An investigation of the characteristics of outpatients with epilepsy and antiepileptic drug utilization in a multicenter cross-sectional study in China.

OBJECTIVES: This study aimed to describe the distribution of seizure types, clinical characteristics, and antiepileptic drug (AED) utilization in patients with epilepsy visiting tertiary hospitals in China. METHODS: This was an observational, cross-sectional epidemiology study conducted at 11 tertiary hospitals across China from May 2014 to November 2014. A total of 1603 patients, of either sex or any age with confirmed diagnosis of epilepsy, visiting outpatient clinics at tertiary hospitals were screened and enrolled. Demographics, seizure types, frequency, etiologies, comorbidities, and current AED therapy were analyzed using descriptive statistics. RESULTS: Overall, the majority (n=1201; 74.9%) of patients were adults (16-59years of age), and the mean (SD) age was 27.5 (15.9) years. A total of 989 (61.7%) patients had partial seizures, and 653 (40.7%) had generalized seizures. The majority experienced monthly (n=663) or yearly (n=625) seizures, with 2.7seizures/month or 2.9seizures/year, respectively. The most commonly reported symptomatic etiologies were traumatic brain injury, encephalitis, and stroke, whereas the most common comorbidities were sleep disorder, headache, anxiety, and depression. Overall, monotherapy was used in 54.1% of patients, while 30.6% of patients used dual therapy. The most commonly prescribed monotherapy for patients with partial seizures was oxcarbazepine (25.9%), while that for patients with generalized seizures was valproic acid (38.9%), and the most common AED combination was valproic acid and lamotrigine. Overall, valproic acid was the most commonly prescribed AED as monotherapy and combination therapy. CONCLUSION: Findings from this study provide extensive information on clinical characteristics and utilization of AEDs in Chinese patients with epilepsy which may help physicians make well-informed clinical decisions.

The Shanghai Aging Study: study design, baseline characteristics, and prevalence of dementia.

BACKGROUND: To establish a prospective cohort to enumerate the prevalence, incidence and risk factors for dementia and mild cognitive impairment (MCI) among residents aged ≥60 in an urban community of Shanghai, China. METHODS: Participants received clinical evaluations including physical measurements, demographic and lifestyle questionnaires, physical and neurologic examinations, and neuropsychological testing. Urine and blood samples were collected, aliquoted, and stored. DNA was extracted for Apolipoprotein (APOE) genotyping. Diagnoses of dementia and MCI were made using standard criteria via consensus diagnosis. RESULTS: Among 3,141 participants aged ≥60, 1,438 (45.8%) were men. The average age of participants was 72.3 years (SD 8.1), and they had an average of 11.6 years (SD 4.4) of education. The most common chronic disease of participants was hypertension (56.4%). The frequencies of APOE-​ε2, ε3 and ε4 were 7.9, 82.7 and 9.4%, respectively. We diagnosed 156 (5.0%, 95% CI 4.3-5.8%) participants with dementia. The prevalence rates of Alzheimer's disease and vascular dementia were 3.6% (95% CI 3.0-4.3%) and 0.8% (95% CI 0.5-1.1%). CONCLUSIONS: The Shanghai Aging Study is the first prospective community-based cohort study of cognitive impairment in China, with a comparable study design, procedures, and diagnostic criteria for dementia and MCI to most previous cohort studies in developed countries.

Differences in intra-foot movement strategies during locomotive tasks among chronic ankle instability, copers and healthy individuals.

Individuals with chronic ankle instability (CAI) suffer from the resulting sequela of repetitive lateral ankle sprains (LAS), whilst copers appear to cope with initial LAS successfully. Therefore, the aim of this study was to explore the intra-foot biomechanical differences among CAI, copers, and healthy individuals during dynamic tasks. Twenty-two participants per group were included and required to perform cutting and different landing tasks (DL: drop landing; FL: forward jump followed a landing). A five-segment foot model with 8 degrees of freedom was used to explore the intra-foot movement among these three groups. Smaller dorsiflexion angles were found in copers (DL tasks and prelanding task) and CAI (DL and FL task) compared to healthy participants. Copers presented a more eversion position compared to others during these dynamic tasks. During the descending phase of DL task, greater dorsiflexion angles in the metatarsophalangeal joint were found in copers compared to the control group. Joint moment difference was only found in the subtalar joint during the descending phase of FL task, presenting more inversion moments in copers compared to healthy participants. Copers rely on more eversion positioning to prevent over-inversion of the subtalar joint compared to CAI. Further, the foot became more unstable when conducting sport-related movements, suggesting that foot stability seems to be sensitive to the task types. These findings may help in designing and implementing interventions to restore functions of the ankle joint in CAI individuals.

