The interaction between tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 promotes the recruitment of neutrophils into the ischemic brain

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in endothelial cells and perivascular astrocytes. Here, we show that TWEAK induces a dose-dependent increase in the expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) in astrocytes, and that this effect is mediated by its interaction with Fn14 via nuclear factor-κB pathway activation. Exposure to oxygen-glucose deprivation (OGD) conditions increases TWEAK and Fn14 mRNA expression in wild-type (Wt) astrocytic cultures. Likewise, incubation under OGD conditions induces the expression of MCP-1 in Wt astrocytes but not in astrocytes deficient on either TWEAK (TWEAK^−/−) or Fn14 (Fn14^−/−). We also found that TWEAK induces the passage of neutrophils to the abluminal side of an in vitro model of the blood–brain barrier. Our earlier studies indicate that cerebral ischemia increases the expression of TWEAK and Fn14 in the endothelial cell-basement membrane-astrocyte interface. Here, we report that middle cerebral artery occlusion increases the expression of MCP-1 and the recruitment of neutrophils into the ischemic tissue in Wt but not in TWEAK^−/− or Fn14^−/− mice. These novel results indicate that during cerebral ischemia, the interaction between TWEAK and Fn14 leads to the recruitment of leukocytes into the ischemic tissue.     

Environmental factors and refractive error in Chinese schoolchildren

We surveyed and assessed 2,323 schoolchildren aged seven to 17 years from four schools in China, two in the city of Tianjin and the other two in a neighbouring rural village, Ban Chau, to investigate the prevalence of refractive error and its relationship with environmental factors. Every child from each of the participating classes was recruited in this study to avoid self-selection. A questionnaire was issued which queried some aspects of the child's visual habits and home. Refraction was canied out using the Canon R-22 autorefractor. The degree and frequency of myopia in these children increased almost linearly from age seven to 17 years. There was little difference between the urban and rural groups. Of the factors explored, the number of hours spent on near work showed the best correlation with the degree of myopia, albeit only weakly.     

Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.     

Ineffectiveness of imipramine in children who fail to respond to methylphenidate

Ten hyperactive children who had failed to respond to methylphenidate were treated with imipramine in a placebo-controlled, crossover design. No significant drug effects were obtained either on parent and teacher ratings of the child's behavior or on the child's performance in a laboratory measure of sustained attention. Findings suggest that imipramine has limited clinical usefulness in the treatment of hyperactive children who fail to respond to methylphenidate. This research was supported in part by a grant to Dr. Winsberg from Ciba-Geigy Pharmaceuticals. The authors gratefully acknowledge Dr. Jeffrey Sverd and Dr. Andrew B. Bremness for their assistance in providing drug management.     

Nontuberculous mycobacteria infection after mesotherapy: preliminary report of 15 cases

BACKGROUND: Mesotherapy is an increasingly used technique which is currently causing several mycobacterial infections owing to contaminated substances being injected, and also to poor aseptic measures being held by nonprofessional practitioners. PATIENTS AND METHODS: We collected 15 cases of nontuberculous mycobacteria (NTM) infection after mesotherapy in a 6-month period. RESULTS: All patients were female with ages ranging from 19 to 52 years; the main substances injected were procaine and lecithin, and the time between mesotherapy and the appearance of the lesions varied between 1 and 12 weeks. Clinical lesions were mostly nodules and abscesses, which were localized in the abdomen and buttocks in the majority of cases. The main patient complaint was local pain but some presented with systemic symptoms such as fever and malaise. Biopsies reported granulomatous chronic inflammation in the majority of cases. Skin cultures were positive for NTM and Mycobacterium chelonae. DISCUSSION AND CONCLUSIONS: Mesotherapy not performed with quality controlled substances can be a predisposing factor for NTM infection.     

Human Capital Questionnaire: Assessment of European nurses' perceptions as indicators of human capital quality

Healthcare accreditation models generally include indicators related to healthcare employees' perceptions (e.g. satisfaction, career development, and health safety). During the accreditation process, organizations are asked to demonstrate the methods with which assessments are made. However, none of the models provide standardized systems for the assessment of employees. In this study, we analyzed the psychometric properties of an instrument for the assessment of nurses' perceptions as indicators of human capital quality in healthcare organizations. The Human Capital Questionnaire was applied to a sample of 902 nurses in four European countries (Spain, Portugal, Poland, and the UK). Exploratory factor analysis identified six factors: satisfaction with leadership, identification and commitment, satisfaction with participation, staff well‐being, career development opportunities, and motivation. The results showed the validity and reliability of the questionnaire, which when applied to healthcare organizations, provide a better understanding of nurses' perceptions, and is a parsimonious instrument for assessment and organizational accreditation. From a practical point of view, improving the quality of human capital, by analyzing nurses and other healthcare employees' perceptions, is related to workforce empowerment.     

Training in endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient’ s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been pro-posed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee’s background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide.