Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

BACKGROUND AND OBJECTIVES: Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. METHODS: Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. RESULTS: Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). DISCUSSION: OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Impacts of regional socioeconomic statuses and global events on solid waste research reflected in six waste-focused journals.

The research pertaining to solid waste is undergoing extensive advancement, thereby necessitating a consolidation and analysis of its research trajectories. The existing biblio-studies on solid waste research (SWR) lack thorough analyses of the factors influencing its trends. This article presents an innovative categorization framework that categorizes publications from six SWR journals utilizing Source Latent Dirichlet Allocation. First analyse changes in publication numbers across main categories, subcategories, journals, and regions, providing a macro-level study of SWR. Temporal analysis of keywords supplements a micro-level study of SWR, which highlights that emerging technologies with low Technology Readiness Level receive significant attention, while studies on widespread technologies are diminishing. Additionally, this study demonstrates the substantial influence of socioeconomic factors and previous SWR publications on current and future SWR trends. Finally, the article confirms the impact of global events on SWR trends by examining the structural breakpoints of SWR and their correlation with global events.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in pediatric opsoclonus myoclonus ataxia syndrome presenting with neuroblastoma.

BACKGROUND: Early precision diagnosis and effective treatment of opsoclonus myoclonus ataxia syndrome (OMAS) patients presenting with neuroblastoma can prevent serious neurological outcomes. OBJECTIVE: To assess the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in pediatric OMAS with neuroblastoma. MATERIALS AND METHODS: A retrospective evaluation of 45 patients diagnosed with OMAS who underwent 18F-FDG PET/CT was performed. A univariate analysis was performed to compare clinical characteristics between OMAS with and without neuroblastoma. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for OMAS with neuroblastoma and to develop the clinical model. Finally, independent risk factors and PET/CT were fitted to build the combined model for the diagnosis of OMAS with neuroblastoma and presented as a nomogram. Receiver operating characteristic curve, decision curve, and calibration curve analyses were conducted to evaluate the performance of the models. RESULTS: Among 45 patients, 27 were PET/CT-positive, 23/27 lesions were neuroblastoma, and four were false positives. One of the false positive patients was confirmed to be adrenal reactive hyperplasia by postoperative pathology, and the symptoms of OMAS disappeared in the remaining three cases during clinical follow-up. The average maximal standardized uptake value of PET/CT-positive lesions was 2.6. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT were 100%, 81.8%, 85.2%, 100%, and 91.1%, respectively. Age at diagnosis, lactate dehydrogenase, and neuron-specific enolase showed statistically significant differences between OMAS with and without neuroblastoma. Lactate dehydrogenase was identified as the independent risk factor to develop the clinical model, and the clinical model demonstrated an area under the curve (AUC) of 0.82 for the diagnosis of OMAS with neuroblastoma, with an AUC as high as 0.91 when combined with PET/CT. The decision curve analysis and calibration curve demonstrated that the nomogram had good consistency and clinical usefulness. CONCLUSION: In patients with OMAS, 18F-FDG PET/CT has a high diagnostic accuracy in detecting tumors of the neuroblastoma, especially when combined with the independent risk factor serum lactate dehydrogenase.

An early diagnosed cerebral small vessel disease in a 12-year-old girl.

Cerebral small vessel disease (CSVD) is a leading cause of ischaemic and haemorrhagic stroke and a major contributor to dementia. It occurs mostly in adult patients, rarely in children. COL4A1 is a candidate gene in monogenic CSVD with a wide clinical and neuroimaing spectrum. Here we presented a 12-year-old girl with recurrent dizziness, mild learning difficulties and inability to concentrate, the brain MRI showed diffuse periventricular leukoencephalopathy, lacunes in bilateral centrum semiovale, periventricles and basal ganglia, dilated perivascular spaces in bilateral basal ganglia with brain MRA and MRV were normal, highly mimicked the neuroimaging of CSVD regardless of the young age and no episodes of cerebrovascular events for now. We found no vascular risk factors and excluded other diseases such as primary angitis of central nervous system (PACNS). Then a trio-whole exome sequencing was performed. We found a de novo variant of COL4A1 gene c.2662G>A (p.Gly888Arg). She was finally diagnosed as a MRI-defined covert CSVD case. Though there are no specific treatments, with the very early diagnosis in our patient, excessive physical activity, trauma, anticoagulant therapy should be avoided for possible strokes in her future life. Therefore, genetic screening should be considered in familial cases and also in sporadic cases even in pediatric patients when the brain MRI showed diffuse periventricular leukoencephalopathy, dilated perivascular spaces, as well as microhemorrhage, and deep intracerebral hemorrhages, associated with early onset ischemic strokes or not.

Hydrolytic degradation and biodegradation of polylactic acid electrospun fibers.

Increased use of bioplastics, such as polylactic acid (PLA), helps in reducing greenhouse gas emissions, decreases energy consumption and lowers pollution, but its degradation efficiency has much room for improvement. The degradation rate of electrospun PLA fibers of varying diameters ranging from 0.15 to 1.33 µm is measured during hydrolytic degradation under different pH from 5.5 to 10, and during aerobic biodegradation in seawater supplemented with activated sewage sludge. In hydrolytic conditions, varying PLA fiber diameter had significant influence over percentage weight loss (W%L), where faster degradation was achieved for PLA fibers with smaller diameter. W%L was greatest for PLA-5 > PLA-12 > PLA-16 > PLA-20, with average W%L at 30.7%, 27.8%, 17.2% and 14.3% respectively. While different pH environment does not have a significant influence on PLA degradation, with W%L only slightly higher for basic environments. Similarly biodegradation displayed faster degradation for small diameter fibers with PLA-5 attaining the highest degree of biodegradation at 22.8% after 90 days. Hydrolytic degradation resulted in no significant structural change, while biodegradation resulted in significant hydroxyl end capping products on the PLA surface. Scanning electron microscopy (SEM) imaging of degraded PLA fibers showed a deteriorated morphology of PLA-5 and PLA-12 fibers with increased adhesion structures and irregularly shaped fibers, while a largely unmodified morphology for PLA-16 and PLA-20.

Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome: a real-world study.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a serious disease in infants, and it usually evolves to other epilepsy types or syndromes, especially refractory or super-refractory focal epilepsies. Although adrenocorticotropic hormone (ACTH) is one of the first-line and effective treatment plans for IESS, it has serious side effects and is not sufficiently effective. METHODS: A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate (MgSO4) therapy for IESS in two hospital centers was conducted. The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography (EEG). To reduce the confounding bias between the two groups, we used SPSS for the propensity score matching (PSM) analysis. RESULTS: We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH alone. Only 1005 patients were enrolled in the treatment (ACTH combined with MgSO4: 744, ACTH: 261), and both treatment plans had a more than 55% response rate. However, compared to patients treated with ACTH alone, those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia EEG. After PSM, the two groups also showed significant differences in responder rate [70.8% (95% confidence interval, CI) = 66.7%-74.8%) vs. 53.8% (95% CI = 47.4%-60.2%), P < 0.001], seizure frequency (P < 0.001) and hypsarrhythmia EEG resolution (P < 0.001). Notably, multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome. Patients with less than 3 months of lead time responded to the treatment much better than those with > 3 months (P < 0.05). In addition, the overall incidence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group (31.4% vs. 63.1%, P < 0.001). During the treatment, only infection (P = 0.045) and hypertension (P = 0.025) were significantly different between the two groups, and no baby died. CONCLUSION: Our findings support that ACTH combined with MgSO4 is a more effective short-term treatment protocol for patients with IESS than ACTH alone, especially for those patients with short lead times to treatment. Video Abstract (MP4 533623 KB).

Unveiling the Microfiber Release Footprint: Guiding Control Strategies in the Textile Production Industry.

Microplastic fibers from textiles have been known to significantly contribute to marine microplastic pollution. However, little is known about the microfiber formation and discharge during textile production. In this study, we have quantified microfiber emissions from one large and representative textile factory during different stages, spanning seven different materials, including cotton, polyester, and blended fabrics, to further guide control strategies. Wet-processing steps released up to 25 times more microfibers than home laundering, with dyeing contributing to 95.0% of the total emissions. Microfiber release could be reduced by using white coloring, a lower dyeing temperature, and a shorter dyeing duration. Thinner, denser yarns increased microfiber pollution, whereas using tightly twisted fibers mitigated release. Globally, wet textile processing potentially produced 6.4 kt of microfibers in 2020, with China, India, and the US as significant contributors. The study underlined the environmental impact of textile production and the need for mitigation strategies, particularly in dyeing processes and fiber choice. In addition, no significant difference was observed between the virgin polyesters and the used ones. Replacing virgin fibers with recycled fibers in polyester fabrics, due to their increasing consumption, might offer another potential solution. The findings highlighted the substantial impact of textile production on microfiber released into the environment, and optimization of material selection, knitting technologies, production processing, and recycled materials could be effective mitigation strategies.

Panaxadiol targeting IL2 inducible T cell kinase promotes T cell immunity in radiotherapy.

Ginseng, as a traditional Chinese medicine, has a good protective effect against radiotherapy, but its mechanism in radiotherapy still needs to be further explored. The active ingredients of Ginseng were analyzed according to pharmacodynamics in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the target genes of active ingredients were screened by UniProt, PubChem and Swiss target prediction database. The differentially expressed genes of GSE6871 and GSE20162 were analyzed from the GEO database. Further, cluster analysis and enrichment analysis were carried out through protein-protein interaction network to determine hub gene. Next, build the drug-disease target network, conduct molecular docking simulation, and determine the key ingredients and targets of Ginseng on radiotherapy. We screened 16 active ingredients of Ginseng and 747 target genes from the TCMSP database. Eighty-two common differentially expressed genes were obtained by the GEO database. After topological analysis, we finally determined CD28, FYN, IL2 inducible T cell kinase (ITK), MYC and CD247 as hub genes. After integrating the drug-disease target network and molecular docking, we found that Panaxadiol, as an active ingredient of Ginseng, can target ITK to participate in T cell signal receptor pathway and act on radiotherapy. Panaxadiol can act on the key target ITK of radiotherapy, participate in T cell signal receptor pathway, and then affect the proliferation, differentiation and immune response of radiotherapy T cells, so as to reduce the side effects of radiotherapy.

Clinical and genetic spectrum of hereditary spastic paraplegia in Chinese children.

AIM: To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children. METHOD: This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP). RESULTS: We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]). clinically diagnosed with HSP and identified genetic causes in 35 patients. Most patients with autosomal dominant HSP had pHSP (16/18), whereas most patients with autosomal recessive HSP tended to have cHSP (14/16). SPG11 was the most common autosomal recessive subtype, followed by FA2H/SPG35, whereas SPAST/SPG4 was the most frequent cause of autosomal dominant HSP. Two patients with CPT1C mutations presented with a complex phenotype. Meanwhile, 10 patients were found to have likely pathogenic variants/variants of uncertain clinical significance in six genes related to HSP. INTERPRETATION: SPG11 and SPG4 were the most frequent subtypes in Chinese children with autosomal recessive HSP and autosomal dominant HSP. However, the prevalence of SPG4 was much lower than that in adults, which might be explained by the late onset of the disease. On the other hand, FA2H/SPG35 was common in our cohort, while it contributed to only a small proportion of adult cases, which might be explained by its rapid progression and early death in some patients. We also expanded the genetic and clinical spectra of SPG73.

Immunogenic cell death-related classifications in breast cancer identify precise immunotherapy biomarkers and enable prognostic stratification.

Background: Immunogenic cell death (ICD) remodels the tumor immune microenvironment, plays an inherent role in tumor cell apoptosis, and promotes durable protective antitumor immunity. Currently, appropriate biomarker-based ICD immunotherapy for breast cancer (BC) is under active exploration. Methods: To determine the potential link between ICD genes and the clinical risk of BC, TCGA-BC was used as the training set and GSE58812 was used as the validation set. Gene expression, consistent clustering, enrichment analysis, and mutation omics analyses were performed to analyze the potential biological pathways of ICD genes involved in BC. Furthermore, a risk and prognosis model of ICD was constructed to evaluate the correlation between risk grade and immune infiltration, clinical stage, and survival prognosis. Results: We identified two ICD-related subtypes by consistent clustering and found that the C2 subtype was associated with good survival prognosis, abundant immune cell infiltration, and high activity of immune biological processes. Based on this, we constructed and validated an ICD risk and prognosis model of BC, including ATG5, HSP90AA1, PIK3CA, EIF2AK3, MYD88, IL1R1, and CD8A. This model can effectively predict the survival rate of patients with BC and is negatively correlated with the immune microenvironment and clinical stage. Conclusion: This study provides new insights into the role of ICD in BC. The novel classification risk model based on ICD in BC established in this study can aid in estimating the potential prognosis of patients with BC and the clinical outcomes of immunotherapy and postulates targets that are more useful in comprehensive treatment strategies.

Clinical Effect of the Guizhi Shaoyao Zhimu Decoction in the Treatment of Hyperuricemia.

