高血压患者常规行眼底镜检查的价值：系统性综述

目的 评价高血压患者常规眼底检查的价值。 设计 系统性综述。 入选患者 ≥19岁的高血压视网膜病变患者。 数据来源 从1990起的Medline、Embase和Cochrane图书馆的数据库。 综述方法 纳入的研究包括：评估了高血压视网膜病变性失明与心血管危险因素之间联系的研究。研究必须由2名或2名以上观察者得出一致评价结果，用K统计分析表示。对于高血压患者，研究高血压视网膜病变与高血压脏器损害之间的联系。对于非选择的血压正常者和无糖尿病高血压患者，评价高血压视网膜病变与心血管危险因素之间的联系。 结果 由于观察者之间的巨大差异限制了对视网膜微血管变化的评价。高血压视网膜病变与血压水平之间的阳性及阴性预测值均较低（分别为47％～72％和32％-67％）。除了视网膜病变与脑卒中之间有联系外，视网膜微血管变化与心血管危险因素之问无明显联系。但在血压正常的视网膜病变患者中同样发现脑卒中增加。这些研究没有对高血压脏器损害的其他预测因子进行调整。 结论 研究表明，高血压患者常规进行眼底检查有额外价值的观点尚缺乏证据。     

Motor profile and cognitive functioning in children with spina bifida

BackgroundSpina bifida is a complex neuroembryological disorder resulting from incomplete closure of the posterior neural tube. Morbidity in the different fields of motor and cognitive neurodevelopment is variable in nature and severity, and often hard to predict.AimsThe current study investigates the relationship between cognitive functioning, fine motor performance and motor quality in children with spina bifida myelomeningocele (SBM) and SB-only, taking into consideration the cerebral malformations.Material and methodsForty-one children were included (22 girls and 19 boys aged between 6 and 14 years, mean age 10;0 years) in the study. A comprehensive assessment was conducted of cognitive functioning and motor profile, including fine motor and visual-motor functioning, and motor quality. The performance outcomes were analyzed for the total group of children and separately for the nonretarded children (FSIQ ≥ 70, N = 30) to eliminate the influence of global intellectual impairment.ResultsAlthough the children with spina bifida showed increased incidence of cognitive and fine motor impairment, and impaired motor quality, after exclusion of the overall retarded children no associations were found between cognitive functioning and motor profile. In the comparison of SBM to SB-only specific differences were found for performance IQ, visual-motor functioning and motor quality, but not fine motor functioning.ConclusionOur findings underscore the role of cerebral malformation in spina bifida and its consequences for neuropsychological functioning. The complicated developmental interactions found strengthen the need for an individualized management of children with SB.     

Passive administration of purified secretory IgA from human colostrum induces protection against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> in a murine model of progressive pulmonary infection

Background

Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections.

Materials and methods

Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated.

Results

The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury.

Conclusions

HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model.

     

NF‐κB‐inducing kinase is a key regulator of inflammation‐induced and tumour‐associated angiogenesis

Angiogenesis is essential during development and in pathological conditions such as chronic inflammation and cancer progression. Inhibition of angiogenesis by targeting vascular endothelial growth factor (VEGF) blocks disease progression, but most patients eventually develop resistance which may result from compensatory signalling pathways. In endothelial cells (ECs), expression of the pro‐angiogenic chemokine CXCL12 is regulated by non‐canonical nuclear factor (NF)‐κB signalling. Here, we report that NF‐κB‐inducing kinase (NIK) and subsequent non‐canonical NF‐κB signalling regulate both inflammation‐induced and tumour‐associated angiogenesis. NIK is highly expressed in endothelial cells (ECs) in tumour tissues and inflamed rheumatoid arthritis synovial tissue. Furthermore, non‐canonical NF‐κB signalling in human microvascular ECs significantly enhanced vascular tube formation, which was completely blocked by siRNA targeting NIK. Interestingly, Nik^?/? mice exhibited normal angiogenesis during development and unaltered TNFα‐ or VEGF‐induced angiogenic responses, whereas angiogenesis induced by non‐canonical NF‐κB stimuli was significantly reduced. In addition, angiogenesis in experimental arthritis and a murine tumour model was severely impaired in these mice. These studies provide evidence for a role of non‐canonical NF‐κB signalling in pathological angiogenesis, and identify NIK as a potential therapeutic target in chronic inflammatory diseases and tumour neoangiogenesis. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain

Manganese‐enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron‐emitting isotope ⁵²Mn has prompted interest in the use of Mn²⁺ as a dual‐modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn²⁺ and radioactive ⁵²Mn²⁺ in the rat brain for MRI and PET, respectively. Additionally, we examined the biodistribution of two formulations of ⁵²Mn²⁺ in the rat. In MRI, maximum uptake was observed one day following delivery of the highest MnCl₂ dose tested (60 mg/kg), with some brain regions showing delayed maximum enhancement 2–4 days following delivery. In PET, we observed low brain uptake after systemic delivery, with a maximum of approximately 0.2% ID/g. We also studied the effect of final formulation vehicle (saline compared with MnCl₂) on ⁵²Mn²⁺ organ biodistribution and brain uptake. We observed that the addition of bulk Mn²⁺ carrier to ⁵²Mn²⁺ in solution resulted in significantly reduced ⁵²Mn²⁺ uptake in the majority of organs, including the brain. These results lay the groundwork for further development of ⁵²Mn PET or dual Mn‐enhanced PET–MR neuroimaging in rodents, and indicate several interesting potential applications of ⁵²Mn PET in other organs and systems. Copyright © 2016 John Wiley & Sons, Ltd.     

IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayers

Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34⁺ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4. Furthermore, we demonstrate that our in vitro tip cell model can be exploited to investigate cellular and molecular mechanisms in tip cells and to discover novel targets for anti-angiogenesis therapy in patients. Small interfering RNA (siRNA) was used to knockdown gene expression of the known tip cell genes angiopoietin 2 (ANGPT2) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), which resulted in similar effects on tip cells and sprouting as compared to inhibition of tip cells in vivo. Finally, we identified two novel tip cell-specific genes in CD34⁺ tip cells in vitro: insulin-like growth factor 2 (IGF2) and IGF-1-receptor (IGF1R). Knockdown of these genes resulted in a significant decrease in the fraction of tip cells and in the extent of sprouting in vitro and in vivo. In conclusion, this study shows that by using our in vitro tip cell model, two novel essential tip cells genes are identified.     

Race,ethnicity, and the risk of sudden death,

Sudden cardiac death (SCD) is a major cause of death worldwide, with an estimated U.S. annual incidence of 350,000 [1]. This review will examine the influence of race and ethnicity on SCD burden and risk factors, and review the available literature on resuscitation outcomes and primary prevention of SCD. An improved understanding of associations between race, ethnicity, and SCD may provide clues to mechanisms, lead to improved prevention of SCD, and ultimately reduce racial and ethnic disparities in the burden of SCD.