Real-Life Efficacy and Tolerability of Lacosamide in Pediatric Patients Aged 4 Years or Older with Drug-Resistant Epilepsy

Purpose The aim of this study was to evaluate the efficacy and safety of adjunctive lacosamide therapy in pediatric patients aged ≥4 years with drug-resistant epilepsy (DRE). Methods Medical records of children aged 4 to 19 years treated with lacosamide as adjunctive therapy for DRE were retrospectively reviewed. The patients were divided into two groups according to their age at the start of lacosamide treatment: group A (aged 4–15 years) and group B (aged 16–19 years). Changes in seizure frequency from baseline, adverse events, and the retention rate were evaluated at each follow-up visit. Results Sixty-two patients (33 males and 29 females) with a mean age of 11.4 years (range, 4 to 19) were included. The mean duration of follow-up was 20.1±12.9 months. The mean maintenance dose of lacosamide was 6.7±4.8 mg/kg/day. Forty-two patients (67.7%) were responders (≥50% reduction in seizures) with 19.4% (12/62) achieving freedom from seizures. The response rate did not differ significantly between groups A and B (67.6% vs. 68.0%, P=0.795) and was not affected by the concomitant use of sodium channel blockers. Significant independent factors associated with a good response to lacosamide treatment were a shorter duration of epilepsy (P=0.035) and fewer concomitant anti-seizure medications (P=0.002). Mild transient adverse events were observed in 20 patients (32.3%). Conclusion Lacosamide adjunctive therapy was efficacious and tolerated in children aged ≥4 years with DRE. Early use of lacosamide may be helpful for a good response to drug-resistant seizures

Genetic associations of in vivo pathology influence Alzheimers disease susceptibility

Introduction Although the heritability of sporadic Alzheimers disease (AD) is estimated to be 60–80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques. Methods Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimers disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups. Results We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features. Conclusions This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.The study was supported by grants from the National Research Foundation of Korea (2014M3C7A1046049 and 2018M3C9A5064708 for Choi M and 2014M3C7A1046042 for Lee DY) and grants from the Ministry of Health and Welfare of Korea (HI18C0630 for Mook-Jung IH and Lee DY, and HI19C0149 for Lee DY)

Effect of Oxide Supports on the Activity of Pd Based Catalysts for Furfural Hydrogenation

We investigated the effect of oxide supports on the hydrogenation of furfural over Pd catalysts on various supports (Al2O3, SiO2, TiO2, CeO2, and ZrO2). Pd catalysts (5 wt%) prepared by chemical reduction on various supports. The dispersion and uniformity of Pd were affected by the properties of the support and by the nucleation and growth of Pd. The conversion of furfural was enhanced by greater Pd dispersion. The selectivity for cyclopentanone and tetrahydrofurfuryl alcohol was affected by physicochemical properties of Pd catalyst and reaction parameters. High Pd dispersion and high acidity of the catalyst led to greater C=C hydrogenation, thereby, generating more tetrahydrofurfuryl alcohol. The Pd/TiO2 catalyst showed the highest cyclopentanone yield than other catalysts. The Pd/TiO2 catalyst exhibited the &gt;99% furfural conversion, 55.6% cyclopentanone selectivity, and 55.5% cyclopentanone yield under the optimal conditions; 20 bar of H2, at 170 &deg;C for 4 h with 0.1 g of catalyst

