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1.
J Clin Periodontol ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38706227

ABSTRACT

AIM: To evaluate the changes in periodontal parameters (reduction in probing pocket depth [PPD], gain in clinical attachment level [CAL] and reduction in full-mouth bleeding on probing [BoP]) after subgingival instrumentation of periodontal pockets at different time points in systemically healthy patients suffering from periodontitis. MATERIALS AND METHODS: Four databases were searched for RCTs that carried out subgingival instrumentation in periodontal pockets and evaluated PPD at a minimum of two consecutive time points other than baseline. The analysis was conducted for both all pocket depths and stratified for initially shallow (4-5 mm) and deep (≥6 mm) pockets and data were extracted for various time points, 1-2, 3-4 and 5-6 months. Weighted mean effects (WMEs) were calculated with 95% confidence interval (CI) and predictive intervals were calculated. RESULTS: Twenty-nine RCTs were identified, and all of them were included in the meta-analysis. The results showed that for both shallow and deep pockets there was a small though clinically meaningful change between 1- to 2-month and 3- to 4-month time points and between these and 5-6 months. CONCLUSIONS: In systemically healthy patients, the greater part of reduction in PPD and gain in CAL occurs within the first 1-2 months after subgingival instrumentation. However, additional benefits in terms of pocket depth reduction occur beyond these early time points.

2.
Int J Dev Neurosci ; 84(4): 305-313, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38566307

ABSTRACT

Segawa syndrome is a rare autosomal recessive form of dopa-responsive dystonia resulting from TH gene dysfunction. Patients typically exhibit symptoms such as generalized dystonia, rigidity, tremors, infantile Parkinsonism, and pseudo-spastic paraplegia. Levodopa is often an effective treatment. Due to its rarity, high heterogeneity, and poorly understood pathological mutation and phenotype spectrums, as well as genotype-phenotype and genotype-treatment outcome correlations, Segawa syndrome poses diagnostic and therapeutic challenges. In our study, through clinical and molecular analyses of three Chinese Segawa patients, we re-evaluated the pathogenicity of a TH mutation (c.880G>C;p.G294R) previously categorized as "Conflicting classifications of pathogenicity" in ClinVar. Also, we summarized the clinical phenotypes of all reported Segawa syndrome cases until 2023 and compared them with our patients. We identified a novel phenotype, "cafe-au-lait macules," not previously observed in Segawa patients. Additionally, we discussed the correlation between specific genotypes and phenotypes, as well as genotypes and treatment outcomes of our three cases. Our findings aim to enhance the understanding of Segawa syndrome, contributing to improved diagnosis and treatment approaches in the future.


Subject(s)
Dystonic Disorders , Mutation , Humans , Male , Female , Dystonic Disorders/genetics , Dystonic Disorders/therapy , Treatment Outcome , Tyrosine 3-Monooxygenase/genetics , Levodopa/therapeutic use , Child , Phenotype , Child, Preschool , Asian People/genetics , China , Heterozygote , East Asian People
3.
Cortex ; 173: 283-295, 2024 04.
Article in English | MEDLINE | ID: mdl-38442567

ABSTRACT

Evidence suggests that some patients with isolated hippocampal damage appear to present with selective preservation of unfamiliar face recognition relative to other kinds of visual test stimuli (e.g., words). Bird and Burgess (2008) formulated a review and secondary analysis of a group of 10 cases all tested on a clinical assessment of word and face recognition memory (RMT, Warrington, 1984), which confirmed the key memory dissociation at the group level. The current work provides an updated secondary analysis of such cases with a larger published sample (N = 52). In addition to group-level analyses, we also re-evaluate evidence using a single case statistical approach (Crawford & Garthwaite, 2005), enabling us to determine how many would make criteria for a 'classical dissociation' (Crawford, Garthwaite, & Gray, 2003). Overall, group-level analyses indicated the key pattern of significant differences confined to words was limited to small control sample comparisons. When using the large control sample provided by Bird and Burgess (2008), hippocampal cases as a group were significantly poorer for both classes of items. Furthermore, our single-case approach indicated few had a performance pattern of a relative difference across face > word categories that would meet statistical significance; namely within individual differences across categories that would warrant a significant 'classical dissociation'. Moreover, these analyses also found several cases with a 'classical dissociation' in the reverse direction: namely preserved recognition of words. Such analyses serve to demonstrate the need for a more conservative statistical approach to be undertaken when reporting selective 'preservation' of a category in recognition memory. Whilst material specificity has important implications for understanding the role of the hippocampus in memory, our results highlight the need for statistical methods to be unquestionably rigorous before any claims are made. Lastly, we highlight other methodological issues critical to group analyses and make suggestions for future work.


Subject(s)
Facial Recognition , Humans , Recognition, Psychology , Amnesia , Hippocampus , Individuality , Pattern Recognition, Visual
4.
Zhongguo Zhen Jiu ; 43(10): 1209-16, 2023 Oct 12.
Article in Chinese | MEDLINE | ID: mdl-37802530

ABSTRACT

OBJECTIVE: To assess the methodological quality, report quality and evidence quality of the Meta-analysis and systematic reviews of acupuncture and moxibustion for children with cerebral palsy, aiming to provide decision-making basis for clinical treatment. METHODS: The systematic reviews and Meta-analysis of acupuncture and moxibustion for children with cerebral palsy were searched in CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed and EMbase. The retrieval time was from the database establishment to June 30th, 2022. AMSTAR 2 (a measurement tool to assess systematic reviews) was used to evaluate the methodological quality, and PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 14 systematic reviews were included, including 37 primary outcome indexes. According to AMSTAR 2 evaluation results, there were 4 low quality studies, 10 very low quality studies, and low scores on items 2, 4, 7, 10 and 16. PRISMA scores ranged from 15 to 25, and the main reporting problems reflected in structured abstracts, program and registration, retrieval, and funding sources, etc. According to the GRADE classification results, there were 3 high quality evidences, 7 medium quality evidences, 10 low quality evidences and 17 very low quality evidences. The main downgrading factors were limitations, imprecision and publication bias. CONCLUSION: Acupuncture and moxibustion has a certain effect for cerebral palsy in children, but the quality of methodology, reporting and evidence in the included literature is poor, and the comparison of curative effect between different acupuncture and moxibustion methods is unclear.


Subject(s)
Acupuncture Therapy , Cerebral Palsy , Moxibustion , Child , Humans , Acupuncture Therapy/methods , Cerebral Palsy/therapy , Moxibustion/methods , Publication Bias , Research Report , Systematic Reviews as Topic , Meta-Analysis as Topic
6.
Front Pediatr ; 11: 1183891, 2023.
Article in English | MEDLINE | ID: mdl-37274821

ABSTRACT

Introduction: Rare genetic diseases are a major cause for severe illness in children. Whole exome sequencing (WES) is a powerful tool for identifying genetic causes of rare diseases. For a better and faster assessment of the vast number of variants that are identified in the index patient in WES, parental sequencing can be applied ("trio WES"). Methods: We assessed the diagnostic rate of routine trio WES including analysis of copy number variants in 224 pediatric patients during an evaluation period of three years. Results: Trio WES provided a diagnosis in 67 (30%) of all 224 analysed children. The turnaround time of trio WES analysis has been reduced significantly from 41 days in 2019 to 23 days in 2021. Copy number variants could be identified to be causative in 10 cases (4.5%), underlying the importance of copy number variant analysis. Variants in three genes which were previously not associated with a clinical condition (GAD1, TMEM222 and ZNFX1) were identified using the matching tool GeneMatcher and were part of the first description of a new syndrome. Discussion: Trio WES has proven to have a high diagnostic yield and to shorten the process of identifying the correct diagnosis in paediatric patients. Re-evaluation of all 224 trio WES 1-3 years after initial analysis did not establish new diagnoses. Initiating (trio) WES as a first-tier diagnostics including copy number variant detection should be considered as early as possible, especially for children treated in ICU, if a monogenetic disease is suspected.

7.
Biomed Chromatogr ; 37(6): e5630, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36949600

ABSTRACT

Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.


Subject(s)
Chrysanthemum , Drugs, Chinese Herbal , Chromatography, High Pressure Liquid/methods , Chrysanthemum/chemistry , Drugs, Chinese Herbal/chemistry , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , Quality Control
8.
Zhongguo Zhen Jiu ; 43(2): 223-31, 2023 Feb 12.
Article in Chinese | MEDLINE | ID: mdl-36808520

ABSTRACT

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION: Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.


Subject(s)
Acupuncture Therapy , Autistic Disorder , Moxibustion , Child , Humans , Acupuncture Therapy/methods , Moxibustion/methods , Publication Bias , Research Design , Systematic Reviews as Topic , Meta-Analysis as Topic
9.
Z Kinder Jugendpsychiatr Psychother ; 51(1): 41-50, 2023 Jan.
Article in German | MEDLINE | ID: mdl-35942650

ABSTRACT

Challenges and Influencial Factors in Autism-Specific Diagnostics in Toddlers Abstract. Objective: What are the particular challenges that make early diagnosis of young children difficult in the clinical routine? What recommendations can be derived from this in practice? Methods: Our interdisciplinary social pediatric team examined 31 toddlers aged 2 to 3 years twice in intervals of 6-9 months in the for outpatient diagnostics regarding suspected autism spectrum disorder (ASD). In addition, we conducted an online survey with further experts. Results: After the first anamnestic interview, 8 of the 31 (26 %) children were diagnosed with a differential diagnosis of ASD. Comorbid disorders, familial peculiarities, and challenges posed by the examination setting and anamnesis made a reliable clinical classification difficult. Conclusion: In our experience, many toddlers can only receive a valid diagnosis after a follow-up examination after starting one or more therapies and regularly carrying out these therapies over a period of 6-9 months and possibly also after structural changes have taken place (care in nursery, implementation of youth welfare measures, or similar).


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adolescent , Child , Humans , Child, Preschool , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/therapy , Autistic Disorder/diagnosis , Early Diagnosis , Diagnosis, Differential , Surveys and Questionnaires
10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-989716

ABSTRACT

Objective:To re-evaluate the reliability of the conclusions of the systematic reviews (SR)/meta-analysis (MA) of Traditional Chinese Medicine (TCM) in the treatment of functional dyspepsia (FD).Methods:CNKI, CBM, WanFang Data, VIP, PubMed, Cochrane Library, and Embase were searched from the establishment of the database to March 30, 2022. Two researchers independently screened literature and extracted data, and included SRs/MAs in the treatment of FD with TCM. The AMSTAR 2 and GRADE tools were used to evaluate the included the study carried out methodological quality evaluation, outcome evidence quality grading, and descriptive analysis of the main outcome.Results:A total of 28 SRs/MAs were included, with 34 outcome indicators. According to the AMSTAR 2 evaluation results, 21 SRs/MAs were of medium quality, and 7 SRs/MAs were of low quality. The GRADE quality of evidence grading results showed that of the 100 evidence bodies, 13 were of high quality, 58 were of moderate quality, 24 were of low quality, and 5 were of very low quality.Conclusion:TCM in the treatment of FD can improve the clinical efficiency, improve the cure rate, reduce the recurrence rate, and improve the clinical symptoms, but the methodological quality and evidence quality of related SRs/MAs have certain defects, so this conclusion should be treated with caution.

11.
Chinese Acupuncture & Moxibustion ; (12): 1209-1216, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1007467

ABSTRACT

OBJECTIVE@#To assess the methodological quality, report quality and evidence quality of the Meta-analysis and systematic reviews of acupuncture and moxibustion for children with cerebral palsy, aiming to provide decision-making basis for clinical treatment.@*METHODS@#The systematic reviews and Meta-analysis of acupuncture and moxibustion for children with cerebral palsy were searched in CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed and EMbase. The retrieval time was from the database establishment to June 30th, 2022. AMSTAR 2 (a measurement tool to assess systematic reviews) was used to evaluate the methodological quality, and PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 14 systematic reviews were included, including 37 primary outcome indexes. According to AMSTAR 2 evaluation results, there were 4 low quality studies, 10 very low quality studies, and low scores on items 2, 4, 7, 10 and 16. PRISMA scores ranged from 15 to 25, and the main reporting problems reflected in structured abstracts, program and registration, retrieval, and funding sources, etc. According to the GRADE classification results, there were 3 high quality evidences, 7 medium quality evidences, 10 low quality evidences and 17 very low quality evidences. The main downgrading factors were limitations, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for cerebral palsy in children, but the quality of methodology, reporting and evidence in the included literature is poor, and the comparison of curative effect between different acupuncture and moxibustion methods is unclear.


Subject(s)
Child , Humans , Acupuncture Therapy/methods , Cerebral Palsy/therapy , Moxibustion/methods , Publication Bias , Research Report , Systematic Reviews as Topic , Meta-Analysis as Topic
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-969976

ABSTRACT

OBJECTIVE@#To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment.@*METHODS@#The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.


Subject(s)
Child , Humans , Acupuncture Therapy/methods , Autistic Disorder , Moxibustion/methods , Publication Bias , Research Design , Systematic Reviews as Topic , Meta-Analysis as Topic
13.
Ann Pediatr Endocrinol Metab ; 28(4): 245-250, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38173380

ABSTRACT

PURPOSE: Congenital hypothyroidism (CH) is diagnosed with neonatal screening and is treated early in the neonatal period. Among these patients, transient CH (TCH) is included and requires re-evaluation. The purpose of this study was to find the best way to discontinue levothyroxine and to find trends in thyroid function tests (TFTs) after re-evaluation. METHODS: We retrospectively reviewed 388 patients diagnosed with CH. They were classified as permanent CH (PCH) and TCH. The total number of the PCH and TCH groups was 83 (51 boys and 32 girls). We compared clinical parameters to predict TCH and to identify the trends of TFT. RESULTS: The first thyroid-stimulating hormone (TSH) value after discontinuation and the average TSH value for 1, 2, and 3 years were all significantly higher in the PCH group (P<0.01). The first fT4 value after discontinuation and the average fT4 value for 1, 2, and 3 years were all significantly higher in the TCH group (P<0.01). The optimal cutoff value on the receiver operating characteristic curve for PCH prediction with an average of 3 years of TSH was greater than 9.05 µIU/mL, which was predicted with a sensitivity of 100% and a specificity of 100%. CONCLUSION: When the TSH value ranges from 10 µIU/mL to 20 µIU/mL, clinicians can discontinue levothyroxine if the next result is around 10 µIU/mL or shows a decreasing trend.

14.
Chin Med ; 17(1): 127, 2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36348487

ABSTRACT

Traditional Chinese medicine (TCM) injection is the combination of modern pharmaceutical technology and traditional Chinese prescription, which was born in 1941 and played a great role in the backward medical conditions at that time. However, the debate over TCM injections has never stopped due to adverse drug reactions (ADRs). The regulation on TCM injections has been further strengthened since 2017, which has prompted many TCM injections to carry out re-evaluations on quality, safety, efficiency as well as pharmacoeconomics, which made significant changes and progress. This review presented an up-to-date analysis of the types, amounts, and ADRs of TCM injections based on the published data and literature. This review also summarized the potential reasons for the ADRs and re-evaluation strategies. This review will provide some useful clues for TCM injections and their clinical use.

15.
J Pediatr Endocrinol Metab ; 35(9): 1141-1146, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36039549

ABSTRACT

OBJECTIVES: An increased incidence of congenital hypothyroidism (CH) has been described worldwide over the years. In this study, we aimed to investigate the epidemiologic characteristics of CH, the iodine status in Guangzhou, China and to investigate which factors might influence the CH incidence during the period 2010-2020. METHODS: We retrospectively reviewed all cases of CH detected by newborn screening during the period 2010-2020. CH was classified as either suspected thyroid dyshormonogenesis (SDH) or thyroid dysgenesis (TD) based on thyroid ultrasound at first diagnosis. Patients were re-evaluated after 4 weeks of L-thyroxine withdrawal at age of 2-3 years to confirm the diagnosis of permanent CH (PCH) or transient CH (TCH). RESULTS: From 2010 to 2020, 1,655 patients with CH were confirmed from 2,400,383 newborns (1:1,450). The CH incidence increased from 1:2,584 in period [2010-2014] to 1:1,086 in period [2015-2020]. Among the 1,337 patients with thyroid ultrasound, 84.29% were SDH whereas 15.71% had TD. Further analysis revealed that more SDH (78.32%) were TCH whereas more TD (87.12%) turned to be PCH. The proportion of blood spot thyrotropin values >5 mIU/L ranged from 8.03 to 20.46%, indicating iodine deficiency. The prevalence of preterm infants increased from 5.50% in period [2010-2014] to 7.06% in period [2015-2020] (p<0.001). CONCLUSIONS: In the past decade, the CH incidence has increased progressively. SDH was the majority of CH, most of which were TCH, while most patients with TD were PCH. The increased incidence might be mainly due to iodine deficiency and increased rates of preterm infants in our study.


Subject(s)
Congenital Hypothyroidism , Iodine , Child, Preschool , China/epidemiology , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/epidemiology , Congenital Hypothyroidism/etiology , Humans , Incidence , Infant , Infant, Newborn , Infant, Premature , Neonatal Screening , Retrospective Studies , Thyrotropin , Thyroxine
16.
Complement Ther Med ; 70: 102860, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35868491

