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1.
J Bacteriol ; 205(8): e0018723, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37439688

ABSTRACT

The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections. IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.


Subject(s)
Acinetobacter baumannii , Rifampin , Animals , Mice , Rifampin/pharmacology , Acinetobacter baumannii/metabolism , Famotidine/metabolism , Prospective Studies , Anti-Bacterial Agents/metabolism , Disease Models, Animal , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial
2.
Ying Yong Sheng Tai Xue Bao ; 33(7): 2001-2008, 2022 Jul.
Article in Chinese | MEDLINE | ID: mdl-36052805

ABSTRACT

With the acceleration of regional economic integration, human activities have played an increasingly crucial role in regional sustainable development. In this study, MODIS remote sensing data and ecological footprint of net primary productivity (EF-NPP) were leveraged to calculate the equivalence factor and yield factor of the six major biologically productive land areas in the Pearl River Delta Urban Agglomeration. We analyzed the changes in per capita ecological footprint, per capita ecological carrying capacity, natural resource utilization efficiency and ecological moderate population from 2000 to 2020. Results showed that the per capita ecological footprint in the Pearl River Delta Urban Agglomeration continued to rise from 2000 to 2020. The ecological occupation of energy land was the highest. The ecological footprint was high in west, low in middle, and higher in northwest of the study area. The per capita ecological carrying capacity was relatively high in Zhaoqing and Jiangmen and low in Shenzhen, Dongguan, Foshan and Zhongshan. The gap between the ecological moderate population and the regional actual population widened over time, reaching 30.62 million in 2020. The regional actual population was much larger than the ecological moderate population, indicating huge population pressure. The natural resource utilization efficiency of the three main industries was high. The economic benefits created by the per capita ecological footprint increased by 36800 yuan·hm-2 during the research period, with an average annual growth rate of 1800 yuan·hm-2. The growth rate of the tertiary industry was the highest. Therefore, the results could provide reference for the study on natural resource utilization efficiency in medium and small-scale regions.


Subject(s)
Ecology , Rivers , China , Cities , Conservation of Natural Resources , Ecology/methods , Humans , Industry , Sustainable Development
3.
Microbiol Spectr ; 10(3): e0186421, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35467404

ABSTRACT

Autism spectrum disorder (ASD), a highly hereditary and heterogeneous neurodevelopmental disorder, is influenced by genetic and environmental factors. Tuberous sclerosis complex (TSC) is a common syndrome associated with ASD. Cytomegalovirus (CMV) infection is an environmental risk factor for ASD. The similarities in pathological and mechanistic pathways of TSC and CMV intrigued us to investigate whether CMV and TSC interacted in ASD's occurrence. We detected CMV IgG seroprevalence of 308 TSC patients from our prospective cohort (September 2011 to March 2021) and 93 healthy children by magnetic particle indirect chemiluminescence immunoassay. A total of 206 TSC patients enrolled were divided into ASD and non-ASD groups, and the relationship between ASD and CMV seroprevalence was analyzed. Nested PCR and Western blot were used to detect CMV DNAs and proteins in cortical malformations of seven TSC patients with and without ASD. No difference was found in CMV seroprevalence between TSC patients and healthy children (74.0% versus 72.0%, P = 0.704). Univariate analysis showed the seroprevalence in TSC patients with ASD was higher than that in TSC patients without ASD (89.2% versus 75.1%, P = 0.063), and multifactorial analysis showed that CMV seroprevalence was a risk factor for ASD in TSC patients (OR = 3.976, 95% CI = 1.093 to 14.454). Moreover, CMV was more likely to be detected in the cortical malformations in TSC patients with ASD but not in those without ASD. The findings demonstrated that CMV may increase the susceptibility of TSC to ASD. IMPORTANCE CMV is an environmental risk factor for ASD, but its role in syndromic autism with known genetic etiology has been rarely studied. The pathogenesis of ASD is related to the interaction between environmental and genetic factors. This study demonstrated that CMV can contribute to the occurrence of ASD related to TSC, a common genetic syndrome associated with ASD. Our findings provided support for the theory of gene-environment interaction (G × E) in pathogenesis of ASD and a new perspective for the prevention and therapy for TSC related ASD.


Subject(s)
Autism Spectrum Disorder , Cytomegalovirus Infections , Tuberous Sclerosis , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/etiology , Child , Cytomegalovirus/genetics , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/epidemiology , Humans , Prospective Studies , Seroepidemiologic Studies , Tuberous Sclerosis/complications , Tuberous Sclerosis/epidemiology , Tuberous Sclerosis/genetics
4.
Seizure ; 97: 23-31, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35286974

ABSTRACT

OBJECTIVE: To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy. METHODS: A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (<12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint. RESULTS: There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged <6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P<0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P<0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004]. CONCLUSION: Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent.


Subject(s)
Epilepsy , Spasms, Infantile , Tuberous Sclerosis , Case-Control Studies , Child, Preschool , Cohort Studies , Epilepsy/complications , Epilepsy/etiology , Humans , Infant , Registries , Seizures/complications , Seizures/etiology , Sirolimus/therapeutic use , Spasms, Infantile/drug therapy , Tuberous Sclerosis/complications , Tuberous Sclerosis/drug therapy , Tuberous Sclerosis/genetics
5.
Seizure ; 95: 64-74, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35007884

ABSTRACT

OBJECTIVE: Syntaxin binding protein 1 (STXBP1) plays an important role in the release of synaptic vesicles. STXBP1-related encephalopathy is a brain dysfunction caused by STXBP1 variation. Levetiracetam (LEV) exerts antiepileptic effects by binding to synaptic vesicle protein 2A (SV2A). This study aimed to analyze the prognosis of LEV treatment of STXBP1 encephalopathy (STXBP1-E) and the correlation among genotype, phenotype, and LEV efficacy. METHODS: Patients with pathogenic STXBP1 variants were collected from multiple centers, and their clinical history, video electroencephalogram (vEEG) characteristics, imaging examination data, and anti-seizure medication (ASM) history were systematically analyzed. The ASMs related to the prognosis were explored. RESULTS: Forty patients with STXBP1-E were enrolled in this study. The detailed ASM usage of 37 patients was recorded without intervening in ASM selection. At the endpoint of six months treatment, the results of Fisher's exact test showed that in all ASMs, LEV affected the prognosis of patients with STXBP1-E. LEV was effective in improving the partial remission rate but did not achieve seizure freedom. However, LEV monotherapy could achieve seizure freedom in patients with other early-onset epileptic and encephalopathy. For refractory West syndrome (WS) or Ohtahara syndrome (OS), LEV combined with other ASMs could improve the seizure remission rate. CONCLUSION: LEV increased the seizure reduction rate and improved the vEEG characteristics in patients with STXBP1-E, but not seizure freedom. LEV combined with other ASMs could increase the seizure reduction rate, especially for refractory WS or OS. Thus, LEV could be considered after identifying the pathogenicity of STXBP1 variants.


Subject(s)
Brain Diseases , Piracetam , Anticonvulsants/therapeutic use , Brain Diseases/drug therapy , Humans , Levetiracetam/therapeutic use , Munc18 Proteins/genetics , Phenotype , Piracetam/therapeutic use
6.
Childs Nerv Syst ; 38(5): 947-952, 2022 05.
Article in English | MEDLINE | ID: mdl-35083513

ABSTRACT

PURPOSE: There was no evidence whether the mammalian/mechanistic target of rapamycin pathway hyperactivation and long-term use of mTOR inhibitors have any effects on the physical development of children. The aim was to evaluate these effects by comparing the physical development of children with TSC and normal children. METHODS: A total of 120 eligible children were enrolled. They were administered sirolimus and followed for at least 12 months. Height, weight, BMI and lipid metabolism index were collected during treatment. Pearson's chi-square and Fisher's exact test were used for comparison of proportions of patients exhibiting normal and abnormal physical growth before and after 1 year of treatment. Logistic regression was used to evaluate the influence of age, sex and abnormal lipid metabolism on the increased BMIs of TSC patients after treatment. RESULTS: Most of the enrolled TSC children were in the normal height, weight and BMI ranges at baseline (91.7%, 95.8% and 78.3%, respectively). Most remained in the normal height, weight and BMI ranges after 1 year of sirolimus treatment (94.2%, 95% and 76.7%, respectively). There was no significant difference in the proportion of physical development before and after treatment (p > 0.05). Thirty-eight (38/106, 35.8%) patients had increased BMIs after 1 year of treatment, but there was no significant correlation between age, sex and lipid metabolism and increased BMI. CONCLUSIONS: Overactivation of the mTOR pathway and long-term administration of sirolimus does not affect the physical development of children with TSC.


Subject(s)
Tuberous Sclerosis , Animals , Child , Humans , Mammals , Sirolimus/adverse effects , Tuberous Sclerosis/drug therapy
7.
Ther Adv Neurol Disord ; 15: 17562864221138148, 2022.
Article in English | MEDLINE | ID: mdl-36601084

ABSTRACT

Background: Vigabatrin (VGB) is currently the most widely prescribed first-line medication for individuals with infantile spasms (IS) and especially for those with tuberous sclerosis complex (TSC), with demonstrated efficacy. Meanwhile, its adverse events, such as vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI; VABAM), have also been widely reported. Objectives: The objectives of this study were to observe the occurrences of VABAM in patients with IS caused by TSC (IST) and further explore the associated risk factors. Methods: Children with IS receiving VGB were recruited from our institution; clinical, imaging, and medication data were collected. Cerebral MRI was reviewed to determine the occurrence of VABAM. Group comparisons (IS caused by TSC and other etiologies) were performed; subgroup analyses on IST were also performed. Next, a retrospective cohort study of children taking VGB was conducted to explore risk/protective factors associated with VABAM. Results: The study enrolled 172 children with IS who received VGB. VABAM was observed in 38 patients (22.1%) with a peak dosage of 103.5 ± 26.7 mg/kg/day. Subsequent analysis found the incidence of VABAM was significantly lower in the 80 patients with IST than in the 92 patients with IS caused by other etiologies (10% versus 32.6%, p-value < 0.001). In subgroup analyses within the IST cohort, VABAM was significantly lower in children who received concomitant rapamycin therapy. Univariate and multivariate logistic regression analysis of the 172 IS children showed that treatment with rapamycin was the independent factor associated with a lower risk of VABAM; similar results were observed in the survival analysis. Conclusion: The incidence of VABAM was significantly lower in IST patients. Further research is needed to examine the mechanisms that underlie this phenomenon and to determine if treatment with rapamycin may reduce the risk of VABAM.

8.
Carbohydr Polym ; 270: 118367, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34364612

ABSTRACT

Temperature-induced structural variations of retrograded starch gel during long-term storage were investigated in a real food system (wet starch noodles). Fresh starch noodles presented a B-type XRD pattern containing 8.82% crystallinity and 16.04% double helices. In the first 2 weeks, double helices of starch chain formed long-range ordered structure leading to increased crystallinity, and such structural transformation was positively correlated with increasing storage temperature (from 4 °C to 35 °C) and storage time. However, with the extension of storage time to 12 weeks, the disorganization of supra-molecular structure was likely to be observed by decreased crystallinity, double helix and water mobility. Besides, we propose that the area and intensity of Raman band at 2910 cm-1 can be a good indicator for evaluating perfection of crystallinity in starch noodles. These results contributed to a better understanding of mechanisms underlying molecular order changes of retrograded starch gel product during long-term storage.


Subject(s)
Food Handling/methods , Ipomoea batatas/chemistry , Starch/chemistry , Gels/chemistry , Oryza/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Temperature , Time Factors , Triticum/chemistry , Water/chemistry , X-Ray Diffraction/methods
9.
Food Chem ; 357: 129744, 2021 Apr 05.
Article in English | MEDLINE | ID: mdl-33878579

ABSTRACT

Cooking performance, micro- and molecular structure, storage stability and shelf-life prediction of high-moisture wet starch noodles (SN) were investigated. SEM images revealed that compared to dried SN, cooked wet SN had more evenly honeycomb-like network with smaller size of pores, indicating stronger interaction among molecules and causing favorable cooking performance. XRD and ATR-FTIR results evidenced that wet SN contained more complete crystallites and higher proportion of crystalline region. During storage, the quality decay of wet SN was mainly associated to the increment of total aerobic viable count (TAVC), titrable acidity and amylase, as well as the decreased textural hardness, overall acceptability and lightness. Based on TAVC, titrable acidity and overall acceptability, predicted shelf-life of vacuum-packed wet SN at 25 °C was 15.31, 21.54 and 16.65 weeks respectively, with relative error all within 20%, proving that the validated model could be an effective tool for monitoring the shelf-life of wet SN.

10.
J Pediatr ; 233: 150-155.e4, 2021 06.
Article in English | MEDLINE | ID: mdl-33631166

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Heart Neoplasms/drug therapy , Rhabdomyoma/drug therapy , Sirolimus/therapeutic use , Tuberous Sclerosis/complications , Age Factors , Child, Preschool , Cohort Studies , Female , Heart Neoplasms/etiology , Humans , Infant , Male , Rhabdomyoma/etiology , Sex Factors
11.
Am J Med Genet A ; 185(2): 377-383, 2021 02.
Article in English | MEDLINE | ID: mdl-33205896

ABSTRACT

Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.


Subject(s)
Brain Diseases/genetics , Intellectual Disability/genetics , Ubiquitin-Protein Ligases/genetics , Zebrafish Proteins/genetics , Adolescent , Animals , Brain Diseases/epidemiology , Brain Diseases/pathology , Child , Child, Preschool , Disease Models, Animal , Genetic Predisposition to Disease , Humans , Infant , Intellectual Disability/epidemiology , Intellectual Disability/pathology , Male , Mutation/genetics , Exome Sequencing , Zebrafish/genetics
12.
Cancer Cell Int ; 20: 510, 2020.
Article in English | MEDLINE | ID: mdl-33088218

ABSTRACT

BACKGROUND: Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. METHODS: Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. RESULTS: Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. CONCLUSION: A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.

14.
Orphanet J Rare Dis ; 15(1): 147, 2020 06 12.
Article in English | MEDLINE | ID: mdl-32532290

ABSTRACT

OBJECTIVE: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with many manifestations, and it involves any organ. In this study, we report a TSC patient with new type skin lesions. METHODS: A 7-month-old TSC boy with multiple cutaneous nodules was admitted in our hospital. We collected the clinical data of the patient. We performed biopsy of cutaneous nodules and whole-exome sequencing in both paraffin block tissue and blood samples. RESULTS: The patient presented with a 2 month history of gradual growth multiple cutaneous nodules. He had cardiac rhabdomyoma, subependymal giant cell astrocytoma (SEGA) and hypomelanotic macules. The pathological finding of cutaneous nodules was consistent with juvenile xanthogranuloma (JXG). After 3 months of sirolimus treatment, the multiple nodules disappeared. The whole-exome sequencing identified TSC1 (c.2356C > T, p.R786*) mutation in both paraffin block tissue and blood samples. We overturned the original pathological diagnosis and finally identified JXG as a new type of skin lesions in TSC. CONCLUSION: This is the first report on the occurrence of JXG skin lesions in TSC patient. Genetic testing is necessary in JXG. These findings expand the phenotype of skin in patients with TSC and contribute to the elucidation of JXG pathogenesis and treatment.


Subject(s)
Hypopigmentation , Tuberous Sclerosis , Xanthogranuloma, Juvenile , Genetic Testing , Humans , Infant , Male , Sirolimus , Tuberous Sclerosis/genetics , Xanthogranuloma, Juvenile/genetics
15.
Seizure ; 79: 20-26, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32416565

ABSTRACT

PURPOSE: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis. METHODS: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs. RESULTS: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up. CONCLUSIONS: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy.


Subject(s)
Anticonvulsants/pharmacology , Epilepsy/drug therapy , Outcome Assessment, Health Care , Protein Kinase Inhibitors/pharmacology , Sirolimus/pharmacology , Tuberous Sclerosis/drug therapy , Adolescent , Anticonvulsants/administration & dosage , Child , Child, Preschool , Epilepsy/etiology , Female , Humans , Infant , Male , Prospective Studies , Protein Kinase Inhibitors/administration & dosage , Sirolimus/administration & dosage , TOR Serine-Threonine Kinases/antagonists & inhibitors , Tuberous Sclerosis/complications
16.
Epilepsy Res ; 164: 106349, 2020 08.
Article in English | MEDLINE | ID: mdl-32446163

ABSTRACT

Collagen type IV, alpha-1 (COL4A1) variants can cause cerebrovascular diseases, such as porencephaly and cerebral hemorrhage, in addition to other autosomal dominant hereditary diseases. Patients with COL4A1 variants can present with epilepsy, most commonly focal epilepsy. In this paper, we present five patients, three of whom were examined by the authors, and two who were previously reported. Clinically, these five patients were characterized by the presence of West syndrome (WS), periventricular leukomalacia (PVL), and microcephaly, but none had a history of premature birth or hypoxic ischemic encephalopathy (HIE). Genetic testing results indicated that all patients had heterozygous variants of COL4A1. Genetic testing for the COL4A1 variants should be considered when a patient without a history of prematurity or HIE develops WS with PVL and microcephaly.


Subject(s)
Cerebral Hemorrhage/genetics , Collagen Type IV/genetics , Spasms, Infantile/diagnosis , Spasms, Infantile/genetics , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/metabolism , Child , Child, Preschool , Female , Heterozygote , Humans , Infant , Male , Mutation/genetics , Spasms, Infantile/complications
18.
JMIR Mhealth Uhealth ; 7(9): e11229, 2019 09 12.
Article in English | MEDLINE | ID: mdl-31516128

ABSTRACT

BACKGROUND: The diagnosis of paroxysmal events in infants is often challenging. Reasons include the child's inability to express discomfort and the inability to record video electroencephalography at home. The prevalence of mobile phones, which can record videos, may be beneficial to these patients. In China, this advantage may be even more significant given the vast population and the uneven distribution of medical resources. OBJECTIVE: The aim of this study is to investigate the value of mobile phone videos in increasing the diagnostic accuracy and cost savings of paroxysmal events in infants. METHODS: Clinical data, including descriptions and home videos of episodes, from 12 patients with paroxysmal events were collected. The investigation was conducted in six centers during pediatric academic conferences. All 452 practitioners present were asked to make their diagnoses by just the descriptions of the events, and then remake their diagnoses after watching the corresponding home videos of the episodes. The doctor's information, including educational background, profession, working years, and working hospital level, was also recorded. The cost savings from accurate diagnoses were measured on the basis of using online consultation, which can also be done easily by mobile phone. All data were recorded in the form of questionnaires designed for this study. RESULTS: We collected 452 questionnaires, 301 of which met the criteria (66.6%) and were analyzed. The mean correct diagnoses with and without videos was 8.4 (SD 1.7) of 12 and 7.5 (SD 1.7) of 12, respectively. For epileptic seizures, mobile phone videos increased the mean accurate diagnoses by 3.9%; for nonepileptic events, it was 11.5% and both were statistically different (P=.006 for epileptic events; P<.001 for nonepileptic events). Pediatric neurologists with longer working years had higher diagnostic accuracy; whereas, their working hospital level and educational background made no difference. For patients with paroxysmal events, at least US $673.90 per capita and US $128 million nationwide could be saved annually, which is 12.02% of the total cost for correct diagnosis. CONCLUSIONS: Home videos made on mobile phones are a cost-effective tool for the diagnosis of paroxysmal events in infants. They can facilitate the diagnosis of paroxysmal events in infants and thereby save costs. The best choice for infants with paroxysmal events on their initial visit is to record their events first and then show the video to a neurologist with longer working years through online consultation.


Subject(s)
Diagnostic Techniques and Procedures/economics , Diagnostic Techniques and Procedures/standards , Smartphone/trends , Videotape Recording/methods , Child, Preschool , China , Cost-Benefit Analysis , Diagnostic Techniques and Procedures/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Seizures/classification , Seizures/diagnosis , Smartphone/economics , Smartphone/instrumentation , Surveys and Questionnaires , Videotape Recording/standards , Videotape Recording/trends
19.
BMC Neurol ; 19(1): 30, 2019 Feb 21.
Article in English | MEDLINE | ID: mdl-30791893

ABSTRACT

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a complication that occurs during various diseases' treatment. Imaging examination is the gold standard for diagnosis. PRES frequently occurrence in patients with hematological malignancies results in poorer prognosis and higher mortality. We aim to establish a practical and operable scale for early prediction, assessment of the severity of the Posterior Reversible Encephalopathy Syndrome, and timely intervention for better prognosis. METHODS: The scale designed by reviewing the literature and by referring to clinical practice. We assessed the reliability and validity of the scale. Scale-based assessment of children undergoing chemotherapy for acute lymphoblastic leukemia conducted as early warning and intervention for those who may have PRES. RESULTS: Establishment of Posterior Reversible Encephalopathy Syndrome early warning scoring (PEWS) scale included three parts, as follows: (1) risk factors, including underlying disease, hypertension, Infection, and drug toxicity; (2) clinical features, including high cranial pressure, visual symptoms, seizure, and disturbance of consciousness; and (3) EEG features, including slow wave and epileptiform discharges. Utility assessment of PEWS scale showed that in 57 patients with acute lymphoblastic leukemia, 54 scored less than 10 and none of them detected as PRES. The other two had scores of 12 and 13 both diagnosed with PRES by brain MRI scan. CONCLUSIONS: PEWS scale can predict PRES early. PRES was highly suspected when the score was 10 points and more. Thus, prophylactic intervention can give to improve the prognosis of PRES.


Subject(s)
Early Diagnosis , Posterior Leukoencephalopathy Syndrome/diagnosis , Adolescent , Child , Child, Preschool , Electroencephalography , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Reproducibility of Results , Risk Factors
20.
Medicine (Baltimore) ; 98(5): e14303, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30702602

ABSTRACT

No matter in or outside hospital, the success rate of cardiopulmonary resuscitation (CPR) is very low. The sign of successful CPR is the recovery of spontaneous circulation. The premise of the recovery of spontaneous circulation is the recovery and maintenance of sinus rhythm, but there is still no related research.We aim to study the factors for the recovery and maintenance time of sinus rhythm in patients with CPR.A single-center retrospective case-control study.Ethical review was obtained (ethical approval number: 20180031).The second affiliated hospital of Xi'an Jiaotong University, Xi'an Shaanxi, China.From January 2011 to December 2016, totally 344 cases met the inclusion and exclusion criteria, sinus rhythm recovered group (SR group) (n = 130 cases), sinus rhythm unrecovered group (SUR group) (n = 214 cases).The multivariate logistic regression analysis showed that red blood cell counts (OR = 1.30, 95% CI:1.04-1.63, P = .02), rescue time (OR = 0.95, 95% CI:0.94-0.97, P <.001), the usage of norepinephrine (OR = 2.14, 95% CI:1.06-4.35, P = .04) were important factor for the recovery of sinus rhythm in patients with CPR. Multivariate linear regression analysis showed that the dosage of epinephrine, the usage of naloxone and diagnosis were important factors for maintenance time of sinus rhythm after resuscitation, P <.05. The rescue time had high accuracy to predict the recovery of sinus rhythm, the area under the receiver operator characteristic (ROC) curve (AUC) was 0.84 (0.80, 0.88), sensitivity and specificity are respectively 71.54% and 93.46%.Red blood cell counts, the rescue time and the usage of norepinephrine might be important factors for the recovery of sinus rhythm, and the dosage of epinephrine, the usage of naloxone and the diagnosis might be important factors for the maintenance time of sinus rhythm in patients with CPR.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest/therapy , Hospitalization , Aged , Blood Cell Count , China , Female , Heart Arrest/mortality , Humans , Logistic Models , Male , Middle Aged , Norepinephrine/therapeutic use , Recovery of Function , Retrospective Studies , Sensitivity and Specificity , Sympathomimetics/therapeutic use , Time Factors , Treatment Outcome
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