Microglia-Impaired Phagocytosis Contributes to the Epileptogenesis in a Mouse Model of Dravet Syndrome.

Dravet syndrome (DS) is a genetic disorder caused by a deficit in the Nav1.1 channel, leading to drug-resistant epilepsy. The Nav1.

Abnormal increased mTOR signaling regulates seizure threshold in Dravet syndrome.

Excessive activation of mTOR has been observed in the brains of mouse models for Dravet syndrome. We aim to confirm whether that the overactivation of mTOR contributes to the neuropathological changes leading to epileptogenesis and neurobehavior deficits to support a novel pharmacological therapeutic approach for Dravet syndrome. The mTOR inhibitor everolimus, as a clinical antiseizure medication, was utilized to investigate whether mTOR is involved in hyperthermia-induced seizures, anxiety-like, and autism-like behaviors, as well as to explore potential pathogenic mechanisms in Scn1a mice, a model of Dravet syndrome.

Combining the AD8 and MMSE for community-based dementia screening.

Background: This study aimed to determine whether a cognitive test the Mini-Mental State Examination (MMSE) and the Ascertain Dementia 8 (AD8) instrument applied in combination could improve the accuracy of dementia detection in a community setting.

Methods: Study participants were recruited from a community-based integrated screening program in Tainan, Taiwan. Participants completed the AD8 and were administered the Chinese version of the MMSE by psychologists.

Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome.

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1a mice).

The impact of active community-based survey on dementia detection ratio in Taiwan: A cohort study with historical control.

Background: Although early dementia detection is crucial to optimize the treatment outcomes and the management of associated symptoms, the published literature is scarce regarding the effectiveness of active screening protocols in enhancing dementia awareness and increasing the rate of early detection. The present study compared the detection ratio of an active community-based survey for dementia detection with the detection ratio of passive screening during routine clinical practice. Data for passive screening were obtained from the National Health Insurance (NHI) system, which was prospectively collected during the period from 2000 to 2003.

Ten existing osteoporosis prediction tools for the successful application of National Health Insurance-reimbursed anti-osteoporosis medications in long-term care residents in Taiwan.

Background/purpose: Osteoporotic fracture introduce enormous societal and economic burden, especially for long-term care residents (LTCRs). Although osteoporosis prevention for LTCRs is urgently needed, obstacles such as frail status and inconvenient hospital visits hurdled them from necessary examinations and diagnoses. We aimed to test 10 existing osteoporosis screening tools (OSTs), which can be easily used in institutions and serve as a prediction, for accurately determining the outcome of a Taiwan's National Health Insurance (NHI)-reimbursed anti-osteoporosis medications (AOMs) application for LTCRs.

Cost-effectiveness of the add-on exenatide to conventional treatment in patients with Parkinson's disease when considering the coexisting effects of diabetes mellitus.

Objective: This study aims to investigate the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy in patients with Parkinson's disease (PD) when considering the coexistence of diabetes mellitus (DM).

Methods: We used the Keelung and Community-based Integrated Screening databases to understand the medical utilisation in the Hoehn and Yahr stages of patients with PD. A Markov model with 1-year cycle length and 50-year time horizon was used to assess the cost-effectiveness of add-on exenatide to conventional pharmacotherapy compared to conventional pharmacotherapy alone.

The psychopathology and happiness of the older adults in Yunlin, Taiwan: What do we need for long-term care service?

Background: The purpose of this study was to investigate the psychopathology and level of happiness and their association with the demographic data of the older population in long-term care situations in Taiwan.

Methods: The study enrolled 500 participants who were the elderly in long-term care situations and used the Brief Symptom Rating Scale (BSRS-5) and Chinese Happiness Inventory (CHI) to determine the psychopathology and level of happiness. Multiple linear regression analysis (using a stepwise method) and a two-step cluster analysis were performed to examine the data.

Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model.

Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome ( ). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in mice.

A proactive remote pharmaceutical care for rural elderly population: The Houston-Apollo polypharmacy project.

Aims: To evaluate polypharmacy-related problems in the elderly people who live in rural through a proactive pharmaceutical care project under a novel remote medical service infrastructure (the Houston-Apollo polypharmacy project).

Methods: It is a prospectively cross-sectional study. The elderly aged 65 years old lived in communities executed the congregate meal service and joined the Houston-Apollo project were included.

Development of the Houston-Apollo model for older people living in remote areas in Taiwan.

Aim: Senior healthcare is challenging in remote areas, particularly in an economically disadvantaged population. This study examined the benefits of a combined healthcare system (Houston-Apollo model) in improvements of physical performance and medical care utilization of local older people.

Methods: People aged ≥65 years who participated in congregate meal services were recruited.

Seizure Frequency Is Associated with Effective Connectivity of the Hippocampal-Diencephalic-Cingulate in Epilepsy with Unilateral Mesial Temporal Sclerosis.

Temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) is a common intractable epilepsy. To seek neural correlates of seizure recurrence, this study investigated aberrant intrinsic effective connectivity (iEC) in TLE with unilateral MTS and their associations with seizure frequency. Thirty patients with unilateral MTS (left/right MTS = 14/16) and 37 age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rsfMRI) on a 3-Tesla magnetic resonance imaging (MRI) system.

Equilibrative Nucleoside Transporters-1 Inhibitors Act as Anti-epileptic Agents by Inhibiting Glutamatergic Transmission.

Adenosine dysregulation is associated with the occurrence of the epilepsy and equilibrative nucleoside transporters-1 (ENT-1) functions as an important regulator of extracellular adenosine in the brain. This study was aimed to prove the anti-epileptic effect of BBB permeable ENT-1 inhibitors, JMF1907 and J4, on animal models of various epilepsy, and the mechanisms that are involved. Maximal electroshock seizure (MES), pentylenetetrazol (PTZ)-induced seizure and kindling models were used as mouse models of generalized tonic-clonic epilepsy, generalized myoclonic epilepsy, and partial epilepsy, respectively.

Cost-Effectiveness Analysis of Deep Brain Stimulation for Parkinson Disease in Taiwan.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost.

Methods: A Markov decision model was constructed on the basis of a societal perspective.

Application of heart rate variability during blood pressure measurement in patients with somatic symptom disorder.

Objective: This study wants to test whether the heart rate variability (HRV) analysis using sphygmomanometers can effectively reflect the physical and emotional distress of somatic symptom disorder (SSD) cases and assist in further health management.

Methods: This study includes 66 female SSD cases and 32 male SSD cases. All cases received a 200-second blood pressure (BP) measurement, after which the numerical figure for the heart rate was obtained from the BP signal for HRV analysis.

Premature white matter aging in patients with right mesial temporal lobe epilepsy: A machine learning approach based on diffusion MRI data.

Brain age prediction based on machine learning has been applied to various neurological diseases to discover its clinical values. By this innovative approach, it has been reported that the patients with refractory epilepsy had premature brain aging. Of refractory epilepsy, right and left subtypes of mesial temporal lobe epilepsy (MTLE) are the most common forms and exhibit distinct patterns in white matter alterations.

Static Magnetic Field Induced Neural Stem/Progenitor Cell Early Differentiation and Promotes Maturation.

The potential impacts of magnetic field exposures on brain development have raised public concern. In the present study, we aimed to investigate the biophysical effects of moderate-intensity (0.5 T, Tesla) static magnetic field (SMF) on mice neural progenitor cells (mNPCs).

Low ambient temperature as the only meteorological risk factor of seizure occurrence: A multivariate study.

Background: The onset of epileptic seizures is influenced by weather, which is multifactorial. It is unknown which specific weather factors affect the occurrence of seizures.

Objectives: We studied the correlation between the onset of epileptic seizures and multiple weather parameters based on a population-based registry profile.

Electrical Abnormalities in Dopaminergic Neurons of the Substantia Nigra in Mice With an Aromatic L-Amino Acid Decarboxylase Deficiency.

Aromatic L-acid decarboxylase (AADC) deficiency causes severe motor disturbances in affected children. A putamen-targeted gene therapy improves the motor function of patients. The present study investigated the electrical properties of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) of mice with an AADC deficiency (Ddc).

Gradient Relationship between Increased Mean Corpuscular Volume and Mortality Associated with Cerebral Ischemic Stroke and Ischemic Heart Disease: A Longitudinal Study on 66,294 Taiwanese.

The gradient relationship between mean corpuscular volume (MCV) and mortality due to ischemic vascular disease has not been researched using a large-scale population-based study. This study evaluated the association between MCV and death attributable to cerebrovascular disease (CVD) and cardiovascular disease (CAD) in a large population- and community-based Taiwanese cohort. A longitudinal study with a 9-year follow-up was conducted to evaluate individuals aged 20 years or older who had participated in the Keelung (the northernmost city in Taiwan) community-based integrated screening (abbreviated as KCIS) program since September 1999.

The Penetration Depth for Hanatoxin Partitioning into the Membrane Hydrocarbon Core Measured with Neutron Reflectivity.

Hanatoxin (HaTx) from spider venom works as an inhibitor of Kv2.1 channels, most likely by interacting with the voltage sensor (VS). However, the way in which this water-soluble peptide modifies the gating remains poorly understood as the VS is deeply embedded within the bilayer, although it would change its position depending on the membrane potential.

The Mycobacterial Adjuvant Analogue TDB Attenuates Neuroinflammation via Mincle-Independent PLC-γ1/PKC/ERK Signaling and Microglial Polarization.

Microglial activation has long been recognized as a hallmark of neuroinflammation. Recently, the bacillus Calmette-Guerin (BCG) vaccine has been reported to exert neuroprotective effects against several neurodegenerative disorders. Trehalose-6,6'-dibehenate (TDB) is a synthetic analogue of trehalose-6,6'-dimycolate (TDM, also known as the mycobacterial cord factor) and is a new adjuvant of tuberculosis subunit vaccine currently in clinical trials.

Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke.

Ischemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated.

Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia.

Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear.