the potential fatal underlying conditions such as infection and metabolic derangement.

Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Seizures are important neurologic complications of spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of the risk factors of seizures following aneurysmal SAH is needed to predict those who will require treatment. METHODS: A total of 137 adult patients were enrolled in this two-year retrospective study. Baseline prognostic variables were analyzed based on Cox's proportional hazards model after a minimum of one-year follow-up. RESULTS: Seizures occurred in 21 patients who had SAH, including acute symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137). None progressed to status epilepticus during hospitalization. After a minimum of one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients with seizures and 3.1 +/- 1.1 for those without. CONCLUSIONS: Higher mean World Federation of Neurological Societies grade on presentation was predictive of seizure, but seizure itself was not a significant prognostic predictor after a minimum of one-year follow-up. Regarding potential side effects of anti-epileptic drugs, anti-epileptic therapy should be carefully administered to patients with seizures after aneurysmal SAH.