A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum,retinopathy, and deafness

The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non‐motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11‐year‐old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy. A homozygous variant, c.870_871del, was identified in the CDK10 gene, predicted to cause a frameshift, p.Trp291Alafs*18, in the cyclin‐dependent kinase 10 protein. CDK10 mRNAs were detected in patient cells and do not seem to undergo non‐sense mediated decay. CDK10 is the binding partner of Cyclin M (CycM) and CDK10/CycM protein kinase regulates ciliogenesis and primary cilium elongation. Notably, CycM gene is mutated in patients with STAR syndrome. Following incubation, the patient cells appeared less elongated and more densely populated than the control cells suggesting that the CDK10 mutation affects the cytoskeleton. Upon starvation and staining with acetylated‐tubulin, γ‐tubulin, and Arl13b, the patient cells exhibited fewer and shorter cilia than control cells. These findings underscore the importance of CDK10 for the regulation of ciliogenesis. CDK10 defect is likely associated with a new form of ciliopathy phenotype; additional patients may further validate this association.     

Penicillin V-conjugated PEG-PAMAM star polymers

Starburst^® PAMAM dendrimers are potential carriers for drug delivery due to their unique structure. Drug-delivery scaffolds were designed and built up based on the polyethylene glycolpolyamidoamine (PEG-PAMAM) star polymer. Penicillin V was used as a model carboxylic group containing drug to conjugate with full- and half-generation PAMAM dendrimers. G2.5 PAMAM (with 32 carboxylic groups on the surface) dendrimers and G3.0 (with 32 primary amine groups on the surface) were typically chosen. There are two strategies given in the paper where a drug carrying a carboxylic group (e.g. penicillin V) was coupled to star polymer via amide and ester bonds, respectively. FT-IR, UV-Vis and ¹H-NMR were used to characterize the intermediates and drug-star polymer conjugates. A single-strain bacterium, Staphylococcus aureus, was grown up for penicillin-conjugated PEG-PAMAM (G3.0) star polymer activity test. The result verified the bioavailability of modified penicillin after the ester bond was cleaved.     

STAR-FAME全自动血液筛查仪器在检验中的应用研究

目的:引进STAR-FAME国外先进设备,使HBsAg、抗-HCV、抗-HIV以及梅毒四项检测由手工向自动化操作的转变,提高血站整体检测水平,保证临床输血安全。方法:通过正交试验设计的方法,优化最佳试验参数,并对仪器的吸液加样液体参数、洗板及进板模式进行选择。结果:①加高粘稠液体优化参数:吸液速度、分配速度、分配传输空气体积、吹吸空气体积、停留时间、预湿体积、止停流速、液面探测下降深度、前舍、后弃体积、针距微孔底部的高度、针距试剂槽底部的高度优选结果依次为:200μl/s、300μl/s、15μl、0μl、3 s、0μl、300μl/s、5 mm、50μl、30μl、13 mm、45 mm。②针尖不挂液体参数:分配样品时针尖距抗-TP、抗-HIV、抗-HCV、HBsAg微孔板底的距离依次为2、4、4、2 mm;将分配过程中液面跟随设置由开改为关。③加样拖带污染情况:STAR钢针拖带污染率为0.079%。④引起整排污染的克服办法:将加HBsAg酶的加样尖距板底的高度设定为13 mm,同时取消液面感应;调整抗-HCV加液顺序。⑤实现不等距离阴阳对照加样。通过序列的编辑,序列定义了工作平台上容器架中容器的加样顺序,实现了加样针不等距离吸入和分配不同量的液体。⑥实施再检单项双孔分配:在Excel工作表中对再检样本信息进行编辑,并通过仪器软件的自动读取,实现了再检样品呈单项双孔分配。⑦缩短FAME处理时间:通过调整进板顺序、进板间隔时间,加液洗液位置,12块免疫试验总的完成时间由原来的191 min减少到138 min。⑧将校正曲线的数值10μl修改为13、16、19μl。结论:完成了STAR-FAME全自动筛查仪器在血站系统4项检测项目由手工向自动化操作,不仅降低了劳动强度,而且克服人为因素,提高血站检验的整体检测水平,保证临床输血安全。     

Clinical features of depressed outpatients with and without co-occurring general medical conditions in STAR*D