ABSTRACT

BACKGROUND: The Buyang Huanwu Decoction (BYHWD) originated from Wang Qingren's "Yi Lin Gai Cuo". It has the effect of tonifying qi and activating blood circulation and dredging collaterals which is recommended for the treatment of Ischemic stroke in China. In recent years, there have been many systematic reviews of Ischemic stroke treated by BYHWD assessing the efficacy of BYHWD in the treatment of Ischemic stroke in the acute, convalescent and sequelae stages. Because of the different methods of analysis, the quality and quality of the evidence obtained in these systematic reviews is different, so a systematic re-evaluation was needed to comprehensively evaluate the strength of these studies. METHODS: Systematic reviews and meta-analyses of Ischemic stroke treated by BYHWD were identified through the Web of Science, PubMed, CNKI, Weipu, and Wanfang databases. The included studies were selected for literature screening, methodological quality evaluation, and evidence level evaluation by two investigators. The methodological quality was evaluated by the 2020 PRISMA guidelines, Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scale, and the evidence quality was evaluated by the GRADE criteria. RESULTS: Overall, 12 studies involving 28,594 patients between 2006-2021 were included in this analysis. The methodological quality evaluation based on 2020 PRISMA guidelines results showed that there were many weaknesses in registration and protocol, support, competing interests, competing interests and availability of data, code and other materials. The AMSTAR scale evaluation results showed that the 12 studies were very low quality. The results of the GRADE criteria evaluation showed that the quality of the evidence was scattered, with mainly low-quality evidence. CONCLUSION: The methodological quality of systematic reviews and meta-analyses of BYHWD in treating Ischemic stroke was generally poor, and the quality of evidence was generally low.


Subject(s)
Drugs, Chinese Herbal , Ischemic Stroke , Stroke , China , Humans
18.
Genes (Basel) ; 13(3)2022 03 18.
Article in English | MEDLINE | ID: mdl-35328090

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease whose causes are unclear. The first ALS gene associated with the autosomal dominant form of the disease was SOD1. This gene has a high rate of rare variants, and an appropriate classification is essential for a correct ALS diagnosis. In this study, we re-evaluated the classification of all previously reported SOD1 variants (n = 202) from ALSoD, project MinE, and in-house databases by applying the ACMG-AMP criteria to ALS. New bioinformatics analysis, frequency rating, and a thorough search for functional studies were performed. We also proposed adjusting criteria strength describing how to apply them to SOD1 variants. Most of the previously reported variants have been reclassified as likely pathogenic and pathogenic based on the modified weight of the PS3 criterion, highlighting how in vivo or in vitro functional studies are determining their interpretation and classification. Furthermore, this study reveals the concordance and discordance of annotations between open databases, indicating the need for expert review to adapt the study of variants to a specific disease. Indeed, in complex diseases, such as ALS, the oligogenic inheritance, the presence of genes that act as risk factors and the reduced penetration must be considered. Overall, the diagnosis of ALS remains clinical, and improving variant classification could support genetic data as diagnostic criteria.


Subject(s)
Amyotrophic Lateral Sclerosis , Superoxide Dismutase-1 , Humans , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/pathology , Computational Biology , Multifactorial Inheritance , Superoxide Dismutase-1/genetics
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014910

ABSTRACT

AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E

20.
Int J Neonatal Screen ; 7(4)2021 Oct 13.
Article in English | MEDLINE | ID: mdl-34698071

ABSTRACT

After several decades of successful newborn screening (NBS) for congenital hypothyroidism, the optimal hypothyroidism NBS algorithm for very preterm infants is still controversial. Due to concerns about an elevated risk of a false-negative initial thyroid-stimulation hormone (TSH) screening, repeat NBS has been implemented for this group. While transient hypothyroidism is known to be more frequent among very preterm infants, the prevalence of permanent hypothyroidism is generally assumed to be the same as in more mature newborns. This study analyses screening and long-term follow-up data from the population-based cohort of 51 infants born from 1999-2017 at less than 32 weeks of gestation and diagnosed with hypothyroidism after NBS in the German Federal State of Bavaria (total number of infants screened 2,107,864). Severe permanent hypothyroidism was always detected at initial TSH screening unless there was a known confounding factor. Cases detected by repeat screening after a negative initial screen most frequently proved to be transient, less frequently mild permanent, or a definitive diagnosis was not possible because of inadequate re-evaluation of the thyroid axis. The prevalence of both permanent and transient hypothyroidism was elevated compared to a cohort of children from the same region born at a higher gestational age. The results seem to support the need for the repeated NBS of very preterm infants. However, as the recommendation to treat mild hypothyroidism is not based on high quality evidence, important issues for future research include treatment outcome studies or even a general review of whether this diagnosis meets the screening criteria. Meanwhile, involving a paediatric endocrinologist in treatment decisions is crucial for optimising the benefit of hypothyroidism screening for this particularly vulnerable group.

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