Integrating an LSTM framework for predicting ankle joint biomechanics during gait using inertial sensors.

The ankle joint plays a crucial role in gait, facilitating the articulation of the lower limb, maintaining foot-ground contact, balancing the body, and transmitting the center of gravity. This study aimed to implement long short-term memory (LSTM) networks for predicting ankle joint angles, torques, and contact forces using inertial measurement unit (IMU) sensors. Twenty-five healthy participants were recruited. Two IMU sensors were attached to the foot dorsum and the vertical axis of the distal anteromedial tibia in the right lower limb to record acceleration and angular velocity during running. We proposed a LSTM-MLP (multilayer perceptron) model for training time-series data from IMU sensors and predicting ankle joint biomechanics. The model underwent validation and testing using a custom nested k-fold cross-validation process. The average values of the coefficient of determination (R2), mean absolute error (MAE), and mean squared error (MSE) for ankle dorsiflexion joint and moment, subtalar inversion joint and moment, and ankle joint contact forces were 0.89 ± 0.04, 0.75 ± 1.04, and 2.96 ± 4.96 for walking, and 0.87 ± 0.07, 0.88 ± 1.26, and 4.1 ± 7.17 for running, respectively. This study demonstrates that IMU sensors, combined with LSTM neural networks, are invaluable tools for evaluating ankle joint biomechanics in lower limb pathological diagnosis and rehabilitation, offering a cost-effective and versatile alternative to traditional experimental settings.

The clinical features of familial focal epilepsy with variable foci and NPRL3 gene variant.

OBJECTIVE: Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with NPRL3 variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various NPRL3 variants and explored the effect of NPRL3 variant on mRNA. METHODS: We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative-polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals. RESULTS: Patients with NPRL3: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe/temporal lobe), different seizure times (day/night) and frequencies (monthly/seldom/every day), different therapeutic effects (refractory epilepsy/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different NPRL3 variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes. CONCLUSION: The clinical features of FFEVF varied, and auxiliary inspection was atypical. NPRL3: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.

Regional plantar forces and surface geometry variations of a chronic ankle instability population described by statistical shape modelling.

BACKGROUND: Understanding detailed foot morphology as well as regional plantar forces could provide insight into foot function and provide recommendation for footwear design for chronic ankle instability (CAI) people. RESEARCH QUESTION: This study presented 3-dimensional statistical shape models of feet from three different populations including CAI, copers and healthy individuals, with regional plantar forces also acquired. METHODS: Sixty-six males (22 participants per group) were included in this study to capture 3-dimensional foot shapes under a standing condition and regional plantar forces during a cutting maneuver. Principal component analysis was performed to generate a mean foot shape of each group as well as modes of variations. A generalized procrustes analysis was used to achieve rapid registration of mean shapes. Besides, regional plantar forces and contact duration among these three populations were compared. RESULTS: For 3-dimensional foot shapes, although no significant differences of the average distance between each mode and mean shape were found among three populations, there were subtle variations in mean shapes. The CAI population presented a more bulging of the lateral malleolus; copers were characterized by the flexion of the lesser toes, a more bulging of the medial foot in the sagittal plane; and healthy individuals showed a greater heel width and a more bulging of the heel in the sagittal plane. In terms of plantar forces, healthy individuals had significantly greater summated plantar forces and greater plantar forces in the lateral heel area during the early contact phase compared to copers and CAI participants. SIGNIFICANCE: Overall, this study suggested that repetitive ankle sprains may lead to the bulging of the lateral malleolus. Further, CAI and copers seem to stabilize the ankle joint by medially shifting the center of pressure compared to healthy individuals under the static and less challenging dynamic conditions.

Effects of plantar fascia stiffness on the internal mechanics of idiopathic pes cavus by finite element analysis: implications for metatarsalgia.

Metatarsalgia occurring in individuals with pes cavus is typically associated with abnormal loading patterns in the forefoot resulting from structural alterations. Simultaneously, the frequent overstress of the plantar fascia (PF) caused by the persistence of this foot deformity may further exacerbate the chronic pain induced by metatarsal overload. We aimed to investigate and quantify the effects of PF stiffness on the internal biomechanics of pes cavus using a computational modelling approach. A patient-specific finite element model of the foot-ankle complex using the actual three-dimensional geometry of idiopathic pes cavus bones and soft tissues was reconstructed. A sensitivity study was conducted to evaluate the effects of varying elastic modulus (0-700 MPa) of the PF on the metatarsal stress distribution, and force transmission through the metatarsophalangeal (MTP) and tarsometatarsal (TMT) joints in the pes cavus. The results indicated that variations in PF stiffness led to stress redistribution in the metatarsal region. Peak stress gradually reduced with decreasing stiffness until the PF was released, eventually resulting in a reduction of 22.39% compared to the reference value of 350 MPa. Furthermore, adjusting the PF stiffness to twice the reference value (700 MPa) increased the contact forces through the TMT and MTP joints by up to 23% and 116%, respectively. The reduction of PF stiffness alleviated focal metatarsal loading, and therefore, surgical fascia release can be considered to alleviate metatarsalgia in patients with pes cavus.

Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Mirogabalin in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Mirogabalin is a treatment option for patients with neuropathic pain; however, safety, tolerability, and pharmacokinetics (PK) data specifically for Chinese individuals are limited to a single-dose study. We aimed to assess these for both single- and multiple-dose mirogabalin in healthy Chinese participants. METHODS: In this randomized, double-blind, placebo-controlled, phase I study, 54 healthy Chinese men and women aged 18-45 years were randomly allocated to receive single- (5, 10, or 15 mg, daily) or multiple-dose (5 mg titrated to 15 mg, twice-daily, over 22 days) oral mirogabalin or placebo. In each of three single-dose groups, 10 participants received mirogabalin and 2 received placebo; in the multiple-dose group, 14 participants received mirogabalin and 4 received placebo. The primary endpoints were PK, safety, and tolerability variables, including treatment-emergent adverse events (TEAEs), laboratory tests, and vital signs. PK data were collected for both single- and multiple-dose cohorts and evaluated by non-compartmental analysis. RESULTS: Single- and multiple-dose mirogabalin was generally well tolerated with no deaths, serious TEAEs, or TEAEs leading to treatment discontinuation. Frequently reported TEAEs included dizziness, nystagmus, increased blood triglycerides, headache, and increased blood uric acid and creatine phosphokinase. Single-dose mirogabalin was rapidly absorbed (median time to maximum plasma concentration, 1.00 h) and eliminated (mean terminal elimination half-life, 2.57-3.08 h). The exposure was approximately dose-proportional. In the multiple-dose cohort, the trough plasma concentration increased dose-proportionally, and exposure and clearance were comparable to that following a single 15-mg dose. The mean cumulative amount excreted into urine up to 48 h post-dose increased in a dose-proportional manner, the mean cumulative percentage excreted into urine was 61.9%-74.3%, and renal clearance remained relatively constant. CONCLUSION: Consistent with previous phase I studies in other populations, mirogabalin was safe and well tolerated in healthy Chinese participants at single and multiple doses of up to 15 mg twice-daily.

Population pharmacokinetics and exposure-safety of lipophilic conjugates prodrug DP-VPA in healthy Chinese subjects for dose regime exploring.

Phospholipid-valproic acid (DP-VPA)is a prodrug for treating epilepsy. The present study explored the pharmacokinetics (PK) and exposure safety of DP-VPA to provide a basis for future studies exploring the safe dosage and therapeutic strategies for epilepsy. The study included a randomized placebo-controlled dose-escalation tolerance evaluation trial and a randomized triple crossover food-effect trial in healthy Chinese volunteers. A population pharmacokinetic (PopPK) model was established to analyze the PK of DP-VPA and active metabolite VPA. The exposure safety was assessed with the adverse drug reaction (ADR) in CNS. The PopPK of DP-VPA and metabolite VPA fitted a two-compartment model coupling one-compartment with Michaelis-Menten metabolite kinetics and first-order elimination. The absorption processes after single oral administration of DP-VPA tablet demonstrated nonlinear characteristics, including 0-order kinetic phase and time-dependent phase fitting Weibull distribution. The final model indicated that the DP-VPA PK was significantly affected by dosage and food. The exposure-safety relationship demonstrated a generalized linear regression; mild/moderate ADRs occurred in some subjects with 600 mg and all subjects with 1500 mg of DP-VPA, and no severe ADRs were reported up to 2400 mg. In conclusion, the study established a PopPK model describing the processing of DP-VPA and VPA in healthy Chinese subjects. DP-VPA showed good tolerance after a single dose of 600-2400 mg with nonlinear PK and was affected by dosage and food. Based on the association between neurological ADRs and higher exposure to DP-VPA by exposure-safety analysis, 900-1200 mg was recommended for subsequent study of safety and clinical effectiveness.

