Emerging Role of Ubiquitin Proteasome System and Autophagy in Pediatric Demyelinating Leukodystrophies and Therapeutic Opportunity.

Leukodystrophies represent a heterogeneous group of disorders characterized by specific genetic mutations, metabolic abnormalities, and degeneration of white matter in the central nervous system. These disorders are classified into several categories, with X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) being the most prevalent demyelinating leukodystrophies in pediatric populations. Maintaining proteostasis, which is critical for normal cellular function, relies fundamentally on the ubiquitin-proteasome system (UPS) and autophagy for the degradation of misfolded and damaged proteins.

Circulating MicroRNAs as a biomarker signature of perinatal asphyxia.

Aim: This study aimed to explore whether microRNAs (miRNAs) could serve as biomarkers of perinatal asphyxia and whether they were correlated with severity of brain magnetic resonance imaging.

Methods: We prospectively enrolled 26 full-term newborns, including 10 with perinatal asphyxia and 16 healthy controls. Plasma samples were collected at 0-6 h and 7 days of age.

Neurological manifestations of SARS-CoV-2 infection in children in Taiwan: A cross-section, multicenter study.

Background: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry.

Methods: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder.

Background: This study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder.

Methods: Consecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated.

Case report: Presentations and cytokine profiles of inflammatory non-pulmonary COVID-19 and related diseases in children.

The coronavirus disease 2019 (COVID-19) pandemic has evolved to dynamic waves of different SARS-CoV-2 variants. Initially, children diagnosed with COVID-19 presented pulmonary involvement characterized by mild diseases. In the later waves of the COVID-19 pandemic, life-threatening non-pulmonary inflammatory diseases such as (1) aseptic meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) multisystem inflammatory syndrome in children (MIS-C) have been reported, affecting the pediatric population.

Factors associated with Tourette syndrome among adolescents in Taiwan: A cross-sectional correlational study.

Purpose: Adolescents with Tourette syndrome (TS) may suffer from learning difficulties (attention-deficit/hyperactivity disorder), challenges in interpersonal interactions (especially with peers), disruptions of daily routines (disruptive behavior disorders), and increased psychosocial stress, which can result in internalizing and externalizing behavioral problems, such as venting depression and stress through self-harm. The aim of this study was to investigate peer attachment in adolescents with TS and associated risk factors.

Design And Methods: Adolescents with TS aged 13-18 years were recruited from the outpatient departments of 2 hospitals in Taiwan.

Rapamycin Alleviates Protein Aggregates, Reduces Neuroinflammation, and Rescues Demyelination in Globoid Cell Leukodystrophy.

We have shown in vivo and in vitro previously that psychosine causes dysfunction of autophagy and the ubiquitin-proteasome system underlying the pathogenesis of globoid cell leukodystrophy (GLD), a devastating lysosomal storage disease complicated by global demyelination. Here, we investigated the therapeutic efficacy of the mTOR inhibitor rapamycin in twitcher mice, a murine model of infantile GLD, in biochemical, histochemical, and clinical aspects. Administration of rapamycin to twitcher mice inhibited mTOR signaling in the brains, and significantly reduced the accumulation of insoluble ubiquitinated protein and the formation of ubiquitin aggregates.

Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma.

Impact of Mitochondrial A3243G Heteroplasmy on Mitochondrial Bioenergetics and Dynamics of Directly Reprogrammed MELAS Neurons.

The MELAS syndrome primarily affecting the CNS is mainly caused by the m.A3243G mutation. The heteroplasmy in different tissues affects the phenotypic spectrum, yet the impact of various levels of m.

Pathogenesis and Preventive Tactics of Immune-Mediated Non-Pulmonary COVID-19 in Children and Beyond.

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower.

Is the Yale Global Tic Severity Scale a valid tool for parent-reported assessment in the paediatric population? A prospective observational study in Taiwan.

Objective: The Yale Global Tic Severity Scale (YGTSS) is the most commonly used clinician-rated evaluation tool for Tourette syndrome (TS), with established reliability and validity. This study aims to determine whether the YGTSS is a valid parent-reported assessment in the TS population.

Design: A prospective cohort study.

Therapeutic effects of children with refractory epilepsy after vagus nerve stimulation in Taiwan.

