Transcranial Direct Current Stimulation for Treatment of Refractory Childhood Focal Epilepsy

BackgroundCathodal transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for suppressing regional cortical excitability. We examine the safety and antiepileptic efficacy of cathodal tDCS in children with refractory focal epilepsy. Although a prior cathodal tDCS trial in adults with epilepsy revealed EEG improvement, neither the antiepileptic potential nor the safety and tolerability of tDCS has been tested in children.MethodThe study consisted of three phases: 1) a 4-week pre-treatment monitoring period with vital sign measures, EEG, seizure diary, and baseline quality of life (QOL) questionnaire; 2) a single treatment with 1 mA cathodal tDCS for 20 min with cathode positioned over the seizure focus and anode on the contralateral shoulder; 3) follow-ups immediately after stimulation, and at 24, 48 h, and 4 weeks after tDCS with continued seizure diary and epileptic discharge counts on EEG; the QOL questionnaire was also repeated 4 weeks after stimulation. Patients were randomized to receive either single session active or sham tDCS 1 mA, 20 min.ResultsThirty six children (6–15 years) with focal epilepsy were enrolled, 27 in active and 9 in sham group. All patients tolerated tDCS well. No serious adverse events occurred. Active tDCS treatment was associated with significant reductions in epileptic discharge frequency immediately and 24 and 48 h after tDCS. Four weeks after treatment, a small (clinically negligible but statistically significant) decrease in seizure frequency was also detected.ConclusionA single session of cathodal tDCS improves epileptic EEG abnormalities for 48 h and is well-tolerated in children.     

Fe3+/Nb5+ Co-doped rutile–TiO2 nanocrystalline powders prepared by a combustion process: preparation and characterization and their giant dielectric response

Fe³⁺/Nb⁵⁺ co-doped TiO₂ (FeNb-TO) nanocrystalline powders were prepared by a combustion process. A pure rutile–TiO₂ phase of powders and sintered ceramics with a dense microstructure was achieved. Both co-dopants were homogeneously dispersed in the ceramic microstructure. The presence of oxygen vacancies was confirmed by Raman and X-ray photoelectron spectroscopy techniques. The low-frequency dielectric permittivity enhanced as co-doping concentration increased. The thermally activated giant-dielectric relaxation of FeNb-TO ceramics was observed. Removing the outer-surface layer had a slight effect on the dielectric properties of FeNb-TO ceramics. Density functional theory (DFT) calculation showed that, in the energy preferable configuration, the 2Fe atoms are located near the oxygen vacancy, forming a triangle-shaped FeV_oTi defect complex. This defect cluster was far away from the diamond-shaped 2Nb2Ti defect complex. Thus, the electron-pinned defect-dipoles (EPDD) cannot be formed. The giant-dielectric relaxation process of the FeNb-TO ceramics might be attributed to the interfacial polarization associated with electron hopping between Ti³⁺/Ti⁴⁺ ions inside the grains, rather than due to the surface barrier layer capacitor (SBLC) or EPDD effect.

Fe³⁺/Nb⁵⁺ co-doped TiO₂ (FeNb-TO) nanocrystalline powders were prepared by a combustion process.     

Prevalence of depression and its correlations: a cross-sectional study in Thai cancer patients

Objectives: Depression is common in cancer patients. However, only limited evidence is available for Asianpopulations. The authors therefore examine the prevalence of depression in Thai patients with cancer. In addition,associated factors were determined. Methods: This cross-sectional study was conducted in cancer patientsadmitted to a university hospital during December 2006 - December 2007. The Patient Health Questionnaire(PHQ-9) was used to assess all cancer patients. Suicidal risk was assessed by using the Mini-InternationalNeuropsychiatric Interview (MINI) in the module of suicidal risk assessment. Results: Of 108 cancer patients,29.6 % were diagnosed with a depressive disorder (mild, 14.8 %; moderate, 5.6 %; severe, 9.3 %). However, only25.0 % of these were recognized as being depressed by the primary physician. According to the MINI., 28.1 % ofthese depressed cancer patients had a moderate to severe level of suicidal risk. In addition, the findings suggestthat increased risk of depression is significantly associated with increased pain score, lower number of cancertreatments (< 2 methods), increased educational duration (>13 years), increased age (> 50 years old) and beingfemale. Conclusions: The prevalence of depression is high in Thai cancer patients. However, depressive disorder inthose patients is frequently undiagnosed. It is associated with several factors including pain, a number of cancertreatments, education duration, age and sex. To improve quality of life, increase compliance with treatmentsand prevent of suicide, screening for depressive disorders in this patient group is strongly recommended.     

Prognostic factors in resectable cholangiocarcinoma patients: Carcinoembryonic antigen,lymph node,surgical margin and chemotherapy

AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation, tumor data, and receiving adjuvant chemotherapy were determined by uni- and multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3- year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.     

Characterization and in vitro evaluation of intestinal absorption of liposomes encapsulating zanamivir

Zanamivir is currently used for the treatment of H1N1 and H5N1 influenza viruses. Due to its highly hydrophilic property, zanamivir has poor oral bioavailability. Liposomal formulations are known to improve oral absorption of hydrophilic drugs. The present study investigates the effect of liposomes encapsulating zanamivir on the permeation of zanamivir across Caco-2 monolayers. Among the formulations studied, neutral liposomes composed of Phospholipon(?) 90 G and cholesterol at molar ratio of 7:3 gave the highest entrapment efficiency of zanamivir. The extrusion of liposomes loading zanamivir (LZV) resulted in the reduced-size liposomal zanamivir (RLZV), which had mean diameter at 283±42 nm and gave higher encapsulation efficiency of zanamivir at 34.69±6.37% compared to 28.32±5.25%. Transport studies across Caco-2 cell monolayers showed that the apparent permeation coefficients (P(app)) of LZV and RLZV were respectively 2.2- and 3.0-fold greater than that of zanamivir solution. The P(app) of RLZV was 1.4-fold higher than that of LZV. On the basis of these results, liposomes are able to improve permeability of zanamivir across the Caco-2 monolayers, thereby possibly enhancing oral bioavailability of zanamivir.     

Outcome of curative resection for perihilar cholangiocarcinoma in Northeast Thailand

AIM: To examine survival outcomes of perihilar cholangiocarcinoma (PCCA) resection including mortality, morbidity and prognostic factors.METHODS: Multivariate analyses were carried out based on the survival data of all patients with histologically confirmed PCCA who underwent curative resection at Srinagarind Hospital from January 2006 to December 2011.RESULTS: There were 29 (19%) cases of intrahepatic CCA that involved hilar and 124 (81%) with hilar bile-duct cancer. R0 resection was carried out on 66 (43.1%) patients of whom 50 (32.7%) also had lymph node metastasis. The other patients underwent R1 resection. The overall 5-year survival rate was 20.6% (95%CI: 13.8-28.4) and median survival time was 19.9 mo. Postoperative mortality was 2%, and 30% of patients had complications. Patients without lymph node metastasis were 60% less likely to die than those with metastasis. Achieving R0 led to a 58% reduction in the chance of mortality as compared to R1.CONCLUSION: To achieve a better survival outcome, focus should center on performing radical surgery and detection of patients with early stage cancer.     

Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy

Background  

Cholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. Timely diagnosis is very important because surgical resection (R0) remains the only hope for a cure. However, at present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. Previous studies have demonstrated that matrix metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in cholangiocarcinoma specimens.     

The effect of prenatal nicotine exposure on PDGFR-mediated anti-apoptotic mechanism in the caudal brainstem of developing rat

Maternal cigarette smoking is a major risk factor for sudden infant death syndrome (SIDS); however, the mechanism underlying this association is currently unknown. Prenatal nicotine exposure is accompanied by a decrease in the magnitude of hypoxic ventilatory depression, the component of hypoxic ventilatory response that activates the PDGF-β receptor (PDGFR) and its downstream anti-apoptotic cascade in the caudal brainstem (CB) of developing rats. In this study, we evaluated the effect of prenatal nicotine exposure on PDGFR activation and the subsequent activation of downstream anti-apoptotic processes through the Akt/BAD pathway. The 5-day timed-pregnant Sprague–Dawley rats underwent surgical implantation of an osmotic pump containing either normal saline (control) or a solution of nicotine tartrate. The CB was harvested from 5-day-old rat pups (n = 8–10 for each time point) in each group after exposure to normoxia or hypoxic challenges with 10% O₂ for 5, 15, 30, 60 or 120 min. Immunoprecipitation and immunoblots of CB lysates revealed phosphorylation of PDGFR, Akt and BAD-136 during hypoxia in control pups. Prenatal nicotine exposure was associated with attenuation of these responses at all time points. Analysis of an early apoptotic marker in the CB revealed that activation of cleaved caspase-3 occurred only at 120 min of hypoxic exposure in the control. Prenatal nicotine exposure accelerated this response, causing early activation at 30 and 60 min. We conclude that prenatal nicotine exposure attenuates the phosphorylation of PDGFR, Akt and Bad-136 during hypoxia in the CB of developing rats. This modulation of anti-apoptotic cascades accelerates activation of the early apoptotic marker. We speculate that prenatal nicotine exposure affects apoptosis in the CB of developing animals and may increase the vulnerability of neural cells in the respiratory control area, a process that may underlie the association between maternal smoking and SIDS.