Cognitive and mood effects of phenobarbital treatment in people with epilepsy in rural China: a prospective study.

BACKGROUND: Phenobarbital is an effective treatment for epilepsy but concerns remain over its potential neurocognitive toxicity. This prospective study evaluated the effects of phenobarbital treatment on cognition and mood in people with epilepsy in rural China. METHODS: We recruited 144 adults with convulsive seizures and 144 healthy controls from six sites in rural China. People with epilepsy were treated with phenobarbital monotherapy for 12 months. At baseline, and at 3, 6 and 12 months, cases and controls were evaluated with a battery of neuropsychological tests: the Mini-Mental State Examination, the Hamilton Depression Rating Scale, a digit span test, a verbal fluency test, an auditory verbal learning test and a digit cancellation test. Efficacy of phenobarbital treatment was evaluated at the end of follow-up for those with epilepsy. RESULTS: Cognitive test scores and mood ratings were available for 136 (94%) people with epilepsy and 137 (95%) controls at the 12 month follow-up. Both groups showed slightly improved performance on a number of neuropsychological measures. The people with epilepsy showed greater performance gains (p=0.012) in verbal fluency. Nine people with epilepsy complained of memory problems during the treatment period. CONCLUSION: In this study, phenobarbital was not found to have a major negative impact on cognitive function of people with convulsive seizures and some cognitive gains were observed, possibly due to improved seizure control.

Treatment of epilepsy in adults: expert opinion in China.

OBJECTIVE: The goal of this study was to survey a group of epileptologists in China regarding the treatment of adult epilepsy. METHODS: A questionnaire on treatment of adult epilepsy was sent to a group of opinion leaders in the field of epilepsy. RESULTS: For initial monotherapy for idiopathic generalized epilepsy (IGE), valproate was rated as the treatment of choice. In symptomatic localization-related epilepsy (SLRE)/simple partial seizures and SLRE/complex partial seizures, carbamazepine and oxcarbazepine were the respective treatments of choice, whereas in SLRE/secondarily generalized tonic-clonic seizures, carbamazepine, lamotrigine, and oxcarbazepine were treatments of choice. For women who were pregnant or trying to conceive, lamotrigine was the treatment of choice for both IGE and SLRE. In people with epilepsy who were HBsAg positive, whether liver function was normal or not, topiramate and levetiracetam were treatments of choice for IGE. Valproate and levetiracetam were treatments of choice for seizures in the emergency department. CONCLUSION: A high level of consensus was reached on most treatments of choice and first-line treatments for patients with epilepsy, which were in accordance with published US expert opinion.

Cognitive dysfunction in people with convulsive seizures in rural China.

One hundred and forty-four people with convulsive seizures (CS) and 144 healthy controls were evaluated for cognitive function, using a battery of neuropsychological tests. People with CS performed significantly worse than the controls on the Mini-Mental State Examination, Hamilton Depression Rating Scale, auditory verbal learning test, digit span test, verbal fluency test, and digit cancellation test. The percentage of patients who had abnormal scores on the Hamilton Depression Rating Scale was higher than that of controls (54.9% vs. 7.6%, p<0.001). Cognitive functional impairment was detected in 65.3% of the patients and 29.2% of the controls (p<0.001). People with CS presented with depressive mood and a wide range of cognitive deficits, particularly deficits in episodic declarative memory, attentional capacity, semantic memory, and mental speed. Years in education were positively associated with the cognitive performance of people with CS (OR=0.655, 95% CI: 0.486-0.882, p=0.005).

Differences in the locomotion biomechanics and dynamic postural control between individuals with chronic ankle instability and copers: a systematic review.

An empirical consensus of differences between chronic ankle instability (CAI) individuals and copers (individuals who sprained ankle once and without recurrent symptoms or injury) has not been reported. This study aimed to review the locomotion biomechanics and dynamic postural control between these two populations. Database of ScienceDirect, PubMed and Web of Science was used to search ('chronic ankle instability' OR 'ankle instability') AND ('ankle sprain' OR 'coper*') until 30 November 2020. Articles that made a comparison about changes in biomechanical parameters between Copers and CAI individuals during locomotor or functional tasks were included in this review. Twenty-three articles met the inclusion criteria. CAI individuals exhibited an increased hip flexion to maintain stability, suggesting the adopted hip strategy compared to copers during landing. Dorsiflexion angle and ankle frontal displacement increased considerably compared to copers, which might increase risks of lateral ankle sprain injury. CAI individuals reduced the ankle displacements in the sagittal plane and indicated worse performance of Star Excursion Balance Test in the posterior-lateral direction compared to copers. Identified motion deficits or altered motion strategies provide opportunities for targeted intervention and scheme after index sprain or in CAI individuals.

