BRAF V600E mutant oligodendroglioma‐like tumors with chromosomal instability in adolescents and young adults

We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with “molecular GBM.” Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of “pediatric‐type” gliomas.     

Collagen XIII and Other ECM Components in the Assembly and Disease of the Neuromuscular Junction

Alongside playing structural roles, the extracellular matrix (ECM) acts as an interaction platform for cellular homeostasis, organ development, and maintenance. The necessity of the ECM is highlighted by the diverse, sometimes very serious diseases that stem from defects in its components. The neuromuscular junction (NMJ) is a large peripheral motor synapse differing from its central counterparts through the ECM included at the synaptic cleft. Such synaptic basal lamina (BL) is specialized to support NMJ establishment, differentiation, maturation, stabilization, and function and diverges in molecular composition from the extrasynaptic ECM. Mutations, toxins, and autoantibodies may compromise NMJ integrity and function, thereby leading to congenital myasthenic syndromes (CMSs), poisoning, and autoimmune diseases, respectively, and all these conditions may involve synaptic ECM molecules. With neurotransmission degraded or blocked, muscle function is impaired or even prevented. At worst, this can be fatal. The article reviews the synaptic BL composition required for assembly and function of the NMJ molecular machinery through the lens of studies primarily with mouse models but also with human patients. In-depth focus is given to collagen XIII, a postsynaptic-membrane-spanning but also shed ECM protein that in recent years has been revealed to be a significant component for the NMJ. Its deficiency in humans causes CMS, and autoantibodies against it have been recognized in autoimmune myasthenia gravis. Mouse models have exposed numerous details that appear to recapitulate human NMJ phenotypes relatively faithfully and thereby can be readily used to generate information necessary for understanding and ultimately treating human diseases. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.     

Serum and Salivary Matrix Metalloproteinases,Neutrophil Elastase,Myeloperoxidase in Patients with Chronic or Aggressive Periodontitis

Salivary, serum matrix metalloproteinase-8 (MMP-8), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), neutrophil elastase (NE), and myeloperoxidase (MPO) levels were investigated in generalized chronic periodontitis (GCP), generalized aggressive periodontitis (GAgP), and healthy groups. Whole-mouth clinical periodontal measurements were recorded. Salivary, serum concentrations of MMP-8, MPO, TIMP-1, and NE were determined by immunofluorometric assay or ELISA in 18 patients with GCP, 23 patients with GAgP, 18 individuals with healthy periodontium. Patients in the GAgP group were younger than the other groups (p?p?TIMP-1 concentrations were lower in the periodontitis groups than the controls (p?相似文献   

Evaluation of Systemic Levels of Neutrophilic Enzymes in Patients With Hypertension and Chronic Periodontitis

Background: Inflammation stimulates neutrophils to release their enzymes into the extracellular matrix. The aim of the present study is to investigate the serum levels of matrix metalloproteinase (MMP)‐8, MMP‐9, tissue inhibitor of MMP (TIMP)‐1, myeloperoxidase (MPO), and neutrophil elastase (NE) in patients with hypertension and chronic periodontitis (CP). Methods: A total of 95 patients were included in the study. Patients were categorized into three groups: healthy control (n = 29), hypertensive control (n = 32), and hypertensive CP (n = 34). Periodontal parameters were recorded, and serum samples were collected from each participant. Serum MMP‐8, MMP‐9, TIMP‐1, MPO, and NE levels in circulation were assessed by enzyme‐linked immunosorbent assay. Results: The hypertensive CP group had significantly higher serum MMP‐8, MMP‐9, and NE levels than the healthy control group (P <0.05). All study groups had similar serum TIMP‐1 levels (P >0.05). Significantly higher serum MPO levels were detected in patients with hypertension and CP than healthy controls and hypertensive controls (P <0.05); however, the difference in serum MPO levels was not significant between the healthy controls and hypertensive controls (P >0.05). There was no significant difference in MMP‐8/TIMP‐1 ratio among the study groups (P >0.05). MMP‐9/TIMP‐1 ratio was significantly higher in patients with hypertension and CP than healthy controls (P <0.05). Conclusions: The presence of hypertension along with CP has a considerable effect on serum neutrophilic enzyme levels, except TIMP‐1. However, the levels of these enzymes do not seem to be affected by the presence of hypertension only. Further studies including patients who have only CP might help illuminate the effect of CP on these enzymes in patients with hypertension.     

Insufficient Fruit and Vegetable Intake and Low Potassium Intake Aggravate Early Renal Damage in Children: A Longitudinal Study

Insufficient fruit and vegetable intake (FVI) and low potassium intake are associated with many non-communicable diseases, but the association with early renal damage in children is uncertain. We aimed to identify the associations of early renal damage with insufficient FVI and daily potassium intake in a general pediatric population. We conducted four waves of urine assays based on our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We investigated FVI and other lifestyle status via questionnaire surveys and measured urinary potassium, β₂-microglobulin (β₂-MG), and microalbumin (MA) excretion to assess daily potassium intake and renal damage among 1914 primary school children. The prevalence of insufficient FVI (<4/d) was 48.6% (95% CI: 46.4%, 50.9%) and the estimated potassium intake at baseline was 1.63 ± 0.48 g/d. Short sleep duration, long screen time, lower estimated potassium intake, higher β₂-MG and MA excretion were significantly more frequent in the insufficient FVI group. We generated linear mixed effects models and observed the bivariate associations of urinary β₂-MG and MA excretion with insufficient FVI (β = 0.012, 95% CI: 0.005, 0.020; β = 0.717, 95% CI: 0.075, 1.359), and estimated potassium intake (β = −0.042, 95% CI: −0.052, −0.033; β = −1.778, 95% CI: −2.600, −0.956), respectively; after adjusting for age, sex, BMI, SBP, sleep duration, screen time and physical activity. In multivariate models, we observed that urinary β₂-MG excretion increased with insufficient FVI (β = 0.011, 95% CI: 0.004, 0.018) and insufficient potassium intake (<1.5 g/d) (β = 0.031, 95% CI: 0.023, 0.038); and urinary MA excretion increased with insufficient FVI (β = 0.658, 95% CI: 0.017, 1.299) and insufficient potassium intake (β = 1.185, 95% CI: 0.492, 1.878). We visualized different quartiles of potassium intake showing different renal damage with insufficient FVI for interpretation and validation of the findings. Insufficient FVI and low potassium intake aggravate early renal damage in children and underscores that healthy lifestyles, especially adequate FVI, should be advocated.     

Annular and subvalvular dynamics after extracellular matrix mitral tube graft implantation in pigs

 Open in a separate windowOBJECTIVESEntire mitral valve reconstruction with an extracellular matrix tube graft is a potential candidate to overcome the current limitations of mechanical and bioprosthetic valves. However, clinical data have raised concern with respect to patch failure. The aim of our study was to evaluate the impact of extracellular matrix mitral tube graft implantation on mitral annular and subvalvular regional dynamics in pigs.METHODSA modified tube graft design made of 2-ply extracellular matrix was used (CorMatrix^®; Cardiovascular Inc., Alpharetta, GA, USA). The reconstructions were performed in an acute 80-kg porcine model (N = 8), where each pig acted as its own control. Haemodynamics were assessed with Mikro-Tip pressure catheters and mitral annular and subvalvular geometry and dynamics with sonomicrometry.RESULTSCatheter-based peak left atrial pressure and pressure difference across the mitral and aortic valves in the reconstructions were comparable to the values seen in the native mitral valves. Also comparable were maximum mitral annular area (755 ± 100 mm²), maximum septal-lateral distance (29.7 ± 1.7 mm), maximum commissure–commissure distance (35.0 ± 3.4 mm), end-systolic annular height-to-commissural width ratio (10.2 ± 1.0%) and end-diastolic interpapillary muscle distance (27.7 ± 3.3 mm). Systolic expansion of the mitral annulus was, however, observed after reconstruction.CONCLUSIONSThe reconstructed mitral valves were fully functional without regurgitation, obstruction or stenosis. The reconstructed mitral annular and subvalvular geometry and subvalvular dynamics were found in the same range to those in the native mitral valve. A regional annular ballooning effect occurred that might predispose to patch failure. However, the greatest risk was found at the papillary muscle attachments.     

维持性血液透析患者心血管钙化的发生率及分布特点

目的:探讨维持性血液透析(MHD)患者心血管钙化分布及相关因素。方法:选择MHD≥3月的患者144例,完善相关实验室检查,螺旋CT检测冠状动脉钙化评分(CACS,Agaston法),腹部侧位平片检测腹主动脉钙化评分(AACS,Kauppila法),心脏超声检测心脏瓣膜钙化情况,计算心血管钙化指数(CCI)。结果:本组患者影像学可见钙化的总发生率为70.83%,29.17%无钙化,普遍钙化者26.39%,选择性钙化者44.44%。冠脉钙化的患者中,CACS100的患者占50.67%,腹主动脉钙化的患者,AACS5者占48.48%,瓣膜钙化以二尖瓣为主(34.25%)。钙化总发生率无性别差异,随年龄和透析龄的增长而增加。AACS与CACS呈正相关(r=0.636),发生瓣膜钙化的患者CACS更高(P0.00 1)。比较普遍钙化与无钙化的患者,年龄、透析龄、体质量指数、腹围、踝臂指数、总胆固醇、低密度脂蛋白、超敏C反应蛋白、是否糖尿病存在差异(P0.05),而收缩压、舒张压、血钙、血磷、全段甲状旁腺激素、磷结合剂和活性维生素D的用药情况未见差异(P≥0.05)。高龄、高血钙、贫血、血脂异常是冠脉钙化的独立危险因素;高龄、血脂异常是腹主动脉钙化的独立危险因素;高龄和长透析龄是心脏瓣膜钙化的独立危险因素。CCI与CACS比较有良好的特异度和灵敏度。结论:本组患者心血管钙化部位不均衡,年龄、透析龄、血钙、血脂及部分传统心血管危险因素与钙化的发生有关。CCI可能是更优质的血管钙化评价指标。     

A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene

Retinal cone photoreceptors mediate fine visual acuity, daylight vision, and color vision. Congenital hereditary conditions in which there is a lack of cone function in humans cause achromatopsia, an autosomal recessive trait, characterized by low vision, photophobia, and lack of color discrimination. Herein we report the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia. Moreover, we show that the spontaneous mouse mutant cpfl1 that features a lack of cone function and rapid degeneration of the cone photoreceptors represents a homologous mouse model for PDE6C associated achromatopsia.