Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice

Pulmonary emphysema is a disease characterized by alveolar cellular loss and inflammation. Recently, excessive apoptosis of structural alveolar cells has emerged as a major mechanism in the development of emphysema. Here, we investigated the proapoptotic and monocyte chemoattractant cytokine endothelial monocyte-activating protein 2 (EMAPII). Lung-specific overexpression of EMAPII in mice caused simplification of alveolar structures, apoptosis, and macrophage accumulation, compared with that in control transgenic mice. Additionally, in a mouse model of cigarette smoke-induced (CS-induced) emphysema, EMAPII levels were significantly increased in murine lungs. This upregulation was necessary for emphysema development, as neutralizing antibodies to EMAPII resulted in reduced alveolar cell apoptosis, inflammation, and emphysema-associated structural changes in alveoli and small airways and improved lung function. The mechanism of EMAPII upregulation involved an apoptosis-dependent feed-forward loop, since caspase-3 instillation in the lung markedly increased EMAPII expression, while caspase inhibition decreased its production, even in transgenic EMAPII mice. These findings may have clinical significance, as both current smokers and ex-smoker chronic obstructive pulmonary disease (COPD) patients had increased levels of secreted EMAPII in the bronchoalveolar lavage fluid compared with that of nonsmokers. In conclusion, we suggest that EMAPII perpetuates the mechanism of CS-induced lung emphysema in mice and, given its secretory nature, is a suitable target for neutralization antibody therapy.     

Electrocardiographic predictors of culprit artery in acute inferior ST elevation myocardial infarction

Background

In acute inferior ST-segment elevation myocardial infarction (STEMI), multiple electrocardiographic algorithms have been proposed to predict the culprit artery. Our purpose is to review these and compare them to ST depression in lead aVR to predict culprit artery in inferior STEMI.

Methods

In 106 patients with acute inferior STEMI who underwent emergent coronary angiography, we correlated electrocardiographic and angiographic findings pertaining to the culprit artery. We then reviewed the algorithms proposed by Fiol et al and Tierala et al, and applied them and our own from Kanei et al using ST depression in aVR for predicting the left circumflex artery (LCx) as the culprit, to the population. Finally, we compared the sensitivities and specificities of the respective algorithms for predicting the culprit artery.

Results

The sensitivity and specificity of ST depression in lead aVR to predict LCx as the culprit were 53% and 86%, respectively, and 86% and 55%, respectively for predicting the right coronary artery (RCA) as the culprit. When their algorithms were applied to our population, the sensitivities and specificities of Fiol et al and Tierala et al were slightly higher.

Conclusion

Compared to other proposed algorithms, ST depression in aVR is a simple method with satisfactory sensitivity and specificity to predict the culprit artery in inferior STEMI.     

Multidomain cognitive impairment in non-hospitalized patients with the post-COVID-19 syndrome: results from a prospective monocentric cohort

Journal of Neurology - A fraction of patients with asymptomatic to mild/moderate acute COVID-19 disease report cognitive deficits as part of the post-COVID-19 syndrome. This study aimed to assess...     

Magnetic resonance imaging of shoulder arthropathies

The role of magnetic resonance imaging in evaluating shoulder arthropathies is evolving. This article reviews 4 of the major arthropathies: septic arthritis, rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) deposition disease, and hydroxyapatite disease (HAD), with special attention to their magnetic resonance imaging features. Comfort with identifying these entities allows appropriate and prompt treatment, which is critical for joint preservation in the case of infection, for maximal therapeutic efficacy of disease-modifying drugs in the case of rheumatoid arthritis, and for expediting symptomatic relief in the cases of CPPD deposition disease and HAD.     

Avoiding CT scans in children with single-suture craniosynostosis

Introduction

During the last decades, computed tomography (CT) has become the predominant imaging technique in the diagnosis of craniosynostosis. In most craniofacial centers, at least one three-dimensional (3D) computed tomographic scan is obtained in every case of suspected craniosynostosis. However, with regard to the risk of radiation exposure particularly in young infants, CT scanning and even plain radiography should be indicated extremely carefully.

Material and methods

Our current diagnostic protocol in the management of single-suture craniosynostosis is mainly based on careful clinical examination with regard to severity and degree of the abnormality and on ophthalmoscopic surveillance. Imaging techniques consist of ultrasound examination in young infants while routine plain radiographs are usually postponed to the date of surgery or the end of the first year. CT and magnetic resonance imaging (MRI) are confined to special diagnostic problems rarely encountered in isolated craniosynostosis. The results of this approach were evaluated retrospectively in 137 infants who were referred to our outpatient clinic for evaluation and/or treatment of suspected single suture craniosynostosis or positional deformity during a 2-year period (2008–2009).

Results

In 133 (97.1%) of the 137 infants, the diagnosis of single-suture craniosynostosis (n?=?110) or positional plagiocephaly (n?=?27) was achieved through clinical analysis only. Two further cases were classified by ultrasound, while the remaining two cases needed additional digital radiographs. In no case was CT scanning retrospectively considered necessary for establishing the diagnosis. Yet in 17.6% of cases, a cranial CT scan had already been performed elsewhere (n?=?16) or had been definitely scheduled (n?=?8).