BACKGROUND: A significant percentage of patients with major depressive disorder (MDD) suffer from concurrent general medical conditions (GMCs). OBJECTIVE: The objective of this preliminary report was to describe the rates of co-occurring significant GMCs and the clinical correlates and symptom features associated with the presence of GMCs. DESIGN: Baseline cross-sectional case-control study of patients enrolling in a prospective randomized multistage treatment study of MDD. SETTING: Fourteen regional U.S. centers representing 19 primary care and 22 psychiatric practices. PATIENTS: One thousand five hundred outpatients with DSM-IV nonpsychotic MDD. MEASUREMENTS: Sociodemographic status, medical illness ratings, psychiatric status, quality of life and DSM-IV depression symptom ratings. RESULTS: The prevalence of significant medical comorbidity in this population was 52.8% (95% CI 50.3-55.3%). Concurrent significant medical comorbidity was associated with older age, lower income, unemployment, limited education, longer duration of index depressive episode and absence of self-reported family history of depression. Somatic symptoms common in MDD were endorsed at a higher rate in those with GMCs. Those without a GMC had higher rates of endorsement of impaired mood reactivity, distinct mood quality and interpersonal sensitivity. CONCLUSIONS: Concurrent GMCs are common among outpatients with MDD in both primary care and specialty settings. Concurrent GMCs appear to influence the severity and symptom patterns in MDD and describe a vulnerable population with sociodemographic challenges to effective assessment and treatment.     

Ocular manifestations of X-linked dominant FAM58A mutation in toe syndactyly,telecanthus, anogenital,and renal malformations (‘STAR’) syndrome

Purpose: To report the newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder.

Methods: The medical and ophthalmic records were reviewed for a mother-daughter pair diagnosed with FAM58A confirmed STAR syndrome on chromosome Xq28.

Results: The mother at birth had left foot syndactyly, telecanthus, anal stenosis, and clitoromegaly and was told at 19 she had a hypoplastic left kidney. The daughter, born at 38 weeks after a complication of oligohydramnios, had a more severe presentation, demonstrating toe syndactyly, telecanthus, anal stenosis, clitoromegaly, bilateral renal hypoplasia, ureteral reflux, urogenital sinus, and congenital heart disease amongst others. The pair shared similar ophthalmic findings, though those of the daughter were more pronounced. They included bilateral, medial upper eyelid prominences with madarosis, mild peripapillary atrophy, and soft macular drusen with the daughter also displaying optic nerve hypoplasia and peripheral anterior synechia in the iridocorneal angle.

Conclusion: These ophthalmic findings are the first reported to our knowledge in association with STAR syndrome. The literature frequently demonstrates that patients with developmental anomalies often have ocular manifestations, warranting a full ophthalmic examination when the diagnosis of STAR syndrome has been made or is being considered.     

全自动血型分析仪与微板法应用于献血者不规则抗体筛查的比较分析

目的比较分析Beckman Coulter PK7300全自动血型分析仪与微板法应用于献血者不规则抗体筛查的效果。方法应用全自动血型分析仪法和STAR加样微板手工比色法检测献血者O细胞(Oc),Oc凝集者送血型室进一步鉴定。结果在12 337份献血者标本中,全自动血型分析仪法与STAR加样微板手工比色法对Oc检出率分别为0.19%和0.15%。微板法检出的1例冷自身抗体,全自动血型分析仪法结果为阴性。全自动血型分析仪法检出的1例抗-E、1例抗-Leb、2例抗-P1、1例冷自身抗体,微板法均未检出凝集。结论全自动血型分析仪用于不规则抗体筛查的灵敏度优于微板法,更易发现盐水介质凝集试验阳性的抗体,在保证临床用血安全方面较微板法具有更广阔的应用空间。     

Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction

Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.     

STAR加样器拖带污染情况分析及其解决办法

目前,国内STAR加样采用的针头有2种,一种是可反复使用的不锈钢加样针头(简称钢针),另一种是一次性的塑料针头.不锈钢加样针头可反复使用,节约成本,但可导致加样拖带污染后边的标本,而一次性的塑料针头虽没有拖带污染,但针头由于一次性使用,费用太高,两者各有优缺点,为此,我们利用本站2台STAR加样器,1台用一次性加样针头做初检,另1台用钢针做复检,通过大量标本同时进行常规检测,研究分析检测污染情况及解决拖带污染的方法,现报告如下.