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BACKGROUND:When evaluating hearing disability in medicolegal cases, an average of thresholds at several frequencies is calculated using pure tone audiometry. Occasionally, there are instances in which thresholds at certain frequencies are omitted. One typical example is the threshold at 3 kHz (H3k). The American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium (1995) suggested that the average of thresholds at 2 kHz and 4 kHz (H24k) could replace H3k for a comparison of results between studies. However, to the best of our knowledge, there is no report in the literature that compares H3k and H24k. OBJECTIVE:This study aimed to investigate the agreement between H3k and H24k. METHODS:This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012, which was conducted by the Korean government. A total of 18,472 participants (unweighted) who represented 39,357,497 Koreans (weighted) were included. To verify the agreement of H3k and H24k, a paired t-test, Cohen's d, Pearson's correlation, Cronbach's coefficient, intraclass correlation coefficient (ICC), a Bland-Altman plot, and linear regression analysis were used. RESULTS:The means of H3k and H24k were 16.2 dBHL and 16.6 dBHL, respectively. They were significantly different in a paired t-test (p<0.0001), which resulted from the large sample size. In contrast, the effect size (Cohen's d) was 0.02, which meant that the two groups nearly overlapped. The means showed strong correlation: Pearson's correlation coefficient = 0.92, Cronbach's alpha = 0.96, and ICC = 0.92. A strong linear predictive relationship between H3k and H24k was found: y = -0.6821 + 1.0186x, where x = H24k, y = H3k, and p<0.0001. However, the Bland-Altman plot showed large upper and lower limits of agreement (LOA) of 15.0 dBHL and -15.8 dBHL, respectively. Irrespective of age and degree of the four-tone average (0.5, 1, 2, and 3 kHz) hearing loss or thresholds at 2 kHz, 3 kHz, and 4 kHz, the absolute LOAs were greater than 10 dBHL. CONCLUSIONS:Despite a very strong correlation between the two thresholds, H3k and H24k showed clinically large LOAs. Therefore, it would be improper to substitute H24k for H3k in an individual requesting a hearing disability rating. However, since the overall means of the H3k and H24k samples were nearly equal, H24k can replace H3k for a mean comparison of results between studies. This result supports the 1995 Committee on Hearing and Equilibrium guideline

Neonatal Lupus Erythematosus as a Rare Cause of Fever in Young Infants

Neonatal lupus erythematosus (NLE) is a rare disease caused by passively transmitted autoantibodies from the mother. NLE is a multi-organ system disease characterized by cutaneous, cardiac, hematological, hepatobiliary, and neurological manifestations. This study aimed to review the various symptoms and clinical manifestations in young infants with NLE and their mothers. We conducted a retrospective review of medical records of patients with NLE who were both examined and treated at Pusan National University Children’s Hospital between January 2009 and December 2020 and their mothers. Twenty-seven patients with NLE comprising 13 male patients (48.1%) and 14 female patients (51.9%) were included. The most common symptom was rash (40.7%), followed by fever (25.9%), arrhythmia (14.8%), splenomegaly (11.1%), and intrauterine growth retardation (7.4%). Seven patients with fever had various organ system manifestations, including cutaneous (100%), hematological (71.4%), hepatobiliary (57.1%), and central nervous system (CNS; 28.6%) manifestations. Two of the febrile patients had aseptic meningitis. Cutaneous, cardiac, hematological, hepatobiliary, and CNS involvement were noted in 44.4%, 18.5%, 51.9%, 40.7%, and 22.2% of the patients, respectively. Systemic lupus erythematosus (SLE) was the most common maternal disease (14/27, 51.9%). Ten mothers (37.0%) had not been diagnosed with any autoimmune disease until their babies were diagnosed. Among them, three were subsequently diagnosed with SLE, five were diagnosed with the Sjögren’s syndrome, and two of them still had no known diagnosis of any autoimmune disorder. Fever is a common symptom of NLE; thus, when there is no clear focus of fever in infants, NLE needs to be considered, especially in cases with skin rashes

Liquid-Phase Hydrogenation of Maleic Acid over Pd/Al₂O₃ Catalysts Prepared via Deposition–Precipitation Method

Succinic acid (SA) is a valuable raw material obtained by hydrogenation of maleic acid (MA). The product selectivity of this reaction is highly dependent on the reaction conditions. This study therefore investigated the effect of the reaction temperature, hydrogen pressure, and reaction time on the liquid-phase hydrogenation of MA by a Pd/Al₂O₃ catalyst. Complete conversion of MA and 100% selectivity for SA were achieved at a temperature of 90 °C, H₂ pressure of 5 bar, and reaction time of 90 min. Fumaric acid (FA) was formed as an intermediate material by hydrogenation of MA under nonoptimal conditions. The impact of the percentage of Pd dispersion and phase of the Al₂O₃ support (γ, θ + α, and α) was also examined. The Pd/Al₂O₃ catalyst with 29.8% dispersion of Pd and γ phase of Al₂O₃ exhibited the best catalytic performance. Thus, catalytic activity depends not only on the amount of Pd dispersion but also on the physicochemical properties of Al₂O₃.Applied Science, Faculty ofNon UBCChemical and Biological Engineering, Department ofReviewedFacult

Demographic data of participants in this study (subset of Korea National Health and Nutrition Examination Survey [KNHANES]).

<p>Demographic data of participants in this study (subset of Korea National Health and Nutrition Examination Survey [KNHANES]).</p