Conclusion

CT scanning is rarely necessary for evaluation of single-suture craniosynostosis. Taking into account that there is a quantifiable risk of developing cancer in further lifetime, every single CT scan should be carefully indicated.     

Concordant hypermethylation of intergenic microRNA genes in human hepatocellular carcinoma as new diagnostic and prognostic marker

Epigenetic inactivation by aberrant DNA methylation has been reported for many microRNA genes in various human malignancies. However, relatively little is known about microRNA gene methylation in hepatocellular carcinoma (HCC). Therefore, a systematic screen for identification of aberrantly hypermethylated microRNA genes in HCC was initiated. The methylation status of 39 intergenic CpG island associated microRNA genes was analyzed in HCC cell lines (n = 7), immortalized hepatocytes (n = 2) and normal liver samples (n = 5). Subsequently, 13 differentially methylated microRNA genes were analyzed in primary human HCC samples (n = 40), benign liver tumors (n = 15) and the adjacent liver tissues employing pyrosequencing. Expression of microRNA genes was measured using quantitative real‐time polymerase chain reaction (RT‐PCR). In addition, DNA methylation and expression of microRNA genes were measured after DNMT1 knockdown or DNMT inhibition. Aberrant hypermethylation and concomitant reduction in expression of intergenic microRNA genes is a frequent event in human HCC: hsa‐mir‐9‐2 (23%), hsa‐mir‐9‐3 (50 %), hsa‐mir‐124‐1 (20%), hsa‐mir‐124‐2 (13%), hsa‐mir‐124‐3 (43%), hsa‐mir‐129‐2 (58%), hsa‐mir‐596 (28%) and hsa‐mir‐1247 (38%). Altogether, it affects 90% of the HCC specimens under study. MicroRNA gene methylation is not found in hepatocellular adenoma (n = 10) and focal nodular hyperplasia (n = 5). DNMT1 knockdown or DNMT inhibition reduced microRNA gene methylation and stimulated expression. In primary human HCC specimens hypermethylation and expression of microRNA genes showed an inverse correlation. Concordant hypermethylation of three or more microRNA genes is a highly specific marker for the detection of HCC and for poor prognosis.     

长波紫外线照射对培养人表皮黑素细胞与真皮成纤维细胞抗氧化活性影响

目的对比观察了长波紫外线（uvA）照射对培养人表皮黑素细胞与真皮成纤维细胞过氧化氢酶（CAT）蛋白表达以及DNA氧化产物8一羟基一脱氧鸟苷（8-oxo—dG）生成的影响,旨在认识除生成黑素以外黑素细胞具有的抗氧化机制。方法建立人成纤维细胞及人黑素细胞原代和传代培养。培养细胞给予不同剂量（0,3,5,25J,cm2）UVA照射,孵育3h后,用间接免疫荧光的方法检测CAT和8-oxo—dG的水平。结果3J／cm。UVA照射后,成纤维细胞CAT蛋白表达与假照射组对比明显增加（尺0．001）,8-oxo—dG荧光强度差别无统计学意义（降0．918）;黑素细胞中CAT蛋白表达与假照射组对比明显减少（P〈0．001）,8-oxo—dG荧光强度显著增加（P=0．002）。结论表皮黑素细胞对氧化应激存在固有的敏感性,且暴露UVA介导的氧化应激后黑素细胞缺乏适应性上调CAT表达,这些机制可能关系到白癜风皮损黑素细胞氧化损伤的发生。     

Protocoles de replacement d’embryons congelés : le cycle spontané donne-t-il de bons résultats ?

ObjectiveFrozen embryos’ transfer optimize the pregnancy rates per retrieval. In France, 60% of transfer cycles occur in stimulated cycles. The aim of this study was to evaluate the outcomes of frozen embryo transfers in spontaneous, substituted and stimulated cycle.Patients and methodsThis retrospective study includes patients who are 18–43 years old and had a frozen embryo transfer between 1st January 2008 and 31st December 2008. Three transfer protocols have been used: the spontaneous cycle (group 1), substituted cycle (group 2), and stimulated cycle (group 3). The characteristics of couples, embryonic parameters and data transfer cycles, and their outcomes were evaluated.Result(s)Among the 333 patients, 132 were included in the first group, 24 in the second group and 177 in the third group. After checking the homogeneity of the three groups, we found pregnancy rates (respectively 20.49 vs 13.04% and 11.32%, P = 0.0348), and deliveries (respectively 13.93 vs 8,7 and 6.29%, P = 0.0314), significantly higher in spontaneous cycles.Discussion and conclusionCurrently there is no consensus on the best technique for endometrial preparation for frozen embryo transfer. Our results support transfers in spontaneous cycle for normo-ovulating patients. Natural cycles can achieve good pregnancy rates while minimizing the costs and side effects.