Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients

AbstractIntroductionThe cognitive and behavioral effect of deep brain stimulation (DBS) administered to the deep cerebral nuclei for epilepsy treatment is unknown. We investigated the cognitive outcomes at least 12 months after DBS to the bilateral anterior thalamic nucleus (ATN) for controlling intractable epilepsy.MethodsNine patients with intractable epilepsy who were not candidates for resective surgery, but who were treated by bilateral ATN DBS underwent cognitive and behavioral assessments before implantation and more than 1 year after DBS surgery. Postoperative cognitive assessments were carried out under a continuous stimulation mode.ResultsThe mean seizure-reduction rate of these patients after ATN DBS was 57.9% (35.6–90.4%). Cognitive testing showed favorable results for verbal fluency tasks (letter and category, p<0.05), and a significant improvement in delayed verbal memory was observed (p=0.017). However, we did not observe any significant changes in general abilities (IQ, MMSE), information processing (digit forward and backward, Trail A, and Digit Symbol), or executive function (Trail B and WCST). Interestingly, we did not observe any significant cognitive decline approximately 1 year (mean, 15.9 months) after ATN DBS surgery.ConclusionsWe showed that ATN DBS not only resulted in promising clinical effects but was also associated with improvements in both verbal recall and oral information processing, which may be related to the bilateral activation of the fronto-limbic circuit following DBS surgery. Further controlled, long-term studies with larger populations are warranted for elucidating the clinical effects of ATN DBS

Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer

AbstractBACKGROUND: We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers (BTCs). Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR), KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid–locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs) were analyzed according to the mutational status. Sixty-four patients (48.1%) were available for mutational analysis in the chemotherapy alone group and 61 (45.1%) in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116) harbored an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harbored a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) harbored a PIK3CA mutation (10 patients, exon 9 and 2 patients, exon 20). The addition of erlotinib to GEMOX in patients with KRAS wild-type disease (n = 109) resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P = .024). In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to RR as compared with GEMOX alone (P = .04). CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs

Deletion of the α subunit of the heterotrimeric Go protein impairs cerebellar cortical development in mice

Go is a member of the pertussis toxin-sensitive Gi/o family. Despite its abundance in the central nervous system, the precise role of Go remains largely unknown compared to other G proteins. In the present study, we explored the functions of Go in the developing cerebellar cortex by deleting its gene, Gnao. We performed a histological analysis with cerebellar sections of adult mice by cresyl violet- and immunostaining. Global deletion of Gnao induced cerebellar hypoplasia, reduced arborization of Purkinje cell dendrites, and atrophied Purkinje cell dendritic spines and the terminal boutons of climbing fibers from the inferior olivary nucleus. These results indicate that Go-mediated signaling pathway regulates maturation of presynaptic parallel fibers from granule cells and climbing fibers during the cerebellar cortical development.Fil: Cha, Hye Lim. Ajou University, School Of Medicine; Corea del SurFil: Choi, Jung Mi. Ajou University, School Of Medicine; Corea del SurFil: Oh, Huy Hyen. Ajou University, School Of Medicine; Corea del SurFil: Bashyal, Narayan. Ajou University, School Of Medicine; Corea del SurFil: Kim, Sung-Soo. Ajou University, School Of Medicine; Corea del SurFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Suh Kim, Haeyoung. Ajou University, School Of Medicine; Corea del Su

Association Between Serum Uric Acid Level and Metabolic Syndrome

OBJECTIVES: Serum uric acid levels have been reported to be associated with a variety of cardiovascular conditions. However, the direct association between uric acid levels and metabolic syndrome remains controversial. Thus, we evaluated the association of serum uric acid levels and metabolic syndrome in a community-based cohort study in Korea. METHODS: We performed cross-sectional analysis of baseline data of 889 males and 1491 females (aged 38 to 87) who participated in baseline examinations of the Korean Genome and Epidemiology Study: Kanghwa study. Blood samples were collected after at least an 8 hour fast. Uric acid quartiles were defined as follows: <4.8, 4.8-<5.6, 5.6-<6.5, ≥6.5 mg/dL in males; and <3.8, 3.8-<4.3, 4.3-<5.1, ≥5.1 mg/dL in females. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III Criteria with adjusted waist circumference cutoffs (90 cm for males; 80 cm for females). The association between serum uric acid quartiles and metabolic syndrome was assessed using multivariate logistic regression. RESULTS: The odds ratio for having metabolic syndrome in the highest versus lowest quartiles of serum uric acid levels was 2.67 (95% confidence interval [CI], 1.60 to 4.46) in males and 2.14 (95% CI, 1.50 to 3.05) in females after adjusting for age, smoking, alcohol intake, body mass index, total cholesterol, HbA1c, albumin, γ-glutamyltransferase, blood urea nitrogen, and log C-reactive protein. The number of metabolic abnormalities also increased gradually with increasing serum uric acid levels (adjusted p for trend < 0.001 in both sexes). CONCLUSIONS: Higher serum uric acid levels are positively associated with the presence of metabolic syndrome in Korean males and females.ope

Airborne Measurements of High Pollutant Concentration Events in the Free Troposphere over the West Coast of South Korea between 1997 and 2011

Aircrafts enable the direct measurement of chemical components in the free troposphere (FT). This study employed airborne measurements to examine the occurrences of high concentrations of SO2 and NOx in the FT over the coastal region west of the Seoul metropolitan area, South Korea. The data from a long-term (1997-2011) airborne measurement campaign were used to determine the meteorological conditions favorable for carrying these pollutants into the Seoul area. The back trajectory analyses of 21 instances of high FT pollutant concentration events showed ascending patterns from the major pollutant sources, mainly the industrial complexes in eastern China, in 9 instances and passing patterns in 12 instances. In the ascending instances, developing low-pressure systems over the source regions provide favorable conditions to uplift air pollutants from the surface into the FT. In the passing instances, an anomalous low-pressure system near the surface prevented airflows from descending into the boundary layer and upper-level anticyclonic systems helped to keep the ascending airflows in the FT. This study proposes the basic mechanisms for predicting air quality in the Seoul area, considering that air pollutants in the FT often entrain into the boundary layer to increase local concentrationsopen0

Cell-free synthesis of functional phospholipase A1 from Serratia sp.

Additional file 1: Figure S1 Gas chromatography analysis of sesame oil incubated with cell-free synthesized PLA1