Understanding Foot Loading and Balance Behavior of Children with Motor Sensory Processing Disorder.

Sensory processing disorder (SPD) could influence the neuromuscular response and adjustment to external sensory discrimination and lead to disruptions in daily locomotion. The objective of the current study was to compare plantar loadings and foot balance during walking, running and turning activities in SPD children in order to reveal the behavioral strategy of movement and balance control. Six SPD children and six age-match healthy controls participated in the test using a FootScan plantar pressure plate. The time-varying parameters of forces, center of pressure and foot balance index were analyzed using an open-source one-dimensional Statistical Parametric Mapping (SPM1d) package. No difference was found in foot balance and plantar loadings during walking, while limited supination-pronation motion was observed in the SPD children during running and turning. The plantar forces were mainly located in the midfoot region while less toe activity was found as well. Findings should be noted that SPD children had limited supination-pronation movement for shock attenuation in the foot complex and reduced ankle pronation to assist push-off and toe gripping movements. Understanding the behavior of plantar loading strategy and balance control during walking, running and turning activities may provide clinical implications for the rehabilitation and training of daily tasks.

Biomechanical Characteristics of the Typically Developing Toddler Gait: A Narrative Review.

Independent ambulation is one of the most important motor skills in typically developing toddlers. Gait analysis is a key evaluation method in basic and clinical research. A narrative review on the literature of toddler gait development was conducted following inclusion criteria, explicitly including the factors of English article, age range, no external intervention during the experimental process of studies involved, the non-symptomatic toddler, and no pathological gait. Studies about toddlers' morphological, physiological, and biomechanical aspects at this developmental stage were identified. Remarkable gait characteristics and specific development rules of toddlers at different ages were reported. Changes in gait biomechanics are age and walking experience-dependent. Gait patterns are related to the maturation of the neuro and musculoskeletal systems. This review thus provides critical and theoretical information and the nature of toddler walking development for clinicians and other scientific researchers. Future studies may systematically recruit subjects with more explicit criteria with larger samples for longitudinal studies. A particular design could be conducted to analyze empirically before practical application. Additionally, the influence of external interventions on the development of toddler gait may need consideration for gait development in the toddler cohort.

Effect of foot pronation during distance running on the lower limb impact acceleration and dynamic stability.

PURPOSE: Foot pronation is not an isolated factor influencing lower limb functions. Exploring gait variability and impact loading associated with the foot posture are crucial for understanding foot pronation-related injury mechanisms. This study aimed to evaluate how foot posture affects impact loading and running variability during running. METHODS: Twenty-five male participants were recruited into this study. Pressure under the foot arch, acceleration and marker trajectory were recorded in the right limb for each runner after 1, 4, 7 and 10 km running, respectively. Linear mixed effects models were used to analyze the statistical difference of the data. RESULTS: FPI-6 has significantly increased after the 10 km running (p〈0.01). For the tibial acceleration, peak resultant acceleration after 10 km running was significantly increased than after 4 km running (p=0.02). At the dorsum of the foot, the short-time largest Lyapunov exponent (LyE) after 10 km running decreased 0.28 bit/s compared with LyE after 7 km running ( p = 0.03). In the tibia, LyE after 4 km and 10 km running was decreased significantly ( p 〈 0.01 and p = 0.01). CONCLUSIONS: The foot was significantly pronated at the middle and at the end of running. Foot pronation during distance running increased the distal tibia peak impact acceleration but did not increase running instability.

Dataset of lower extremity joint angles, moments and forces in distance running.