Traditional Chinese Medicine (TCM) is a medical system with a distinctive theoretical framework and extensive experience in identification and treatment acquired by the Chinese people in long-term medical practice and life practice. It is a complete, integrated, and complex knowledge system in epistemology. This study is aimed at exploring the clinical effectiveness of TCM called the Guizhi Shaoyao Zhimu Decoction in the treatment of hyperuricemia. A total of 100 patients with hyperuricemia at the Medical College of the Second Clinical College, Shandong, China, from January 2019 to January 2022 are selected as the research subjects and divided into group A and group B according to the random table method, with 50 cases in each group. Group A is treated with oral allopurinol tablets, 100 mg, 2 times a day, and group B is treated with the modified Guizhi Shaoyao Zhimu Decoction based on group A. For observation, serum uric acid (SUA) levels, urinary uric acid (UUA) levels, levels of serum inflammatory response factors (IL-6, CRP, and TNF-α), vascular endothelial function indexes (serum malondialdehyde (MDA) content, nitric oxide (NO) content), an acute attack of gout, and the incidence of adverse reactions are measured. Results show that after 2 w and 4 w of treatment, the levels of blood uric acid in each group gradually decreased compared with those before treatment, and group B is lower than group A (P < 0.05). After treatment, the vascular endothelial function indexes and inflammatory factor levels in each group are significantly improved compared with those before treatment, and the indexes in group B are better than those in group A. There is no significant difference in the incidence of related adverse reactions and acute attack of gout (P > 0.05). This shows that the TCM Guizhi Shaoyao Zhimu Decoction has a significant curative effect in the treatment of patients with hyperuricemia, which is worthy of clinical reference application.

Mycophenolate mofetil: An alternative disease-modifying agent for MOG-IgG-associated disorders in childhood: A single-center bidirectional cohort study.

OBJECTIVE: To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of childhood MOG-IgG-associated disorder (MOGAD). METHODS: Thirty patients diagnosed with relapsing MOGAD and treated with MMF for >1 year from a childhood MOGAD ambispective cohort were included in the study. The clinical characteristics, therapeutic regimen, side effects, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores of these patients were evaluated. RESULTS: The median age of disease onset was 7.05 (2.50-12.75) years. The male to female ratio was 1:1.31. All patients used MMF as first-line maintenance treatment. The median time to add MMF from disease onset was 1.08 (0.25-5.00) year. The median number of attacks before MMF initiation was 2 (2 - 8). The median duration of MMF therapy was 2.13 (1.00-3.58) years. Twenty (66.67%) patients did not experience further attacks during MMF therapy. The Kaplan-Meier curves showed a 3-year relapse-free rate of 59.8% (95% CI, 36.62-76.88%). ARR decreased during MMF therapy (0 (0 - 1.72) vs. 1.25 (0.60-4.00); P < 0.05). EDSS stabilized during MMF therapy (1.0 (0 - 2.0) vs. 0 (0 - 2.0); P = 0.206). None of the patients stopped the use of MMF due to intolerable side effects. Onset age, sex, phenotype of the first attack, ARR before MMF, MOG-IgG titers, and combined long-term prednisone (prednisone <10 mg daily for patients >40 kg or <5 mg daily for patients ≤40 kg longer than 6 months) did not predict recurrence during MMF therapy in univariate analysis. CONCLUSIONS: MMF was effective and safe for treating childhood MOGAD. No clinical feature that could predict efficacy of MMF was found in pediatric patients with MOGAD.

A 5-year-old child presenting with tumor-like primary angiitis of the central nervous system.

Introduction: Primary angiitis of the central nervous system (PACNS) is a vasculitis confined to the CNS. A small proportion of the lesions may present as a tumor-like mass, which is rarely seen in children. Case presentation: A 5-year-old girl was admitted to our hospital because of an intermittent headache. Brain imaging suggested a space-occupying lesion in the right cerebral hemisphere. The final diagnosis was PACNS with a lymphocytic pattern by stereotactic brain biopsy. Her condition improved after immunotherapy. Conclusion: Pediatricians should consider the possibility of PACNS when encountering intracranial tumor-like lesions. Early diagnosis of tumor-like PACNS and prompt immunotherapy could improve the long-term prognosis and avoid surgery.

[Analysis of IQSEC2 gene variant in a child with X-linked mental retardation].

OBJECTIVE: To analyze the clinical phenotype and genetic variants of a child with X-linked mental retardation caused by IQSEC2 gene mutation, and provide reference for the diagnosis of the disease. METHODS: The child was subjected to next generation sequencing (NGS), and the diagnosis was made by taking consideration of her clinical characteristics. RESULTS: The child has presented with global developmental delay, particularly in fine motor skill and language development, in addition with intellectual disability. Genetic testing revealed that she has harbored a heterozygous c.1861dup variant of the IQSEC2 gene, which was not detected in either parent. CONCLUSION: The de novo c.186ldup variant of the IQSEC2 gene probably underlay the X-linked mental retardation in this child. Above finding has, expanded the spectrum of IQSEC2 gene mutations and provide a basis for the diagnosis of similar cases.

Chinese patients with p.Arg756 mutations of ATP1A3: Clinical manifestations, treatment, and follow-up.

Importance: The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3. Objective: To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3. Methods: We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children's Hospital from January 2014 to December 2019. Results: Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism. Interpretation: Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.

Expanding the mutational spectrum of Rahman syndrome: A rare disorder with severe intellectual disability and particular facial features in two Chinese patients.

BACKGROUND: The study aimed to investigate the clinical and genetic features of Rahman syndrome caused by HIST1H1E gene mutations. METHODS: We retrospectively analyzed the clinical information and genetic testing results of a Rahman syndrome family in an outpatient clinic in August 2020 and summarized the clinical characteristics of the HIST1H1E gene mutations in conjunction with peer-reviewed reports. RESULTS: A 4-year-old boy was diagnosed with severe developmental delay and with specific features (large head, full cheeks, high hairline, low-set ear, sparse eyebrows, and short neck) similar to his mother (mild intellectual disability, high hairline, reduced hair, ptosis, sagging skin, and hyperkeratosis) and premature aging. Trio whole exome sequencing (WES) revealed a novel maternal c.368dup (p.G124Rfs*72) heterozygous mutation in the HIST1H1E gene. There have been only a few reported cases with mainly de novo mutations. Only six peer-reviewed articles in English and one in Chinese have been published regarding this syndrome. From 48 children with Rahman syndrome, 21 were males and 27 were females encompassing 25 mutations in the HIST1H1E gene. All mutations located in C-terminal tail were frameshift mutations leading to premature protein termination. CONCLUSION: Rahman syndrome, caused by the HIST1H1E gene mutation, is a rare autosomal dominant disorder in which the patient has an unusual facial appearance with high hairline and full cheeks, and clinical manifestations of mild to severe intellectual disability, motor delay and speech delay. Genetic testing may assist in the diagnosis of these patients. This diagnosis will permit early speech rehabilitation to improve their quality of life.

Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study.

Mitochondrial DNA (mtDNA) associated mitochondrial diseases hold a crucial position but comprehensive and systematic studies are relatively rare. Among the 262 patients of four children's hospitals in China, 96%-point mutations (30 alleles in 11 genes encoding tRNA, rRNA, Complex I and V) and 4%-deletions (seven of ten had not been reported before) were identified as the cause of 14 phenotypes. MILS presented the highest genetic heterogeneity, while the m.3243A > G mutation was the only "hotspot" mutation with a wide range of phenotypes. The degrees of heteroplasmy in the leukocytes of MM were higher than MELAS. The heteroplasmy level of patients was higher than that in mild and carrier group, while we found low-level heteroplasmy pathogenic mutations as well. Some homoplasmic variations (e.g., m.9176 T > C mutation) are having high incomplete penetrance. For a suspected MELAS, m.3243A > G mutation was recommended to detect first; while for a suspected LS, trios-WES and mtDNA genome sequencing by NGS were recommended first in both blood and urine.

Polylactic acid face masks: Are these the sustainable solutions in times of COVID-19 pandemic?

The global massive consumption of disposable face masks driven by the ongoing COVID-19 pandemic has emerged as a blooming disaster to both the land and marine environment that might last for generations. Growing public concerns have been raised over the management and control of this new form of plastic pollution, and one of the proposed sustainable solution is to use renewable and/or biodegradable resources to develop mask materials in order to minimize their environmental impacts. As a representative biodegradable polymer, polylactic acid (PLA) has been proposed as a promising candidate to produce non-woven face masks instead of those fossil-based polymers. To further explore the feasibility of this alternative mask material, the present work aims to study both the hydrolytic and bio-degradation behaviors of pure PLA-derived 3-ply disposable face masks at ambient temperature. Hydrolytic degradability was investigated at different pH conditions of 2, 7 and 13 with the whole piece of face mask soaked for regular timed intervals up to 8 weeks. Weight loss study showed neutral and acidic conditions had minimal effect on PLA masks, but rapid degradation occurred under basic conditions in the first week with a sharp 25% decrease in weight that slowly tapered off, coupled with solution pH dropping from 13 to 9.6. This trend was supported by mechanical property, bacterial filtration efficiency (BFE) and particulate filtration efficiency (PFE) studies. Masks soaked in basic conditions had their modulus and tensile strength dropped by more than 50% after 8 weeks where the middle layer reached 68% and 90% respectively just after 48 h, and BFE and PFE decreased by 14% and 43% respectively after 4 weeks, which was much more significant than those in neutral and acidic conditions. Base degradation was also supported by nuclear magnetic resonance (NMR) and fourier transform infrared (FTIR), which disclosed that only the middle layer undergo major degradation with random chain scission and cleavage of enol or enolate chain ends, while outer and inner layers were much less affected. Scanning electron microscopy (SEM) attributed this observation to thinner PLA fibers for the middle layer of 3-7 µm diameter, which on average is 3 times smaller. This degradation was further supported by gel permeation chromatography (GPC) which saw an increase in lower molecular weight fragment Mw ~ 800 Da with soaking duration. The biodegradation behavior was studied under OECD 301F specification in sewage sludge environment. Similarly, degradation to the middle meltblown layer was more extensive, where the average weight loss and carbon loss was 25.8% and 25.7% respectively, double that of outer/inner spunbond layer. The results showed that the face masks did not completely disintegrate after 8 weeks, but small solubilized fragments of PLA formed in the biodegradation process can be completely mineralized into carbon dioxide without generation of secondary microplastic pollution in the environment. PLA masks are therefore a slightly greener option to consider in times of a pandemic that the world was caught unprepared; however future research on masks could be geared towards a higher degradability material that fully breaks down into non-harmful components while maintaining durability, filtration and protection properties for users.

HPDL deficiency causes a neuromuscular disease by impairing the mitochondrial respiration.

Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes. A nuclear gene HPDL (4-hydroxyphenylpyruvate dioxygenase-like), which encodes an intermembrane mitochondrial protein, has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes. Here, we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity, including developmental delay/intellectual disability, spasm, and hypertonia. Seven different pathogenic variants are identified, of which five are novel. Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function, which is also observed in HPDL-knockdown (KD) HeLa cells. In these HeLa cells, overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate. In addition, a decreased activity of the oxidative phosphorylation (OXPHOS) complex II is observed in patient-derived lymphocytes and HPDL-KD HeLa cells, further supporting an essential role of HPDL in the mitochondrial respiratory chain. Collectively, our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.

Age-dependent characteristics and prognostic factors of pediatric anti-N-methyl-d-aspartate receptor encephalitis in a Chinese single-center study.

OBJECTIVE: To describe the clinical features and prognosis of pediatric anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis from a single center in northern China. METHODS: The clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by age, were retrospectively studied. Risk factors including relapse and long-term (follow-up ≥1 year) outcomes were analyzed. RESULTS: A total of 273 patients were included between November 2011 and December 2019, and the average age of onset was 7.5 ± 4.0 years (0.5-15.8 years). Of them, 159（58.2%） were female, and the proportion of females increased with age. Seizures were the most common initial symptom. Movement disorders（86.1%） and psychiatric（82.4%） symptoms were most frequent in the acute phase. In the acute stage, the incidence of movement disorders decreased with age (χ2 = 10.676, p = 0.011), while the proportion of psychiatric symptoms increased with age (χ2 = 21.85, p < 0.001) The recurrence rate was 9.6% (24/250). Demyelination was an independent risk factor for relapse (p = 0.006, OR = 5.877, 95% CI: 1.658-20.835). Among the 210 patients who were followed up for more than one year, 28 patients had a poor prognosis (mRS ≥3). Onset age (p = 0.038，OR = 0.844, 95% CI: 0.720-0.991), precursor of viral encephalitis (p = 0.007，OR = 9.876, 95% CI: 1.878-51.940), and ICU admission (p = 0.023，OR = 5.924, 95% CI: 1.280-27.064) significantly affected the prognosis. The mortality rate was 2.9%. CONCLUSIONS: The characteristics of anti-NMDAR encephalitis in children are age-dependent. Early-onset, the precursor of viral encephalitis, and ICU admission may indicate poor prognosis. Demyelination may be a risk factor for recurrence.