Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder ...characterized by hyperactivity and inattentiveness level disproportional to the child's developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients' clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.
Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging ...to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (
) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.
Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. ...aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.
Glioblastoma multiforme (GBM) is a type of brain tumor that is notorious for its aggressiveness and invasiveness, and the complete removal of GBM is still not possible, even with advanced diagnostic ...strategies and extensive therapeutic plans. Its dismal prognosis and short survival time after diagnosis make it a crucial public health issue. Understanding the molecular mechanisms underlying GBM may inspire novel and effective treatments against this type of cancer. At a molecular level, almost all tumor cells exhibit telomerase activity (TA), which is a major means by which they achieve immortalization. Further studies show that promoter mutations are associated with increased TA and stable telomere length. Moreover, some tumors and immortalized cells maintain their telomeres with a telomerase-independent mechanism termed the "alternative lengthening of telomeres" (ALT), which relates to the mutations of the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), the death-domain associated protein (DAXX) and H3.3. By means of the mutations of the telomerase reverse transcriptase (TERT) promoter and ATRX/DAXX, cancers can immortalize and escape cell senescence and apoptosis. In this article, we review the evidence for triggering GBM cell death by targeting telomerase and the ALT pathway, with an extra focus on a plant-derived compound, butylidene phthalide (BP), which may be a promising novel anticancer compound with good potential for clinical applications.
While Parkinson’s disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and ...neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan’s Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.
SURF1 encodes the assembly factor for maintaining the antioxidant of cytochrome c oxidase (COX) stability in the human electron respiratory chain. Mutations in SURF1 can cause Leigh syndrome (LS), a ...subacute neurodegenerative encephalopathy, characterized by early onset (infancy), grave prognosis, and predominant symptoms presenting in the basal ganglia, thalamus, brainstem, cerebellum, and peripheral nerves. To date, more than sixty different
mutations have been found to cause SURF1-associated LS; however, the relationship between genotype and phenotype is still unclear. Most SURF1-associated LS courses present as typical LS and cause early mortality (before the age of ten years). However, 10% of the cases present with atypical courses with milder symptoms and increased life expectancy. One reason for this inconsistency may be due to specific duplications or mutations close to the C-terminus of the SURF1 protein appearing to cause less protein decay. Furthermore, the treatment for SURF1-associated LS is unsatisfactory. A ketogenic diet is most often prescribed and has proven to be effective. Supplementing with coenzyme Q and other cofactors is also a common treatment option; however, the results are inconsistent. Importantly, anti-epileptic drugs such as valproate-which cause mitochondrial dysfunction-should be avoided in patients with SURF1-associated LS presenting with seizures.
•The predominant therapeutic approach was monotherapy, especially for elder adults.•Valproic acid was the most prescribed AED monotherapy in Taiwan.•The PDD/DDD ratio of each antiepileptic ...monotherapy was less than 1 in adult patients.
To evaluate the prescription patterns and prescribed daily dose (PDD)/defined daily dose (DDD) ratios of antiepileptic drugs (AEDs) in prevalent patients with epilepsy in Taiwan.
A nationwide retrospective cross-sectional study was conducted for prevalent patients with epilepsy in 2016 using the Taiwanese National Health Insurance Research Database. The prescription records of AEDs of all prevalent patients with epilepsy were retrieved. The mean PDDs and PDD/DDD ratios of AEDs in adult patients were obtained to evaluate dosing adequacy. A chi-square test and two-sample t test were used to analyze the differences in AED prescription patterns and dosages, respectively, among patients with different ages, sexes, comorbidities, and therapeutic approaches.
A total of 118,937 prevalent patients with epilepsy were enrolled. The predominant therapeutic approach was monotherapy, especially in the elder adults, accounting for 82.9% of elder adult patients with epilepsy. The proportion of AED monotherapy was higher in patients with dementia (78.9%) and stroke (80.6%). The top three antiepileptic monotherapies were valproic acid (28.7%), levetiracetam (19.1%), and phenytoin (16.9%); however, oxcarbazepine (22.8%) was substituted for carbamazepine (3.9%) as monotherapy for patients aged 0–17 years. Among adult patients with epilepsy, the PDD/DDD ratio of each AED in monotherapy was less than 1.00. The mean PDD of each AED was higher in polytherapy than in monotherapy (p < 0.01), except for lacosamide. The mean PDDs of all evaluated AEDs in monotherapy were lower in elder adult patients than in younger adult patients, most of which reached statistical significance (p < 0.001).
In Taiwan, valproic acid was the most prescribed AED for prevalent patients with epilepsy. The mean PDDs of most AEDs were lower than the DDDs developed by the World Health Organization.
Gastric cancer (GC) is among the most treatment-refractory epithelial malignancies. Aberrant activation of Wnt/β-catenin-signaling has been implicated in a variety of human cancers, including gastric ...cancer. Here we report that the elevated expression of lymphoid enhancer binding factor 1 (Lef1) is associated with the TNM (tumor- node-metastasis) stage of gastric cancer. Subsequently, 2,4-diamino-quinazoline (2,4-DAQ), a selective inhibitor of Lef1, was identified to suppress the expression of Wnt/β-catenin target genes such as AXIN2, MYC and LGR5 and result in the suppression of gastric cancer cell growth through the apoptotic pathway. The 2,4-DAQ also exhibited an inhibitory effect on the migration/invasion of gastric cancer cells. Importantly, the treatment of human gastric tumor xenograft with 2,4-DAQ suppressed tumor growth in a nude mouse model. Furthermore, 2,4-DAQ appears effective on patient-derived organoids (PDOs). Transcriptome sequencing analysis also revealed that 2,4-DAQ are more effective on the gastric cancers that exhibit higher expression levels of Wnt-signaling pathway-related genes than their adjacent normal gastric tissues.
We applied a stochastic method for the finite-fault modeling of strong ground motions to the 2016 Meinong, Taiwan earthquake. Newly developed attenuation models in Southern Taiwan with the ...frequency-dependent
Q
= 86.4
f
0.73
and the high-frequency decay factor
κ
0
were used in the synthetic model. The horizontal-to-vertical spectral ratios (HVSR) were calculated from weak motions and the Meinong mainshock and used for the site amplification correction of the synthetic waveforms produced by the stochastic ground motion simulation. Simulations incorporating the attenuation models and site correction improved the prediction of the S-wave envelope, duration, and peak ground acceleration (PGA). The nonlinear site response during the Meinong mainshock was identified by the degree of nonlinear site response (DNL), which is a summation of HVSR differences between weak motions and the Meinong mainshock as recorded by the Taiwan Strong Motion Instrument Program. The DNL showed a positive correlation with ground motion intensity. The surface site conditions influenced DNL strength. The percentage of PGA reduction calculated in this study can be an indicator of the spatial distribution of the degree of nonlinear soil effects on the Meinong earthquake in the time domain. Areas that had high levels of PGA reduction overlap with areas that had high liquefaction potential. Based on the residual analysis, forward directivity was identified in a 105° range in the northwestward direction. The amplification of forward rupture directivity was three times greater than the backward rupture directivity.
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