This study presents a database of joint angles, moments, and forces of the lower extremity from distance running at a submaximal speed in recreational runners. Twenty recreational runners participated in two experimental sessions, specifically pre and post a 5k treadmill run, with a synchronous collection of markers trajectories and ground reaction forces for both limbs in walking and running trials. The raw data in C3D files could be used for musculoskeletal modelling. Extra datasets of joint angles, moments, and forces are presented ready-for-use in MAT files, which could be as reference for study of biomechanical alterations from distance running. Applying advanced data processing techniques (Machine Learning algorithms) to these datasets ( C3D & MAT ), such as Principal Component Analysis, could extract key features of variation, thus potentially being applied for correlation with accelerometric and gyroscope parameters from wearable sensors during field running. Dataset of multi-segmental foot could be another contribution for the investigation of foot complex biomechanics from distance running. The dataset from Asian males may also be used for population-based studies of running biomechanics.

The Effect of Arch Stiffness on the Foot-Ankle Temporal Kinematics during Gait Termination: A Statistical Nonparametric Mapping Study.

This study compares foot-ankle temporal kinematics characteristics during planned and unplanned gait termination (PGT and UGT) in subjects with different arch stiffnesses (ASs) based on the statistical nonparametric mapping (SnPM) method. By measuring three-dimensional arch morphological parameters under different loading conditions, 28 healthy male subjects were classified and participated in gait termination (GT) tests to collect metatarsophalangeal (MTP) and ankle-joint kinematics data. The two-way repeated-measures ANOVA using SnPM was employed to assess the impacts of AS on foot-ankle kinematics during PGT and UGT. Our results show that joint angles (MTP and ankle joints) were altered owing to AS and GT factors. The flexible arches hahadve periods of significantly greater MTP and ankle joint angles than those of stiff arches during the stance phase of GT, whereas subjects exhibited significantly smaller ankle and MTP joint angles during UGT. These results add additional insights into the morphological arch biomechanical function, and the comprehensive compensatory adjustment of lower-limb joints during gait stopping caused by unplanned stimulation.

ROS-Mediated Anti-Angiogenic Activity of Cerium Oxide Nanoparticles in Melanoma Cells.

Angiogenesis plays a key role in cancer progression, including transition to the metastatic phase via reactive oxygen species (ROS)-dependent pathways, among others. Antivascular endothelial growth factor (VEGF) antibodies have been trialed as an anti-angiogenic therapy for cancer but are associated with high cost, limited efficacy, and side effects. Cerium oxide nanoparticles (nanoceria) are promising nanomaterials for biomedical applications due to their ability to modulate intracellular ROS. Nanoceria can be produced by a range of synthesis methods, with chemical precipitation as the most widely explored. It has been reported that chemical precipitation can fine-tune primary particle size where a limited number of synthesis parameters were varied. Here, we explore the effect of temperature, precipitating agent concentration and rate of addition, stirring rate, and surfactant concentration on nanoceria primary particle size using a fractional factorial experimental design approach. We establish a robust synthesis method for faceted nanoceria with primary particle diameters of 5-6 nm. The nanoceria are not cytotoxic to a human melanoma cell line (Mel1007) at doses up to 400 µg/mL and are dose-dependently internalized by the cells. The intracellular ROS level for some cells that internalized the nanoceria is reduced, which correlates with a dose-dependent reduction in angiogenic gene expression including VEGF. These findings contribute to our knowledge of the anti-angiogenic effects of nanoceria and help to develop our understanding of potentially new anti-angiogenic agents for combination cancer therapies.

Determinants of quality of life in people with epilepsy and their gender differences.

Improving the patient's quality of life (QOL) is the most important goal of epilepsy management. We performed this study to determine the factors associated with QOL in people with epilepsy and to assess whether there are gender differences in these determinants. Patients were interviewed using the Quality of Life in Epilepsy Inventory-31(QOLIE-31), the Adverse Event Profile (AEP), the Self-Rating Anxiety Scale (SAS), and the Hamilton Depression Rating Scale (HAMD). Two hundred forty-seven patients (152 men, 95 women) were included in the analysis. Among all patients, regressive analyses showed that AEP score was the strongest predictor of the QOLIE-31 overall score, accounting for 10.4% of the variance. The next strongest predictors were the number of currently used antiepileptic drugs (AEDs) (3.6%), the HAMD score (2.5%), and the SAS score (1.2%). Importantly, there were gender differences in these predictors of QOL. The strongest predictors of the QOLIE-31 overall score in women were the AEP score and the number of AEDs. In contrast, the strongest predictors in men were the SAS score, the AEP score and the frequency of seizures. These results indicate that perceived adverse effects of treatments and number of AEDs exerted greater effects on QOL in women, whereas anxiety and seizure-related variables had a stronger impact on QOL among men. Accordingly, it may be necessary to individualize interventions to improve the QOL of people with epilepsy.