Recent progress in the preparation of bioactive peptides using simulated gastrointestinal digestion processes.

Bioactive peptides (BAPs) represent a unique class of peptides known for their extensive physiological functions and their role in enhancing human health. In recent decades, owing to their notable biological attributes such as antioxidant, antihypertensive, antidiabetic, and anti-inflammatory activities, BAPs have received considerable attention. Simulated gastrointestinal digestion (SGD) is a technique designed to mimic physiological conditions by adjusting factors such as digestive enzymes and their concentrations, pH levels, digestion duration, and salt content. Initially established for analyzing the gastrointestinal processing of foods or their constituents, SGD has recently become a preferred method for generating BAPs. The BAPs produced via SGD often exhibit superior biological activity and stability compared with those of BAPs prepared via other methods. This review offers a comprehensive examination of the recent advancements in BAP production from foods via SGD, addressing the challenges of the method and outlining prospective directions for further investigation.

Age-Dependent Phenomena of 6-Hz Corneal Kindling Model in Mice.

Although numerous studies have acknowledged disparities in epilepsy-related disease processes between young and aged animals, little is known about how epilepsy changes from young adulthood to middle age. This study investigates the impact of aging on 6-Hz corneal kindling in young-adult mice and middle-aged mice. We found that the kindling acquisition of the 6-Hz corneal kindling model was delayed in middle-aged mice when compared to young-adult mice. While the seizure stage and incidence of generalized seizures (GS) were similar between the two age groups, the duration of GS in the kindled middle-aged mice was shorter than that in the kindled young-adult mice. Besides, all kindled mice, regardless of age, were resistant to phenytoin sodium (PHT), valproate sodium (VPA), and lamotrigine (LGT), whereas middle-aged mice exhibited higher levetiracetam (LEV) resistance compared to young-adult mice. Both age groups of kindled mice displayed hyperactivity and impaired memory, which are common behavioral characteristics associated with epilepsy. Furthermore, middle-aged mice displayed more pronounced astrogliosis in the hippocampus. Additionally, the expression of Brain-Derived Neurotrophic Factor (BDNF) was lower in middle-aged mice than in young-adult mice prior to kindling. These data demonstrate that both the acquisition and expression of 6-Hz corneal kindling are attenuated in middle-aged mice, while hippocampal astrogliosis and pharmacological resistance are more pronounced in this age group. These results underscore the importance of considering age-related factors when utilizing the 6-Hz corneal kindling model in mice of varying age groups.

Nanotechnology-based analytical techniques for the detection of contaminants in aquatic products.

Food safety of aquatic products has attracted considerable attention worldwide. Although a series of conventional bioassays and instrumental methods have been developed for the detection of pathogenic bacteria, heavy metal residues, marine toxins, and biogenic amines during the production and storage of fish, shrimp, crabs et al., the nanotechnology-based analyses still have their advantages and are promising since they are cost-efficient, highly sensitive and selective, easy to conduct, facial design, often require no sophisticated instruments but with excellent detection performance. This review aims to summarize the advances of various biosensing strategies for bacteria, metal ions, and small molecule contaminants in aquatic products during the last five years, The review highlights the development in nanotechnologies applied for biorecognition process, signal transduction and amplification methods in each novel approach, the nuclease-mediated DNA amplification, nanomaterials (noble metal nanoparticle, metal-organic frameworks, carbon dots), lateral flow-based biosensor, surface-enhanced Raman scattering, microfluidic chip, and molecular imprinting technologies were especially emphasized. Moreover, this study provides a view of current accomplishments, challenges, and future development directions of nanotechnology in aquatic product safety evaluation.

How human capital and energy prices play their role to enhance renewable energy: defining the role of innovations and trade openness in G-11 countries.

It is crucial to switch from nonrenewable energy to renewable energy sources to improve environmental quality. For this reason, innovations play a crucial part, yet the use of renewable energy is insufficient. This work contributes to the literature by Using both aggregate and disaggregated data, this study investigates the relationship between energy consumption, trade openness, human capital (HCA), and innovations in G11 nations. This study analyzed yearly data from 1990 to 2020 using empirical methods of augmented mean group (AMG) and cross-sectional autoregressive distributed lag (CS-ARDL) techniques. The findings highlight the significance of human capital, energy pricing, and innovations in fostering the growth of renewable energy in G-11 nations. A 1% increase in GDP and trade openness will enhance total energy consumption by 0.47% and 0.07%. GDP and trade are also increasing non and renewable energy consumption. A 1% increase in human capital and eco-innovations are increasing renewable energy by reducing non-renewable energy consumption. In addition, the G-11's rising commerce and GDP have increased their reliance on energy sources that rely on fossil fuels. The authors of this study suggest raising HCA as a means of encouraging the G-11 to use cleaner forms of energy. The need to bolster renewable energy to achieve a cleaner environment in the G-11 countries.

Identification of Diagnostic Variants in FGFR2 and NPR2 Genes in a Chinese Family Affected by Crouzon Syndrome and Acromesomelic Dysplasia, Type Maroteaux.

This study aims to conduct a comprehensive clinical and genetic investigation on a large family with members having various phenotypes, including acromesomelic dysplasia, type Maroteaux (AMDM), idiopathic short stature (ISS), Crouzon syndrome (CS). Prenatal diagnosis was performed on the high-risk fetus. We performed the whole-exome sequencing on three members with AMDM, ISS, or CS. Detailed genotypes and phenotypes were investigated on members of this 4-generation family. Genetic analysis identified three variants, which were designated as p.Val548del, p.Arg989Gln in natriuretic peptide receptor B/guanylate cyclase B (NPR2), and p.Cys342Tyr in fibroblast growth factor receptor-2 (FGFR2). Compound heterozygous variation consisting of p.Val548del and p.Arg989Gln caused AMDM. NPR2 heterozygous variant carriers exhibited normal height or ISS. The p.Cys342Tyr mutation of FGFR2 causes the typical clinical phenotype of CS. The fetus carried the heterozygous p.Val548del and p.Cys342Tyr mutations, with ultrasound results showing exophthalmos, parrot-beaked nose, low and flat frontal skull, and intrauterine growth retardation at the second and third trimesters of gestation. We are reporting those two novel mutations (p.Val548del and p.Arg989Gln) in NPR2 and a p.Cys342Tyr mutation in FGFR2 in an extended Chinese family. This finding extended the genotype-phenotype spectra of ISS, AMDM, and CS related to pathogenic variants.

Efficacy and safety of bisphosphonates on childhood osteoporosis secondary to chronic illness or its treatment: a meta-analysis.

Background: Bisphosphonates are a type of medication that prevents the loss of bone density. Secondary childhood osteoporosis reduces bone strength and results in an increased risk of fragility fracture. This meta-analysis aims to explore the efficacy and safety of bisphosphonates on secondary childhood osteoporosis. Methods: We performed a systematic search of PubMed, Cochrane library, and Web of Science databases up to 31 July 2022 to screen for random clinical trials (RCTs) on bisphosphonate treatment for childhood secondary osteoporosis. Data from selected studies, mainly changes in lumbar spine (LS) bone mineral density (BMD), changes in LS BMD Z-scores, fracture events, and adverse events (AEs), were extracted and analyzed. Results: Nine RCTs (n = 429 in total) were included in our meta-analysis. The meta-analysis indicated that bisphosphonates improved the changes in LS BMD [mean difference (MD) = 0.04, 95% confidence intervals (CIs) = 0.01-0.07, p < 0.01] and LS BMD Z-scores [MD = 0.52, 95% CI = 0.23-0.81, p < 0.01]. Use of bisphosphonates did not increase the risk of AEs [odds ratio (OR) = 1.61, 95% CI = 0.87-2.99, p = 0.13]. Subgroup analysis showed that routes of administration, but not causes of secondary osteoporosis, might influence the efficacy of bisphosphonates. IV bisphosphonates close to significantly improved the incidence of fracture (OR = 0.34, 95% CI: 0.11-1.08, p = 0.07). Conclusions: The use of bisphosphonates improves LS BMD without increasing AE rates, which supports the clinical use of bisphosphonates in secondary childhood osteoporosis. Further large RCTs are still warranted, especially for their long-term effects on fracture rates.

Marketing by live streaming: How to interact with consumers to increase their purchase intentions.

Live streaming e-commerce, as a kind of new information technology-based business model, is currently the most popular marketing approach, especially in China. This research divides live streaming interactions into three dimensions, interactions for obtaining product information (IPI), interactions for grasping the purchase dynamics of others (IPD), and interactions for obtaining monetary incentives (IMI), and proposes a comprehensive framework to examine whether live streaming interactions with consumers promote both social presence and consumer conformity, and thereby enhance their purchase intentions. Covariance-based structural equation modeling (CB-SEM) with AMOS was conducted to analyze data collected from 576 Chinese consumers. The main findings are that, first, both IPI and IPD can exert a direct impact on social presence and consumer conformity; second, IMI has a positive impact only on social presence; third, among the three dimensions of interactions, both IPI and IPD tend to increase purchase intention through social presence and consumer conformity, while IMI increases purchase intention only via social presence. Furthermore, given the differences between experience and search products, the results of the multigroup analysis indicate inconsistent path coefficients between the two product groups. This study provides a novel perspective on live streaming e-commerce with evidence on how interactions matter in driving purchase intentions, enriches the content of live streaming e-commerce literature and explores the practical implications for marketing managers are looking for marketing by live streaming.

A familial 3q28q29 duplication induced mild intellectual disability: case presentation and literature review.

The 3q29 duplication syndrome is an uncommon imbalanced chromosomal disorder with highly variable manifestations, mainly characterized by a mild mental anomaly, eye abnormalities, and developmental delay. Only a few such cases have been reported with significant phenotypic heterogeneity. Here, we reported a case with familial 3q28q29 duplication that was 8.5 Mb in length, covering all fragments from previous reports. A series of genetic detection techniques, including karyotyping, chromosomal microarray, and fluorescence in situ hybridization, demonstrated that the rearrangement, in this case, was due to a three-chromosome translocation of the paternal grandmother of the fetus. Interestingly, only mild intellectual disability in the father and slightly thick nuchal translucency (NT) in the fetus were observed. The fetus was delivered at term and showed normal developmental milestones. Our study increased the understanding of this syndrome and highlighted the necessity and importance of the rational use of multiple genetic techniques in prenatal diagnosis.

Recent development in functional nanomaterials for sustainable and smart agricultural chemical technologies.

New advances in nanotechnology are driving a wave of technology revolution impacting a broad range of areas in agricultural production. The current work reviews nanopesticides, nano-fabricated fertilizers, and nano activity-based growth promoters reported in the last several years, focusing on mechanisms revealed for preparation and functioning. It appears to us that with many fundamental concepts have been demonstrated over last two decades, new advances in this area continue to expand mainly in three directions, i.e., efficiency improvement, material sustainability and environment-specific stimulation functionalities. It is also evident that environmental and health concerns associated with nano agrochemicals are the primary motivation and focus for most recent work. Challenges and perspectives for future development of nano agrochemicals are also discussed.

Clinicopathological characteristics of placental chorioangioma: A clinicopathological study of 77 cases.

OBJECTIVE: To explore clinicopathological characteristics, diagnosis, differential diagnoses, treatment, and prognoses of placental chorioangioma (PCA). METHODS: Placenta of 77 cases of PCA firmly diagnosed by pathology from 2009 through 2019 were collected, and clinicopathological characteristics of the patients were retrospectively analyzed. RESULTS: Seventy-seven patients were 20-41 (mean age, 28.8) years old at onset. Thirty patients showed pregnancy comorbidity. In one patient with the largest tumor (diameter, 16 cm), intrauterine fetal demise occurred at 33 weeks of gestation. Tumors were macroscopically manifested. The placental fetal surface showed a raised dark red to a pale pink nodule, quasi-round, with a maximum diameter of 0.2-16 cm. Microscopically, the tumors had a lot of capillaries and some interstitial loose connective tissue. One case was of atypical cellular chorioangioma. Immunophenotypically, CD34 (+) and Ki-67 proliferation indexes were less than 10%. CONCLUSIONS: Large PCA often accompanies pregnancy comorbidity. Atypical cellular chorangioma is rare and may be misdiagnosed as a malignant tumor. Therefore, improvement of understanding of such tumors can provide a basis for clinical diagnosis and intervention.

Azithromycin pretreatment exacerbates atopic dermatitis in trimellitic anhydride-induced model mice accompanied by correlated changes in the gut microbiota and serum cytokines.

Atopic dermatitis (AD) is a common inflammatory skin disease. This study aims to investigate the effect of azithromycin (AZI) pretreatment, a common macrolide-type antibiotic, on the trimellitic anhydride (TMA) induced AD-like symptoms in mice. AZI (25 mg/kg, once daily, 5 days) was administered intragastrically before the 10-day TMA challenge. AD-like symptoms were assessed by ear thickening, scratching behavior, and pathological or immunofluorescence staining; Cytokines in the skin tissue and serum were measured by cytometric bead array; and the compositions of gut microbiota were assessed by 16S rRNA gene sequencing. AZI pretreatment accelerated the development of ear thickening and enhanced the severity of developed AD-like symptoms. AZI pretreatment promoted the infiltrations of neutrophil-like cells, T cells, and mast cells in ear skin. AZI pretreatment elevated the levels of IL-4, IL-6, and IL-17A in the ear skin of AD model mice, but it increased serum TNF-α and IL-6. AZI-pretreatment increased four gut bacterial genera (Bacteroides, Candidatus_Saccharibacteria_unclassified, Acetatifactor, Firmicutes_unclassified) but depleted three short-chain fatty acids producing gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). AD-associated symptoms were positively associated with skin IL-4 and IL-17A, serum TNF-α, and IL-6, and Acetatifactor, but they negatively correlated to the three decreased gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). Thus, our results demonstrate that AZI exposure deteriorates TMA-induced AD-like symptoms in mice, which is related to the imbalances of gut microbiota and skin/serum cytokines.

Chitosan-Based Glycolipid Conjugated siRNA Delivery System for Improving Radiosensitivity of Laryngocarcinoma.

Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.

Analysis of microRNA expression profiling during paraquat-induced injury of murine lung alveolar epithelial cells.

Paraquat (PQ) as a non-selective heterocyclic herbicide, has been applied worldwide for over a few decades. But PQ is very harmful to humans and rodents. The lung is the main target organ of PQ poisoning. It is an important event that lung epithelial cells are injured during PQ-induced acute lung injury and pulmonary fibrosis. As a regulator of mRNA expression, microRNA (miRNA) may play an important role in the progress. Our study was to investigate the mechanisms of PQ-induced injury of pulmonary epithelial cells through analyzing the profiling of miRNAs and their target genes. As a result, 11 differentially expressed miRNAs were screened, including 1 upregulated miRNA and 10 downregulated miRNAs in PQ-treated murine lung alveolar epithelial cells (MLE-12 cells). The bioinformatic analyses suggested that the target genes of these miRNAs were involved in mitochondrial apoptosis pathway and DNA methylation, and participated in the regulation of PI3K-Akt, mTOR, RAS, TNF, MAPK and other signal pathways which related to oxidative stress and apoptosis. This indicated that miRNAs were an important regulator of oxidative stress and apoptosis during PQ-induced injury of murine lung alveolar epithelial cells. The findings would deepen our understanding of the mechanisms of PQ-induced pulmonary injury and might provide new treatment targets for this disease.

Risk of epilepsy in rheumatoid arthritis: a meta-analysis of population based studies and bioinformatics analysis.

BACKGROUND: An increasing number of studies support an association between rheumatoid arthritis (RA) and brain disorders. This study aims to determine the association between RA and epilepsy. METHODS: A comprehensive search of databases in both English and Chinese was performed. Data from the selected studies were extracted and analyzed independently by two authors. Genes associated with epilepsy and RA were also collected and analyzed. RESULTS: We included six nationwide population based studies (n = 7,094,113 cases in total) for the meta-analysis. The risk of epilepsy was increased in RA patients [risk ratio (RR) = 1.601; 95% confidence interval (CI): 1.089-2.354; p = 0.017; n = 3,803,535 cases] and children born to mothers with RA (RR = 1.475; 95% CI: 1.333-1.633; p < 0.001, n = 3,290,578 cases). Subgroup analysis and meta-regression showed the RR of epilepsy in RA was negatively correlated with age. Furthermore, we found that 433 identified genes in a coexpression network from the hippocampi of 129 epileptic patients were enriched in the RA and related Kyoto Encyclopedia of Genes and Genomes pathways, while 13 genes (mainly related to inflammatory cytokines and chemokines) were identified as potential key genes bridging the RA and epilepsy. CONCLUSIONS: Our study, utilizing meta-analysis and bioinformatical data, highlights a close association between epilepsy and RA. Further studies are still warranted to expand these findings, especially for a population that is exposed to RA during fetal and childhood periods.

Numerical Studies on Damage Behavior of Recycled Aggregate Concrete Based on a 3D Model.

This paper develops a 3D base force element method (BFEM) based on the potential energy principle. According to the BFEM, the stiffness matrix and node displacement of any eight-node hexahedral element are derived as a uniform expression. Moreover, this expression is explicitly expressed without a Gaussian integral. A 3D random numerical model of recycled aggregate concrete (RAC) is established. The randomness of aggregate was obtained by using the Monte Carlo random method. The effects of the recycled aggregate substitution and adhered mortar percentage on the elastic modulus and compressive strength are explored under uniaxial compression loading. In addition, the failure pattern is also studied. The obtained data show that the 3D BFEM is an efficient method to explore the failure mechanism of heterogeneous materials. The 3D random RAC model is feasible for characterizing the mesostructure of RAC. Both the substitution of recycled aggregate and the percentage of adhering mortar have a non-negligible influence on the mechanical properties of RAC. As the weak points in the specimen, the old interfacial transition zone (ITZ) and adhered mortar are the major factors that lead to the weakened properties of RAC. The first crack always appears in these weak zones, and then, due to the increase and transfer of stress, approximately two-to-three continuous cracks are formed in the 45°direction of the specimen.

Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome.

BACKGROUND: Autosomal recessive Robinow syndrome (ARRS) is a rare genetic disorder, which affects the development of multiple systems, particularly the bones. OBJECTIVES: The aim of this study was to investigate the genetic cause of a ARRS fetus and to evaluate the reliability of whole-exome sequencing (WES) in prenatal diagnosis on cases with indistinguishable multiple malformation. METHODS: Clinical and ultrasonic evaluations were conducted on the fetus, and multiplatform genetic techniques were used to identify the variation responsible for RS. The pathogenicity of the novel variation was evaluated by in silico methods. Western blotting (WB) and immunohistochemistry (IHC) were performed on fetal tissues after the fetus' stillbirth and postabortal autopsy. RESULTS: A compound heterozygous variation consisting c.613C > T and c.904C > T in ROR2 gene was identified. In silico prediction suggested that c.904C > T was a deleterious variant. IHC result demonstrated that ror2 expression level of the proband in osteochondral tissue significantly increased comparing with that of the control sample. CONCLUSIONS: For the first time in Chinese population, we characterized a novel variation in ROR2 gene causing ARRS. This study extended the mutation spectrum of ARRS and provided a promising strategy for prenatal diagnosis of cases with ambiguous multiple deformities.

Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation.

AIMS: Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early-life FSs could transmit across generations or not. METHODS: The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects. RESULTS: Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs. CONCLUSIONS: Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases.

Correction to: Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures.

In the original publication of the article, the representative EEG of female rat pups with FS in Figure 1 C and D was incorrectly intercepted from that of male rat pups. This correction does not affect the conclusions of the paper. Figure 1 has been corrected on the online PDF version and displayed below.

Treatment of rheumatoid arthritis with combination of methotrexate and Tripterygium wilfordii: A meta-analysis.

AIMS: Extracts of Tripterygium wilfordii Hook F (TwHF), a traditional Chinese herbal medicine, have been widely used for treating rheumatoid arthritis (RA) in combination with methotrexate (MTX) in China for several decades. However, the efficacy and safety of MTX plus TwHF treatment remain unclear. MAIN METHODS: A comprehensive search of databases in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors. KEY FINDINGS: Six randomized controlled trials were included in the final analysis with a total of 643 patients. All trials added TwHF (in the form of Tripterygium glycosides) to the MTX-based therapy. For efficacy, the addition of TwHF increased 50% responder rates (RR) (RR 1.337, 95% confidence interval [CI]: 1.188-1.505, P<0.001), and it reduced swollen and tender joint counts, shortened the duration of morning stiffness, decreased the erythrocyte sedimentation rate, and decreased the level of C-reactive protein and rheumatoid factor. For safety, the addition of TwHF did not increase the rate of adverse events (RR 0.824, 95% CI: 0.635-1.068, P=0.143). SIGNIFICANCE: MTX plus TwHF therapy may be a more effective and similar safe strategy for treating RA compared to MTX monotherapy. Further large clinical trials to investigate the TwHF add-on therapy are warranted.

The efficacy and safety of rufinamide in drug-resistant epilepsy: A meta-analysis of double-blind, randomized, placebo controlled trials.

OBJECTIVE: To evaluate the clinical efficacy and safety of rufinamide in drug-resistant epilepsy. METHODS: We searched PubMed, Web of Science and Clinical trial.org up to August 6, 2015. Study selection, extraction and risk of bias assessment were performed independently by two authors. A random or fixed-effect model was used to derive pooled effects risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Five randomized controlled trials were included in the final analysis with a total of 1512 patients. Rufinamide increased the 50% (RR 1.852, 95%CI 1.446-2.372, P<0.001) and 75% (RR 8.547, 95%CI 2.534-28.832, P<0.001) responder rates but not the seizure-free rate (RR 1.740, 95%CI 0.511-5.924, P=0.376) compared to placebo. Subgroup analysis demonstrated that the effect of rufinamide may be dose-dependent and related to seizure type. Regarding safety, rufinamide increased the rate of at least one adverse event (RR 1.103, 95%CI 1.047-1.161, P<0.001) and the withdrawal rate due to adverse events (RR 2.341, 95%CI 1.556-3.522, P<0.001), but it did not increase the rate of severe adverse events (RR 1.454, 95%CI 0.945-2.241, P=0.090). Individual adverse events (headache, dizziness, fatigue, somnolence, nausea, diplopia and vomiting) were significantly higher in the rufinamide group. CONCLUSIONS: This study confirmed significant effects of rufinamide as adjunctive treatment for drug-resistant seizures, both partial and tonic-atonic. However, rufinamide may induce more tolerable (but not severe) adverse events. Further large clinical trials to investigate the long-term efficacy and safety of rufinamide are warranted.