Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

PurposePathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort.MethodsWe perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays.ResultsOur data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants.ConclusionInsights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.     

An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum

We have isolated a human excision repair gene ERCC5 which complements the defect of the mouse UV-sensitive mutant XL216 (rodent complementation group 5). Here we report cDNA cloning of human and mouse ERCC5 genes using an exon containing an ERCC5 fragment as a probe. The ERCC5 cDNA encodes a predicted 133-kDa nuclear protein that shares some homology with the product of the yeast DNA repair gene RAD2. Transfection with mouse ERCC5 cDNA restored normal levels of UV resistance to XL216 cells. Microinjection of ERCC5 cDNA specifically restored the defect of xeroderma pigmentosum group G cells (XP-G) as measured by unscheduled DNA synthesis, and XP-G cells stably transformed with ERCC5 cDNA showed nearly normal UV resistance.     

Association of Adolescent Obesity with Nonalcoholic Fatty Liver Disease and Related Risk Factors in Xi ’an,China

Introduction and aim. To investigate the association of adolescent obesity with nonalcoholic fatty liver disease (NAFLD) and related risk factors in Xi ’an, China.Material and methods. A total of 4141 adolescents (2,061 girls and 2,080 boys, mean age: 18.62 ± 0.66 years, age range 15-22 years) were enrolled in this investigation. Anthropometric index was measured, and liver ultrasonography and liver function biochemical test were performed in all the subjects. T test, χ² test and logistic regression analysis were used for statistical analyses. Results. The total rates of obesity was 7.9% (08/4,141). The prevalence rate of NAFLD was 8.1% (335/4141) with a declining trend from obesity, overweight to normal BMI. NAFLD prevalence rate in obese boys was significantly higher than in girls (χ² = 56.5, P < 0.01). BMI, body weight, ALT, and AST in NAFLD group were higher than in non-NAFLD group (P < 0.05). The tangent point of ALT was 36 U/L using Youden index in boys, and 33 U/L in girls.Conclusion. The prevalence of obesity and NAFLD in adolescents is higher in Xi’an than anticipated. Body weight and BMI may be the associated independent risk factors of NAFLD.     

Chinese guidelines for the diagnosis and treatment of hand,foot and mouth disease (2018 edition)

Background

Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed.

Methods

National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD.

Results

Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases.

Conclusion

The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

     

How does a novel knitted titanium nucleus prosthesis change the kinematics of a cervical spine segment? A biomechanical cadaveric study

BackgroundTotal disc replacement is a possible treatment alternative for patients with degenerative disc disease, especially in the cervical spine. The aim is to restore the physiological flexibility and biomechanical behavior. A new approach based on these requirements is the novel nucleus prosthesis made of knitted titanium wires.MethodsThe biomechanical functionalities of eight human cervical (C4-C7) spine segments were investigated. The range of motion was quantified using an ultra-sound based motion analysis system. Moreover, X-rays in full flexion and extension of the segment were taken to define the center of rotation before and after implantation of the nucleus prosthesis as well as during and after complex cyclic loading.FindingsThe mean range of motion of the index segment (C5/6) in flexion/extension showed a significant reduction of range of motion from 9.7° (SD 4.33) to 6.0° (SD 3.97) after implantation (P = 0.037). Lateral bending and axial rotation were not significantly reduced after implanting and during cyclic loading in our testing. During cyclic loading the mean range of motion for flexion/extension increased to 7.2° (SD 3.67). The center of rotation remained physiological in the ap-plane and moved cranially in the cc-plane (−27% to −5% in cc height) during the testing.InterpretationThe biomechanical behavior of the nucleus implant might lower the risk for adjacent joint disorders and restore native function of the index segment. Further in vivo research is needed for other factors, like long-term effects and patient's satisfaction.     

红景天提取物对微粒体LPO模型的影响

背景与目的： 探讨红景天醇提物和水提物的抗氧化作用及其剂量反应关系。 材料与方法： 回流法和煎煮法分别制备红景天醇提物和水提物。钙沉淀法提取雄性SD大鼠肝微粒体。采用四种激发剂Vc/Fe2＋、过氧基异丙苯(Cumine hydroperoxide,CHP)、 CCl4/辅酶Ⅱ(Nicotinamide-adenine dinucleotide phosphate, NADP)和还原型辅酶Ⅱ(Reduced form of nicotinamide-adenine dinucleotide phosphate,NADPH)-腺苷二磷酸(Adenosine diphosphate,ADP)／Fe2＋建立微粒体脂质过氧化(Lipid peroxidation,LPO)模型,加入浓度为 25 mg/ml、12.5 mg/ml、6.25 mg/ml、3.13 mg/ml、1.56 mg/ml的红景天醇提物和水提物,观察在4 种模型系统中抗氧化作用。在VC/Fe2＋、CHP、 CCl4/NADP模型中通过比色法测定对丙二醛(Malondialdehyde,MDA)的抑制作用,NADPH-ADP／Fe2＋模型通过氧电极法测定对耗氧量的抑制作用。 结果： 红景天水提物在浓度为6.25～25.00 mg/ml范围内,其CHP模型中的MDA含量显著低于阳性模型对照组。在 Vc/Fe2＋、CHP和CCl4/NADP 模型中,红景天醇提物和水提物各浓度组MDA含量均非常显著低于对照组,并且在一定终反应浓度内有剂量-反应关系。在NADPH-ADP／Fe2＋模型中,最高浓度的醇提物和水提物的抑制率分别达到76％和43％。 结论： 红景天的两种提取物都具有较强的抗氧化作用,并存在一定的剂量效应关系。其中红景天醇提物对酶参与性反应的作用强于水提物。该研究初步探讨了红景天抗氧化作用的机制,其结果为红景天在自由基损伤中的保护作用提供了实验依据。     

Evaluation of the Precision ID Ancestry Panel for crime case work: A SNP typing assay developed for typing of 165 ancestral informative markers

The application of massive parallel sequencing (MPS) methodologies in forensic genetics is promising and it is gradually being implemented in forensic genetic case work. One of the major advantages of these technologies is that several traditional electrophoresis assays can be combined into one single MPS assay. This reduces both the amount of sample used and the time of the investigations.This study assessed the utility of the Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) in forensic genetics. This assay was developed for the Ion Torrent PGM™ System and genotypes 165 ancestry informative SNPs. The performance of the assay and the accompanying software solution for ancestry inference was assessed by typing 142 Danes and 98 Somalis. Locus balance, heterozygote balance, and noise levels were calculated and future analysis criteria for crime case work were estimated. Overall, the Precision ID Ancestry Panel performed well, and only minor changes to the recommended protocol were implemented. Three out of the 165 loci (rs459920, rs7251928, and rs7722456) had consistently poor performance, mainly due to misalignment of homopolymeric stretches. We suggest that these loci should be excluded from the analyses.The different statistical methods for reporting ancestry in forensic genetic case work are discussed.