Background: Vagus nerve stimulation (VNS) is used as an add-on treatment for epilepsy. This study aimed to use Taiwanese nationwide registry data to analyze the therapeutic effects of VNS in children with refractory epilepsy (RE) and try to explore predictive factors of VNS treatment effectiveness.

Methods: This retrospective study collected data from December 2007 to December 2014.

Impairment of Proteasome and Autophagy Underlying the Pathogenesis of Leukodystrophy.

Impairment of the ubiquitin-proteasome-system (UPS) and autophagy causing cytoplasmic aggregation of ubiquitin andp62 have been implicated in the pathogenesis of most neurodegenerative disorders, yet, they have not been fully elucidated in leukodystrophies. The relationship among impairment of UPS, autophagy, and globoid cell leukodystrophy (GLD), one of the most common demyelinating leukodystrophies, is clarified in this study. We examined the ubiquitin and autophagy markers in the brains of twitcher mice, a murine model of infantile GLD, and in human oligodendrocytes incubated with psychosine.

Application of Sonography in the Diagnosis and Follow-Up of Trapped Temporal Horn of Lateral Ventricle: Two Case Reports.

Trapped temporal horn of lateral ventricle (TTHLV) is a rare condition of isolated focal hydrocephalus. We report two cases with different presentations, etiologies, and surgical managements. The first case involved an extremely preterm male baby with a history of ventriculitis and intraventricular hemorrhage; he received external ventricle drainage twice due to obstructive hydrocephalus.

Effects of preferred music therapy on peer attachment, depression, and salivary cortisol among early adolescents in Taiwan.

Aims: To explore the effects of preferred music therapy on peer attachment, depression, and salivary cortisol among early adolescents.

Background: As adolescents enter puberty, they start to seek partnering relationships among peers. Peer attachment is central for adolescents and greatly influences their physical and psychological development.

Oxidative Insults and Mitochondrial DNA Mutation Promote Enhanced Autophagy and Mitophagy Compromising Cell Viability in Pluripotent Cell Model of Mitochondrial Disease.

Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects.

A Transcriptome Study of Progeroid Neurocutaneous Syndrome Reveals POSTN As a New Element in Proline Metabolic Disorder.

Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) deficiency, which causes a progeroid syndrome, may not only shed light on its genetic contribution to autosomal recessive cutis laxa (ARCL) but also help elucidate the functional mechanisms associated with aging. In this study, we used RNA-Seq technology to examine gene expression changes in primary skin fibroblasts from healthy controls and patients with mutations.

Posterior Fossa Hemorrhage in a Term Neonate with Hemophilia A.

Posterior fossa hemorrhage is rare in term baby and difficult to assess. The clinical signs are nonspecific and usually delay the diagnosis. We present a 5-day-old male neonate of posterior fossa hemorrhage with the initial presentations of fever and seizure and early deduced by cranial ultrasonography findings as hyperechoic, asymmetric, ill-defined density and complicated with hydrocephalus.

Rare Brain Tumor in a Neonate.

Neonatal brain tumor is rare and its outcome is generally poor. We reported a 17-day-old neonate presented as enlarged head girth. The pathological finding showed an embryonal tumor with multilayered rosettes.

Clinical study of children with cryofibrinogenemia: a retrospective study from a single center.

Background: This study aimed to evaluate the demographic, clinical features, laboratory data, pathology and other survey in pediatric patients with cryofibrinogenemia.

Methods: A 12-year retrospective chart review identified eight pediatric patients at Mackay Memorial Hospital, Taipei, Taiwan.

Results: The female-to-male ratio was 3:1.

Inflexibility of AMPK-mediated metabolic reprogramming in mitochondrial disease.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is most commonly caused by the A3243G mutation of mitochondrial DNA. The capacity to utilize fatty acid or glucose as a fuel source and how such dynamic switches of metabolic fuel preferences and transcriptional modulation of adaptive mechanism in response to energy deficiency in MELAS syndrome have not been fully elucidated. The fibroblasts from patients with MELAS syndrome demonstrated a remarkable deficiency of electron transport chain complexes I and IV, an impaired cellular biogenesis under glucose deprivation, and a decreased ATP synthesis.